ROBERT A. BILOTT 859.547.4306 bilott@taftlaw.com Taft/ 1717 Dixie Highway, Suite 910/ Covington, Kentucky 41011-4704 Tel: 859.331.2838 Fax: 513.381.6613 September 5, 2017 CERTIFIED MAIL RETURN RECEIPT REQUESTED Brenda Fitzgerald, MD. Director Centers for Disease Control and Prevention Administrator, Agency for Toxic Substances and Disease Registry US. Department of Health Human Services 1600 Clifton Road Atlanta, GA 30329-4027 Patrick Breyese, CIH Director Agency for Toxic Substances and Disease Registry Center for Disease Control 200 Independence Ave, SW. Washington, DC 20201 Scott Pruitt Administrator United States Environmental Protection Agency William Jefferson Clinton Building 1200 Ave, NW. Mail Code: 1101A Washington, DC 20460 Jeff Sessions, Esq. United States Attorney General United States Department of Justice 950 Ave, NW. Washington, DC 20530?0001 Re: Request for Coordinated Nationwide PFAS Health Study and Testing and Notice of Intent to Sue Ladies and Gentlemen: For many years, unusually high rates of cancer and other adverse health effects have been observed among our nation?s fire fighters and emergency responders (collectively ?Responders?), particularly among Responders who handle or use firefighting foams made with highly fluorinated chemicals (per? and polyfluoralkyl substances, including PFOA and PFOS) collectively referred to as or wear gear Taft Stettinius Hollister LLP Chicago Cincinnati Cleveland Columbus/ Dayton Indianapolis! Northern Kentucky] Phoenix September 5, 2017 Page 2 treated or made with such PFAS materials (collectively Equipment?). EPA acknowledged the risks posed by the entire family of PFAS in its ?Long?Chain Perfluorinated Chemicals (PFCs) Action Plan,? which was released over seven years ago, but has never been fully implemented. (See Ex. A (excerpts).) EPA has, however, recently confirmed that at least one PFAS PFOA - poses sufficient ?potential adverse effects for the environment and human health based on its toxicity, mobility, and bioaccumulation potential? to support investigating and addressing its presence under the federal Superfund law codified in the Comprehensive Environmental Response and Liability Act of 1980, as amended, 42 U.S.C. 9601 et seq. (See Ex. (excerpts) at 9.) Through the authority granted to ATSDR under that same Superfund law, ATSDR has classified PFAS as a class of chemicals that meet the definition of ?toxic substance? within the scope of purview.1 Consequently, ATSDR has developed a draft toxicological profile for PFAS, issued various statements and guidance to impacted individuals and physicians dealing with certain PFAS exposures, and even agreed to partner with a handful of state or local entities investigating specific instances of specific types of PFAS contamination in specific communities. (See Ex. C.) To date, however, ATSDR has not embarked on any coordinated, comprehensive nationwide study or investigation of the impacts on the health of Responders from their use and exposure to PFAS Equipment, or associated testing of all such impacted individuals. We write to request that ATSDR move forward immediately with such a national study and testing. As explained below, ATSDR has the clear power and authority to mandate a national study of PFAS health impacts and associated testing among Responders exposed to PFAS Equipment, has access to mechanisms to secure funding from responsible parties, and has a proven model to follow to implement such a study/testing. Based on our past decade of experience designing and overseeing a project to assess human health impacts from one such PFAS PFOA we stand ready to assist ATSDR in overseeing the design and implementation of a nationwide study and testing focusing on Responder exposure to the entire class of PFAS chemicals through a program that could encompass and involve all affected parties, including manufacturers, impacted Responders, and affected governmental entities/contractors and regulators, in a way that provides everyone with independent, credible scientific answers and certainty. l. ATSDR Has The Authority To Require A National PFAS Health Study and Testing And Ability To Secure Full Funding For Such Work. Under Section 104 of CERCLA, ATSDR shall "provide medical care and testing to exposed individuals, including but not limited to tissue sampling, chromosomal testing where appropriate, epidemiological studies, or any other assistance appropriate under the circumstances? in situations involving ?public health emergencies caused or believed to be caused by exposure to toxic substances.? (42 U.S.C. 1 See also 42 U.S.C. 9604(i)(18). September 5, 2017 Page 3 This is a non-discretionary mandate. Thus, under this provision of CERCLA, ATSDR (which, as noted above, already has classified PFAS as a ?toxic substance?) is not only authorized to conduct epidemiological studies and testing in circumstances where there have been excessive PFAS exposures, but is required to do so. EPA repeatedly has indicated that situations involving excessive levels of PFAS exposure qualify as public health emergencies mandating cessation of such exposures. For example, as early as 2002, EPA entered a consent order in which it found that levels of a PFAS (PFOA) exceeding the non-regulatory threshold used by EPA at that time presented a sufficient threat of ?imminent and substantial endangerment? to warrant the provision soon as practicable? of alternative drinking water to those exposed. (See Ex. (excerpts).) EPA entered similar orders noting the threat of such ?imminent and substantial endangerment? from excessive PFAS levels in drinking water, mandating immediate alternate drinking water supplies, after EPA adopted its first provisional health advisory guidelines for short-term exposures to two different PFAS materials (PFOA and PFOS) in 2009. (See Ex. (excerpts).) EPA reaffirmed this position as recently as January 2017 when it modified one of those same consent orders to require immediate clean water if levels of PFAS exceeded new long? term health advisory level of no more than 0.07 for individual or combined levels of PFOA and PFOS. (See Ex. F.) EPA noted that these new, lower PFAS drinking water guidelines were based on review of ?the best available peer-reviewed studies" indicating that exposure to these PFAS ?may result in adverse health effects, including developmental effects to fetuses during pregnancy or to breastfed infants low birth weight, accelerated puberty, skeletal variations), cancer testicular, kidney) liver effects tissue damage), immune effects antibody production and immunity), thyroid effects and other effects cholesterol changes)? (Ex. G.) actions to date confirm its recognition that studying PFAS contamination issues falls squarely within its broad authority. As recently as May 23 of this year, ATSDR released the results of its own assessment of whether an epidemiological study by the Agency of those exposed to PFAS contamination would be feasible. (Ex. (excerpts).) ATSDR confirmed in the context of evaluating the feasibility of studying adverse health effects among the adults, children, and military personnel exposed to multiple PFAS compounds in drinking water at the Pease International Tradeport that undertaking such a study could generate important ?scientific knowledge about the health effects of PFAS exposures, in particular, PFOS and exposures,? if the study could be designed to encompass a sufficiently large population of impacted people. (Id. at 2.) In order to properly and thoroughly study certain types of less common diseases (including cancer) associated with these PFAS exposures, ATSDR acknowledged that there would need to be far more than the couple hundred or even couple thousand anticipated study participants at that one site, which might be feasible if a much larger number of individuals was incorporated into the study. (Id. at 43.) September 5, 2017 Page 4 II. A Proven Model Exists For Developing A National PFAS Health Study. Settlement of a prior class action lawsuit in which we represented the plaintiff class resulted in the creation of an independent scientific panel that studied the effects of PFOA?contaminated drinking water among a class of approximately 70,000 people whose drinking water supplies in West Virginia and Ohio had been contaminated with quantifiable levels of the chemical (0.05 at the time) attributable to releases from the Washington Works manufacturing plant then-owned by E. l. du Pont de Nemours Company (?DuPont?). Through an innovative settlement with DuPont in that case (known as the ?Leach Case?), we were able to secure sufficient funds to pay for: 1) blood testing of approximately 69,000 people through a Health Project"; 2) creation of a new Science Panel? of independent, world-class epidemiologists charged with confirming which diseases were linked to PFOA exposure among the class being studied; 3) the design and implementation by the C8 Science Panel of approximately a dozen extensive epidemiological studies and retrospective exposure modeling work, including class?wide studies of the exposed population; 4) provisions for immediate and long-term clean water/water filtration; and 5) medical monitoring/testing for all class members for each disease linked to their PFOA exposure. (See and Through that settlement, we also were able to secure a binding agreement up front on how the results of the independent scientific work would be used in connection with future injury and compensation claims among the Leach Case class members, including the extent to which the independent scientific work would conclusively resolve issues of general causation as between the PFAS chemical at issue and the class member exposures. The settlement also included an agreement that all active litigation among the parties would be stayed and future filings barred (yet with all claims preserved and statutes of limitations tolled), pending the final outcome of the agreed scientific process. The work of the C8 Science Panel (and the related CB Health Project) under this prior class settlement involved only one PFAS compound (PFOA) and only one responsible party (DuPont). There is no reason, however, why this same model cannot be expanded to the current situation facing Responders across the United States involving one or more (or a combination of) the other PFAS compounds in PFAS Equipment, potentially attributable to the actions of multiple responsible parties. In fact, expanding the model to include multiple responsible parties and regulators provides the opportunity for creating a much bigger pool of funds and the opportunity to spread costs among a much bigger and more diverse group. Likewise, addressing the issue within the context of a national class provides the opportunity for the responsible parties to fashion common, global remedies that allow for uniform, consistent relief and treatment of impacted parties and greater financial, scientific, and regulatory certainty. ATSDR already has acknowledged the significance and utility of the C8 Science Panel/C8 Health Project model and work for addressing health issues related to PFAS exposures. As noted by ATSDR in its May 23, 2017, draft feasibility assessment for September 5, 2017 Page 5 studies at the Pease International Tradeport, the 08 Science Panel's/08 Health Project?s work, which focused on human impacts from PFOA contamination, allows ATSDR to focus future PFAS studies on the effects from exposure to other PFAS compounds, such as PFOS and and the synergistic/combined effects of being exposed to multiple PFAS compounds (including PFOA) at the same time. (See Ex. at 3.) In short, the C8 Science Panel and 08 Health Project work allows ATSDR to start from what is already known and addressed by the 08 Science Panel and 08 Health Project with respect to the adverse effects of PFOA, and direct its resources toward studying the effects of Responders being exposed to one or more (or a combination) of the other PFAS materials through their use of PFAS Equipment. Now Is The Time To Act. It is imperative that ATSDR take action now to respond to this ongoing, imminent and substantial threat to the health of Responders across this country. Every day, more Responders are being diagnosed with cancer or other serious illnesses after working for years with PFAS-based firefighting foams or other PFAS Equipment. Every day Responders across the country are spraying PFAS?based foams or donning gear that was made or coated with PFAS materials. (See e.g. Ex. J.) Our nation?s Responders deserve nothing less than immediate, credible, scientific answers to exactly what this mix of PFAS compounds in PFAS Equipment has done or will do to them. We already know that this particular group of Americans suffers from unusually high levels of serious disease, including multiple forms of cancer. (See Ex. I (example health study excerpts).) They have a right to know whether the same equipment they relied upon to help save lives the firefighting foam, fire-protection gear, and other PFAS Equipment has put their own lives at risk for these terrible diseases. ATSDR is uniquely endowed with the legal authority and ability to fashion a response that addresses this problem in a comprehensive, coordinated, national basis among all necessary parties. ATSDR also has the rare ability and power to require those deemed responsible for such harm, including any military or other governmental entities, to pay for and/or fund such work. (See 42 U.S.C. 9604(i)(5)(D), Given own recognition of the feasibility, importance, and need to study the effects of multiple PFAS exposures and its statutory authority and authorization to do so, continuing failure to do so provides a basis for a national class of all Responders who used PFAS Equipment to bring a citizens? suit against ATSDR to force such action in the United States District Court for the District of Columbia, sixty days after ATSDR receives written notice of its failure to comply with this statutory mandate. (See id. 9659.) This letter serves as such a notice to ATSDR on behalf of our client, Mr. John Jeffrey Hermes, 6441 Cottontail Trail, Burlington, Kentucky 41005 as a representative of a national class of all such Responders. Mr. Hermes is a prostate cancer survivor who has been a career Responder for over 25 years and has used 2 See also 42 U.S.C 9604(i)(17), 9620. September 5, 2017 Page 6 PFAS Equipment during most of that career, including PFAS-based firefighting foams and gear made and/or coated with PFAS chemicals. We remain hopeful that this matter can be resolved within the next sixty days without the need for pursuing any citizens' suit. We are available to meet with you to discuss and fashion a Consent Order or other document that will allow the matter to be addressed and resolved in a coordinated, uniform manner among all impacted parties, using the prior CB Science Panel/08 Health Project and related settlement model. If? Ince?r/ely, . fl a ., tux/Robert A. Bilo RAB: Encls. (Exs. Cc: Mr. John Jeffrey Hermes (w/encls.) EXHIBIT A US. Environmental Protection Agency . 12I3012009 Long-Chain Per?uorinated Chemicals (PFCs) Action Plan I. Overview Long?chain perfluorinated chemicals (PF are found world?wide in the environme it, wildlife, and humans. They are bioaccumulative in wildlife and humans, and are persistent in the environment. To date, signi?cant adverse effects have not been found in the general human population; however, significant adverse effects have been identi?ed in laboratory animals ar wildlife. Given the long half-life of these chemicals in humans (years), it can reasonably be anticipated that continued exposure could increase body burdens to levels that would result it adverse outcomes. (.3 Sinoe 2000, the Agency has taken various actions to help minimize the potential impa on human health and the environment, including the publication of three Signi?cant New Use Rules on perfluoroalkyl sulfonate' (PFAS) chemicals and the review of substitutes )r long?chain PFCs as part of its review process for new chemicals under New Chemicals Program. Although such actions are important steps to reducing exposure to these chemicals, EPA continues to be concerned with long?chain PFCs. Consequently, EPA intends to propose actions in 2012 under the Toxic Substances Control Act (TSCA) to address the potential risk: from long?chain PFCs. EPA intends to consider initiating SCA section 6 rulemaking for managing long?cha 11 PF Cs. If EPA can make certain ?ndings with respect to these chemicals (further analysis of 6 information will be performed as part of TSCA section 6 rulemaking), TSCA section 6 provi es authority for EPA to ban or restrict the manufacture (including import), processing, and use 0 these chemicals. A rule addressing the PFAS sub-category could expand beyond the reach of he SNURs that the Agency has promulgated over the past decade. For example, the rule could address PFAS-containing articles. A rule addressing the perfluoroalkyl carboxylate (PFAC) b- category could expand the reach of the 2010/15 PFOA Stewardship Program beyond the eighl participating companies and further address the concerns for potential PFAC exposure througi the use of PFAC?containing articles. will develop more detailed assessments to support he TSCA section 6(a) "presents or will present an unreasonable risk? ?ndings. If these more detailed assessments indicate that a different approach to risk management is appropriate, EPJ will consider additional approaches. 1 I Long-chain PF Cs are a concern for children?s health. Studies in laboratory animals have demonstrated developmental toxicity, including neonatal mortality. Children?s exposures are greater than adults due to increased intakes of food, water, and air per pound of body weight, as well as child?speci?c exposure pathways such as breast milk consumption, mouthing and ingestion of non-food items, and increased contact with the floor. Biomonitoring studies have found PFCs in cord blood and breast milk, and have reported that children have higher levels 3f 1 The terms long-chain PFCs, long?chain per?uoroalkyl sulfonate (PFAS), and long-chain per?uoroalkyl (PFAC) chemicals in this document refer only to chemicals described in the chemical identity sectio 1, including certain polymers that contain per?uorinated moieties. They do not include other PFCs, particularly thcise having shorter chain U.S. Environmental Protection Agency 1213012009 some PFCs compared to adults. Thus, given the pervasive exposure to PFCs, the persistence o" PFCs in the environment, and studies ?nding deleterious health effects, EPA will examine the potential risks to fetuses and children. 11. Introduction As part of EPA's efforts to enhance the existing chemicals program under the Toxic Substances Control Act the Agency identi?ed an initial list of widely recognized chemicals, including PF Cs, for action plan development based on their presence in human blood; persistent, bioaccumulative, and toxic characteristics; use in consumer products; production volume; and other similar factors. This Action Plan is based on initial review of readily available use, exposure, and hazard information4 on PFCs. EPA considered which of the various authorities provided under TSCA and other statutes might be appropriate to address potentialconcerns with PF Cs in developing the Action Plan. The Action Plan is intended to describe the courses of action the Agency plans to pursue in the near term to address its concerns. The Action Plan does not constitute a ?nal Agency determination or other ?nal Agency action. Regulatory proceedings indicated by the Action Plan will include appropriate opportunities for public and stakeholder input, including through notice and comment rulemaking processes. Scope of Review Continuing contributions of to the environmental/human reservoir are bes addressed using a category approach. The precursors may be polymers that are coated on a speci?c substrate. action is considering only the contribution of precursors as a source of and not ti inherent toxic effects of the polymer or exposure to dust that contains fluorinated polymers. Long-Chain Perfluoroalkyl Sulfonate (PFAS) Sub-Category The PFAS sub-category includes per?uorohexane sulfonic acid perfluorooctane sulfonic acid (PFOS) 6, and other higher homologues. The category also incluc the acid salts and precursors. 215 U.S.C. ?2601 et seq. 3 Information on PBT chemicals can be found on the EPA website at 4 Information sources customarily employed include Inventory Update Reporting (IUR) submissions; Toxic Relea? Inventory (TRI) reporting; data submitted to the I-IPV Challenge Program; existing hazard and risk assessments performed by domestic and international authorities including but not limited to US. Federal government agencies the Organization for Economic COOperation and Development, the Stockholm Convention on Persistent Organic Pollutants, Health and Environment Canada, the European Union; and others. Action plans will reference speci?c sources used. 5 cameras-scan; CAS RN: [355?46?4]. 5 org-(crag-soaH; CAS RN: [1763-23-1]. lie .65 3 5 U.S. Environmental Protection Agency 12/30/2009 Long-Chain PFAS Sub-Category PFOS Higher Homologues Salts Precursors The similarities of the chemicals within the PFAS sub-category can be establishedwhe reviewing representative structures of the different category member compounds: a. 803 where or any other group where a formal dissociation can be mad and b. where 0 2 and is any chemical moiety. where 4. Long-Chain Per?uoroalkyl Carboxylate (PFAC) Sub-Category The PFAC sub? ?category includes per?uorooctanoic acid (PF 0A) 7 and other higher homologues. The category also includes the acid salts and precursors. Long-Chain PFAC Sub-Category PFOA Higher Homologues Salts Precursors These similarities within the PFAC sub-category can be established by reviewing representative structures of the different category member compounds: a. where or any other group where a formal dissociation can be made; b. c. where is any chemical moiety; d. where is any chemical moiety; and e. where non?S, non?N hetero atom and where is any chemical moiety. 7 CA8 RN: [335-67-1]. L9 U.S. Environmental Protection Agency 12/30/2009 wheren>50rm>6. IV. Uses and Substitutes Summa? Production Volume PFAS Chemicals Commercial production of PFAS chemicals began over half a century ago. Total production from 1970 to 2002 was estimated to be about 100,000 tons (Paul A.G., 2009). By 2003, PFOS chemicals were no longer manufactured by 3M, the principal U.S. producer. However, production of PF OS-related chemicals is still ongoing in other countries, though to a much smaller extent than before 2003 (POPRC, 2007). As PFOS-based products became more strictly regulated in developed countries, production shifted to other countries. For example, manufacturers in China began large scale production in 2003 at the advent of 3M?s 2002 globa PFOS phase?out. China had an annual production in 2004 of less than 50 tons, but has increasei production dramatically in recent years, with an estimated production of more than 200 tons in 2006. Approximately 100 tons of that amount is designated for export (POPS, 2008). PFAC Chemicals World~wide production of?uorotelomers was estimated at 20 million pounds in 2006. The United States accounts for more than 50 percent of world-wide ?uorotelomer production. Textiles and apparel account for approximately 50 percent of the volume, with carpet and carp: care products accounting for the next largest share in consumer product uses. Coatings, including those for paper products, are the third largest category of consumer product uses. l?l? Fluorotelomer release sources, and consequent exposure to fluorotelomers, can be explained through the examination of the life cycle of this category of chemicals: Manufacture of Monomers 9 Manufacture of Polymers 9 Processing and Use -) Product Lille The manufacture of non?polymeric chemicals (surfactants, wetting agents, cleansers, eti.. is included in the manufacture of monomers. Some residual monomers are present in the varior raw materials and ?nal products of the different steps of manufacturing. Because each intermediate contains the same Rf moiety, the polymers also contain this moiety. The 2010/15 PFOA Stewardship Program encourages the elimination of PFAC precursors in product content. Companies reportng under PFOA Stewardship Program differentiate between the amounts of PFAC precursors present in the final polymer product as residuals and the amount present in th polymer as Rf moities. The availability of PFAC precursor from the content of residuals in fluorotelomer based polymer products (FTBP) would be small in comparison to the amount released should polymeric materials biodegrade in the environment. Potentially all monomeric, not just the small amounts of residual monomers and other monomer raw material and intermediates released at each of the four steps in the sequence above, could be PFAC precursors. VJ LU U.S. Environmental Protection Agency - 1213012009 Uses PFCs are substances with Special preperties that have thousands of important manufacturing and industrial applications. They impart valuable properties, including ?re resistance and oil, stain,- grease, and water repellency. For example, they are used to provide nc n? stick surfaces on cookware and waterproof, breathable membranes for clothing, and are used in many industry segments, including the aerospace, automotive, building/construction, chemical processing, electronics, semiconductors, and textile industries. PFAS Chemicals PFAS are chemicals that do not occur naturally in the environment. Long-charm PFAS chemicals, as de?ned in this action plan, are no longer manufactured in United States. However, there is a limited set of existing uses for which alternatives are not yet available, and which are characterized by low volume, low exposure potential, and low releases. The existing SNUR regulations on PFAS chemicals do not affect the continued use of existing stocks of the listed chemicals that had been manufactured or imported into the United States prior to the effective date of the SNURs. Existing products and formulations already in the United States containing these chemicals for example, PFOS-based ?re fighting foams produced before the rules took effect in 2002 can also still be used without providing notice to the Agency. Because the PFAS SNURs exempt articles, PFOS may be imported or processed 2 part of an article without the Agency receiving prior notice. U) PFAC Chemicals PFAC are chemicals that do not occur naturally in the environment. PF 0A is manufactured for use primarily as an aqueous dispersion agent [as the ammonium salt] in the manufacture of ?uoropolymers, which are substances with special properties that have thousan ds of important manufacturing and industrial applications. PFOA also be produced unintentionally by the degradation of some ?uordtelomers, which are not manufactured using PFOA but could degrade to PF 0A. luorotelomers are used to make polymers that impart soil, stain, grease, and water resistance to coated articles. Some fluorotelomer based products are also used as high performance surfactants in products where an even flow is essential, such as paints, coatings, cleaning products, and ?re-fighting foams for use on liquid fuel ?res. Fluorotelomer-based products can be applied to articles both at the factory and by consumers and commercial applicators in after-market uses such as carpet treatments at water repellent Sprays for apparel and footwear. FluorOpolymers, such as polytetra?uoroethylene (PTFE), which may contain some PFAC centamination, or that use PFOA as an emulsion stabilizer in aqueous dispersions, have a large U.S. market. The wire and cable industry is one of the largest segments of the ?uoropolymer market, accounting for more than 35 percent of total U.S. fluoropolymer use. Apparel makes u] about 10 percent of total ?uoropolymer use, based on total reported production volume.- Fludropolymers are used in a wide Variety of mechanical and industrial components, such as . In 2008. U.S. Environmental Protection Agency 12/30/2009 plastic gears, gaskets and sealants, pipes and tubing, O-rings, and many other products. Total US. demand for flucropolymers in 2004 was between 50,000 and 100,000 metric tons. The between 25 and 50 percent of the world consumption of other ?uoropolymers. PTFE IS the moI United States accounted for less than 25 percent of the world consumption of PTFE in 2007, aEd commonly used ?uoropolymer, and the United States consumed less than 50,000 metric tons Substitutes EPA is reviewing substitutes for PFOS, PFOA, and other long-chain PFCs under the Chemicals Program. EPA established the program under section 5 of TSCA to help manage th . potential risk from chemicals new to the marketplace. review of alternatives to long-chain PF Cs has been ongoing since 2000 and is consistent with the approaches to alternatives encouraged under the PFOA Stewardship Progra Through 2009, EPA has received and reviewed over 100 perfluorinated alternatives of various types. EPA reviews the new substances against the range of toxicity, fate, and bioaccumulatior- issues that have caused past concerns with per?uorinated substances, as well as any issues that may be raised by new chemistries (EPA, 2009b). V. Hazard Identi?cation Summary The information used by EPA for this Action Plan includes the Organisation for Economic Cooperation and Development?s (OECD) assessments of PFOS (OECD, 2002) and PFOA (OECD, 2006), Office of Pollution Prevention and Toxics? (OPPT) draft risk assessment of PFOA (EPA, 2009d), Environment Canada?s assessment (Canada, 2006), the assessment of PF OS by the Stockholm Convention on Persistent Organic Pollutants (POPS, 2009), and other sources. The summary of the toxicity information is based on these previous assessments, and where appropriate, additional'information on short? and long?chain is provided. World-Wide Distribution of PFAS and PFAC Presence in Humans PFAS and PFAC have been detected in human blood samples throughout the world. Blood samples have?been collected in countries world?wide including the United States, Japan, Canada,'Peru, Colombia, Brazil, Italy, Poland, Germany, Belgium, Sweden, India, Malaysia, Korea, China, and Australia. In addition, PFAS and PFAC have been detected in breast milk, liver, umbilical cord blood, and seminalplasma. In most cases, the analytes most often detected in human matrices, and usually in the highest concentrations, were PFOS, PFOA, and Other PFAS and PFAC detected in human tissue include per?uorooctane sulfonamide (PFOSA), sulfonamido) acetic acid sulfonamido) acetic acid or PFOSAA), perfluoroheptanoic acid per?uorononancate (PFNA), per?uorodecanoic acid (PFDEA or PFDA), per?uoroundecanoic acid (PFUA), per?uorododecanoic acid m. U.S. Environmental Protection Agency 12/30/2009 perfluorcpentanoic acid per?uorohexanoic acid (PFHXA), and per?uorobutane sulfonate (PFB S). National Health and Nutrition Examination Survey (NHANES) data show that mean levels PFOA and in the general US. population older than 12 years declined between the sampling period of 1999-2000 and 2003-2004 (Calafat, 2007). In addition, 3M reported a decline of the same chemicals from 2000 to 2006 in a group of 600 adult American Red Cross (ARC) blood donors (G. W. Olsen, Mari DC, Church TR, Ellefson ME, Reagen WK Boyd TM, Herron RM, Medhdizadehkashi Z, Nobiletti .113, Rios JA, Butenhoff JL, Zobel LR 2008). The biggest drop reported in both surveys was in PFOS in NHANES and ~60% the ARC study). Both reported ~25% decline in PFOA. NHANES reported a 10% decrease in while the ARC study reported a 30% drop. Conversely, PFNA increased by approximately 50% over 4 years in NHANES and by 100% over 6 years in the ARC study. 3N also reported a 100% increase in while the increase in NHANES was 60%. 3M report an 80% increase in PFUA. It appears that most of PFAS and PFAC do not vary much across adolescents participating in however, pooled data from 2001 -2002 indicate that most of the leve ofperfluorinated compounds are higher in children ages 3-11 years compared to adults (individual samples 2001?2002), especially for (Kate, 2009). More recent data on children are not available. It is clear that there are individuals who have been exposed to perfluorinated compounc at levels much higher than the majority of the population. Recent data indicate that individuals living near a U.S. facility that uses PFOA may have much higher PFOA serum concentrations than those currently reported for the general population (Calafat, 2007; Emmett, 2006). Presence in the Environment and Wildlife Water Log KOW values for PFOA, PFOS and other commercially available ammonium salts range from -0.52 to 6.8 (De Silva, 2008; Tomlin, 2005) and have water solubilities that range from 0.10 to 500,000 (Hekster, 2003; Kissa, 2001). Long-chain PFAC have been measured in surface waters of remote areas such as the north shore of Lake Superior, the Hudson Bay regio of Northeastern Canada, tributaries of the Pearl River in Guangzhou, China and the Yangtze River. Ice surface samples in the Canadian Arctic (Northwest Territories and Nunavut) had levels of that ranged from 5?246 pg/L for C9~Cll compounds. - Multiple studies have reported a global distribution of PFAC and PFAS that have been reported in wildlife tissue and blood samples. PFAS have also been found in a variety of aquat organisms. Most recently, four per?uorinated analytes (PFOS and PFAS: C10, C11, and 012) were found in ?llets from bluegill in selected rivers in Minnesota and North Carolina (Delinskj general, the highest concentrations in wildlife have been found in the livers of ?sh? eating animals close to industrialized areas. :d is w. U.S. Environmental Protection Agency 12/30/2009 Soil and Sediment PFOA and PFOS are considered to be resistant to degradation in soil. Levels of 09-01] PFAC have been found in remote Arctic region sediment ranging from 0.68 ug/kg 2.5 8 ug/k, PFAC are known to increase over time in sediment as observed in a 22-year study (1980-2002: of the Niagara River discharge. Sediment dwelling invertebrates such as amphipods, zebra mussels, and cray?sh have also been found to have PFOA concentrations ranging from 2.5 9 ng/ in the Raisin, St. Clair, and Calumet Rivers (MIXKannan, 2005). At the 3M Decatur, AL site, PFOA concentrations in Asiatic clams ranged from 0.51 ng/g to 1.01 ng/ g. Mussels an oysters in Tokyo Bay were found to contain PF 0A concentrations 0.660 ng/ ww and worms from the Ariake Sea in western Japan had concentrations of PFOA of 82 ng/g WW. PFAS and PFAC are Persistent, Bioaccumnlative, and Toxic Persistence and Bioaccumulatz'on in Humans and Laboratory Animals Animal studies of the straight?chain PFAS and PFAC have shown that these compound . are well absorbed orally, but poorly eliminated; they are not metabolized, and they undergo extensive uptake from enterohepatic circulation. Studies of PFOS and PFOA have shown that these compounds are distributed mainly to the serum, kidney, and liver, with liver concentratio being several times higher than serum concentrations; the distribution is mainly extracellular. Both compounds have a high af?nity for binding to B-lipoproteins, albumin, and liver fatty aci binding protein. Studies have reported PFOS, PFOA, and several other PFAS and PFAC in umbilical cord blood indicating these chemicals cross the placenta. The elimination half~lives of several PFAS and PFAC are summarized in Table 1. In general, the rate of elimination decreases with increasing chain length, although the half-life of (C6) is longer than the half-life of PFOS (C8) in humans. There is a tremendous specie difference in elimination, and elimination is greatly reduced in humans. Thus, the half-life of PFOS is 7 days in rats, 150 days in monkeys, and 5.4 years in humans. There is a gender difference in the elimination of PFOA and other PFAC in laboratory animals. Studies of PFOA in rats have shown that the gender difference is developmentally regulated, and the adult patter is achieved by sexual maturation. The reason for the species and gender differences in elimination are not well understood. These differences are hormonally controlled, and may alsi be due to the actions of organic anion transporters. A gender difference has not been found in humans, although uncertainty exists due to the small sample size. Table Comparative Rates of Elimination?r DH L.) Serum PFOS PFOA PFNA PFDA Half-life (C6) (C8) (C8) (C9) (C10) Rat 7 days 2-4 hours 2 days 59 days 6-7 days 31 days 40 days . Mouse 16 days 41 days 22 days 64 days Monkey 87 days 150 days 30 days 141 days 21 days U.S. Environmental Protection Agency I 12/3012009 Human 8.5 years 5.4 years 2.3?3.8 years *Red females; blue - males Regardless of chain length, it is critical to note that the half-lives of these compounds a 'e measured in hours to days to months in rats, mice and monkeys, but years in humans. This met ns that these compounds will persist and bioaccumulate in humans, and comparatively low exposures can result in large body burdens. The gender and species differences in elimination also indicate that comparisons of toxicological effects must utilize some measure of body burd :11 rather than administered dose. Persistence and Biodccumulation in the Environment PFOS and longer chain PFAC C8) bioaccumulate and persist in protein-rich compartments of fish, birds, and marine mammals such as carcass, blood, and liver (Condor, 2008). Studies have found fish bioconcentration factor (BCF) values for C8 to C14 PFAC ranging from 4 40,000 in rainbow trout (Martin, 2003). Fish BCF values for PFAS are relatively lower (4-4900). There are two BCF study results for long chain PFAC with BCF values from 4,7000 to 4,800 for perfluorohexadecanic acid (016) in carp and BCF values from 320 to 430 for per?uorooctadecanoic acid (018) in carp (Martin, 2003). Available evidence shows the likely potential for bioaccumulation or biomagni?cations in marine or terrestrial species. This is due to conformational changes into a helical structure in the molecule resulting in a smaller cross-sectional diameter as chain length increases which can lead to the ability to accumulate in organisms (NITB, 2002a, 2002b). Additional evidence that C14 and C15 PFAC bioaccumulate and are bioavailable is their presence in ?sh, invertebrates, and polar bears. The bioaccumulation of PFOS and PFAC (C8 through C14) in air?breathing animals birds an mammals) is thought to represent biomagni?cation due to high gastrointestinal uptake and slow respiratory elimination (B. Kelly, MG Ikonomou, JD Blair, Surridge, Hoover, Grace, APC Gobas 2009; B. C. Kelly, Ikonomou MG, Blair JD, Morin AE, Gobas APC, 2007). In addition Conder et a1. state that the bioaccumulation and bioconcentration potential of PFAC are directly related to the length of the per?uorinated chain, and PFAS are more bioaccumulative than PFAC of the same chain length (Conder, 2008). H.- Within the PFAC and PFAS categories, the perfluorinated and sulfonic acids (Rf from C5 to C20) are persistent chemicals that are resistant to degradation under environmental conditions. Even the reaction of precursors with hydroxyl radicals in the atmosphere are considered to be so slow that long range transport is considered a viable exposure pathway (Hurley, 2004; G. W. Olsen, DC Mari, WK Reagen, ME Ellefson,? DJ Ehresman, Butenhoff, LR Zobel, 2007). Toxicity in Humans Until recently, epidemiological and medical surveillance studies have been conducted primarily in the United States on workers occupationally exposed to POSF?based fluorochemicals. These studies specifically examined PFOS or PFOA exposures and possible adverse outcomes. One occupational study of exposures to a PFNA surfactant blend was U.S. Environmental Protection Agency - 1213012009 undertaken. The studies on PFOS and PF 0A include mortality and cancer incidence studies, a study examining potential endocrine effects, an ?episcides-ofpare? study evaluating worker insurance claims data, and worker surveillance studies examining associations between primar 1y PFOS and/or PFOA serum concentrations and hematology, hormonal and clinical chemistry parameters. The PFNA study examined liver enzymes and blood lipid levels. In general,'no consistent association between serum ?uorochemical levels and adverse health effects has been observed. Toxicity in Laboratory Animals PFOA The toxicity has been extensively studied. Repeated?dose studies in rats have shown reduced body weight, hepatotoxicity, reduced cholesterol, and a steep dose-response curve for mortality. Due to gender differences in elimination, adult male rats exhibit effects at lower administered doses than adult female rats. Thus, dietary exposure for 90 days resulted in signi?cant increases in liver weight and hepatocellular hypertrophy in female rats at 1000 ppmi (76.5 .mg/kg?day) and in male rats at doses as low as 100 (5 Studies in i nonhuman primates have shown similar effects at doses as low as 3 mg/kg?day, although the reduction in cholesterol has not been observed. The carcinogenic potential of PFOA has been investigated in two dietary carcinogenicity studies in Sprague-Dawley rats, and has been shown to induce hepatocellular adenomas, Leydig,r - cell tumors, and pancreatic acinar tumors. It has not been shown to be mutagenic in a variety of assays. There is sufficient evidence to indicate that PFOA is a PPARd-agonist and that the liver carcinogenicity (and toxicity) of PFOA is mediated by PPAROL in the liver in rats. There is no evidence that the liver toxicity in nonhuman primates is due to PPARot-agonism. There is controversy over the relevance of this particular mode of action for humans. The mode of actio for the Leydig cell tumors and pancreatic acinar tumors has not been established, and therefore these are assumed to be relevant for humans. Several studies have shown that PFOA is immunotcxic in mice. PFOA causes thymic and splenic atrophy, and has been shown to be immun'osuppressive in both in vivo and ex vivo systems. Studies using transgenic mice showed that the was involved in causing the adverse effects to the immune system. Standard prenatal developmental toxicity studies in rats and rabbits in which pregnant . animals are exposed only during gestation and sacri?ced prior to the birth of the pups have not! shown many effects. Thus, there was no evidence of developmental toxicity after exposure to doses as high as 150 mg/kg?day in an oral prenatal developmental toxicity study in rats. In a rat inhalation prenatal developmental toxicity study, the NOAEL and LOAEL for developmental toxicity were 10 and 25 mg/m3, respectively. In a rabbit oral prenatal developmental toxicity study there was a signi?cant increase in skeletal variations after exposure to 5 mg/kg?day, and the NOAEL was 1.5 mg/kg?day. However, the potential developmental toxicity of PFOA is evident when the pups are evaluated during the postnatal period. Thus, a two-generation reproductive toxicity study in rat; 10 U.S. Environmental Protection Agency 1213012009 showed a reduction in F1 pup mean body weight during lactation at 30 mg/kg-day group and during the post-weaning period at 10 mg/kg-day. In addition, there was a signi?cant increase it mortality mainly during the ?rst few days after weaning, and a signi?cant delay in the timing sexual maturation for F1 male and female pups at 30 mg/kg-day. Due to the rapid elimination of PFOA in female rats, many researchers have examined the developmental toxicity of PFOA in mice. These studies have shown a pattern of developmental effects similar to those observed with PFOS. Full liter resorptions were noted a1 40 mg/kg?day and the percent of live fetuses and fetal body weight were reduced at 20 mg/kg- day. The most notable effect of prenatal eXposure to PFOA was the severe compromise of postnatal survival at doses as low as 5 mg/kg-day, and the postnatal growth impairment and developmental delays noted among the survivors; the BMD5 and BMDL5 for neonatal survival 'Were estimated at 2.84 and 1.09 mg/kg?day, respectively. Additional studies in mice have shov that PFOA exposure causes a signi?cant reduction in mammary gland differentiation in and stunted mammary gland development in the female pups. Several studies have examined the mode of action for the developmental effects. These have shown that exposure to a dose of 20 mg/kg?day for 2 days late in gestation is suf?cient to cause the neonatal mortality in mice. Studies with PPARCL knockout mice have shown that the is required for the neonatal mortality and expression of one copy of this gene is suf?cient. This is in contrast to the studies showing that PPARDL is not involved in the neonatal; mortality associated with PFOS exposure. Although there is controversy over the human relevance of the PPARor-agonist hepatotoxicity observed in rodents, the role of in development and particularly in the PFOA-induced neonatal mortality observed in mice is unknown; therefore this mode of action is assumed to be relevant for humans. Other Chemicals Although there is an extensive database for PFOA, few studies have examined the toxicity of the shorter or longer chained PFAC. However, the data suggest that the toxicity pro?le is quite similar to that of PF 0A, albeit at different dose levels presumably due to the differences in elimination half-life. Although standard repeated-dose toxicity studies have not been conducted on the with chain greater than PFOA, many studies have been conducted examining the potential for hepatomegaly and peroxisome proliferation (a marker for the activation of . Kudo et. al. found that PFOA, PFNA, and PFDA induced the activity of peroxisomal oxidation in male rats (2000). Kudo et al. showed that all PFAC with six? to nine-carbon lengtl chains induced hepatomegaly and peroxisomal B-oxidase activity in mice, and the potency was in the order of PFNA PF CA perfluoroheptanoic acid (2006). Permadi et al. also showed PFDA induces hepatomegaly and hepatic peroxisomal palmitoyl?CoA oxidase (1993). Thus, . these studies indicate that the PFAC with a carbon chain length of eight and greater activate The differences in potency probably re?ect the differences in the half-life of the varying chain Despite the lack of traditional toxicity studies, it is reasonable to conclude that these compounds would likely produce similar effects as those observed with PF 0A. 11 the dams 1 in 1 US. Environmental Protection Agency . 12/30/2009 With respect to the potential developmental effects of PFAC with carbon chain greater than C8, EPA is completing a developmental toxicity study of PFNA in mice (C. Lau, personal communication, 2009). Maternal body weight gain was reduced at 3 mg/kg?day, and severe toxicity was observed at 10 mg/kg?day. Neonatal survival was compromised at 5 mg/kg day, and signi?cant lags in neonatal growth were observed at 3 mg/kg-day. Thus, this study shows a pattern of effects very similar to those observed with PFOA. It is likely that PFAC with carbon chain greater than nine would also result in similar effects, and that the potency would be dependent on the half-life'of the compound. PF OS The toxicity of PF OS has also been extensively studied and was summarized in OECD. report (2002) and by Lau et al. (2006). Repeated~dose studies in rats and nonhuman primates 5 have shown reduced body weight, hepatotoxicity, reduced cholesterol, and a steep dose-respon Se curve for mortality. These effects occur in nonhuman primates at doses as low as 0.75 mg/kg- day, and in rats at 2 mg/kg?day. The carcinogenic potential of PFOS has been investigated in a dietary carcinogenicity study in Sprague-Dawley rats, and has been shown to induce hepatocellular adenomas at 20 ppm. In addition, thyroid follicular cell adenomas were observed in male rats that had been allowed to ?recover? for a year following treatment for one year; the reason for this is unclear. However, thyroid follicular tumors have also been observed in rats exposed to a major i precursor of PFOS. PF OS has not been shown to be mutagenic in a variety of assays. Although PFOS can activate the data are not suf?cient to establish a PPARor-agonist mode of action for the liver tumors. A standard prenatal developmental toxicity study in rats has shown a signi?cant decrease in fetal body weight and signi?cant increase in external and visceral anomalies, delayed ossi?cation, and skeletal variations; of 1 mg/kg-day and a LOAEL of 5 mg/kg-day for developmental toxicity were indicated. In rabbits, signi?cant reductions in fetal body weight ahd signi?cant increases in delayed ossi?cation were observed; a NOAEL of 1.0 mg/kg?day and a LOAEL of 2.5 mg/kg?day for developmental toxicity were indicated. A two-generation reproductive toxicity study in rats showed neonatal mortality. All F1 pups at the highest dose of 3.2 mg/lcg?day died within a day after birth, while close to 30% of the F1 pups at 1.6 mg/kg-day died within 4 days after birth. As a result of the pup mortality in the two top dose groups, only the two lowest dose groups, 0.1 and 0.4 mg/lcg?day, were continued into the second generation. The NOAEL and LOAEL for the F2 pups were 0.1 mg/kg?day and 0.4 mg/lcg?day, respectively, based on reductions in pup body weight. The results of this study prompted additional research. Studies in which pregnant rats and mice were closed during gestation and the pups were followed postnatally provided a BMD5 a 'd BMDL5 for neonatal survival of 1.07 and 0.58 mg/kg?day in rats, respectively, and 7.02 and 3. 38 mg/kg?day in mice, respectively. Studies have shown that the critical period of exposure is during late gestation. Mode of action studies initially focused on the lung and found signi?cant histological and morphometric differences in the lungs of pups treated with PFOS. However, 12 U.S. Environmental Protection Agency 1213012009 subsequent studies did not find any effect on lung phospholipids and rescuing agents failed to mitigate the neonatal mortality. Thus, the mortality does not appear to be related to lung immaturity. In contrast to PFOA, studies with knockout mice have shown that the is not involved in the neonatal mortality. Current research is focusing on the possibilit/ that the physical properties of PFOS may interfere with the normal function of pulmonary surfactant, leading to neonatal mortality. Other PFAS Chemicals A combined reproductive/developmental toxicity study of has been conducted rats. In the parental males there was a signi?cant reduction in cholesterol at doses as low as 0.3 mg/kg-day, and hepatotoxicity at doses as low as 3 mg/kg-day. There was no evidence of developmental or reproductive toxicity at doses as high as 10 mg/kg?day. Toxicity to Wildlife Adverse effects on exposed populations of organisms have been observed with exposure to perfluorinated compounds in the parts per million range. Studies have shown a reduction in hatchability of chickens when they were exposed in ovo to PFOS, and a reduction in survival in 14-day old Northern bobwhite quail from hens exposed to 10 of PFOS in the diet. In addition, a delay in growth and metamorphosis in the Northern leopard frog exposed to 3 mg/I; of PFOS has been reported, as well as reduced cumulative fecundity and fertility effects in fathead minnows exposed to 0.1 mg/L PFOS. Further evidence of potential reproductive effects has been observed with exposure to PFAC. A significant induction of vitellogenin in rainbow trout was observed in a dose-dependent manner at concentrations of C10 PFAC 0.025 6- 2000 ug/ in the diet as 'well as a weak af?nity demonstrated for the hepatic estrogen receptor from C9-CIZ PFAC. Mortality in sediment dwelling organisms such as the nematode, Caenorhabdz?tz?s elegans has been observed with concentrations of C9 up to 0.66 mM and subsequent effects in generations were found at concentrations up to as evidence by a 70 decline in fecundity. i VI. Fate CharaCterization Summary The PFAS and PFAC acids are strong acids that exist in equilibrium between the neutral form and the anionic form. Both the anionic and neutral forms of PFOA are soluble in water. While the Henry?s law constant values suggests partitioning to air for the neutral, protonated form, predicting the amount that partitions into air is complicated because there is uncertainty over the degree to which carboxylic and sulfonic acids partition from the water to atmosphere. The uncertainty arises with regard to the value of the acid dissociation constant pKa), or the fraction of the acid form present at environmentally relevant pH. PFAC and PFAS have been 3 detected in air, water, and soil samples collected throughout the world. The oceans have been suggested as the final sink and route of transport for per?uorinated carboxylic and sulfonic aci is, where they have been detected on the surface and at depths 1,000 meters (Y amashita, 2005). Some have the potential for long-range transport. They are transported over 13 U.S. Environmental Protection Agency 12/30/2009 long distances long?range transport) by a combination of dissolved-phase ocean and gas- phase atmospheric transport; however, determining which is the predominant transport pathway is complicated by the uncertainty OVer water to atmosphere partitioning. Furthermore, there is evidence that transport and subsequent oxidation of volatile alcohol precursors may contribute to the levels of PFAS PFAC in the environment. Studies by industry and academic researchers have shown that ?uorotelomer alcohols (FTOH) can be degraded by microorganisms and by abiotic processes. 8-2 FTOH and TOH cif other chain and related chemicals in mixed microbial cultures, activated sludge and soil systems have been shown to be easily degraded to form PF 0A and related perfluorinated acids. some studies have also shown that groups can be mineralized, forming shorter chain I per?uoro acids. If FTOH are absorbed from ingestion, inhalation, dermal or ocular exposure or formed in vivo by from other compounds they can be metabolized by mammals and other organisms to form per?uorinated acids and other ?uorinated compounds. FTOH can be degraded by abiotic processes in water and air to produce PFAC and various intermediates. FTOH are 5' fairly volatile. Based on atmospheric half-lives determined in chamber studies, FTOH can be transported globally. Deposition or degradation in areas far from the source can result in contamination in high latitudes and other remote locations and contribute to global background levels of PFAC and PFAS. Data submitted by industry and in the open literature show that per?uorooctane sulfonyl ?uoride (POSF) and its derivatives can be degraded under environmental conditions to form I per?uoroalkyl sulfonates and carboxylic acids. Reaction of POSF (CF with methyl or ethyl amines is used to produce N-ethyl or N?methyl per?uorooctane sulfonamidoethanols . (FUSE). Similar reactions are used to make shorter and longer chain analogs to POSF and POSF derivatives. FOSE compounds, (or CF Where R1 and R2 can be i hydrogen, methyl or longer alcohols or other organic chains), such as N?methyl and N-ethyl OSEs can be degraded though a series of intermediates to form both per?uoro carboxylic aci . and per?ucroalkyl sulfonates. Data on the degradation of individual intermediates has been us to identify these pathways and has con?rmed that these compounds can be degraded by a I number of microbial and abiotic mechanisms. Reaction with other chemical intermediates I produces other FOSA derivatives, including phOSphate esters, fatty acids esters, silanes, I carboxylates, and polymers with acrylate, urethane and other linkages. Longer and Shorter cha gn perfluoro sulfonyl derivatives have also been produced intentionally and as unintended reactioL products. Based on existing data from the open literature and CBI data, it is expected that that most, if not all, of these POSF and other chain length sulfonyl ?uorides and their derivatives will be degraded to carboxylic acids and/or sulfonate over time. Most of these compounds will hav environmental and metabolism half?lives of weeks to months. Some will be degraded faster an some will degrade more slowly, but all will eventually be degraded. Very little data?is available on the behavior of other per?uorochemicals in the environment and in vivo but the existing data suggest that they will also be degraded to form PFAC. For example, recent studies have shown that ingested mono and di polyfluoroalkyl phosphates (PAPs) can be degraded in rats to form PFOA and other PFAC in the body. They an also be degraded by microbial processes in soil and wastewater to form per?uorinated acids (D?eon, 2007). l4 U.S. Environmental Protection Agency 12/30/2009 A limited number of studies on the degradation of ?uorotelomer?based polymers have - been submitted in support of PMN submissions and existing chemicals, and published in the . open literature. Based on studies, some fluorotelomer?based polymers are subject to hydrolysis: photolysis and biodegradation to some extent. Studies have shown half-lives of a few days to hundreds of years. "n In addition, preliminary research on degradation of fluorotelomers has shown that some urethanes and acrylates biodegrade; however, half-lives and kinetics of the fluorotelomers are not yet well-de?ned. Ongoing research by Of?ce of Research and Development (0RD: research is designed to generate high quality data that will help the Agency address some key uncertainties in pathways of exposure and potential risks ?'orn PFOA These studies have shown that the per?uorinated portion of some polymers is released as the polymer is degraded by microbial or abiotic processes to form telcmer alcohols or other intermediates and that they eventually form PFAC. Polymers based on POSF and other chain length chemistries show similar degradation rates and release intermediates that further degradj to form per?uorinated acids and sulfonates. Studies have shown that some polymers can undergo indirect photolysis in soil and in aquatic systems and be degraded with half-lives of days to several years. CD VII. Exposure Characterization Summary The pattern of PFAS and PFAC contamination varies with location and among species which suggests multiple sources of emission and patterns of migration into environmental media from the sources of emission. Major pathways that enable PFOA and PFOS to get into human blood-in small quantities are not yet fully understood. Manufacturing releases are known to have contaminated local drinking water supplies in the immediate vicinity of some industrial plantsf leading to localized elevated blood levels. The widespread presence of PFOA and PFOS i precursors in human blood samples nationwide suggests other pathways of exposure, possiblyi including long range air transport, and the release of PFOA and PFOS from treated articles. Summarv of Exposure to Consumers and Children from PF Cs in Indoor Environments PFCS in Articles of Commerce '1 0RD has conducted research on 116 articles of commerce documenting that PFGL, contained in articles of commerce have the potential to be released from those articles. Article; tested and found to contain the highest levels of PFAC were carpet and carpet treatment products, various types of apparel, home textiles, thread sealant tape, floor wax and other sealants, and food contact paper and paper coatings. Carpet and carpet treatment products contained individual PFAC in levels from 0.04?14100 ng/g; food contact paper and paper coatings: ng/g; thread sealant tape and apparel: ND ng/g and ND-4640ng/g respectively; floor wax and sealer: 0.03-3720 ng/ g; and home textiles: ND-S 19 ng/g. Some of the more commonly found PFAC measured in these articles were PFNA, PFDA, PFOA and PFOS. Inhalation levels of PFOA and total 15 U.S. Environmental Protection Agency 12/30/2009 measured in carpet were 53 85 pg/cm3 and 32500 pg/cm3 respectively (Guo, 2009). Children are particularly susceptible to exposure from inhalation of PFC off-gassing carpet and carpet protectants during their earliest years when they are lying, crawling and i spending large amounts of time playing on the carpet. The signi?cantly high levels of PFC found by 0RD in carpet and carpet protectants pose an exposure concern for children through this pathway. Adults can also be exposed to PFCs in carpets through inhalation and dermal contact; Consumers and children may also be exposed to PFCs in apparel, home textiles, thread sealant; tape, ?oo?r wax, contact paper and paper coatings. Some of these articles such as paper coating for foods cannot be' ruled out for the ingestion exposure pathways for children and adults depending upon how the PFCs in the paper contacts the food and subsequently humans. ?i PF Cs in Indoor Air Another source of PFCs to the indoor environment is dust containing not only PFAC an PFAS but also fluorotelomer alcohols. Maximum indoor dust air measurements of 6:2 FTOH . were found at 804 ng/g in the house dust of eastern United States 2008). The PFAS . (ET-FOSA, chemicals were measured at 646 ng/g, 75440 ng/g, and 8860, ng/g respectively in indoor air in Canada (Shoeib, 2005). PFOA was found at 3700 ng/g in Japanese household vacuum cleaner dust (Moriwaki, 2003). Summary of Exposure to the General Ponulation PFCs in Groundwater, Freshwater, Saltwater, and Rainwater PFAC and PFAS have been found in many countries as well as in Unites States in untreated groundwater, rivers, streams, bays, estuaries, oceans and rain water. Levels of groundwater near the 3M Cottage Grove, MN industrial site have been measured as high as . 846,000 ng/l (PFOA) and in freshwater as high as 178,000 ng/l (PFBA) (Department of Health and Human Services, 2005). PFOS has been found near Cottage Grove, MN in groundwater at? levels of 371,000 ng/l and in freshwater at 18,200 ng/l. PFAC in rainwater has been measured in the United States between 0.1 and 1006 ng/l (Scott BF, 2006). Saltwater levels of PFOS have been measured in the Paci?c Ocean at 57,700 ng/l and i '1 precipitation from snow and rain in China at 545 ng/l (Liu W, 2009; Yamashita, 2005). While 3 the general population may not directly ingest these groundwater, freshwater and saltwater levels as drinking water, the ground water and freshwater containing PFCs may discharge to. surface waters from which municipalities withdraw drinking water. The general population may also experience dermal, ingestion and inhalation exposures when coming into contact with freshwar containing PFCs. Rainwater containing PFCs may contribute PFCs to vegetables and fruits in home gardens, crops grown on commercial crop lands, drinking water reservoirs, and surface waters from which drinking water is withdrawn. PF Cs in Freshwater and Saltwater ish Freshwater ?sh have been found to contain levels of PFAS and PFAC. The highest love 16 . U.S. Environmental Protection Agency 12/30/2009 of PFAS measured in the United States to date were near the 3M Cottage GroVe, MN site (Oli sci F, 2006). Liver samples of bass, walleye and carp ranged from 130-6350 ng/g PFOS wet weight. Blood samples of these same fish ranged from PFOS levels of 136-29600 ng/ml in serum. Total PF CS for the blood. of freshwater ?sh in the same area was measured at 32248 ng/ml serum. 1e highest levels of PFAC for freshwater ?sh were found near the 3M Cottage Grove, MN site at were measured for blood samples of bass, walleye, and carp in the range of2.53?21 0 ng/ml serum. For comparison, saltwater ?sh in Danish seas had measured levels of PF OS up to 156 ng/g and saltwater ?sh in Charleston Harbor South Carolina were found with PFOS levels up to 101 ng/g (Bossi R, 2005; Houde M, 2006). Risk Management Considerations Current Risk Management Summary PFAS Chemicals Following the voluntary 3M phase?out of PFAS chemicals in the United States in 2002 EPA issued SNURS to control the reintroduction of these chemicals into the US. market. Fina i rules were published on March 11, 2002 (EPA, 2002b) and December 9, 2002 (EPA, 2002a), to limit any future manufacture or importation of 88 PFAS chemicals speci?cally included in tha? phase?out. On October 9, 2007, EPA published another SNUR on 183 additional PFAS chemicals (EPA, 2007). Those actions were necessary because data showed that certain alkyl chain of the PFAS chemicals are toxic to human health,.bioaccumulate, and are persistent in the environment. PFAS chemicals are no longer manufactured in United States. However a limited set of existing uses was excluded from the SNURs because alternatives were not yet available. . Similar to the PFAS SNURS in United States, PFOS has also been restricted in the European Union, Canada, Australia and other countries, and has been nominated for inclusion in the Stockholm Convention and the Convention on Long-Range Transboundary Air Pollution (LRTAP) Persistent Organic Pollutants (POPS) protocol. At the fourth Conference of the Pattie (COP) to the Stockholm Convention on POPS, held in May 2009, delegates agreed to add PFOS, its salts, and perfluorooctane sulfonyl ?uoride (PFOSF) to Annex B, subjecting it to restrictions on production and use. Parties agreed that while the ultimate goal is the elimination of PFOS, production of the chemical may continue for limited purposes, including coatings for semiconductors, ?re?ghting foam, photo imaging, aviation hydraulic ?uids, metal plating, and certain medical devices. Countries must notify the Convention Secretariat whether they intend continue production for acceptable purposes. Countries can also ask for speci?c exemptions allowing the production of PFOS for use in the production of chemical substances used in goods such as carpets, leather and apparel, textiles, paper and packaging, coatings, and rubber and plastics (POPS, 2009). PFAC Chemicals core strategy for working towards the elimination of PFAC chemicals has beer through the PFOA Stewardship Program. Under the program, eight major companies operating 17 (D to U.S. Environmental Protection Agency 12/30/2009 in the United States committed to reduce global facility emissions and product content of PFAC chemicals by 95 percent by 2010, and to work toward eliminating emissions and product conte by 2015 (EPA, 2009a). Companies provide annual progress reports, and most companies have; reported signi?cant progress in meeting program goals. On March 7, 2006, EPA published a proposal to amend the polymer exemption rule to exclude polymers containing certain per?uoroalkyl moieties from eligibility for the exemption: :ed to go through the pre-manufacture noti?cation (PMN) review process so that EPA can better evaluate these polymers for potential effects on human health and the environment. This change to the current regulation is necessary because, based on current information, EPA can no long: (EPA, 2006). Under this proposal, polymers containing these perfluoroalkyl moieties would nc conclude that these polymers ?will not present an unreasonable risk of injury to health or the environment? under the terms of the polymer exemption rule, which is the determination necessary to support an exemption under section of TS CA. This amendment to the polymer exemption rule is a necessary complement to the PF 0A Stewardship Program and wi give EPA the necessary tools to review and control risk of PFC-based and related polymers, including those PFAS and PFAC containing polymers. In January 2009, Of?ce of Water (OW) developed Provisional Health Advisory. (PHA) values for PFOA and PFOS to mitigate potential risk from exposure to these chemicals through drinking water (EPA, 2009c). Due to limited information on the toxicity of PFCs othe than PFOA and PFOS, no attempt was made by OW at that time to develop PHA values for th. other PF Cs. OPPT and OW are working together to determine whether revised health advisory: values are needed for PFOA and PFOS. In October 2009, Of?ce of Solid Waste and Emergency Response (OSWER) us to derive sub-chronic values for PFOA and PFOS. These values may be use in the Superfund program's risk?based equations to derive Removal Action Levels and/or Screening Levels for water and other (media, as appropriate. EPA has taken the leadership role in raising the pro?le of PFCs at an international leve. stemming from Agency concerns about the role of long range transport in the environmental distribution of PFCs, and US. importation of products containing these chemicals (UNEP, 2009b). As a result of these activities, in May 2009, during the International Conference on Chemicals Management (ICCM2), delegates to the Strategic Approach to International Chemicals Management (SAICM) agreed to consider the development of stewardship pro gran and regulatory approaches to reduce emissions and content of PFAC and PFAS chemicals in products and to work towards their elimination, where feasible (UNEP, 2009a). Remaining Issues and Concerns . PFAS Chemicals PFAS chemicals are no longer manufactured in the United States but continue to be manufactured outside of the United States. Although the PFAS SNURs are an important step toward controlling any future manufacture or import of PFAS chemicals, these chemicals may 13. nt 940 (I: . U.S. Environmental Protection Agency 12/30/2009 continue to be imported into United States in articles, such as carpets, leather and apparel, textiles, paper and packaging, coatings, and rubber and plastics. - Possible scenarios of concern: 0 Direct releases to the environment from U.S. facilities as a result of few existing uses. 0 Direct releases to the environment from non-U.S. facilities, resulting in transboundary environmental tranSport to United States. 0 Articles containing PFAS chemicals. Recent research by 0RD has shown that consumer articles could release PFCS, signi?cantly increasing the magnitude and duration; exposure to humans and the environment to these chemicals. PFAC Chemicals Although the 2010/15 Stewardship Program is expected to eliminate the production of CS-based ?uorotelomers by the eight participating companies by 2015, the potential remains for continued environmental and human loading of PFAC in the United States. This is in part because companies not participating in the PFOA Stewardship Program may follow the market opportunity presented when the eight PF 0A Stewardship Program companif leave the PFAC market by 2015. This occurred with PFAS production in some Asian ccuntrie; after the 3M 2002 phase-out of PFAS chemicals in United States-(Wenya, 2008). Possible scenarios of concern: 0 Direct releases to the environment from U.S. facilities not participating in PFOA Stewardship Program. - . 0 Direct releases to the environment from non?U.S. facilities not participating in PFOA Stewardship Program, resulting in transboundary environmental transport to United States; 0 Articles, including imports, containing PFAC chemicals. These articles could release PFAC as a result of their residual content in fluorotelomer?based products and/or as the fluorotelomers-based polymers in articles biodegrade. IX. Next Steps To date, signi?cant adverse effects have not been found in general human population; however, signi?cant adverse effects have been identified in laboratory animals and wildlife. Given the long half-life of these chemicals in humans (years), it can reasonably be anticipated that continued exposure could increase body burdens to levels that would result in adverse outcomes. Consequently, EPA intends to propose actions in 2012 under TSCA to address the potential risks from long-chain PFCs. EPA intends to consider initiating TSCA section 6 rulemaking for managing long-chai? PFCs. If EPA can make certain findings with respect to these chemicals (further analysis of th -, information will be performed as part of TSCA section 6 rulemaking), TSCA section 6 provides authority for EPA to ban or restrict the manufacture (including import), processing, and use of these chemicals. A rule addressing the PFAS sub-category could expand beyond the reach ofthe SNURs that the Agency has promulgated over the past decade. For example, the rule could address PFAS?containing articles. A rule addressing the PFAC sub-category could expand the 19 of 5-1 U.S. Environmental Protection Agency 12/30/2009. reach of the 2010/15 PFOA Stewardship Program beyond the eight participating companies at further address the concerns for potential PFAC exposure through the use of PFAC~containing articles. EPA will develop more detailed assessments to support the TSCA section 6(a) or will present an unreasonable risk" ?ndings. If these more detailed assessments indicate that different approach to risk management is appropriate, EPA will consider additional approaohe EPA will continue with the 2010/15 PFOA Stewardship Program to work with ccmpar toward the elimination of long-chain PFCs from emissions and products. EPA will also contin to evaluate alternatives under New Chemicals Program and collaborate with other countries on managing PFCs. As part of the Agency?s efforts to address these-chemicals, EPA also intends to evaluate the potential for diaproportionate impact on children and other sub-populations. 20 ?its a ies ue U.S. Environmental Protection Agency 12/30/2009 X. References Bossi R, R. F., Dietz R, Sonne C, Fauser P, Dam M, Vorkamp (20 05). Preliminary screening of per?uorooctane sulfonate (PFOS) and other ?uoroohemicais in fish, birds, and marine mammals from Greenland and the Faroe Islands Environmental Pollution, 136(2), 323-329. Calafat AM, Wong LY, Kuklenyik Z, Reidy IA, Needham LL (2007). Poly?uoroalkyl chemicals in the U.S. Population: data-from the National Health and Nutrition Examination Surve}r (NHANES) 2003?2004 and comparisons with NHANES 1999-2000. . Environmental Health PerSpective, 115(11), 1596-1602. Canada (2006). Ecological ScreeningAssessment Report on Peiy?luorooctane Sub?bnate, Its Salts and Its Preours am that Contain CgijtS'Oz, CanSOg or From TOC.cfm> Condor lit/1., Hoke RA, de Wolf W, Russell MH, Bunk, RC (2008). Are PFCAs bioaccumulative? A critical revir and comparison with regulatory criteria and persistent lipophilic compounds. Environmental Science and Technology, 42, 995-1003. D'eon JC, Mabury SA (2007). Production of perfluorinated carboxylic acids (PFCAs) from the biotransformatior poly?uoroalkyl phosphate surfactants (PAPs): exploring routes of human contamination. Environmental Science and Technology, 41 (13), 4799-4805. De Silva A0 (2008). Per?uorooarboxylate isomer analysis as a tool for source elucidation Unpublished Dissertation University of Toronto. Delinsky AD, MJ, Nakayama SF, Varns JL, Ye XB, McCann PI, AB (2009). Determination ten per?uorinated' compounds in bluegill sunfish (Lepomis macrochirus) ?llets Environmental Research, 109, 97. 984. Department of Health and Human Services (2005). Health Consultation 3M Chemolite, Per?uorochemical Releo at the 3M-Cottage Grove Facility, City of Cottage Grove, Washington County, Minnesota. Emmett EA, Zhang H, Shofer FS, Freeman D, Rodway NV, Desai C, Shaw LM (2006). Community exposure to per?uorooctano ate: relationships between serum levels and certain health parameters Journal of Occupational Environmental Medicine 48(8). EPA (2002a). Peijluoroallgil Sulfonates; Signi?cant New Use Rule. from TOXJ2002/December/Day-09/t3 01 1.11 tm> EPA (2002b). Sulfonates; Signi?cant New Use Rule. . from 1 [1'5 746.htm> EPA (2006). Premanufacture Notification Exemption Polymers; Amendment of Polymer Exemption Rule to Exclude Certain Per?uorinated Polymers. from 07/12152.htm> EPA (2007). Per?uoroallgil Suljhnates; Signi?cant New Use Rule. from EPA (2009a). 2010/2015 PF 0A Stewardship Program ??om EPA (2009b). New Chemical Review of Alternatives for PFOA and Related Chemicals from EPA (2009c). Per?uorooctanoic Acid (PFOA) and Per?uorooctanoe Sulfonate (PFOS): Provisional Health AdvisU.S. Environmental Protection Agency 12/30/2009 information, from: EPA (2009d). PFOA Risk Assessment from Guo Z, Liu X, Krebs K, Roache (2009). Perfluorinated carboxylic acids (PFACs) in articles of commerce (AOCs) - II. PFAC Content in 120 New AOCs. . Environmental Science and Technology Submitted Hekster FM, Laane RW, de Voogt (2003). Environmental and toxicity effects of per?uoroalkylated substances Reviews of Environmental Contamination and Toxicology 79, 99-121. Houde MBT, Small J, Wells RS, Fair PA, Bossart GD, Solomon KR, Muir DC (2006). Biomagni?cation of per?uoroalkyl compounds in the Bottlenose Dolphin (Tursiops truncatus) food web Environmental Science and Technology, 40(3), 4138-4144. Hurley MD, Sulbaek?Anderson MP, Wellington TJ, Ellis DA, Martin JW, Maybmy SA (2004). Atmospheric chemistry of per?uorinated carboxylic acids: reaction with OH radicals and atmospheric lifetimes Journal of Physical Chemistry 108(4), 615-620. Kannan K, Tao L, Sinclair E, Pastva SD, Jude DJ, Giesy JP (2005). per?uorinated compounds in aquatic organisms at various trophic levels in a Great lakes food chain.- Archives of Contamination and Toxicology, 48, 559?566. Kato K, Calafat AM, Wong LY, Wanigatunga AA, Caudill SP,Needham LL (2009). Polyfluoroalkyl compounds in pooled sera from children participating in the National Health and Nutrition Examination Survey 2001-2002. Environmental Science and Technology, 43(7), 264172647. . Kelly B, MG Ikonomou, JD Blair, Surridge, Hoover, Grace, APC Gobas (2009). Per?uoroalkyl contaminants in an artic marine food web: Trophic magni?cation and wildlife exposure. Environmental Science and Technology, 43, 4037-4043. Kelly C, Ikonomou MG, BlairlD, Morin AB, Gobas APC (2007). Food web~speci?c biomagnifications of persistent organic pollutants. Science 317, 23 6239. Kissa, E. (2001). Fluorinated surfactants and repellents (2 New York, New York Marcel Dekker. Kudo N, Bandai N, Suzuki E, Katakura M, Kawashima (2000). Inducation by per?uorinated fatty acids with different carbon chain length peroxisomal beta-oxidation in the liver of rats Chemicology - Biological Interaction. 124, 119-132. Kudo N, Suzuki~Nakajima E, Mitsumoto A, Kawashima (2006). Responses of the liver to per?uorinated fatty acids with different carbon chain length in male and female mice: in relation to induction of heptomegaly peroxisomal beta-oxidation and microsomal Biological Pharmaceutical Bulletin 29Thibodeaux JR, Hanson RG, MG, Rogers .lM, AB, MI (2006). Effects of perfluorooctanoic acid exposure during pregnancy in the mouse. Toxicology Science 90, 510-518. Lin W, Jin Y, Quan X, Sasaki K, Saito N, Shoji F, Sato 1, Tsuda S, (2009). Per?uorosulfonates and per?uorocarboxylates in snow and rain in Dalian. Environment International 35(4), 73 7-742. Martin JW, Mabury SA, Solomon KR, Muir DC (2003). Bioconcentration and tissue distribution of perfluorinated acids in rainbow trout mykiss). Environmental Toxicology Chemistry 22, 196-204. Moriwaki H, Takata Y, Arakawa (2003). Concentrations of per?uorooctane sulfonate (PFOS) and per?uorooctanoic acid (PFOA) in vacuum cleaner dust collected in Japanese homes Journal of Environmental i Monitoring 5, 753-757. 22 U.S. Environmental Protection Agency 12/30/2009 INITE (2002b). Biodegradation and Bioaccumulation of the Existing Chemical Substances under the Chemical Substances Control Law, from start OECD (2002). Per?uorooctane Sulfonate (PFOS) and related chemical products, ?em 2649 34375 23 84378 1 1 I 37465.00.html> OECD (2006). SIDS Initial Assessment Report for Ammonium Peif?uorooctanoate and Pet?uorcoctanoic Acid. 5 Oliaei F, Kriens D, Kessler K, (200 6). Investigation ofpei?uorochemical (PF C) contamination in Minnesota, Phase One, Report to Senate Environment Committee Olsen GW, Mari DC, Reagen WK, Ellefson ME, Ehresman DJ, ButenhoffJL, Zobel LR (2007). Preliminary evidence of a decline in per?uorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) concentrations in American Red Cross blood donors. 68(1), 105-111. . Olsen GW, Mari DC, Church TR, Ellefson ME, Reagan WK, Boyd TM, Herron RM, Medhdizadehkashi Z, Nobiletti JB, Rios JA, Butenhoff IL, Zobel LR (2008). Decline in per?uorooctane sulfonate and other poly?uoroalkyl chemicals in American Red Cross adult blood donors 2000-2006. Environmental Science and Technology, 42(13), 4989-4895. Paul AG, Jones. KC, Sweetman A.J. (2009). First Global Production, Emission, and. Environmental Inventory fc Per?uorcoctane Sulfonate. Environmental Science and Technology 43, 386-392. Permadi H, Lundgren B., Anderson K, Sundberg C, DePierre (1993). Effects of per?uoro fatty acids on peroxisome proliferation and mitochondrial size in mouse liver; dose and time factors and effect of chain length. Xenbiotica, .23, 761-770. POPRC (2007). Addendum to the PFOS: Risk Management Evaluation Paper presented at the POPRC. POPS (2008). China?s Production Paper presented at the Stockholm Convention on Persistent Organic Pollutants POPS (20 09). Meeting of the Conference of the Parties of the Stockholm Convention Pap e?r presented at tl? Stockholm Convention on Persistent Organic Pollutants, Geneva, Switzerland Scott BF, Moody CA, Spencer C, Small JM, Muir DCG, Mabury SA (2006). Analysis for per?uorocarboxylic acids/anions in surface waters and precipitation using and analysis from large-volume samples Environmental Science and Technology, 40(20), 6405-6410. Shoeib M, Hamer T, Wilford BH, Jones KC, Zhu (2005). Perfluorinated sulfonamides in indoor and outdoor ai and indoor dust: occurrence, partitioning, and human exposure Environmental Science and Technology, 39(17), 6599-6606. Snynar Ml, AB (2008). Per?uorinated compounds in house dust-from Ohio and North Carolina, USA. Environmental Science and Technology, 42(10), 375 1-3 756. . Tomlin, C. (2005). N?ethyl pei?uorooctane szzb?cnamide (4151?50?2) (13 Surrey, England British Crop Protection Council UNEP (2009a). Second session of the International Conference on Chemicals Management (ICCMZ): Strategic Approach to International Chemical Management, Geneva, Switzerland 5 UNEP (2009b). Workshop on Managing Petj?luorinated Chemicals and Transitioning to Sa?er Alternatives. from i Washington W, Ellington H, Thomas Ml, Exians I Hoon Yoo, Ha?ier SC (2009). Degradability of an acrylate? 23 U.S. Environmental Protection Agency 12/30/2009 linked, fluorotelomcr polymer in soil Environmental Science and Technology, 43(17), 6617?6623. Wenya, H. (2008). PFOS related action in China Paper presented at the International. Conference on Chemicals Management Yamashita N, Kurunthachalam K, Taniyasu S, Horii Y, Petrick G, Gamo (2005). A global survey of per?uorinated acids in oceans. Marine Pollution Bulletin (8-12), 65 8-668. 24 EXHIBIT Bilott. Robert A. From: Sent: To: Subject: EPA Adds Saint-Gobain Performance Plastics Site in Hoosick Falls, N.Y. to the Federal Superfund List Contact: Elias Rodriguez, (212) 637-3664, rodrigucz.elias@epa.gov (New Yorkl N.Y. July 31, 2017) The U..S Environmental Protection Agency has added the Salnt?Gobain Perform: nce Plastics site in the Village of Hoosick Fallsl NY. to its Superfund National Priorities List (NPL) of the country?s most hazardous Waste Sites. US Environmental Protection Agency Monday, July 31, 2017 11:23 AM Bilott, Robert A. . EPA Adds Saint-Gobain Performance Plastics Site in Hoosick Falls, NY. to the Federal -. Superfund List Groundwater at the Saint?Gcbain Performance Plastics facility, located at '14 McCaffrey Street. and in other iocatio in Hoosick :Palls is contaminated with Per?uorooctanoic Acid (PFOA) and Trichlorcethylene (TCE). Adding the site to the federal Su :erfund list wil allow the EPA to work with New York State to ensure that the contamination is cleaned up and that people's health 5 protected. "My goal as Administrator is to restore the Superfund program to its rightful place at the center of the agency?s core mission. To ay; we are adding sites to the Superfund National Priorities List to ensure they are cleaned up for the bene?t of these 0 ammunities," said EPA Administrator Scott Pruitt, "When We clean up these sites, we make communities healthier places to live and ear the Way or deVelopment and increased economic activity." The McCaffrey Street facility was built in 1951. and had been used to manufacture circuit board laminates. (PTFE)-coated ?berglass and other PTFE products. In 1999, Saint?Gobain Performance Plastics purchased the facility and beg 11 operations thereI Using PFOA in its manufacturing process. PFOA belongs to a group of chemicals Used to make household an commercial products that resist heat and chemical reactions and repel oil, stains. grease and water. PFOA was wit ely used in . n- stick pots and pans, stain-resistant carpets. and water-resistant outerwear. In 2005. the EPA reached a nationwide agreement eight mantifacturers to phase out the production and use of PFOA. These manufacturers stopped using PFOA in $115. PFOA i and can pose adverse effects to human health and the environment. TCE is a volatile organic compound widely used as an industrial solvent. Exposure to TCE can have adverse health impacts. including liVer damage and persistent in the environmen increased risk of cancer. After PFOA was discovered in the public drinking water supplyI a carbon ?ltration system was installed on the Village. of Hoosic Falls water supply wells to treat the water and protect consumers. PFOA was also discovered in private wells. and spec al systems 0 ?point of entry treatment systems," or POETS. hays been installed on a number of priVate drinking water Wells. Th New York Department of Environmental Conservation (NYSDEC) and Department of Health. with Input from the EPA. have o'verseen me to address the drinking water contamination. in January 2016. the NYSDEC added the Saint-Gobain site to New York State's Superfund list and requested that the EPA incl . the site on EPA's federal Superfund list. - in April and May 2016, the EPA installed monitoring wells to sample groundwater at and around the Saint-Gobain Performance Plastics facility (McCaffrey Street facility) and sampled the Village water supply wells. The EPA also collected soil samples fro McCatfrey Street facility, Village ball?elds and recreational areas. I In June 2016, the NYSDEC entered into a legal agreement with Saint?Gobain Performance Plastics Corporation atd Honeywel international Inc. and initiated a study of the nature and extent of contamination at the site. In September 2016, the EPA proposed adding the Saint-Gcbain Performance Plastics site to the federal Superfund list. 1 The EPA has determined that the appropriate course of action to address contamination from the Saint-Gobain facility '3 to list the si on the NPL. The EPA took public comment and considered public input before ?nalizing the decision. The EPA is coorc inating all Investigation and cleanup efforts with New York State. To learn more about the Saint-Gobain Performance Plastics Sut erfund site, ease visit: t'e For Federal Register notices and supporting documents for ?nal and proposed sites. visit: und/current? Todayfs NPL update follows the announcement of the Superfund Task Force recommendations to improve the Superfund program. The task force's recommendations focused on ?ve overarching goals: expediting cleanup and remediation, reinvigorati ig cleanup and reuse efforts by potentially responsible parties. encouraging private investment to facilitate cleanup and reuse, promoting redevelopment and community revitalization and engaging with partners and stakeholders. Work to prioritize and reinvigorate the program by the task force has been initiated and will be ongoing into the future. The Superfun Task Force Recommendations can be viewed at Follow EPA Region 2 on Twitter at and visit our Facebook page, 17?049 . If you would rather not receive future communications from Environmental Protection Agencyl let us know by clicking here. Environmental Protection Agency, 290 Broadway. New York" NY 10007-1866 United States L2. United States Protection h' Agency as mg . SAINT-GOBAJN PERFORMACE PLASTICS Village of Hoosick Falls, New York Rensselaer County NATIONAL PRIORITIES LIST (NPL) G) Site Location: on, DC 204 July 20' The Saint-Gobain Performance Plastics (SGPP) site is located at 14 McCaffrey Street' 1n the Village of oosick Fal Rensselaer County, New York. The facility' IS situated" 1n the southwest corner of Hoosick Falls and along the east 31 of the Hoosic RiveI. a Site History: ls, 'de SGPP manufactures plastic materials tapes, and foams and has operated in Hoosick Falls from 1999 t: The McCaffrey Street facility was originally built In 1961 and was used for manufacturing extruded board laminates polytetra?uoroethylene (PTFE) coated ?berglass, and molded and extruded PTFE before SGPP began operations. The facility used perfluorooctanoic acid ~containing mate manufacturing process until they began phasing them out in 2003. I Site Contamination/Contaminants: the prose tapes, ciro mtermedia ials in th on ?63 eir Ground water underlying the SGPP facility and withdrawn by the public supply wells for the Village of is contaminated with PFOA above the Health Advisory and with chlorinated solvents, such as trichloroet and vinyl, chloride. tin Potential Impacts on Surrounding Community/Environment: loosick Fe Tylene (TC .E) The public supply wells in the Village of Hoosick Falls, which serve approximately 4,000 people as the drinking water, are contaminated with PFOA at concentrations above the EPA Health Advisory. In ad has been found in several private wells. Response Activities (to date). ain source .of lition, PFQA Saint?Gobain Performance Plastics installed a carbon ?ltration system. Drinking water now meets all fed standards. El Need for NFL Listing: oral and st as Ground water contaminated with PFOA 1n the public supply wells requires cleanup to protect human Ir environment. NPL listing has been determined to be the most effective approach f01 cleanup. The EP letter of support f01 placing the site on the NPL from the state of New York. [The descv I'ption of the site (Ielease) is based on information available at the time the site was evaluated with the HRS. The change as additional in?rmation is gathered on the sources and extent of contammatIon See 56 FR 5600, Februaiy 11, 199, notices. For more information about the hazardous substances identi?ed in this narrative summary, including general information regarding the at to these substances on human health, please see the Agency for Toxic Substances and Disease Regishy (ATSDR) ATSDR 'l?oxFI on the Internet at or by telephone at or 1-300-232?4636. ealth and I A receive: description or subseqn 'fects of expos- gQ_s can be fo :he i a may ent ure Ind SITE SUMMARY The Saint-Gobain Performance Plastics (SGPP) site as scored consists of. soil and ground water contaminated with trichloroethyle'ne (TCE), vinyl chloride (VC), biphenyls (PCBs), and per?uorooctanoic acid (PFOA) as a result of historical releases from the SGPP facility located at 14 McCaffrey Street in Hoosick Falls, NY. Sampling and analysis of soil and ground water by EPA in April?May 2016 document the presence of TC in facility soils, and TCB, VC, and PFOA in ground water at concentrations that meet the criteria for observed release by chemical analysis [see Section 3.1.1 of this HRS documentation record]. Sampling and analysis by EPA "the Village of Hoosick Fails municipal water supply in May 2016 document Level I actual contamination of drin.:ing water wells with VC and Level 11 actual contamination with PFOA that is attributable at least in part to the site [see Section In addition, information provided by SGPP to EPA in December 2014 documehts an obse ved . release by direct observation of PFOA to the aquifer of concern [see Section A Site Location Map is presented in Figure 1. For the SGPP site, EPA is evaluating the ground water migration pathway. The source is evaluated as soil . contaminated with cis-1,2-dichloroethylene (DCE), TCE, and F035 (Source 1) as further discussed in Section 2 4.1. Sampling and analysis by EPA in April and May 2016 showed the presence of PF 0A in soil; how ver, due to laboratory quality control issues, the data are cpnsidered unusable and will not be evaluated in this RS Documentation Record Package. The facility that currently houses SGPP was originally built in 1961 for Dodge Fibers Corp. and was used firs for producing extruded tapes and then circuit board laminates; prior to 1961 the property was vacant land [Ref 3 23]. Oak Materials Group Oak Blectronetics; a.k.a. Oak Industries) purchased the property ?om dge Fibers between 1969 and 1971 [Ref 39, p. 23]. Oak Industries operated the facility until 1987 when it was so Jd to Allied Signal Fluorglas [Ref 39, p. 23]. The property was sold to Furon Company in February 1996 [Ref 4 p. 24]. Allied Signal Fluorglas and Furon Company used the facility to manufacture polytetra?uoroethylene (PT coated ?berglass, and molded and extruded PTFE intermediates [Ref 40, p. 24]. Manufacturing processes a the facility included the use of certain non-stick coatings [Ref 40, p. 24]. Fluor0polymers used to manufacture non? stick coatings are known to include PFOA [Ref 13, p. 20; 52, p. SGPP has operated at 14 McCaffrey Street (Tax Map/Parcel No. Section 37.6, Block 3, Lot 1) since 1999 [Ref 4, p. 1; 18, p. SGPP is a Paris-based multinational corporation which manufactures a variety of polymer-based products [Ref 14, pp. The McCaf?'ey Street facility manufactures high-performance polymeric films and membranes, as well as foams for bonding, sealing, acoustical and vibrational damping, and thermal management; the facility previously used PFOA in its manufacturing processes [Ref The facility is situated near the southwest corner of Hoosick Falls and along the east side of the Hoosic River [Figure 1; Ref. 4, p. 1; 5, p. The McCaffrey Street facility historically used PFOA or raw materials containing PFOA in its manufactuing processes; since 2003, the facility has participated in the industry?s voluntary PFOA phase-out effort by purcha .ing raw materials with decreasing levels of PFOA as an ingredient. [Ref 4, p. l; 19, p. PFOA is a man?tr ade chemical that belongs to a group of ?uorine-containing chemicals called per?uorinated chemicals (PFC) [Ref 12, p. 2; 15, p. PFOA was once widely used in nonstick cookware, in surface coatings for stain?resistantcarpets land fabric, and in paper and cardboard food packaging [Ref 12, p. PFOA was also used in ?re-?ghting foam and in many products for the aerospace, automotive, building/construction, and electronic industries [Ref 12, p. 10A and related compounds are persistent in water and soil, and resistant to typical environmental degradation proce ses [Ref 15, p. PFOA poses potential adverse effects for the environment and human health based on its toxi-ity, mobility, and bioaccumulation potential [Ref 15, pp. 1, PFOA exists as a white powder or waxy white sol at room temperature, and it is water-soluble and can readily migrate from soil to ground water [Ref 15, pp. Former employees of the McCaffrey Street facility describe a powder-like smoke plume that was routinely discharged to the air from the facility?s smokestacks and settled in the valley surrounding the plant [Ref 4, The powder Was observed to cover equipment and other surfaces within the facility as well [Ref 4, p. After approximately 15 years of un?ltered emissions, filters were installed in the facility?s smokestacks in the early 19 805 [Ref 4, p. A former employee stated that the ?lters and other equipment contacted by the white powder were cleaned weekly by washing them on a hillside outside the plant [Ref 4, p. ed The Village of Hoosick Falls operates three public supply wells (Village Wells 3, 6, and the well ?eld is locr SD- Hazardous Substan Source No: 2.4.1 Hazardous Substances As discussed above, soil samples collected by SGPP in August 2015 document the presence of PFOA in feel soils. Soil and ground Water samples collected by EPA in April 2016 document the presence of TCE, cis-1,2-D and PCBs in site soils and TCE and VC in the aquifer of concern. As all of these compounds are man-m 365 lity 113) [de chemicals and do not naturally occur in the environment, the data for the samples discussed above are being considered for source documentation and are presented in Tables 1?7. The source type is contaminated 5 therefore, background soil samples are used for comparison purposes. Sampling and analysis by EPA in April May 2016 showed the presence of PFOA in SGPP facility soil; however, due to laboratory quality control issz the data are considered unusable and will not be evaluated in this HRS Documentation Record Package. oil; Imd res, TABLE 1. BACKGROUND AND SOURCE SAMPLE INFORMATION sis-1,2-DCE and TCE Field Sample CLP Sample Sample Depth Solids References ID ID Date Time (feet) Back ground Sample SGPP-SOI 5/3/2016 1550 042 I 81.7 I Source Sam Ie SGPP-SSO7B IBDSBI 4/27/2016 1710 I 1'0?12 88.7 I 22, p.24; 23,p. 84;.49, p113, 168 TABLE 2. BACKGROUND AND SOURCE SAMPLE INFORMATION PCBs Field Sample CLP Sample Sample Depth Solids References ID ID Date Time (feet) Background Sample - SGPP-SOI IBD371 I 5/3/2016 1550 0?2 I 81.7 22, p.29; 1220 Source Sam le BD3A9 4/27/2016 1650 I 0?2 7884; 49, pp.3, 1200 TABLE 3. BACKGROUND AND SOURCE CONCENTRATIONS and TCE - Maximum Background Source Concentration Concentration Field Sample ID SGPP-SOI I SGPP-SSO7B Sample Date 5/3/2016 4/27/2016 CLP Sample ID BD371 BD3B1 Depth (feet) 0?2 10-?12 - Result Result 5.1 5.1 8.4 4.2 TCE 5.1 5.1 160 4.2 References 22, p.29; 23, p. 11284; 32, pp. 3?6, 59, 160pp. 2?6, 28, 122Concentrations reported in micrograms per kilogram (pg/kg). 3 RDL Reporting Detection Limit. The analyte was analyzed for, but was not detected at a level greater than or equal to the level of the adjusted Contract Required Quantitation Limit (CRQL) SQL) for sample and method. *The RDL for each result is the CRQL adjusted for sample and method [Ref. 33, p. Since the samples were analyzed Sections through CLP, these adjusted are used in place of the HRS-de?ned sample quantitation limit (SQL) [Ref. 1.1 and - 23 . Hazardous Substances Released: . Trichloroethylene (TCE) Vinyl chloride (VC) Per?uorooctanoic Acid (PFOA) 48 GW?Observzad Rel: ase. No. 79-0143 CAS No. 75-01-4 CAS No. 335-67-1 EXHIBIT Overview Per?uorinated chemicals (PFCs) ATSDR Page 1 of2 ATSDR Agency for Toxic Substances and Dlsecxse Reglsiry Overview Per- and Polyfluoroalkyl Substances (PFAS) are a large group of man?made chemicals that have been used in industry and consumer products worldwide since the 19505. In the United Sta ges, making and using these chemicals in consumer products has greatly decreased during the laI 10 years, but people can still be exposed to PFAS because they are still present in the environ ent. Scientists have studied how PFAS affect animals? health but are still trying to understand how exposure to PFAS affects human health. Over the last decade, interest in PFAS has been grolwing. ATSDR and our State health partners are investigating exposure to PFAS at a number ofsite s. PFAS are heat oil, grease and water reSistant. The two best known groups of this family of chemicals are the perfluorocarboxylic acids (PF which include perfluorooctanoic acid (PFOA, sometimes called C8), and the perfluorosulfon ates (PFSAs), which include per?uorooctane sulfonate (PFOS). PFCAs and PFSAs do not break down easily in the environment. They also bioaccumulate, or build p, in the blood and organs of exposed humans and animals and remain there for extended periods of time. Some PFAS are precursors to PFCAs and PFSAs and can break down to those chemicals' In tt body or the environment. The largest manufacturer of PFOS voluntarily stopped producing it' In 2002. However, other countries still produce PFOS, and it can be imported into the United States' In limited quantit es. In 2006, EPA and major companies in the PFAS industry launched the 2010/2015 PFOA Stewardship Program. Companies participating in the program are working to stop producing PFOA and related chemicals by 2015. These companies include Arkema, Asahi, BASF Corporation (successor te Ciba), Clariant, Daikin, 3M/Dyneon, DuPont, and Solvay Solexis. List of Perfluorosulfonates and Perfluorocarboxylic Acids and Their Abbreviations Chemical Abstracts Chemical Abbreviation Service Registry Chemical Fo 'mula Number (CAS No.) Perfluorosulfonates (PFSAs) 8/10/2017 Overview Per?uorinated chemicals (Pli?Cs) I ATSDR age 2 of 2 Perfluorobutane suifonate PF 375?73-5 C4H F9035 Perfluorodecane sulfonate PFDS 335-77-3 F21 2335 Perfluoroheptane sulfonate - 375-92-8 C7HF15035 Perfluorohexane suifonate 432-50-7 Perfluorooctane sulfonate - P-FOS 1763~23~1 F17035 Per?uorooctanesuIfonamide PFOSA 754-91-6 025 Perfluorocarboxylic acids (PFCAs) Perfluorobutanoic acid PF BA 375-22-4 C4H F702 Perfluorodecanoic'acid PFDA 335-76?2 F19 C32- Per?uorododecanoic acid 307-55-1 . C12H F23 32 Perfluoroheptanoic acid PFH pA . 375-85?9 C7H F1302 Perfluorohexanoic acid PFHXA 307-24-4 C6H F1102 Perfluorononanoic acid PFNA 375-95-1 chFyo2 Per?uorooctanoic acid PFOA 385-67?1 caH'Flso2 Perfluor-oundecanoic acid PF UA 205 8-94?8 C11H F21 32 A Igm?mge Page last reviewed: September 18, 2015 Page last updated: May 26, 2016 Content source: Agency for Toxic Substances and Disease Registry . - 8 i1 0/2017 Health Effects of PF AS Per?uorinated chemicals (PFCs) ATSDR 1ge10f2_ Agency for Toxic Substances and Disease Registry ATSD . Health Effects of PFAS On this Page a How can people reduce the risk of exposure to How can PFAS affect people?s health?- Scientists are not yet certain about the possible health effects resulting from human exposu PFAS at levels typically found in our water and food. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate and perfluorononanoic (PFNA) have been more widely studied than other PFAS. For the most part, laboratory anim exposed to high doses of PFOA or PFAS, including the PFAS mentioned above, have shown in the liver thyroid, and pancreatic function as well as some changes In hormone levels. Bec animals and humans do not always process chemicals the same way, scientific methods are account for these differences and ensure their conclusions about chemicals are protective 0 public. Some PFAS accumulate in the human body and the levels decrease slowly over time. The ab these compounds to be stored in the body, also known as body burden, increases concerns a the possible effects on human health. Some, but not all studies in humans have shown that certain PFAS may: - affect the developing fetus and child, including possible changes in growth, learning, and behavior. decrease fertility and interfere with the body?s natural hormones, increase cholesterol, affect the immune system, and increase cancer risk. At this time, there is not enough information to evaluate the health effects of exposures to or re to add ab :hanges ause sedto fthe '2lity of ?bout ixtu res of PFAS. Further studies are needed to understand whether the same effects are caused by the same mechanism of action. 10/2017 Health Effects Per?uorinated chemicals (PFCs) ATSDR How can people reduce the risk of exposure to PFAS are found in the blood of people and animals all over the world and are present at low a variety offood products and in the environment '(air, water, soil, etc). Therefore, complet preventing exposure to PFAS is unlikely, and no effective recommendations can be made to reducing individual exposures in the general population. However, if you live near known sc PFAS contamination, you can take steps to reduce your risk of exposure to PFAS. Minnesota, Michigan, and Alabama have issued advisories cautioning consumers to either 5 limit eating fish from waters contaminated with PFOS or other PFAS. Check with your state health and environmental quality departments for any advisories in place in your area and the types and local sources of fish that are safe to eat. . A variety of consumer?products such as non-stick coatings on cookware and surface-protec coatings on clothing, carpets, and paper packaging have contained different types of PFAS ii past. But recent efforts to remove PFAS in many of these products have reduced the likelihc PFAS exposure. In addition, research has suggested that exposure from consumer products usually low, especially when compared to the impact of exposure in contaminated drinkingi contaminated food such as fish. You can contact for updated information on this topic at If you have questions or concerns about the products you use in your home, contact the Cor Prbduct Safety Commission at (800) ,638?2772. A TOE.) Page last reviewed: August 16, 2016 Page last updated: August 30, 2016 Content source: Agency for Toxic Substances and Disease Registry age 2 of2 ily 00 levels in 5 urces of 9 :op or public 9 learn :ive i the mi of is vater or - sumer {10/2017 How is ATSDR involved investigating PFAS in the environment? I Per?uorinated Page 1 of 4 ATSD Agency for Toxic Substances and Disease Registry How is ATSDR involved investigating PFAS in the environment? i ATSD is inVolved at a number of PAS-related sites, either directly orthorough assisting state and federal partners (Figure 1). As of now, most sites are related to contamination connected with PFAS production facilities or fire training areas where aqueous ?lm-forming ?re?ghting foam (AFF 1) was regularly Used. We are working with one state partner on a site where consuming contaminated fish is the concern. ATSDR involvement at sites with poly~ and per?uoroalkyl substances (PEAS) . I. Patelnlrenlianaimdei'on, I him mopzcmu ilanl?rSulionJ-nhu?esmt Basel?nlivamrJ?A hung??j .3.- mammiiay?nlent . I Emulerfauniy?ii Exposuelmungnim Dmluul [leimniirfouemm . Explanation - ?s 9 Puenmco Mi?iarysite[MSDRIpailnemadl A A - . ceSu ri?e is. ?agswiigiui?fiawa Figure 1. Perfluorlnated com pound (PFAS) sites with ATSDR. state health department, US Environmental Protection Agency, or Department of Defense anOIVement Examples include: Region 1 Joint Base Cape Cod, MA Military activities have contaminated soil at theJoint Base Cape Cod facility and the aquifer below. The contaminated aquifer provides to some raidents ofCape Cod. The MA Department of Health (MA DPH). under the AEDR Coopera?vg Agreement Erggcam 2 is evaluating whether people have been exposed to per- and polyfiuoroaikyi substances (PFAS) in the drinking water at levels high enough to cause health effects. provide help as needed. For more information about PFAS in drinking water, visit the PFAS Website at MA DPH has reviewed PFAS in recreational waters. The MA DPH fact sheet about PFAS in recreational waters is at tt .mass. 0 eohhs docs a mental invest' ations ca bcc- ec-wtr-fact-sheet. df North Bennington. VT 8/ ATSDR 10/2017 How is ATSDR involved investigating PFAS in the environment? Per?uorinated Pa The Vermont Department of Environmental Conservation (VDEC) has found perfluorooctanoic acld(P FDA) in priVate well water samples collected Ige 2 of4 North Bennington. PFOA is one ofthe chemicals In theper- and polyfluoroalkyl substances (PFAS) family. Is testing private Wells within a 1.5 mile ra iius of the former ChemFab site. which is the source of the PFOA to see how widespread the contamination Is. The Vermont Department of Health (VDH) ask I for technical support in addressing health' Issues. Visit the VT DPH for more information about PFOA at - health ont. our information about PFAS in drinking Water, visit the ATSDR PFASwebsite at foe wen/vs cdc. 0v ver 0 av envir dex. oa.as Merrimack area ofsouthern NH Cl . =or more it! . The New Hampshire Department of Environmental Services (NHDES) tested public and private drinking watersupplies in the Merrimack area. Som- of the wel is are contaminated with perfluorooctanoic acid (PFOA). The sources of PFOA are factories in the area. The New Hampshire Department of Health anicl Human Services (NH DHHS) ls attending public smeetings to address residents' health concerns. Is helping the NH DHHS address health issues through the eA ree tPro ram sclr. cdc. 0 states' I .NHDES collected water samples from public and private drinking supoplles. ATSDR is evaluating the test rsesults to determine the water may harm people's health and will provide the findings in a written more information about PFAS in drinking water. visit the ATSDR PFAS website at tt 9: Pease International Tradeport, Portsmouth, NH .atsd .cdc. ov Indexhtm The City of Portsmouth, Workingwith the NH Department ofEnvironmentai Services and the NH Department of Health and Human Services. tested Mater sport. For the Pease internationalTradeport drinking Waterwelis for chemicals in May 2014. One of three wells had elevated levels of perfluorooctane sulfonic acid the City of Portsmouth took theWell off-line. Other PFAS Were also found in Weliwater samples. and in some residential private wells located near the site. Firefighting foam used at the former Pease Air Force Base is the presumed source of PFAS. Approximately 8,000 people Work at orvislt the Pease Tradeportciai Iy. TWO daycare centers operate on the property. . The New Hampshire Department of Health and Human Services (NH DHHS). through the WW asked to help them evaluate how drinkingwater contaminated with PFOS may affect Jeople? 5 health. ATSDR is Working with NH DHHS to answer these questions and to make recommendations to protect people from further PFAS exposure. NH DHHS will write two reports, one evaluating PFAS exposure in Water at the Pease Tradeport, and one evaluating exposure from private waterwells. The re sorts will answerthe question if drinking PFAS contaminated Water at these sItes could harm people? 5 health. I NH DHHS has released a report on the blood testing results. Acopy ofthe report Is at . ATSDR has created a Community Assistance Pa nel (CAP) to receiVe in}: potential of having future health studies usingt data from the site. For more information, CAP website athtt atsdr. ov a.tsdr. .ov sites se .The NH DHHS provides information about the site at?M?Mggy?pMm?g?eas Region; Community Water Systems (CW5) and Private Wells, Gloucester County, New Jersey The Delaware River Keeper NetWork petitioned ATSDR to investigate whether residents ofGloucester County. NJ were exposed to harmful levels 0 perfluorononanoic acid (PFNA) and other PFAS in their drinking water. tit aboutthe ease ca . tm tm The NewJersey Department of Health, through the Coo ratl ent Pro . 0 states I I . is revletiting public and private watersample results to see ifpeopie have been exposed to PFAS and ifthe exposure could harm their health. Focmore information abou PFAS in drinking water. visit theATS DR PFAS website at cdc. ov fc i ht s: atsdr.cdc. ov de .ht Beglon 3 Nava Air Station Joint Reserve Base. Willow Grove, PA GroundWater at the Willow Grove Air Station Joint Reserve Base is comtamlnated with per? and polyfluoroalkyl substances (PFAS) (mainly perfluorc octane sulfonlc acid, PFOS for short. and perfluorooctanolc acid. PFOA for short). Some public water in Horsham and Warrington, and some private wells nearby are also contaminated with PFOS and PFOA. PFAS in the groundwater are likely a result ofpast use of aqueoUs film-forming ?refighting foam 5 in the area. The Department of Defense asked the Environmental Protection Agency EPA) to test private well water atthe site. Public Water utilities re collecting water samples from their systems. - EPA asked ATSDR to evaluate PFAS water test results to see if drinkingWater contaminated with these levels of PFAS could harm people's health. is eValuatlng the available water test results. For more information about PFAS in drinking water ATSDR PFAS Website .cdc. ov i. ATSDR is working with the Mid Atlantic Center for Children's Health and the Environment to answer the community's health questions and to educalie local health professionals about possible health effects caused by exposure to PFAS. ATSDR continues to Work with the PA Department of Health, throu ?i the to summarize available cancer statistics forthis area because com unity members are concerned about cancer in their community. The cancer data review for selected zip codes ofWarminster. Warrington. and Horsham. Pris is available at tt. atsdr. cdc. a CancerDataRev a DataReview 508. i atsdr. PA _508.pclf). AirWarfare Center. Wa rminster. PA 8/710/2017 How is ATSDR involved investigating PFAS in the environment?'l Per?uorinated go 3 of 4 Groundwater at the former Naval Air Warfa re Center Warminster site is contaminated with per- and polyfiuoroaikyl substances (PFAS) (mainly per sulfonlc acid, PFOS for short, and perfiuorooctanoic acid. PFOA for short). Some public water supply wells in Warminster, and some private Wells contaminated with PFOS and PFOA. PFAS in the grou ndwater are likely from past use ofaqueous in the area. Departmentof Defense asked EPA to test private well samples at this site. Public water utilities are co liecting water samples from their systems. The Environmental Protection Agency (EPA) asked ATSDR to eValuate PFAS levals in the drinking Water supplies to see if exposure to PFAS in drink could harm people?s health. ATSDR evaluated the available off~siteWater test results. The report is available at tt .atsdr.cdc. AC 3 Na 3 i Warfa Ce ter Naval a re Cente 01-20-20 6 508. ATSDR is workingwith the Mid Atlantic Center for Children's Health and the. Environment to answer health questions and to educate local health pr about potential health effects caused by exposure to PFAS. In addition, ATSDR has worked with the PA Department of Health, through the Agreement Program to summarize available cancer statistics for this area.The cancer data review to codes Warringtonl and Horsham. PA is available at .atsci be Ca aRev ewP aRevlew Dover Air Force Base, Boyer, DE uorooctane ng Water afessionais era 'v selected zip 50%pr Groundwater at the Dover Air Forcce Base is contaminated with per? and poiyfluoroalkyi substances (PFAS), but no off-base drinking water contamination has been found at this time.The Department of Defense sampled onsite and most off-site wells, and asked EPA to test one off?site Well. PFAS in the grou likely a raultof past use ofaqueous film-forming firefightingfoams in the area. The Environmental Protection Agency (EPA) asked ATSDR to address public health issues at this site. For more information about PFAS in drinking the ATSDR PFAS website at hi: 5.- .cdc. ov fc de .ht s: .atsd cdc. ov fc indexht Naval Auxiliary Landing Field Fentress, Chesapeake. VA The groundwaterat the Naval Auxiliiary'Landing Field Tentress site is contaminated with per; and poiyfiuoroaikyl substances (PFAS) and in nearby drinkingwater Wells. PFAS in the grouudwater are likely a result of past use of aquaous film-formingfirefighting foams In the area. The US. groundwatersampies at this site. 1dwaterare ater, visit 'rivate avy is testing The U. 5. Navy asked ATSDR to answar health questions. ATSDR isworking with the VA Department of Health, through the ATSDB Cooperating Agreement Pro s: ov states mde .and with local health departments to answer health questions from residents and health or! For more information about PFAS in drinkingwater, visit the ATSDR PFAS Website at i. New Castle County Airport/Delaware State Air Guard, New Castle. DE Groundwater in the New Castel area.and some of the city public water supply wells. are contaminated with per- and poiyfluoroalkyi substances (PFA source ofthe PFAS is unknown. The state and EPA are testing groundwater samples at this site. EPA asked ATSDR to address public health issue. For more information about PFAS in drinkingwater, visit the ATSDR PFAS Website at ex. - tsdr.cdc. ov fc index.html . .atsdr.cdc. Region 4 Decatur (vicinitYi. AL-Bioioglcai Sampling of Per- and Polyfluoroalkyl Substances (PFAS) in the Vicinity of Lawrence, Morgan, and Limestone Alabama fessionals. 5. The 'Junties, in 200?, a PFAS manufacturer in Decatur, AL notified the EPA that it had discharged PFAS into the Decatur Utilities wastewatertreatmentplant. resulting in environmental contamination. In 2009. the Environmental Protection Agency (EPA) asked ATSDR to condUctan investigation to see if people who liv vicinity of Decatur, Alabama, of PFAS factories have been exposed to PFAS. in the in 2010, ATSDR tested residents' blood and found that some oftheir blood contained PFCs [now called PFAS). ATSDR condUCted follow-up blood an: urine testing in 2016. information aboutATSDR?s activities can be foUnd below. a PFAS and Urine Sampling - 2916 Exposure investigation Report . Eer?pprochemlcai gpnim 5ampl'lng- 2g} 3 ingestigg?pn Report s?erum% 205ampiing.pdf) - Blood psting and Health Summary, Morgan, Lawrence and Alabama nformationpdf) - information update to the ATSDR ijeaith Consultation Exposure investigation Report: Perfluorochemical Serum Sampling in the vicinl?nr of Decat un?labama Morgan, Lawrence, and Limestone Counties dated April 1, 2013, NALDRAFTadditionalcomment31 JAN 14.pdf) For more information about PFAS. visit the ATSDR PFAS website at - . - sd .cdc. ov fc lndexh ml}. Region 5 I Wurtsmith Air Force Base, Oscocia. Ml ://Www.atsdr.cdc. 3i;10/2017 How is ATSDR involved investigating PFAS in the environment? Per?uorinated chemie. .-. Page 4 of 4 . The Michigan Department of Health and Human Services through the ATSDB Cooperativg Agreemgni; Program WM is evaluating people's eXposures to PFAS in the environment. Releases of PFAS from activities atthe former Wurtsmith Air Force Base haVe resulted in contamination ofgroundwater and surface water. Sampling by the Michigan Department of Environmen al Quality and the U.S. Air Force has identified elevated levels of PFAS contamination in some locally caught fish and drinkingwater wells. has conclu education in the community. installed fish advisory signs. and helped the local health department provide an alternate water supply to the communl information is available 528? (httg?iwl 2945 . For more information about PFAS. visit the ATSDR PFAS Website at Egg?uucgalkyi Substanges and Health Region 10 Eielson Air Force Base, Fairbanks AK . in March 2015, Eielson Air Force Base tested the base drinkingwater wells and found that some were contaminated with per? and (PFAS). The Air Force has taken the contaminated wells offline. The Air Force continues to monitorthe remaining wells to ensure that PFAS levelslr? the Water system are not abOVe the HA. . Air Force investigations conducted in late spring and summer of 2015 determined that the PFAS mDVed into private drinking WaterWEIls in the Moo Creek community (north ofthe Elelson Air Force Base). The Air Force is providing alternative drinking water to the impacted homes. The Alaska Division of iPublic Health (ADPH). under the SD ativeA eementP s: .atsdr.cd 0 state .ht? I .will evaluate the test results to see if the past exPosure may harm people's health. For more information about PFAS,visit the ATSDR PFAS website at 5: ad .cdc. ind i dcdc.vcde l. A ?Fngge File Formats Help: How do I view different?le fonnats (PDF, DOC, PPT, MPEG) on this site? . a i Page last reviewed: September 6. 2016 Page last updated: February 9, 2017 Content source: Agency forToxic Substances and Disease Registry ://moN.atsdr.cdo. 8/10/2017 Interim Guidance -. . I "?nal; assist I. .- a. Revisedan 6/7/2017 Introduction The purpose ofthis fact sheet Is to provide interim guidance to aid physicians and other clinicians with patient consultations on perfluoroalkyl and polyfluoroalkyl substances (PFAS). lt highlights what PFAS are, which :hemicals fall into this category of substances, identifies health effects associated with exposure to various PFAS, and suggests - . answers to specific patient questions about potential PFAS exposure. 1 Background What are PFAS, sometimes known as PFCs, are chemicals that do not occur naturally' In the environm lant. There are many different types of PFAS such as perfluorocarboxylic acids g. ., PFOA, sometimes called C8, and PFNA) and perfluorosulfonates PFOS and PFAS may be used to keep food from sticking to cookware, to make sofas and carpets resistant to stains, to make clothes and mattresses more waterproof, and to make some food packaging resistant to grease absorption as well as use in some firefighting mateI ials. Because PFAS help reduce friction, they are also used In a variety of other industries, including aerospace, automotive, building and construction, and electronics. Why are PFAS a possible health concern? According to the US. Environmental Protection Agency (EPA), PFAS are considered emerging contaminants. An ?emerging contaminant? is a chemical or material that is characterized by a perceived, potential, or real threatto human health orthe environment or by a lackof published health standards. PFAS are extremely persistent in the environment and resistant to typical environmental degradation processes. The pathway for dispersion of these chemicals appears to be long?nange atmospheric and ciceanic currents transport. Several PFAS and their potential precursors are ubiquitous in a variety of environments. Some long?chain PFAS bioaccumulate in animals and can enterthe human food chain. PFOS and PFOA are two ofthe most studied'PFAS. Exposure to PFOA and PFOS is widespread and gl abal. PFOS and PFOA also persist in the human body and are eliminated slowly. Both PFOS and PFOA can i efound in blood, and at much lower levels in urine, breast milk and in umbilical cord blood. PFOS and PFOA may pose potential adverse effects for human health given their potential toxicity, mobility, and bioaccumulation potential. The likelihood of adverse effects depends on several factors such as amount and concentration of PFAS ingested as well as the time span of exposure. Routes of Exposure and Health Effects What are the main sources of exposure to Forthe general population, ingestion of PFAS is considered the major human exposure pathway. The major types of human exposure sources for PFAS include: . Drinking contaminated water. - lngesting food contaminated with PEAS, such as certain types of fish and shellfish. - Until recently, eating food packaged in materials containing PFAS g. ., popcorn bags, fastfoo containers, and pizza boxes). Using PFAS compounds has been largely phased out offood packaging materials. - Hand-to- mouth transfer from surfaces treated with -containing stain protectants, such as which? [5 thought to be most significant for infants and toddlers. carpets, um- am is: tepfor Enwronrpen Eli-:1! lI- 9' i '01- {EA-kt}; {Egg-:1 3.731% .4v'E; "El-d Workers In industries or activities that manufacture, manipulate or use products containing PF. be exposed to higher levels than the general population. What are other low level exposure sources? individuals can also be exposed by breathing airthat contains dust contaminated with PFAS (from soil upholstery, clothing, etc. orfrom certain fabric sprays containing this substance. i Dermal exposure is a minor exPosure pathway. Dermal absorption Is slow and does not result In signifI absorption. What are the potential PFAS exposure risks to fetuses and children? Recent research evaluating possible health effects to fetuses from PFAS eXposures have shown that cl fetuses can be exposed to PFAS when umbilical cord blood from their mothers crosses the placenta dL pregnancy. It Is important to note that different PFAS have varying levels of permeability to the placer barrier . Newborns can be exposed to PFAS through breast milk. The level of neonatal exposure depends on th duration of breastfeeding. Older children may be exposed to PFAS through food and water, similarto; largely due to time spent lying and crawling on floors in their early years. How long do PFAS remain in the body? PFAS with long carbon chains have estimated half-lives ranging from 2-9 years such as: 0 PFOA 2 to eyears PFOS 5 to 6 years 8 to 9 years What are exposure limits for PEAS in drinking water? 3 adults. in RS may carpets, CB l'l'l: eveloping ring 'tal addition, young children have a higher risk of exposure to PFAS from carpet cleaners and similar products, The Environmental Protection Agency (EPA) has published a Lifetime Health Advisory (LTHA) recommending that the concentration of PFOA and PFOS in drinking water, either individually or combined, should nalt be greaterthan 70 parts pertrillion (0.07 parts per billion). The LTHA concentrations do not represent def cut-offs between safe or unsafe conditions, but rather provide a margin of protection for individuals th their life from possible adverse health effects. EPA health advisories are non?regulatory recommendat are not enforceable. What are PFAS levels in the U.S. population? Most people' In the United States and? In other industrialized countries have measurable amounts of PF their blood. hnwe roughout onsand AS in The National Health and Nutrition Examination Survey Is a program conducted by the Can Disease Control and Prevention United States. NHAN ES (zone-2012) measured the concentration of PFAS In the blood of a represent sample ofthe population (12 years of age and older). The average blood levels found were as folio PFOS: 6.3 parts per billion, with 95% ofthe general population at or-below 21.7 parts per billion 1.3 parts per billion, with 95% ofthe general population at or below 5.4 parts per billion in the last decade, major manufacturers of PFOA and PFOS related productsjoined EPA in a global ste program to phase out production of these agents by 2015. Based on data collected from previous NHA i CDC) to assess the health and nutritional status of adults and children In the PFOA: 2.1 parts per billion, with 95% ofthe general population at or below 5.7 parts per billion rs for tive WS: Nardship cycle years, levels of PFOA and PFOS are generally decreasing In the blood ofthe general population 1: a result ofthis important initiative. Health Studies How can PFAS potentially affect human health? Studies in humans and animals are inconsistent and inconclusive but suggest that certain PFAS may affect a variety of possible endpoints. Confirmatory research is needed. Below are summaries of studies in animals and humans. Animal Studies: Adverse health effects have been demonstrated in animal studies, but these occurred at exposure levels higher than those found' In most people. The main health effects observed were: enlargement and changes' In?. the function ofthe liver changes In hormone levels g. ., reduced testosterone potential to affe'cth, and TS levels) and adverse developmental outcomes. Developmental and reproductive effects including reduced birth weight, decreased gestational le_,ngth structural defects, delays In postnatal growth and develop nent, increased neonatal mortality, and pregnancy loss have all been associated with prenatal rodent expos ?re to PFOS and PFOA. Human Studies: C8 Health Project The C8 Health Project was a large epidemiological study conducted because drinking water in six watefr districts across two states near Parkersburg, West Virginia were contaminated by release of PFOA (also called from the 19505 until 2002 (when the contamination was discovered). These releases migrated and contamir ated the air, parts ofthe Ohio River, and ground water. The study included 69,030 >18 years ofage. Th A C8 Science Panel analyzed study data and found probable links (as defined by litigation) between elevated PFOA blood levels and high cholesterol (hypercholesteremia), ulcerative colitis, thyroid function, testicular cancer, kidney cancer, preeclampsia, as well as elevated blood pressure during pregnancy. Residents in the area of these releases showed 500 percent higherPFOA-concentrations In blood compared to a representative U. 5. population MNHANES) - Table 1: Overview of C8 and Other Human Studies Cholesterol Some epidemiological studies demonstrated statistically significant associations between serum PFOA and PFOS levels and total cholesterol in: - workers exposed to PFAS, and residents of communities with high levels of PFOA in the drinking water compared to NHAN ES data that is representative of the U.S. population. Other studies have found no association between PFAS exposures and the to :al cholesterol levels. Uric acid Several studies have evaluated the possible association between serum PFOA and serum PFOS levels and uric acid. Significant associations were found . between serum PFOA and uric acid levels at all evaluated eXposure levels. (U Liver effects A number of human studies have used liver enzymes as biomarkers of possibl liver effects. In occupational studies, no associations between liver enzymes and serum PFOA or PFOS levels Were A study of highly exposed residents demonstrated significant associations but the increase in liver enzymes was small and not considered to be biologically significant. Cancer possibly carcinogenic to humans. other studies report otherwise and most did not control for other potential factors including heavy smoking. Additional research is needed to clarify if there is an association. The international Agency for Research on Cancer has classi?ed PFOA possibly carcinogenic and EPA has concluded that both PFOA and PFOS are Some studies have found increases in prostate, kidney, and testicular cancer: workers exposed to PFAS and people living neara PFOA facility. Findings frc' Note: Additional studies have identified possible associations between ulcerative colitis, thyroid disease and pregnancy induced hypertension and higher exposure to PFAS. What health screenings were used in the C8 study? The C8 Medical Panel suggested health screening to evaluate the C8 study population that include tests for cholesterol, uric acid, thyroid hon'nones and liverfunction as well as other age or situation appropriate screenings like blood pressure and urine protein measures. For individual patients exp .PFAS who are not among the C8 study screening population, there are no official guidelines suppo i:l blood ially ased to ting health screening. Howeverthe tests listed above are well established In clinical medicine and may be a consideration to discuss with your patient based on the patient history, concerns and What are potential health effects from prenatal PFAS exposure to fetuses? Multiple studies have reported an association between elevated maternal blood and cord blood concentrations of PFAS (primarily PFOS and PFOA) and decreased birth weight. Specifically, one analysis suggests that each 1 ng/mL' Increase in prenatal PFOA levels Is associated with up to 18. 9 reductions In birth weight (Johnson, 2014). Studies have also observed decreased birth weight with exposures to PFOS. The association between maternal PFAS level and decreased birth weight Is no statistically significant across all studies. Further, the observed reduction in birth weight does not consistently equate with-increased risk of a low birth weight (LBW) infant. Only one study revealed statistically significant association between LBW risk and PFOS (Stein 2009); no studies have founc statistically significant association between LBW risk and PFOA. meta- l: . prenatal i: a . . a Additional studies are needed to conclusively linkthe relationships between fetal PFAS exposure and health effects. Patient Questions and Key Message Answers As a clinician, you know careful listening and patient engagement is critical for ensuring quality patient care, especially when health concerns are raised. Perhaps the most difficult challenge in speaking with patients about their health concerns is addressing uncertainty. If your patient has concerns about an exposure to PFAS, yo face the challenge of helping your patient cope with the uncertainty of potential health effects from a PFAS exposure. Based on feedback from clinicians and from individuals who have spoken to their health care provider abou .l may ttheir PFAS exposure concerns, a set of patient questions have been identified. To assist you in speaking with yotlr patients about their concerns, key messages and supporting facts needed to answerthe anticipated patient questions are provided' In the table below for your information and potential use. Table 2: Patient Questions and Key Message Ask!? l5 tIen . r" use if? 1' atlaq?t- gs. - as: imamf; ?g media"? . -- There are high levels of In lfthe water you use is above the my water. What should I do? EPA health advisory level for PFOA and PFOS, you can reduce exposure by using an alternative water source for drinking, food preparation, cooking, brushing teeth or any activity that might result in ingestion of water. . - a: are 13% . . is: as.? re Potential health effects' are associated with exposure to PFAS. EPA has established a lifetime health advisory for PFOA and PFOS in drinking water. This advisory . states that the con centratio *1 of PFOA and PFOS in drinking water, either individually or combired, should not be greaterthan 70 parts per trillion. There needs to be additiona research to establish levels cf health risk, but patients may. want to reduce exposures below the EPA health advisory level to be 0 i1 the safe side. A home water filtration em can reduce the contaminant lev Is in drinking water. Researchers are still clarifying how to best use home filtration for PFAS contamin: tion. Installing a home filtration stem or using a pitcher-type filterlmay reduce PFAS levels. Howev these filters may not reduce PFAS enough to meet the EPA Lifetime Health Advisory (LTHA) levell. Three factors determine ho much PFAS are removed by filtrati n. These factors are the PFAS contaminant levels, the type, of filter, and how well the filteri?Is maintained. Manufacturers ?fthe filtration system may be abl . to make recommendations to optimize removal of PFAS. "his may include more sophisticated media cartridges or increasirjg the frequency of exchanging filter media. For bottled water questions how it is treated and if it Is safe) contact the CFSAN Information Cenler at 3366). - Could my health problems be caused by PFAS exposure? (Based on the health problems the patient has, there are two possible responses to this question.) if the patient?s health problem is in the list below, it may potentially be associated with PFAS exposure, based on limited evidence from human studies. The potential health effects include: Thyroid function (potential to affect T4 and TSH levels) - High cholesterol - Ulcerative colitis - Testicular cancer - Kidney cancer - Pregnan cy?induced hypertension - Elevated liver enzymes - High uric acid if the patient?s health problem is not in the bulleted list above, then there is no current evidence that it is related to PFAS exposure. (However, research is ongoing and not all health outcomes have been adequately studied.) Although the evidence is not conclusive, your health problem could potentiaily be associated with exposure to PFAS. However, health effects can be caused by many different factors, and there is no way to know if PFAS exposure has caused your health problem or made it worse. Based on what we know at this time, there is no reason to think your health problem is associated with exposure to PFAS, For supporting facts on the isted health effects in this questic see ?How can PFAS potent ally affect human health." The . information on potential illresses and health effects will be briefly reviewed for each ofthese i .Inesses or health effects. This information can be found in this fact sh et on page 3 and 4. if your patient presents witj health concerns that might be ass lciated with PFAS exposure, it is appropriate to discuss the p, tient?s concerns and perform a tho:ough health and exposure histo ?and also a physical exam relative to any reported. Are there future health problems that might occur because of PFAS exposure? We know PFAS can cause health issues but there is no conclusive evidence that predicts PFAS exposure will result in future health problems. We can watch for related to PFAS associated health problems and investigate any that you notice, especially those that reoccur. Studies in humans and anirr'als are inconsistent and inconclusive but suggest that certain PFAS ?,3n cause possible health effects. Additional research is needed to better understand health risks associated with PFAS exposure. Should i getE? a ?blood test for (JP . - lfyou are concerned and choose to have your blood tested, test results will tell you how much of each PFAS is in your blood but it is unclear what the results mean in terms of possible health effects. The blood test will not provide information to pinpoint a health problem nor will it provide information'fortreatment. The blood test results will not predict or rule?out the development of future health problems related to a PFAS exposure. There currently IS no establi. hed ?cameras-?as . PFAS blood level at which a [health effect is kn own nor is there 3 level that predicts health probler?s. Most people in the US will have measureable amounts ofP AS in their blood. There are no he lth- based screening levels for yecific PFAS that clinicians can compare to concentrations measure .in blood samples. As a result, 1 interpretation of measured FAS concentrations' In individual" is limited In its use. The patie it may be aware of blood and urine testfor PFAS being taken at other locations. These tests are ed by public health officials to investigate community~wide exposure in order to understand the kinds and amounts of PFAS exposures in a community and howthose exposures compare to those. in other populations. Serum PFAS measuremenm are most helpful when they are part of a carefully designed research study. What do my PFAS blood tests results mean? The blood test for PFAS can only tell us the levels of specific PFAS in your body atthe time you were tested. The blood tests results cannot be interpreted and used in patient care. The blood test results cannot predict or rule-out the development of future problems related to a suspected exposure. There is currently no establi :hed PFAS blood level at which a ealth effect is known nor is there a level that is clearly associated witl past orfuture health problems. The individual patient?s blood concentration of PFAS can only be compared to the average background blood concentration levels for different PFAS that are nationally identified through'the representative sampling ofthe NHANES studies conducted by CDC. A patient?s PFAS concentrat ons can only show the patient if 1is or her blood levels are.within range of the national norms or ifthe Whigs?; '15 seats?rpwu .2 e, ?at-1e. thessages 1r . - ?was? ?as: - -. .- . I Earn-?Pita g: 0 {libs individual's levels are hi compared to the nation background averages. mm b: it!" 0 .. An adult patient asks: ?Should I be tested for any of the potential health effects associated with PFAS exposure (like cholesterol and uric acid levels, or liver and thyroid function, etc)?? Let?s look at your health history and past lab results and discuss what steps we may want to consider moving forward. One way we can address cholesterol is through your annual physical. . For others PFAS associated conditions, we need to watch for and investigate any that you notice, especially those that reoccur. if any unusual occur, we ?will investigate those and treat as needed. Laboratory tests will not tell us if PFAS are the cause of any of your health or abnormal lab results, but conducting these' routine health screenings and watching for any related do offer us a way to better understand your current health status. Health effects associated w' PFAS are not specific and ca caused by many otherfacto There are no guidelines to laboratory testing to monitc health concerns. However, if your patient is cdncerned about PFAS exposure, discussing routine cholester sereening can reassure the that his or her PFAS exposu Bpport Jr PFAS ol jatient ?e concerns are being addressed. Some ofthe other possible effects can be screened forl on :eahh Jased A parent asks: ?Should I have my child tested for any of the potential health effects associated with PFAS exposure (like cholesterol and uric acid levels, or liver, thyroid function, The American Academy of Pediatrics has endorsed cholesterol testing for children starting at 9 years of age. Following this guidance cholesterol level testing can be done for older children. If cholesterol level measures are outside the normal range, we can discuss options for bringing cholesterol levels within the normal range for your child. For very young children, keeping well child visits is the best plan of action to monitor your child?s According to guidelir yes endorsed by the American Academy of Pediatrics, all children should be screened for chol isterol levels between ages 9 and 1 and again between ages 17 and 21 years, even those who are increased risk of high cholesterol and heart disease. Health effects associated wi PFAS are not specific and ca caused by many otherfactoi . There are no guidelines to 5 use of laboratorytesting to monitor PFAS health concerns. yearslipport illness. We can discuss any you notice, especially those that reoccur. If any unusual occur, we will investigate those and treat as needed. Laboratory tests will not tell us if PFAS are the cause of any of your child's health and are not recommended. Conducting routine well child visits and watching forany related do offer us a Way to better understand your child?s current health status. fess5:135 19' -. 'l I 'ix' - 'tati?rdb?; is? 5* . However, if your patient pr llsents with health concerns that have been associated with PFAS exposures, discussing recommended cholesterol screening, can reassure the patient?s parents that their concerns are being?addressed. Some ofthe other possible i ealth effects can be screened for based on How will exposure to PFAS affect my pregnancy? Exposure to PFAS before pregnancy has been associated with pregnancy-induced hypertension and pre-eclampsia. We will monitor your blood pressure closely, as we do for all pregnant women; however, there is no need for additional blood pressure measurements as a result of your exposure. Health effects associated PFAS are not specific and ca caused by many otherfacto Pregnancy induced hyperte occurs in many pregnancies the specific etiology is often: unknown. Is it safe for me to breastfeed my ba by? Breastfeeding is associated with numerous health benefits for infants and mothers. At this time, it is recommended that you as a nursing mother continue to breastfeed your baby. - The science on the health effects of PFAS for mothers and babies is evolving. However, given the scientific understanding at this time, the bene?ts of breastfeeding your baby outweighs those of not breastfeeding. 7 Extensive research has documented the broad and compelling advantages of breastfeeding for infants, families, and society. Some of the many benefits? immunologic advantages, lc obesity rates, and greater cc development forthe infant; as a variety of health advant forthe lactating mother. Even though a number of environmental pollutants re pass to the infant through milk, the advantages of others, nclude ,wer lgnitive is well iages adily Jman . Bili-SilMFa. A Far ?lial Mai?? . - . ?g?g?-?Y?l?gtlemgl? a es? ?fe-E" nearly every circumstance. tinue to glreat outweigh the potential risks; I in How-will exposure to PFAS affect my child's immunizations? Although few studies have reported that PFOS and PFOA might lowerthe immune reSponse to some immunizations, these studies have not suggested a need to re?evaluate the normal immunization schedule. A study with 656 children reported that elevated level PFOA and PFOS in serum at 5301? associated with reduced humoral immune response to some childhood immunizations (r tetanus and diphtheria) am: children aged five to seven 3 ou?ne Jbella, mg (ears. Will I need to get my child There is no recommendation for StUdles have not suggested a need ccinated a ain? repeating any vaccinations to re-evaluate the normal I va 9 - immunization schedule nor the use of an immunize booster for impacted children. I have been very anxious about it is normal to be anxious-about Listen sympathetically and. health risks from PFAS exposure. uncertain risks. explore the concerns ofthe :Iowrctan ltdeal With this I am here to listen to your patient nce am y. questions and will do my best to Check for serious stress issues such, provide honest answers. First let?s identify ways to reduce ongoing exposures to PFAS so that overtime we can lower your health risks. I Let?s set up appointment for (X date) and we can discuss any new questions you have and check to see ifthere are any changes in how you feel. in the meantime, I have more information that may answer questions that you may have later about PFAS.- as ongoing depression and treat accordingly. Review resources/reference end of this fact sheet. satthe 10 Below is a list of resources that can be helpful to clinicians. These include the Pediatric Environ mental Heal Specialty Units (PEHS U). The PEHSU are a national network of experts available to provide consultation ar education to clinicians and communities wishing to learn more about PFAS and other hazardous substance units are staffed by clinicians with environmental health expertise in pediatrics, reproductive health, occup and environmental medicine, medical toxicology, and other related areas of medicine. Resources th id ational Resource Link ATSDR: PFAS Overview Toxic Substance Portal 0v toxfa stf.as ?id=1116&tid=2 CDC: PFCS FactSheet.html C8 Science Panel C8 Medical Panel http- inl<.html panel education docpdic EPA: PFAS tea.- - NIEHS: PFAS chemicals 508 edi NHLBI Lipid Screening?in Children Adolescents faith; PEHSU Uncertainty and Stress in the Clinical Setting Helping Patients and Clinicians Manage Uncertainty During Clinical Care - uncertainty-durino-clinical-ca rel Navigating the Unknown: Shared Decision~Making in the Face of Uncertain Gen Intern Med. 2015 May,- 3o(5): 675-678. Patient Health Questionnaire to determine if patient is suffering from depression. Uncertainty Toolbox: Principles in the Approach to Uncertainty in the Clinic Encounter-J Gen Intern Med. 2015 May; 30(5): 675?678. i? 5. These 11 "n ?Mrgg1-43"- jrimg?PFAS are a large group of man?made chemicals that have been used since the 19505. Use of some ofthese, chemicals has decreased in the United States over the last 10 years. People can still be exposed to PFAS be they are still present in the environment. PFAS do not break down easily in the environment. They also bui the bodies of exposed humans and animals. Over the last decade, interest in PFAS has grown. How can i be exposed to cause ld up in ATSDR and our state health partners are studying exposure to PFAS at a number of sites. PFAS are found-near areas where they are manufactured or used. Listed below are places where they can be found. a Public water systems and drinking water wells, soil, and outdoor air near industrial areas with frequent i Indoor air in spaces that contain carpets, textiles, and other consumer products treated with PFAS to res a Surface water (lakes, ponds, etc.) and run~off from areas where aqueous (water?based) film?forming fire foam was often used (like military or civilian airfields) . Locally caught fish from contaminated bodies of water a Food items sold in the marketplace Consumer products can be source of exposures to PFAS. These products include . Some grease-resistant paper, fast food wrappers, microwave popcorn bags, pizza boxes, and candy wra 0 Nonstick cookware I) Stain resistant coatings used on carpets, upholstery, and other fabrics Water resistant clothing Cleaning products Personal care products (shampoo, dental floss) and cosmetics (nail polish, makeup) Paints, varnishes, and sealants Recent efforts to stop using some PFAS in consUmer products appearto have lowered exposure in the US. population. CDC surveys have shown that blood levels of PFAS have dropped over time. People who work PFAS are more likely to be exposed than the general population. Workers may be exposed to PFAS by inha them, getting them on their skin, and swallowing them, but inhaling them is the most likely route for expo How can I reduce my exposure to PFAS are found in people and animals all over the world.They are found in some food products and in the environment (air, water, soil, etc.). Completely stopping exposure to PFAS is unlikely. But, if you live near so PFAS contamination you can take steps to reduce your risk of exposure to PFAS: I: Some states have warnings about eating ?sh from bodies of water with high PFAS levels. Check with use ist stains ?gh?ng ppers with ing sure. urces of i? state public health and environmentallquality departments to learn the types and local sources of fish that are safe to eat. If your water contains PFAS, you can reduce exposure by using an alternative or treated water source for: drinking, food preparation, cooking, brushing teeth, and any activity that might result in ingestion of we a it is safe to shower and bathe in PFAS?contaminated water. Neither routine showering or bathing are a si source of exposure. Studies have shown very limited absorption of PFAS through the skin. ter. gnificant - {Er 1 . Toff: 1,4. g: 7 ,ry. ?rst? [en/3,1 giem'geft?p? tromseeat .- .. - 17-C52657MB_Updaied March 9,2017 Haw can PFAS affect peep?e?s health? List of Common Scientists are not sure about the health effects of human exposure and Their AbbreVia tions to PFAS. Some studies In humans have shown that certain PFAS may - affect the developing fetus and child, including possible changes' In growth, learning, and behavior. In addition, they may decrease Perfluorobutane fertility and interfere with the body?s natural hormones, Increase sulfonate cholesterol, affect the Immune system, and even increase cancer risk. Perfluorohexane PFAS build up and stay in the human body and the amount goes down sulfonate very slowly over time. So scientists and doctors are concerned about Perfluorooctane their effects on human health. sulfonate Some studies show that animals given PFAS have changes in the liver, Perfluoroheptanoic thyroid, pancreas, and hormone levels. Scientists are not sure what acid I animal data means about human health. PFAS act differently Perfluorooctanoic acid PFOA. in humans than they do in animals and may be harmful in different ways. Perfluorononanoic acid PFNA: Perfluorodecanoic acid PFDA- HQW can [1 team Perfluoroundecanoic Contact for updated information on this topic. acid Contact the Consumer Product Safety Commission Pe?rfluorododecanoic PFDCA at (800) 638-2772 if you have questions about the products you use in am! your home . Perfluorooctane PFOSA sulfonamide -5 Visit the following websites for more information: 2-(N-Methyl? per?uorooctane . AcOl- ATSD Websites sulfonamide) acetate . - 2- l- . pefrfluorzoctane Ac Oi- . Environmental Protection Agency sulfonar'nido) acetate Notes ?Use oftrade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention/Agency forToxic Substances and Disease Registry, the Public Health Service, or the U. S. Department of Hea th and Human Services a. I .. anuytree Ipolyflui?orOalkyl substances (PFAS) i 6/9/17 This fact sheet tells you about chemical names within the family of perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their basic chemical structure. it also spellsout abbreviations for common PFAS. PFAS are a family of man- -made chemicals that contain carbon, fluorine, and other elements. The family tree image below, Figure 1, shows some ofthe different families of PFAS. For simplicity, it does not include all PFAS subfamilies. Follow along starting at the ?fallen apple? of PFC and then continuing up the tree trunk Into. the branches. - a I, Per?uoro- ii, Figure 1. Family Tree _of . a? perfluoroalkyl and PFAS polyfluoroalkyl . Substances PFC in the past, scientists used the abbreviation PFC to stand for perfluorinated chemicals. However, using the abbreviation PFC can be confusing because it is alsc abbreviation for perfluorocarbons. Perfluorocarbons are an entirely diffe family of chemicals, also known as greenhouse gases. I The term PFC has fallen off the family tree, but it remains in the diagram. reminder of past use. You may still see informational materials using the ?PFC?instead of PFAS. PFAS Perfluoroalkyl substances and polyfluoroalkyl substances are called PFAS for short. The PFAS family includes hundreds of chemicals. The different - structures of the PFAS molecules are the basis for different chemical properties and different chemical names. See Table 1 for abbreviations a chemical names. Table 1. Common PFAS: Abbreviations and Names - . . -- Chemical name . - r. PFOS Perfluorooctane sulfonic acid an rent as a term nd PFOA (aka C8) . Per?uorooctanoic acid PFNA Perfluorononanoic acid PFDA Perfluorodecanoic acid PFOSA (aka FOSA) - Per?uorooctane sulfonaminde (aka sulfonamido) acetic ac id (aka sulfonamido acetic acid 3 Per?uorohexane sulfonic acid Fag .- PUBLIC HEALTH STATEMENT i? Division of Toxicology and Human Health Sciences August 2.015 This Public Health Statement summarizes the Division of Toxicology and Human Health Science?s ?ndings on tells you about them, the effects of exposure and describes what you can do to limit that exposure. - The US. Environmental Protection Agency (EPA) identi?es the most serious hazardous waste sites ir the nation. These sites make up the National Priorities List (NFL) and are sites targeted for long-term fedl'eral clean-up activities. have not been reported at EPA NPL sites; however, it is unknown how many of the 1,699 current or former NPL sites have been evaluated for the presence of As more sites are evaluated, the sites at which is found may increase This information is important because these ?iture sites may be sources of exposure, and exposure to may be harmful. If you are exposed to many factors determine whether you?ll be harmed. These include how much you are exposed to (close), how long you are exposed to it (duration), and how you are exposed (route of exposure). You must also consider the other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, and state of health. WHAT ARE are a family of human?made chemicals "that do not occur naturally in the environment, Thirteen per?uoroalkyl compounds are discussed in this pro?le. The names of these are as follows: per?uorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), per?uorododecanoic acid per?uorodecanoic acid per?uorobutyric acid (PFBA), per?uoroheptanoic ac per?uorononanoie acid (PFNA), per?uoroundecanoic'acid (PFUA), per?uorohexane sulfonic acid per?uorobutane sulfonic acid perfluorcoctane sulfonamide (PFOSA), sulfonamide) acetic acid and 2-(N-ethyl? perfluorooctane sulfonamide) acetic acid DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry Telephone: 1?800-232-4636 {gyr?lu/n?a 5' DR PUBLIC HEALTH STATEMENT sh . ll Division of Toxicology and Human Health Sciences August 2,7015 are unique because they repel oil, grease, and water. They have been used in surface protection products such as carpet and clothing treatments and coatings for paper and cardboard packaging. Some have also been used in ?re-fighting foams._ WHERE ARE can be released into the air, Water, and soil at places where they are produced or used. were made in large amounts in the United States. PFOA and PFOS are the two per?uoroalkyl compounds made in the largest amounts. Companies have stopped production or have begun changing manufacturing practices to reduce releases and the amounts of these chemicals in their products. Some facilities are replacing many of the with other substances. have been found in both air and dust; surface water and groundwater; and soil and sediment. The highest levels of in the environment are typically found near facilities that have made or used these substances. However, they have also been found at remote locations such as the Arctic and the open ocean. They may be subject to long-range transport. are very stable compounds and are resistant to being broken down in the environment. in the air are expected to settle to the ground within days to weeks. may be carried through soil by groundwater and ?ooding and become airborne during windy conditions. HOW MIGHT I BE EXPOSED TO Exposure to perfluoroalkyl compounds is widespread. PFOA, PFOS, PFNA, and were detected in 95.4 00% of samples of people?s blood in 1999?2000 and 2003?2004. More recent monitoring data st] show widespread exPosure; however, the levels of these substances in peOple?s blood appear to be declining. You may be exposed to from the air, indoor dust, food, water, and various consumer products. Food is expected to be the primary source of exposure to such as PFOA and PFOS for most people. Some communities near facilities where PFOA and PFOS were previously manufactured had high levels of these substances in drinking water supplies, and this is the primary route of exposure for these populations. Limited information has been located regarding ll DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry W.atsdr.cdc.govl Telephone: 1-800-232-4636 have been detected in human breast milk. You may also be exposed to from treated AGENCY FOR 105ch SUBSTANCES AND DISEASE I: DR PUBLIC HEALTH STATEMENT [1 Division of Toxicology and Human Health Sciences August ZEOIS pathways of human exposure to most of the other discussed in this toxicological profil Human breast milk may contribute to the exposure of infants to since these substances carpets and upholstery; this is especially true for children. The greatest source of exposure to PFOA and PFOS for toddlers and children is hand-to-mouth activities from treated carpets. People who work where are made or used are exposed to higher levels of these substa ces than the general population. Levels of PFOS and PFOA measured in the blood of some people who hive worked at these locations were higher than levels in people from the same communities who did not work at these locations. Workplace exposure also occurred for people with jobs that required frequent handing or use of perfluoroalkyl-treated substances, such as carpet installers. At sites where aqueous ?lm-forming foam that contained perfluoroalkyl substances was used' ?re?ghting, workers could be exposed to these substances and possibly transport them home from contaminated clothing. HOW CAN ENTER AND LEAVE MY :3 Perfluoroalkyis can enter your body if you breathe air, eat food, or drink water containing ther . We do not know how much will enter your body through your lungs or your digestive tract. It (.2 ydur skin comes into contact with dusts or aerosols of perfluoroalkyl or with liquids containin, it is possible that a small amount may enter the body through your skin. Once in your body, tend to remain unchanged for long periods of time. The most commonly used (PFOA and PFOS) stay in the body for many years. It takes approximately 4 years for the level in the body to go down by half, even if no more is taken in. It appears that, in general, the shorter the carbon?chain length, the faster the per?uoroalkyl lea lies the body. leave the body primarily in the urine. DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry Telephone: 1-800-232-4636 PUBLIC HEALTH STATEMENT :2 AGENCY FOR TOXIC SUBSTANCES all!) i s. Division of Toxicology and Human Health Sciences August 2015 HOW CAN AFFECT YOUR A large number of studies have examined the possible health effects of PFOA and PFOS in humans. The effect of inhalation exposure to PFOA and PFOS has been examined in workers exposed to high concentrations of these compounds. Studies have also examined a large community exposed to high levels of PFOA in the drinking water and compared this community to the general population; ingestion was the primary route of exposure for these two groups. Most human studies have looked for a relationship between levels of in the blood and a health effect. It is dif?cult to interpret the results of these studies because they are not consistent; some studies have found associations, but others looking at the same health effect have not found these associations. Even though some studies have found signi?cant associations between serum per?uoroalkyl levels and adverse health effects, it in does not mean that caused these effects. The effects may have been due to other facto- that were not considered by the researchers. The available studies suggest that increases in blood cholesterol levels are associated with higher PFOA or PFOS blood levels in workers inhaling PFOA and/or PFOS as well as in peeple ingesting these compounds. There are data to suggest'an associatio between serum PFOA and PFOS levels and increased uric acid levels, which may be associated with; increased risk for high blood pressure. There is also some evidence that PFOA and PFOS exposure ay cause liver damage. Humans and rodents react differently to PFOA and PFOS, and not all of the effects observed in rats and mice may occur in humans. The liver appears to be the most sensitive target in animals ingesting The effects include increases in liver?Weight, changes in the liver cells, and changes in blood cholesterol and triglyceride levels. Studies in mice also found that the immune system is a sensitive target of PFOA and effects include decreases in the size of the spleen and thymus and impaired immune function. A short exposure of rats to very high levels of PFOA in the air caused irritation of the eyes-and nose. Damage to the liver and weight loss were observed in rats exposed to lower levels of PFOA in the air. DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry Telephone: 1?800-232-4636 . .me {4/41- DR PUBLIC HEALTH STATEMENT an Division of Toxicology and Human Health Sciences August 2.015 Short?term application of large amounts of PFOA to the skin of animals has caused skin irritation and changes in the liver. These liver effects indicate that PFOA can be absorbed into the body through the? skin and affect other parts of the body. There is limited information on whether can cause cancer in humans. Some increases in? prostate, kidney, and testicular cancers have been found in workers or in community members livingr Tear a PFOA facility. These results should be interpreted cautiously because the effects were not consiste tly found and most studies did not control for other potential factors such as smoking. Feeding PFOA an PFOS to rats caused them to develop tumors. Some scientists believe that, based on the way this hap ens in rats and the differences between rats and humans, humans would not be expected to get cancer. 0t - ers believe that it is possible for to cause cancer in humans, and the studies in rats should ot be dismissed. More research is needed to clarify this issue. The International Agency for Research OT Cancer and the Department of Health and Human Services have not yet evaluated the carcinogenicity of The EPA has begun an evaluation. HOW CAN AFFECT This section discusses potential health effects of eXposure in humans from when they? re ?rst conceived to 18 years of age, and how you might protect against such effects. No associations between serum PFOA and birth defects were observed in children of mothers living in an area with high PFOA levels in the water. Some studies of the general population and people living near a PFOA manufacturing facility have found that higher levels of serum PFOA or PFOS are associated with lower infant birth weights. However, the decrease in birth weight is small and may not affect the infagt?s health. A study in children exposed to high levels of PFOA in drinking water found increases in bloo cholesterol, which was similar to the ?ndings in adults. Birth defects were seen in mice born to females that ingested relatively high amounts of PFOS during pregnancy. The blood PFOS levels associated with these effects were at least 10 times higher than thr1 highest PF OS levels measured in workers. Oral exposure to PFOA and PFOS has resulted in early de ith DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry ww.atsdr.cdc.gov/ Telephone: 1-800-232-4636 WJIIKJ '4 PUBLIC HEALTH STATEMENT i .h?A ?3?"me Division of Toxicology and Human Health Sciences August i015 and delayed development of mouse and rat pups, but this did not occur in animals exposed to PFBA oi Alterations in motor activity have also been observed in mouse pups exposed to PFOA, PFO S, or but not Scientists believe that some of the effects observed in rats and mice exposed to PFOA or PFOS may not be relevant to humans. HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO If your doctor ?nds that you? have been exposed to signi?cant amounts of ask whether your children might also be exposed. Your doctor might need to ask your state health department to investigate. In the past, some such as PFOA and PFOS were used in the manufacture of many consumer products, and low levels of these substances were detected in things such as treated carpeting, treated apparel, and paper food packaging. Companies are no longer using PFOA in the manufacture of non?stick coatings or PFOS in the manufacture of stain resistant carpet treatments; however, older products and imported materials may still contain these substances. Families may choose. to use prodL that do not contain pre-treated stain repellent products or grease resistant food packaging. Families th it have been told that their tap or well water contains high levels of may choose to drink or cook with bottled water or to install activated carbon water ?lters in their drinking water system. Consuming bottled water and the use of activated carbon water ?lters have been shown to lead to lowe "3 PFOA levels in the blood over time by decreasing exPosure to per?uoroalkyI compounds. ARE THERE MEDICAL TESTS TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO Pel?uoroalkyl compounds can be measured in blood, but this is not a routine test that can be performed in a doctor?s of?ce. You should, however, see a physician if you believe that you have been exposed to high levels of have been measured in blood samples in 2009?2010 from a representative sample of the US. general population; the geometric mean serum PFOA and PFOS concentrations were 3.07 and 9.32 pg/L, respectively. Elevated serum PFOA levels were reported in DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry Telephone: 1-800-232-4636 us. DR PUBLIC HEALTH STATEMENT itch antennasaaence Division of Toxicology and Human Health Sciences . August 2.015 Mid~Ohio Valley residents who had environmental exposure to PFOA from drinking'water contaminated by a nearby industrial facility. The range of median serum PFOA levels across several communities was 111?224.] ng/mL and the mean serum PFOA concentration across all of the communities was 83.6 tug/L in 2005. Higher serum per?uoroalkyl concentrations have been reported in fluorochemical product workers. Mean serum PFOA and PFOS levels for at one facility were 1,780 and 1,320 ug/L, respectiyely. Workers at another facility had serum PFOA levels of 1,000 pig/L. WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN The federal government develops regulations and recommendations to protect public health. Regulations can be enforced by law. Federal agencies that develop regulations for toxicsubstances include the Environmental Protection Agency (EPA), the Occupational Safety and Health Administration (OSHA), and the Food and Drug Administration (FDA). Recommendations provide valuable guidelines to protect public health but cannot be enforced by law, Federal organizations that develop recommendations for. toxic substances include the Agency for Toxic Substances and Disease Registry (ATSDR) and the National Institute for Occupational Safety and Health (NIOSH). Regulations and recommendations can be expressed as ?not-to-exceed? levels; that is, levels of a toxic, substance in air, water, soil, or food that .do not exceed a critical value usually based on levels that affect animals; levels are then adjusted to help protect humans; Sometimes these not-to-exceed levels differ among federal organizations. Different organizations use different exposure times (an 8-hour {workday or a 24-hour day), different animal studies, or emphasize some factors over others, depending on? their mission. Recommendations and regulations are also updated periodically as more information becomes available. For the mostcurrent information, check with the federal agency or organization that issued the regulation or recommendation. DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry .Telephone: 1-800?232-4636 yum!" 4 PUBLIC HEALTH STATEMENT . if? Division of Toxicology and Human Health Sciences August 2015 The EPA has recommended provisional drinking water health advisories of 0.4 ng/L for PFOA and 0.2 jig/L for PFOS. OSHA has not set any legal limits for per?uoroalkyl compounds in air. NIOSH las not set any recommended limits for per?uoroalkyl compounds in air. WHERE CAN I GET MORE If you have any questions or concerns, please contact your community or state health or environmental quality department, or contact ATSDR at the address and phone number below. ATSDR can also provide publically available information regarding medical specialists with expertise and experience recognizing, evaluating, treating, and managing patients exposed to hazardous substances. 0 Call the toll-free information and technical assistance number at (1-800-232-4636) or 0 Write to: Agency for Toxic Substances and Disease Registiy Division of Toxicology and Human Health Sciences 1600 Clifton Road NE Mailstop Atlanta, GA 303 29-4027 Toxicological pro?les and other information are aVailable on web site: DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry Telephone: 1-800?232-4636 EXHIBIT UNITED suns ENVIRONMENTAL mores-non AGENCY REGION Ill REGION 106!) ARCH STREET 7T ?31' JAGRIDN IOULEVARD PA 1910: CHICAGO, IL HIM . INTHE MATTER OF: . i ORDER ON CONSENT 7 I I. Pantchummn-a am! Cmnpany, 111W Whitman-section 1431mm af?x: Act, . 42 11.8.0. 5 30mm) Futility I 110111: 892 DozictNOI. Wilmington. 26131 STATUIUEY AUTHORITY 1. This hubs Admininmmof?znm?lnd?um 1431mm of the 825: D?nkinng-?Lct 42 autumn). 9. Dalmatian (hind May 3. and thin?nsmtulmrcu. IL DEFINITIONS 4. The term "Undmm?SauruofD?zdem' mania-I1 ?aquifer? or consumption, or tannin: Ham 10,009 milligrams par liner haw) total dissolved maids, and is aquifer. 35:40an 5144.3. . 23:91 aa?a?I t?aw Baud wig 308 a?gsos-a term '20, wee SST ?on 311;; an?. FINDINGS OF FACT AND CONCLUSIONS OF LAW 5. and is therefore a "pawn? within tumor-55650:! 140??) 05316 SDWA, 42 U33 6. knma?nwa?mm' Waring Wood - . 8. i . I-Iiinfcr . . . m. MWM Walk: my mum: ass. 1995; 1.4.5 and {Wall 332. 19992 . Panama WmTapI: mammu?mu? 5.19993 1999) OMMCBu?dmial. 1999: Uni: OH, PWSI 1.840 uy?l Wall 1. Lyon . mam; 0.855113? Wall 3. 12/01) 7.690 ?0?1 :er1 5, 1.7mm Well 1.1/02: - mo um Man a. #02) 0.744 113/! Midi 3. 1/02} zI/va'd ?21191 ma?It?Hdace a?seoa-u '"umundmazm 2mm 30; 11/20 661 - GAAOI 31536 mo um (Wall 1/02) 11. mm Lem ?Mb? [in-db: maxim; We.? 51,000 (1998 Qua-aim monitoring null HWY-2A 990 #111998}, $0.42 I 0.295 edmg' mm Momentum. a reportmpuul EPWIRONI bunniannl?arp'onh 1mm 24.. 2002 War momma fut-DuPont. m" 13. DuPont, Bomb {*wvn E1: . Humm?nomm mammin (humanist. M. mr Order, DuPumand tin: furpmvilimof thum?ahs-mreql?md 17ol?1hil Order. 15. bcelhb?died by 18 hom?? 121ndI-lof??301dcr. 16. HAIR: conmlbed with mm (in DHoEnVir?mnanlal pmmcuon Agency ramp?; and Han chap Osman-1m mum to con?rm that die information on mam-mt! localumhodtlca max-win bc wt. OEPA, am} OBI-{knew nuke this adim. EPA has 50112111de thata? M13111: cant??am hum. hem u?x?ad for EPA Faction untim- Stc?un- ll?lw?) of th: 43 5 BGIHHU336:! ms was. ace - a-ssos?a 'WI?lmmz?l emu ac. wee 66: 311:: 01537 IV. Pmuantbo?tm?'n?yhundhmeEPA 31mm, 4.2 5 menu). mud am In the Ragioml Achmumuon ORDERED hunky mm to 111: following: 2 5? Elba-mt: murmurs-well, WW ?atm- 1::de (3.3.11.5 141 md puan-lnfC-Smm?unuqdh Gully 19. The Alternainankhu-Watu-Phn . mes-1 ofmy?PWS anti unyp?vatn Ohio, identi?ed 1::ch Order. wah?x-ilba bepmvidniatno math: Walla. Except?nrusual musofthe mica H31 (IND of the. DuPont is mad uaiug?lmatpnacudurt and prim drmkingwatcr 59:91 awe-11w 1 Z. 335d 12m w. 309 a?eeos?a '1mm0mumm1 awn an. wee eat 'oNgmu m?uu? GAAOJISBB . uf?Clks 141 . mam ?luupgridedln: 20. af?IcAhzmabeDn'nhnEW EPA, 11: {mutilation hulk mm. and DEPAJ: Won: are necessary and: mn'?p?mywcu?l? mathem?rmmofdi: Urdu-and lubmita?wiwd Aliza-nah: (45) d?m??u?anbyEPA. '31. 1:ng mvuad? mm earth: Plan (or reused? MUM Wm Rama: diam be}. ?16m Wm WMer mw?mhm?m?gww. Duan?m?cm?inuecomhmit a I in . . . Irilhannomuhutimrcpommnolom ?lhp?wh cumin Mam the . them than: Ema}: ?3:91. me-tI?tm - an. .. -- haul?i? 8 396d 171.179 Vii. 306 . 3-3808-{1 817:.? 80. 11/80 661 ?Of GAAG 4 311:! 01539 umndiuntu unearths $25 million (in swam! climax-1980 doll-ta). Emlhmity in tip: 23. 0:21kaan the following A: to EPA: As to DIE-PA: EI/m'd 6 356d Roger new (W932) 115- Rcsim 1650 Arch Enact . Menuhin, PA 1910:1202!) v.5. EPA Russet; 75" Bandung-a Victor Word Dividon of 'Daputmuntd? thmm?mnnummu 815 0mm Suit: 413 Prat-dim Section Division ofWalerenourm Wmm?m?w Protuctiau 1201 ?G?rcculn'chh?aet - 95801 Baker Division ufDr'mking 05mm! Water: Ohio Envimnmm Protection Agency 122m humane Culmnbua, OH 43215 VLVQ 172.2. 308 SW23 80; 11/80 831 Gum-31540 Ll . nu Urdu. . '25. 35513115: A 98. mack. . . 31. Pursuant: Scc?m 14310:) ofthe SDWA. 43 11.8.0. 5 Emilia). violation 0mm 0111a, this my ofuptu occm or Him: to as massed by inappropshb: Un?zd 321 When DuPonxknom orthouk! Wham by thz; ?sturdy: ofdus d?igmcc, arm Odd-,Dqutshall rustic: to width: turn (16) barium thy: l?nrDuPont?ratknew. wit: the and: chin: diligence. shank! have known, ofmch cunt. The in detail the bus. for the delay, including wh??ler ibis 1 Force Mideun: went, and {1113:6516 ?n Imath Hf. mum) of, and mammals to nuchevem comm: Fm: Majcmu. EPA shall ma H1: time Bax: ofsuch in 7 5:?:sz - b95291 Ema?thaw u?u-u?n. . . - or 336:! . have 308 a?seoe?a am: an. wee as: 'on 311:1 L: ?l-ll-ZMI {Indian Ira-am US EPA Drum"! hm DIV. +312 mu PJJWUIU hm .mezuna ism 104 Is: 2135 near 5131?? man's-mm 3102? Lung. 33. WWMbeme?cnbn?m mmammMa . wimhumm. 34 This 85. In SO ORDERED: 4mm ?51? 4.5m? . Reina} Adm 1.8, 8mm); Ralf-w 21.431; 'd SB :51; meant?aw TI VAVS V2.2.- 308 3-9808-{1 Whit 30? SST 311:! .. u?u-u? GAAOC 1542 Ll. 34.. wait. if?utpmindm?lodurwmm augment-1nd In atecumd anar Hm H1 .mmwmomw?numnmm by SO ORDERED: . I . 1? um- 13mm . RWA?mMsu-m [73.En?run5nmanmmbuAmmz?on?I usu. - Du: Thoma: U-S. Wu Agency. Mon 93:91 3992-:th 2 BI 38% {72.178 FM. 308 3-9808-{1 'WImmcn?n?mI 30: ?780 561 ?Hum?- u. - GAAOC Ems 1543 Li ACREEDTTM mg WMMJ 4; ?002.. Ell. WW balsam-L" 81' 395d H.179 Vii. 306 - 59191: 3533-41-31:! 84580841 '1muomzal WHAT 30; 11/80 66T- 311:1 nun?.0. GAAO 01544 LII ?d 'PdlL'lJ. 'd W: 331d WW unof??sOx-der mammom 11751113141130.1319? DuPuni magma-an 1001mm sum Wilmington. 13319898 Paul Emmi, ?lm Mauser DUPnnt Wumnm Worm Faulty Rent: 892 gm} 1/ 551.. 2,44% Jun-t3. Stalin-(313000) 3min: Autknninnsl (In-[mil O?im Compiling, dem-imnmumlm?nu 1650mm 191031-2029 WHEN. 172.179 Vii. 308 8?9808?41 ENE 30. SSI 311:! GAAOC1545 EXHIBIT 1L 1 United States Environmental Protection Agency The 2009 consent order is available at: W/dupont/index.htm The 2006 consent order is _.available at: .'nt/dupot order.pdf For information on the risk assessment activity see: For reference materials and information on the 0?8 Health . Project, residents and can refer to: the' documents 13:, fissile: epa.gcv/reg1003/enforceme SteWardship Program and on the 'ava?able on these Websites odh. chic. gov/othrograms/ eh/hlth as/chemfsl.aspx and WW. cBheaIthproj ect. org 3.. DuPont Agrees to Lewer or PFOA in Drinking Water DuPont Washington Works Parkersburg, West Virginia llt/larch 2009 A new legal agreement between U. S. Environmental Protection Fgency and 1 du Pont de Nemours Co. will lower the limit of PFOA 1n rinking water for people who live near DuPont?s Washington Works fac lity' 1n Parkersburg, ?Va Under terms of the agreement-:- -known as a f?consent order" DuPont will offer water treatment or bottled water to ople on public or private watet systems When the level of a chemical cal 'ed PFOA - also known as per?uorooctanoic acid or -- in water supplie reaches 0.40 parts per billion (ppb). EPA's Office of Water issued a Provisional Health Advisoxy (P A) in Januarv for PFOA that establishes a reasonable, health?based vall above which action should be taken to reduce exposure to 1n drinking water. The time frame for action is short?term? meaning weeks to men :hs. This prompted the new agreement to lower the allowable concer tration of PFOA in drinking watel from 0.50 to 0.40 in communit es near the Washington Works facility. If affected homes cannot be connected to a publi Water system or a treatment system within 30 days, DuPont must; offer bottle Water People who liVe 1n the PFOA?contaminated water areas a?jfected by th new action level may reduce their exposure by not drinking the later until treatment systems are installed, or they are connected to a publicjwater system- L?m C) i EPA expects a limited number of residents will be affected by the new action level. Current data identi?es about 14 private residences that may need a treatment system?installed or connection to a public water system. If these residences cannot be connected to a public water system or treatment system within 14 days after the order is signed, then DuPont must offer alternative water. In addition, there may be a small number of private drinkiig water wells, installed after 2006, that need to be tested for PFOA. EPA is also assessing monitoring data and other information to detennine 1ftl1ere are any previously untested areas that need to be surveyed. Under a2006 consent order, all public and private water systems that had PFOA levels above 0.50 were offered alternative water or treatment, and DuPont is maintaining the alternative water or treatment 'at those systems today. EPA issued the 2006 order' 1n response to a study available at the time that eValuated about 340 residents living' 1n the most heavily affected :ommunities in Ohio near DuPont?s Washington Works plant. That study sho red residents had an average PFOA level of 298 to 369 1n their More recent data gathered under a PFOA health study involving some ?54 ,000 people, indicates the average PFOA levels in the bloodstreams everyone in the affected communities to be about 28 ppb. These values are still much higher than the average 5 level found In the national populati 1n. II. The 2006 order also relied on other studies that demonstrated various kinds of toxic effects on . experimental animals. EPA believed the results were a concern for public health. Of?ce of Water used new information, an advanced risk assessment technique and a different principal study from the one used in 2006 to establish the new national limit for PFOA of 0.4 ppb. Boiling does not remove PF CA from water. That is done by treatment with granular activated carbon. Where this treatment has been installed in a water system, consumers are receiving water with either undetectable PFOA levels or very low concentrations of .003 ppb, well below the 0.40 action level. All of the area?s large public water systems, including Belpre, Little Hocking, Lubeck, Mason County, Tupper Plains/Chester and Pomeroy, are already treating water for PFOA. As for private Water systems primarily water wells for private homes?- since 2006 DuPont tested a large number of systems and either connected them to a public water system or installed treatment equipment on 50 systems that had PFOA levels of 0.50 or above. Order requires expanded survey DuPont is required under the terms of the new consent order to survey geographical areas defined by EPA to determine if additional public or private water systems contain water that exceeds the new 0.40 PFOA action level. These areas will be further evaluated and re?ned in consultation with Ohio and West Virginia of?cials as analytical data become available. Residents with newly drilled drinking water wells or wells not previously tested for PFOA may be eligible for sampling. They should contact EPA at 866675?8543. EPA does not certify labs for analysis of PFOA. Due to the complex nature of analytical procedures for this substance, EPA strongly encourages residents to allow DuPont to sample their water. There is no consensus on how PFOA may affect people. However, concerns have been raised because of data from animal experiments and data from blood samples ?from people who live near the Washington Works facility. More studies are in progress but results may not be available for several more years. In the meantime, the new action level will reduce local exposure to PFOA from drinking water and reduce the possibility of adverse health effects. 1 continues to conduct its risk assessment?undcr Technical background: What is PFOA, or OS, is a man-made chemical that re sists heat, water, oil, grease and stains. It has been used 0 making common household and industrial items such as non-stick pots and pans, ?ame resistant and water-proof clothing, wire coatings, and chemical resistant tubing. can also be formed by the breakdown of other hi 11y ?uorinated chemicals used in stain-resistant carpets and fabrics, stain-resistant paints, fire ?ghting foa in, arid oil- and grease?resistant food cartons and wrappers. PFOA does not occur naturally in the environment an is highly persistent, with little or no degradation occurr ng in air, water or soil. History of legal orders This order supersedes the Emergency 'Adminiitrative Order on Consent that was issued in 2006 no er the authority of the Safe Drinking Water Act. Section 1431 of the Act requires a ?nding that ?a contamin nt is present in or is likely to enter a public Water sf stem or may present an imminent and substantial endanger ant to the health of persons.? It does not require a conclusive ?nding that a contaminant has, or de?nitely will, cause underground source of drinking Water wet?? harm. The 2006 order contained a temporary threshc ld value of 0.50 PFOA based on information available at the time about blood serum levels of the chemical in the local population and scienti?c studies. The 2006 order was a revision to a 2002 order, which established an action level of 150 ppb. The new order?s revised action level of 0.40 PFOA is based on new and different information than what was used to calculate th action level. The former 0.50 site-speci?c level for PFOA was a threshold for DuPont to 2006 action provide treatment or alternate Water to public and private water users in the vicinity of the facility, and the new action level of 0.40 is an Updated threshold. The authority of the federal Toxic Substances Cont Until that process is complete there will not be reference dose or an of?cial maximum contam for drinking water. West Virginia and Ohio authorities have relied Agency the rol Act. a inant level on EPA to review the existing 2006 order and have requested assistance with this matter. PFOA levels in drinking water and human blood The average human blood serum PFOA concentration in the United States is around 5 ppb. PFOA can be absorbed though swallowing, breathing and skin exposure. We do not know which exposure routes account for the background levels of PFOA in the general population. Some residents in the vicinity of the Washington Works plant had median blood serum levels ranging from around 298 to 369 PFOA. Data from a more recent study indicate the average has dropped to about 28 ppb. The high blood serum levels in residents are attributed to accumulation of PFOA in the bloodstream and its slow elimination from the human body. The half-life in humans_is approximately 3.8 years. Half-life is the time required to reduce the chemical to one-half the initial concentration. For example, with no additional PFOA input it will take approximately four years for blood values of mo to be reduced to 50 ppb. Ingestion of PFOA through drinking Water is considered a major source of the chemical found in the blood of residents in the vicinity of the DuPont facility. Reducing exposure to PFOA in drinking water will reduce the accumulation of the chemical in residents. The drinking water levels in nearby water systems have historically aVeraged from 1 to 20 PFOA. For the six public water systems in the area and for private residences. that accepted treatment, PFOA levels in drinking water have been significantly reduced to undetectable concentrations and most often less than .003 ppb. While much is known about the occurrence of PFOA in the vicinity of this DuPont facility, the substance is not a regulated drinking water contaminant. Therefore, public water systemsare not required to monitor for PFOA. Recent scientific information Of?ce of Water used new scienti?c information, an advanced risk assessment technique, and a different principal study from the one Used in 2006 to develop the FHA. The principal study the Office of Water used involves peer-reviewed research in mice that looked at developmental effects of PFOA as the toxicological endpoint. The 2006 calculation used an earlier study of monkeys that looked at mortality rates as the toxicological endpoint. Additionally, since the 2006 order was issued new information and data has become available on PFOA half-lives in some animal species that the Of?ce of Water used in its calculation. The Of?ce of Water also applied a more advanced risk assessment - the risk assessment process. Department of Health Human Resources wanted to have technique that resulted in an update to some of 6 values used to calculate the new Provisional Health Advisory from public health. EPA and DuPont agreed to rcvise?the existing order. - . Other legal actions . In 2001 DuPont, the West Virginia Department Environmental Protection and the West Virgini :Departmen of Health and Human Resources entered into a ,onsent agreement. The legal order required a toxicolog Cal and human health risk assessment of C-8 be conduc ed under the supervision of a 0?8 assessment of toxicity tea Ground? water and surface?water monitoring and plume i: enti?oation in West Virginia and Ohio were conducted undetr the SUpervision of a ground?water investigation tealI: Wood County, (Leach, et a! v. de Nemours Company) required collection of bl bd serum an health data from about 70,000 people who live ear DuPont? Washington Works facility. The collection of bl ,od serum and health data is known as the Brookmar Stud provided for the installation of carbon ?lters for six public water service districts in West Virginia and Ohi . EPA was not a party to the civil action or the settlement. PA will, however, evaluate data produced by these studie as well as other information generated as part of its ongoin' review in An order issued in 2005 in response to c3 il suit in Major human health studies in progre PFOA Health Project: In 2006 about 64,000 people completed questionnaires and had blood drawn. . rookmar Inc. has been hired to collect and compile the he 1th data and blood serum levels. Then a three?member scienci panel will assess whether there are adverse health effects to-humans associated with elevated levels of PF DA in the blood serum. Although the full results of the study are not exp cted until about 201 I, the blood serum concentrations are allvailable to the people who participated. Ohio Department oil Health, the federal Agency for Toxic.Substances and Diseas? Registry, Ohio Environmental Protection Agency, West Virginia Department of Environmental Protection and West Virginia reference materials available to local physicians as their patients received data. Information is available at: .aspx ll. Status of EPA risk assessment Under the Toxic Substances Control Act, EPA is evaluating PFOA and related perfluorochemicals. A formal risk assessment process is under Way- Science Advisory Board completed a review of a dra? risk assessment of PFOA in 2006, and the board made recommendations for the further development of the assessment. A ?nal risk assessment may not be completed for several years. Once a ?nal risk assessment is completed, or if further information about the health effects indicates it is necessary the action level of 0.40 PFOA established in the latest legal order with DuPont will be re?evaluated. The Agency is funding additional research regarding the toxicity of PFOA and other per?uorochemicals, as well as research to help identify where these chemicals are coming from and how people may be exposed to them. The EPA risk assessment activity on PFOA Other EPA actions ori PFQA salts will take time to complete, but the Age: already taken action to reduce the amount of and its. icy has getting into the environment. In 2006 EPA invited major companies in the industry to committ voluntary, global PFOA SteWardship Progra invited companies, including DuPont, [never to the goals of the program, which include re facility emissions and product content of PF related chemicals by 95 percent by'2010 and toward elimination of releases and product these chemicals by 2015DuPont had reduced annual air discharges oi chemical from the Washington Works facilit percent and had reduced annual water discha 99.2 percent since 2000. DuPont and the oth companies are submitting reports to EPA on a tn. All lommitted ducing DA and !working patent of '06, "the by 99.1 tees by er their past activities and on their progress toward the Stewardship Program goals. l! . Resin LEE i i 11131;], . MAR 102 9 REGIONAL Hmong etuuc - . . .- v.5. ENVIRONME. I. i. :a l' int?Ho . UNITED STATES PROTECTION AG INCYJ ENVIRONMENTAL PROTECTION AGENCY REGION REGION 1650 Arch Street 77 West Jackson Boulevard Philadelphia, PA 19103-2029 Chicago, IL 60604 IN THE MATTER OF: 3 13.1. du Pont de Nemours and Company ORDER ON CONSENT 1007 Market Street Wilmington, DE 19898 Proceeding under Section 143 1) ResPondent. of the Safe Drinking Water Act, 42 U.S.C. 300i(a)(1) Washington Works Facility Route 892 South Washington, WV 26181 Docket Nos. DS I. STATUTORY AUTHORITY 1. This Order on Consent ("Ordef'J is issued pursuant to the authority vested in the Administrator of the United States Environmental Protection Agency by Section 1431(a)(1) of the Safe Drinking Water Act or ?the Act"), 42 U.S.C. 300i(a)(i), and supersedes the Order on Consent (Docket Nos. and 001) issued on November 20, 2006. 2. The authority to issue this Order was delegated to the Regional Administrators by Delegation No. 94 7, dated May 11, 1994. Under the SDWA, Congress has authorized EPA to exercise broad authority for the protection of public health from contaminants entering a public water system or an underground source of drinking water. II. STIPULATIONS . 4. 13.1. du Pont de Nemours and Company (?DuPont") consents to EPA?sjurisdiction to issue this Order. DuPont does not admit to the EPA Findings in this Order. .. 3. DuPont waives any defenses it might have as to jurisdicrion and venue and agrees not to contest any of the ?ndings of fact or conclusions of law herein in any action to enforce this Order. Except as to any proceeding brought by EPA to enforce this Order, in agreeing to this Order, DuPont makes .no admission of fact or law and reserves all rights and defenses available regarding liability or responsibility in any other legal proceeding related to the subject matter of this Order. DuPont ?thher waives any rights to appeal this Order that would be otherwise applicable under the SDWA. lli. DEFINITIONS AND BACKGROUND 6. "Contaminant" means ?any physical, chemical, biological, or radiological substance or matter in water." ?g 42 U.S.C. 300116). 7. The term "underground source of drinking water" means an aquifer or a portion thereof which supplies a publicwater system or which contains a suf?cient quantity of ground water to supply a PWS and which currently supplies drinking water for human consumption, or contains fewer than 10,000 milligrams per litertotal dissolved solids, and is not an exempted aquifer. geetlo C.F.R. 144.3. 8. C-8, for purposes of this Order, is per?uorooetanoic acid, CAS 33 5-67-1 (PFOA) and its salts. including ammonium per?uorooctanoate, CAS 3825?26-1 (APFO). These are man? made perfluorinated compounds that do not occur naturally in the environment. 9. The term ?day" means calendar day. When a stated time expires on a Saturday, Sunday or Federal Holiday, the stated time period shall be extended to include the next business day. 10. Micrograms per liter (pg/l) is the same as parts per billion (ppb). 1 l- The term ?source water" shall mean water prior to any kind of treatment. 12. A ?public water system," hereafter provides piped drinking water for human consumption to persons within the meaning of Section (4) of the Act, 42 U.S.C. ?300f?4) and 40 CPR ?l41.2. 13. A private water system is used by individual residents, or serves less than 25 persons per . year from a well or other surface or ground water source and is otherwise not a 14. The term ??nished water" shall mean water that has passed through all the processes in a system?s water treatment plant and is ready to be delivered to consumers. IV. EPA FINDINGS 15. DuPom is a corporation and is therefore a ?person" within the meaning of Section 140M112) ofthe SDWA, 42 - I 2 6. DuPont owns and Operates a manufacturing facility known as the Washington Works ("Facility"), located in Washington, Wood County, West Virginia. 17. DuPont has used (3-8, in the form in its manufacturing processes at the Facility since the ear1y_195(ls. 18. On November 15, 200] DuPont, the West Virginia Department of Environmental Protection and the West Virginia Department of Health and Human Resources entered into an agreement on consent Order"), which provided for, inter cite, a toxicological and human health risk assessment of 08 to be conducted under the supervision of 11 08 Assessment of'l?oxicity'C?CAT?) Team. Ground water and surface water monitoring and plume identi?cation in West Virginia and Ohio was conducted under the supervision of a Ground Water Investigation Steering Team. 19. - In April 2002, the CAT Team conducted a toxicological and human health risk assessment ofC-8 and deveJOped a screening level of150 for GB in drinking water. 20. From 2000 to 2006 DuPont implemented recycling and abatement technologies that reduced both air emissions and water discharges of C-8 ?'om the Facility. Annual emissions to air in 2005 were reported to be approximately 12,600 kilograms lower than annual air emissions since 2000.[ 21. On November 20, 2006, DuPont and EPA entered into an Order on Consent (?2006 Order"), which required DuPont to offer,1'nteralia, alternative drinking water or treatment to public water systems or owners of residences using private water systems living in the vicinity of the Facility where levels of detected in the finished water of public and private drinking water systems were equal to or greater than 0.50 ppb. 22. The 0.50 action level established in the 2006 Order was a precautionary level to reduce exposure from (3?8 to the population living in the vicinity of the Facility. 23. On January 8, 2009, the EPA Of?ce of Water issued a Provisional Health Advisory which established a national value of 0.4 for PFOA.2 DuPont. "Data Assessment DuPont Washington Works 13 PFOA Site-related Environmental Assessment Program,? (October 2, 2008). 2 United States Environmental Protection Agency?s Of?ce of Water. "Provisional Health Advisories for Port] urooctanioic Acid (PFOA) and Periluorooctanc Suit?onate (2009). (including Administrative Record thereto). A vai lable: 3 (J 24. Provisional Health Advisory values re?ect reasonable, health-based hazard concentrations above which action should be taken to reduce exposure to PFOA in drinking water. 25. Sampling conducted through the 613 Team effort since 2001, and by DuPont, has detected (3-8 in private and public drinking water sources in Ohio and West Virginia at concentrations ranging ?rom below the limits ofquantitation up to 21.1 ppb."1 As set forth in more detail inparagraphs 26, 27 65 28, DuPont has already taken measures to address PFOA in drinking water at or above 0.50 ppb. 26. The 2006 Order achieved comprehensive identification of private and public water systems in the vicinity of the Facility and ensured altemate water and/or treatment was offered, installed, and maintained at all public and private water systems that exceeded 0.50 of GB in their finished water. - 27. Prior to the 2006 Order, DuPont had o?'ered a granular activated carbon water treatment Treatment") at two public water systems that contained levels of (2-8 that exceeded 0.50 in their ?nished water. Those public water systems are the Little Hocking Water Association (?Little Hocking"), located in Ohio, and the Lubeck Public Service District (?Lubeck?), located in West Virginia. Upon acceptance of the offer "and completion of construction, DuPont has provided for operation and maintainence of GAC Treatment at Little Hocking and Lubeclc pursuant to the 2006 Order. 28. Initiating prior to and continuing pursuant to the 2006 Order, DuPont has offered to either connect to a public water system or install GAC Treatment to owners of residences using private water systems for which data have demonstrated levels of (2-8 at or above 0.50 in their ?nished water. DuPont has either connected to a public or has installed and is operating GAC Treatment at approximately 50 private water systems with ?nished water that exceeded 0.50 of C-8 and whose owners have accepted DuPont ?3 offer. 29. To date, approximately four owners of private water systems in the vicinity of the Facility with'?nished water that exceeds?0.50 ofC-B have declined or not responded to DuPont 's o?'er for installation of treatment or connection to a public water system. 30. With the issuance of the Provisional Health Advisory for PFOA, EPA has identi?ed additional geographic areas in the vicinity of the Facility where USDWs may contain (3-8 at concentrations at or above 0.40 ppb. 3 id. 4 Harden, Andrew 3., Project Director, DuPont. "Amended 3Q05. and 4Q05 and [(206 Residential Sampling Results. West Virginia and Ohio DuPont Washington Works, Washington, WV (EPA Docket ll} Number OPPT 2004-01 l3 PFOA Site-Related Environmental Assessment Program,"submitted to Chad Board, West Virginia Department of Environmental Protection (April 5. 2006). 4 31. GS is currently not a contaminant for which a national primary drinking water regulation, including a maximum contaminant level has been established pursuant to the SDWA. 32. EPA is conducting a risk assessment ofC?8 under the Toxic Substances Control Act 15 U.S.C. 2601 et seq. 33. DuPont has released 08 to the air, discharged (2?8 to surface waters," and diaposed of residues containing at the Facility. DuPont has also disposed of residues containing 08 to its Dry Run, Local. and Letart Land?lls in West Virginia and has otherwise shipped residues containing C-B off?site for destruction and/or disposal. 34. The releases, discharges, and/or diaposal referred to in Paragraph 33 have resulted in releases of to air, ground water, surface water, and-soil. - 35. The releases referred to in Paragraph 33 have entered USDWS and surface waters and resulted in levels of at concentrations at or above 0.40 in some of the receiving waters. 36. Public and private water systems in the vicinity of the Facility are using water sources contaminated with GB at levels that may be at or above 0.40 ppb; and therefore ?n?ther investigation is warranted. 37. Based on existing data, there are approximately 10-15 private water systems in the vicinity of the Facility that. contain levels ofC~8 at or above 0.40 in their ?nished water.5 38. Although EPA has not yet completed its risk assessment for G8, EPA has determined that the 0.50 Site?Speci?c Action Level requires modi?cation. 39. Section 1431 of the SDWA requires a ?nding that ?a contaminant which is present in or is likely to enter a public water system or an underground source of drinking water.. .may present an imminent and substantial endangerment to the health of It does not require a conclusive ?nding that a contaminant has, or de?nitely will, cause harm. As required by Section 1431 of the SDWA and for purposes of this Order, EPA has determined that 61-8 is a contaminant present in or likely to enter a PWS ora USDW which may present an imminent and. substantial endangerment to human health at concentrations at or above 0.40 in drinking water. 6 The 0.40 action level is a precautionary Site-Speci?c Action Level to reduce exposure to the population living in the vicinity of the Facility. 5 A., Project Director, DuPont, concentration at or above 0.40 ug/L" (Tables and 2). (dated 2/16/2009). 6 United States Environmental Protection Agency?s Ol??ce ofWatcr, "Provisional Health Advisories for Per?urooctanioic Acid (PFOA) and Pcr?uorooctane Sulfonate (2009). (including Administrative Record thereto J. Available: ?11303.ng 5 40. State and local authorities rely on the expertise and resources to review and evaluate unregulated contaminants. The WVDEP, OEPA, the Ohio Department of Health and local authorities are relying on the EPA to establish a Site?Speci?c Action Level for GB in drinking water that reduces exposure to (2-8 for residents in the vicinity of the Facility. State agency actions taken to date, including actions taken by WVDEP, OEPA, and have been based on the Site?Speci?c Action Level of 0.50 established in the 2006 Order. 41. EPA has consulted with WVDEP, OBPA, and ODI-I to con?rm that the information upon which this Order is based is correct. The WVDEP, WVDI-IHR, OEPA, and ODH have requested that EPA take this action. Therefore, all requisite conditions have been satis?ed for EPA action under Section the SDWA, 42 U.S.C. 300i(a)(l). V. ORDER ON CONSENT 42. Pursuant to the authority given to the EPA Administrator by Section of the SDWA, 42 U.S.C. 300i(a)(1 and delegated to the Regional Administrators, DuPont is ORDERED and hereby consents to the following: a) Temporarv Provision of Alternate Drinking.r Water. For those private water systems where existing validated data demonstrates levels ofC-S at or above 0.40 in their ?nished water, DuPont shall provide an alternate drinking water supply as soon as practicable, but in any event no later than fourteen (l 4) days after the execution of this Order. Where DuPont conducts a water system survey pursuant to Paragraphs 42(e) or and identi?es private and public water systems where the level of (3-8 in the ?nished water is at or above 0.40 ppb, DuPont shall provide an alternate drinking water supply as soon as practicable, but in any event no later than thirty (30) days, Earn the receipt of validated data. An ?alternate drinking water supply" shall mean: water from some other source, acceptable to EPA, that meets the water quality requirements of40 C.F.R. Part 14] and has a leVel of (3?8 less than 0.40 in ?nished water where applicable; is in suf?cient quantity for drinking and cooking; and is provided in a manner convenient to the users. DuPont shall continue to provide an alternate drinking water supply until it can ?tlly implement the permanent remedies described fa?-a pursuant to Paragraph 42 of this Order or the resident declines the offer or is non-responsive to the offer of treatment (as determined DuPont shall be responsible for all costs of? the provision of alternate drinking water. b) Private Water 8 stems Rec iv' Treatmen . For private water systems at order, including but not limited to timely replacement of carbon ?lters, until it demonstrates to the satisfaction of EPA that the source prior to GAG Treatment 6 8) cl) contains less than 0.40 ofC?S For four consecutive quarters, or the conditions of Paragraph 46 have been met. DuPont may also elect to satisfy any ongoing obligation under this Paragraph by connecting a particular location to a public water system that contains less than 0.40 of OS in ?nished water. Public Water Systems Receiving Treatment. For public water systems, at which DuPont has already installed GAC Treatment, DuPont shall provide for operation and maintenance of each GAC Treatment system in good working order, including but not limited to timely carbon bed changes, until it demonstrates to the satisfaction of EPA that the source water in the system prior to GAC Treatment contains less than 0.40 of GB for four consecutive quarters, or the conditions of Paragraph 46 have been met. Actiou at Private Water Systems Based On Existing Data. For those private water systems where existing validated data demonstrates levels of 08 at or above 0.40 in their ?nished water, DuPont shall, within fourteen (l 4) days of execution of this Order, submit to EPA for approval, and to WVDEP, OEPA, and ODI-I for review, a written Water Treatment Plan for each - of these water systems in accordance with the provisions of Paragraph 42(g). Survey and Identi?cation of Additional Private and Public Water Systems. For geographical areas de?ned by EPA (upon consultation with West Virginia and Ohio), DuPont shall conduct a water system survey and where any private or public water system (not already sampled) is identi?edhmonitor the ?nished and source waters for the presence of C-8. DuPont shall notify EPA of' monitoring results immediately, but in any event no later than 7 days; after the data are ?nalized through DuPont?s internal data quality control/quality assurance procedures. DuPont shall also notify or operators of private and public water systems of monitoring results within 7-10 days after the data are ?nalized through DuPont?s intemal data quality controlz'quality assurance procedures. Newly Activated or Permitted Water Systems. Upon noti?cation by EPA of any newly activated public water system or any newly constructed/pennitted/put into use private water system that conforms to state and local code and is located in the geographical areas de?ned by EPA (upon consultation with West Virginia and Ohio), {DuPont shall monitor the ?nished and source waters for the presence of C-8 in accordance with the provisions of Paragraph 42(e). On the anniversary date of the e??ective date of this Order and annually thereafter, DuPont shall survey the geographical areas dei'med by EPA for any new private or public water systems until DuPont demonstrates to the satisfaction of EPA that the USDWs in these geographical areas (or a subset of those areas) contain less than 0.40 of GB for four consecutive quarters, or the conditions of Paragraph 46 have been met. DuPont shall monitor the ?nished and source 7 waters of any new systems for the presence of (3?8 in accordance with the provisions of Paragraph 42(c). g) Water Treatment Plan. If any additional private or public water systems covered by this Order contain 08 at or above 0.40 in their ?nished water, DuPont shall, within 30 days of receipt of validated data, submit to EPA for approval, and to OEPA, and ODl-l for review, a written Water Treatment Plan for each of these Water systems. DuPont shall perform all monitoring using a reliable procedure published in the scienti?c literature by Moody, MP1 (formerly known as Exygen Research),3 other equivalent publication or an EPA approved analytical method. The Water Treatment Plan shall include: i. a Written offer to install and provide for operation and maintenance of GAG Treatment (including a draft operation and maintenance agreement); ii. identi?cation of anticipated necessary permits; a schedule for design and implementation of the GAC Treatment system; and iv. identi?cation of technical and other information needed ?'orn the owner or operator of the water source in order for DuPont to design and install the system. - h) lmlementation QfWater Treatment Plan. Following approval ?'orn EPA, DuPont shall implement the Water Treatment Plan for any additional water system whose OWner or operator accepts DuPont?s offer. DuPont shall act with all deliberate speed to design treatment, seek necessary regulatory permits, and install GAC Treatment or an alternative apprOVed by EPA. If an owner or Operator ofa water system rejects DuPont?s o?'er, either through express rejection or silence, DuPont shall inform EPA of this rejection and provide documentation. i) DuPont's oration and Maintenance 0in ations. DuPont has or will execute operation and maintenance agreements Agreements") with each water system owner or operator who has accepted the offer for treatment. DuPont will I provide for operation and maintenance of the GAC Treatment, or an alternative 7 Moody, Kwan. W.C.: Martin. Muir, D.C.G. Mabury. 3A., "Determination ofPeriluorinatcd Surfactants in Surface Water Samples by Two Independent Analytical Techniques: Liquid Mass Spectrometry 19F Anal. Chem. vol. 73, pp. 2200-2206 (2001). 8 Risha, Willa. R.: Buck. Morandi, F. lsemura, T.. "Method for Trace lava! Analyst's OTC-8, 0?10, l, and (1-13 Per?uorocarbon Carboxyh'c Acids in Chem. vol. 77, pp. 1503-1508 (2005). 8 approved by EPA consistent with the speci?c terms of these Agreements until it demonstrates to the satisfaction of EPA that the water system?s source water prior to treatment is less than 0.40 of (2-8 for four consecutive quarters, or the conditions of Paragraph 46 have been met. . j) Follow-up Monitoring. After GAC Treatment is terminated, DuPont shall monitor annually the source water at EPA-Specified public and priVatc water systems for a period of ?ve (5) years. 43. Proggess Reports. DuPont shall submit Progress Reports as follows: a) b) C) Beginning April 1, 2009, and quarterly therea?er, DuPont shall submit to EPA, WVDEP, OEPA and ODH written reports summarizing all actions taken in response to Paragraph 42 herein (?Progress Reports"). This reporting requirement shall remain in e?ect until DuPont submits a written request to EPA to submit Progress Reports on an annual basis and EPA approves such a request. DuPont shall continue to submit Progress Reports until such time as EPA provides written notice that the reports are no longer necessary, or this Order is terminated. All Progress Reports required by this Paragraph shall contain the follovi/ing certi?cation, which shall be. signed by a responsible corporate of?cer: certify under penalty of law that this document and all attachments were prepared under my direction or supervision in accordance with a system designed to assure that quali?ed personnel properly gather and evaluate the information submitted. Based on my inquiry of the person or persons who manage the system, or those persons directly reSponsible for gathering the information, the information submitted is, to the best of my knowledge and belief, true, accurate, and complete. I am aware that there are signi?cant penalties for submitting false information, including the possibility of ?ne and imprisonment for knowing violations." For purposes of this Order, a reaponsible corporate official shall be: (A) a president, secretary, treasurer, or vice-president of DuPont in charge of a principal business function, or any other person who performs similar policy or decision-making iterations for DuPont; or (B) the manager ofDuPont?s Washington Works, West Virginia Facility, so long as authority to sign documents has been delegated in writing to the manager in accordance with corporate procedures. - VT. QENERAL PROVISIQNS 9 44. The Administrative Record to this Order is incorporated herein by reference. 45. Nothing in this Order is intended to supersede, impede, interfere with or otherwise a?'ect the development of an MCL or other regulatory limit for C-S that may be established by EPA through its regulatory processes in the future. 46. The Site-Speci?c Action Level identi?ed in this Order for (2?8 in drinking water is a temporary value that will be re?evaluated when EPA determines a reference dose under TSCA or establishes a drinking water standard for (3-8, whichever comes ?rst. 47. Notwithstanding any other provision of this Order, the EPA reserves the right to modify the Site-Speci?c Action Level identi?ed in this Order if information previously unknown to EPA is received and EPA determines that this previously unknoWn information, together with any other relevant information, indicates that the Site-Speci?c Action Level may not be pretective of human health, and DuPont reserves all rights and, defenses should EPA take action under this Paragraph.? - . 48. All submissions, including Progress Reports, required under this Order shall be submittedto the following addressees: As to EPA: Roger Reinhart Groundwater and Enforcement Branch US. EPA Region 1650 Arch Street (3WP22) Philadelphia, PA 19103?2029 Ryan Baht Ground Water and Drinking Water Branch U.S. EPA Region 77 West Jackson Boulevard (WG-1 SI) Chicago, IL 60604 As to Walter Ivey, Director Division of Environmental Engineering Office of Environmental Health Services Dept. of Health and Human Resources Capital and Washington Streets One Davis Square, Suite 200 Charleston, WV 25301-1798 1.0 IL As to WVDEP: William Timmermeyer Groundwater Protection Section Division of Water and Waste Management Dept. of Environmental Protection 601 57th Street, SE Charleston, WV 25304 As to OEPA: Mike Baker, Chief Division of Drinking and Ground Waters Ohio EPA l22 South Front Street Columbus, OH 43214 As to ODH: W. Gene Phillips, RS, Bureau Chief Bureau of Environmental Health Ohio Department of Health 246 North High Street P.O. Box 118 Columbus, OH 43216 - 49. This Order shall apply to and be binding upon DuPont and its agents, successors and assigns. 50. Nothing in this Order shall be construed as prohibiting, altering or in any way eliminating the ability of EPA to seek any other remedies or sanctions available by virtue of DuPont?s violations of this Order or of the statutes and regulations upon which this Order is based or for DuPont?s violation of any applicable provision of law. 51. This Order shall not relieve DuPont of its obligation to comply with all applicable provisions of federal, state or local law, nor shall it be construed to be a ruling on, or determination of; any issue related to any federal, state or local permit. 52. Nothing in this Order is intended to nor shall beconsrrued to operate in any way to .resolve any criminal liability of DuPont. Compliance with this Order shall notbe a defense to any actions subsequently commenced for any violation of federal laws and regulations administered by EPA, and it is the reSponsibility ofDuPont. to comply with such laws and regulations. EPA reserves the right to undertake action against any person, including DuPont, ll in response to any condition which EPA determines may present an imminent and substantial endangerment to the public health, public welfare or the environment. 53. The undersigned representative of DuPont certi?es that he or she is fully authorized by DuPont to enter into the terms and conditions of this Order and to execute and legally bind DuPont to it. 54?. Pursuant to Section 1431(b) of the SDWA, 42 U.S.C. and the Adjustment of Civil Monetary Penalties for In?ation, 4O C.F.R. Part 19, as revised (74 Fed. Reg. 626 (Jan;7. 2009)), the violation of any term of this Order, or failure or ratings] to comply with this Order, may subject DuPont to a civil penalty not to exceed $16,500 for each day in which such violation occurs or failure to comply continues. 55. When DuPont knows or should have known, by the eXercise of due diligence. of an event that might delay completion of any requirement of this Order, DuPont shall provide notice to EPA, in writing, within two (2) business days after DuPont first knew, or in the exercise of due diligence, should have know, of such event. The notice shall describe in detail the basis for the delay, including whether it is aforce majew-e eVent, and describe the length of, precise cause(s) of, and measures taken or to be taken to prevent or minimize such delay. agrees that such event constitutes force mcy'eure, EPA shall extend the time for performance of such requirement, in Writing, to compensate for the delay caused by the force mm?eure event. DuPont?s failure to notify in writing in accordance with this Paragraph shall render this Paragraph void and of no effect concerning such event. For purposes of this Order, ?ares majeure is de?ned as an event arising from causes beyond the control 'of DuPont, and any entity controlled by DuPont, which delays or prevents the performance of any obligation under this Order. Unanticipaled or increased costs or expenses associated with implementation of this Order and changed financial circumstances shall not, in any event, be considered force majeure events. In addition, Failure to apply for a required permit or approval or to provide in a timely manner all information required to obtain a permit or approval that is necessary to meet the requirements of this Order, or to obtain or approve contracts, shall not, in any event, constitute force majeure events. - 56. This Consent Order may be executed in any number of counterpart originals, each of which shall be deemed to constitute an original agreement, and all of which shall constitute one agreement. The execution of one counterpart by any party shall have the same force and effect as if that party had signed all other counterparts. 57. All of the terms and conditions of this Order-together comprise one agreement, and each of the terms and conditions is in consideration of all of the other terms and conditions. In the event that this Order is not executed by all of the signatories in identical form, or is not approved in such identical form by the Regional Administrators, then the entire Order shall be null and void. 12 58. The etchtive date of this Order is the date on which, a?cr approval by the Regional Administrators. this Order is ?led with the Regional Hearing Clerks ot?both Region Ill and Region V, if not. then on the day. 59. This Order shall remain in effect until DuPont fulfills its obligations pursuant to Paragraphs =12 and 43 herein. submits a written request to EPA to terminate this Order. and EPA approves such termination rcqucsl. 60. This Order constitutes ?nal agency action. I SO ORDERED: I Date: William T. Wisniewski Acring Regional Administrator U.S. Environmental Protection Agency, Region MAR102009 . a, I Dana: 31 ?01 OT Bharn! Mathur Acting Regional Adminismz 1.1.8. Environmental Protection Agency, Region I4 AGREED TO: "Dam.- 5/5/7200? William H. Hopkins Plant Manager, Washinglon Works Facility EJ. du Pont dc Ncmours and Company, Incorporated EXHIBIT Bilott. Robert A. From: U.S. Environmental Protection Agency Sent: Monday, January 09, 2017 1:51 PM To: Bilott, Robert A. Subject: EPA Amends Drinking Water Order to DuPont UNITED STATES ENVIRONMENTAL PROTECTION AGENCY REGION OFFICE OF COMMUNICATIONS GOVERNMENT RELATIONS ?650 Arch Street Philadelphia, 19103?2029 Phone 21518146100 Fax - 215/814-5102 EPA Environmental News Contact: David Sternberg 215-8 14?56 15 dandrea.michael.@epa.gov EPA Amends Drinking Water Order to DuPont PHILADELPHIA (January 9, 2017) - The U.S. Environmental Protection Agency today announced an amendment to the 2009 Safe Drinking Water Act consent order between EPA and 13.1. (111 Pent de Nemours and Company (DuPont). The amendment adds The Chemours Company (Chemours) to the 2009 order, and requires both DuPont and Chemours to take additional actions to reduce exposure to perflnorooctanoic acid (PFOA) in drinking Water for residents in Ohio and West Virginia living near the Washington Works facility in Parkersburg, WV. he? amendment contains a new action level of .07 parts per billion (ppb) of PFOA which triggers the temporary provision of an alternate source of drinking water by DuPont and Chemours. The temporary provision of drinking water will continue until a permanent alternate drinking water supply is provided. The amendment also expands the geographic areas to be investigated and requires appropriate action if levels in drinking water of .07 or more are discovered. This amendment to the 2009 Order, which had included a temporary action level of .40 ppb, is supported by site-speci?c data, as well as the Lifetime Health Advisory issued by EPA on May 19, 2016, that established .07 ppb, of PFOA in drinking water as protective of human health. if you would rather not receive future communications from Environmental Protection Agency. let us know by clicking here, Environmental Protection Agency. 1650 Arch Street, Fhlladelphia. PA 19103-2029 United States EXHIBIT . ?0 EPA FACT SHEET United Stateg PFOA 8.: PFOS Drinking Water Environmental Protection . Agency Health Adulsorles . .. 5 EPA has established health advisories for FDA and PFOS based on [the agency?s assessment of the latest peer?reviewed science to provide;i drinking water system operators, and state, tribal and local officials who haxle the primary responsibility for overseeing these systems, with informati an on the health risks of these chemicals, so they can take the appropriate actions to protect their residents. EPA is committed to supporting states arid public water systems as they determine the appropriate steps to reduce exposure to PFOA and PFOS in drinking water. As science on health effects of these chemicals evolves, EPA will continue to evaluate new evidencePFOA and PFOS are fluorinated organic chemicals that are part of a larger group of chemicals referred to as perfluoroalkyl substances PFOA and PFOS have been the most extensively produced and studied of these chemicals. They have been used to make carpets, clOthing, fabrics for furni- r? .. ture, paper packaging for food and other materials cookware) that are ?if? 3 . resistant to water, grease or stains. They are also used for firefighti 1g at air- ?Th I ?wt? fields and in a number of industrial processesIsa?; Because these chemicals have been used In an array of consumer products, ?Live ?Esi'?gil?iu 1" I FFOS ?b most people have been exposed to them. Between 2000 and 2002, it?; was voluntarily phased out of production in the US. by its primary :anufac? I turer. In 2006, eight major companies voluntarily agreed to phase 0 i their global production of PFOA and PFOA?related chemicals, although th re are a limited number of ongoing uses. Scientists have found PFOA and PF in the blood of nearly all the people they tested, but these studies show thlat the 44! levels of PFOA and PFOS in blood have been decreasing. While con %umer products and food are a large source of exposure to these chemical ifor most people, drinking water can be an additional source in the smal aper- centage of communities where these chemicals have contaminated ater supplies. Such contamination is typically localized and associated th a spe- cific facility, for example, an industrial facility where these chemicalslwere 3 sired?. 1,3363%; produced or used to manufacture other products or an airfield at ich they 3* were used forfirefighting. . - 53?2" Jah? . . "Jim-t 13$. EPA develops health advisories to provide information on contaminants that can ca use human health effect and are known or anticipated to occur in drinking water. EPA's health advisories are non-enforceable and non?regulatory and provide technical information to states agencies and other public health officials lon health effects, analytical methodologies, and treatment technologies associated with drinking water contam? . ination. In 2009, EPA published provisional health advisories for PFOA and PFOS based on the evider ce avail~ able at that time. The science has evolved since then and EPA is now replacing the 2009 provisional adviso- ries with new, lifetime health advisories. US Environmental Protection Agency 1 November 2016 FACT SHEET To provide-Americans, including the most sensitive populations, with a margin of protection fro a life? time of exposure to PFOA and PFOS from drinking water, EPA established the health advisory laurels at 70 parts per trillion. When both PFOA and PFOS are found in drinking water, the combined concen rations of PFOA and PFOS should be compared with'the 70 parts per trillion health advisory level. This health advi? sory level offers a margin of protection for all Americans throughout their life from adverse health effects resulting from exposure to PFOA and PFOS in drinking water. ?tr p' 1. I How the Health Advisories were developed health advisories are based on the best available peer-reviewed studies of the effects of PFOA and PFOS on laboratory animals (rats and mice) and were also informed by epidemiological studies of populations that have been expoSed to PFASs. These studies indicate that exposureto PFOA and certain levels may result in adverse health effects, including developmental effects to fetuses durin? nancy or to breastfed infants low birth weight, accelerated puberty, skeletal variations), cancer testicular, kidney), liver effects tissue damage), immune effects antibody production anc im- munity), thyroid effects and other effects cholesterol changes). health advisory levels were calculated to offer a margin of protection against adverse health effects to the most sensitive populations: fetuses during pregnancy and breastfed infants. The health advi-'ory lev? els are calculated based on the drinking water intake of lactating women, who drink more water th an other people and can pass these chemicals along to nursing infants through breastmilk. 5?55. - ?ii-t - twining.? emit? Steps to Assess Contamination if water sampling results confirm that drinking water contains PFOA and PFOS at individual or combined concentrations greater than 70 parts per trillion, water systems should quickly undertake additional sam? pling to assess the level, scope and localized source of contamination to inform next steps Steps to Inform If water sampling results confirm that drinking water contains PFOA and PFOS at individual or comb ned concentrations greater than 70 parts per trillion, water systems should notify their State drinking water safety agency (or with EPA in jurisdictions for which EPA is the primary drinking water safety a gency) and consult with the relevant agency on the best approach 'to conduct additional sampling. Drinking water systems and public health officials should also provide consumers with infor- mation about the levels of PFOA and PFOS in their drinking water. This notice should include specifitf infor- mation on the risks to fetuses during pregnancy and breastfed and formula-fed infants from exposu to drinking water with an individual or combinedconcentration of PFOA and PFOS above health dviso- ry level of 70 parts per trillion. In addition, the notification should include actions they are taking and identi? fy options that consumers may consider to reduce risk such as seeking an alternative drinking waterisource, or in the case of parents of formula-fed infants, using formula that does not require adding water. US Environmental Protection Agency 2 November 2016 EPA sour-164303: FACT SHEET PFOS Drinking Water Health Advisories rim-r2. with! em43!. . . "$111! 12$, E?i?i?h? 33-3 I 5 ?ag: . shutoffit?t' 3' Recomm his. Steps to Limit Exposure - A number of options are available to drinking water systems to lower concentrations of PFOA and PFOS in .their drinking water supply. in some cases, drinking water systems can reduce concentrations of perfluo- roalkyi substances, including PFOA and PFOS, by closing contaminated wells or changing rates of blending of water sources. Alternatively, public water systems can treat source water with activated carbor? or high pressure membrane systems reverse osmosis) to remove PFOA and PFOS from drinking water. These treatment systems are used by some public water systems today, but should be carefully designed?and maintained to ensure that they are effective fortreating PFOA and PFOS. In some communities, ertities have provided bottled water to consumers while steps to reduce or remove PFOA or PFOS from dr 'nking water or to establish a new water supply are completed. - .. Many home drinking water treatment units are certified by independent accredited third party organizations against American National Standards Institute (ANSI) standards to verify their contaminant removal claims. NSF International has developed a protocol for NSF/ANSIStandards 53 and 58 that establishes minimum requirements for materials, design and construction, and performance of point-of-use (POU) activated carbon drinking water treatment systems and reverse osmosis systems that are designedto reduce PFOA and PFOS in public water supplies. The protocol has been established to certify systems home treatment systems) that meet the minimum requirements. The systems are evaluated for contam nant reduction by challenging them with an influent of 15-50% ug/ (total of both PFOA and PFOS) andLmust ireduce this concentration by more than 95% to 0.07 ug/L or less (total of both PFOA and PFOS) thr' ughout the manufacturer?s stated life of the treatment system. Product certification to this protocol for testing home. treatment systems verifies that devices effectively reduces PFOA and PFOS to acceptable levels. '31 Between 2000 and 2002, PFOS was voluntarily phased out of production in the US. by its primary anufac- turer, 3M. EPA also issued regulations to limit future manufacturing, including importation, of PFOS and its precursors, without first having EPA review the new use. A limited set of existing uses for PFOS (fire re- sistant aviation hydraulic fluids, photography and film products, photomicrolithography process to produce semiconductors, metal finishing and plating baths, component of an etchant) was excluded from th -se reg- ulations because these uses were ongoing and alternatives were not available. la. in 2006, EPA asked eight major companies to commit to working toward the elimination-of their production and use of PFOA, and chemicals that degrade to PFOA, from emissions and products by the end of 2015. All eight companies have indicated that they have phased out chemicals that degrade to PFOA, from emissions and products by the end of 2015. Additionally, PFOA is included in proposed Toxic Substance Control Act?s Significant New Use Rule (SN UR) issued in January 2015 which will ensure that EPA has an opportunity to review any efforts to reintroduce the chemical into the marketplace and take action, as necessary, to ?address potential concerns. US Environmental Protection Agency 3 November 2016 EPA FACT SHEET PFOA PFOS Drinking Water Health Advisories S?was ?eggs.- gar-asides- ll?vith?b . . .. 1- 4. has not established national primary drinking water regulations for FOS. EPA is eva ing Water Act (SDWA). To regulate a contaminant under SDWA, EPA must find that it: (1) may hav health effects; (2) occurs frequently (or there is a substantial likelihood that it occurs frequently) at public health concern; and (3) there is a meaningful opportunity for health risk reduction for peopl by public water systems. EPA included PFOA and PFOS among the list of contaminants that water systems are required to under the third Unregulated Contaminant Monitoring Rule (UCMR 3) in 2012. Results ofthis monit effort are updated regularly and can be found on the publicly?available National Contaminant Occu Database (NCOD) rule#3). In accordance with SDWA, EPA will consider the occurrence data from 3, along Witl? reviewed health effects assessments supporting the PFOA and PFOS Health Advisories, to make a -ulatory determination on whether to initiate the process to develop a national primary drinking wa lation. In addition, EPA plans to begin a separate effort to determine the range of PFAS for which an lntegr information System (IRIS) assessment is needed. The IRIS Program identifies and characterizes the hazards of chemicals found in the environment. IRIS assessments inform the first two steps of the assessment process: hazard identification, and dose-response. As indicated in the 2015 IRIS Multi-Y Agenda, the Program will be working with other EPA offices to determine the range of PFAS cor found at PFOA and PFOS as drinking water contaminants in accordance with the process required by the Safe Drink- pounds and the scope of assessment required to best meet Agency needs. More about this effort can be El: . . luatlng a adverse levels of 3 served onnor anng rnence tonne- the peer terregu? ated Risk health risk ear 19.391, :3 or t- I .7 pply to exposure scenarios involving drinking water.'They are not app for use, in identifying risk levels for ingestion of food sources, including: fish, meat produced from li1 that consumes contaminated water, or crOps irrigated with contaminated water. The health advisories are based on exposure from drinking water ingestion, not from skin contact or The advisory values are calculated based on drinking water consumption and household use of drinl during food preparation cooking or to prepare coffee, tea or soup). To develop the advisorie considered non-drinking water sources of exposure to PFOA and PFOS, including: air, food, dust, anc products. In January 2016 the Food and Drug Administration amended its regulations to no longer a and PFOS to be added in food packaging,.which will likely decrease one source of non?drinking water exposure. ropriate restock breathing. ring water EPA consume- ,low PFOA US Environmental Protection Agency 4 - November 2016 a I w' I h??q on- "ash-1? throat: . Drinkingm Water Health Advisories for PFOA and PFOS can be found at: eoa. Irov/ ground?water?and? and? pfos . PFOA and PFOS data collected under Unregulated Contaminant Monitoring Rule are avai able: gov/dwucmr/occurrence- data- unregulated con taminant?monito'ring?rule . . stewardship program for PFAS related to TSCA: aging- chemicals?under?tsca/and ?p . research activities on PFASs can be found at: . The Agency for Toxic Substances and Disease Registry?s Perflourinated Chemicals and Your Health webpage at: VEPA United States Envimnmental Protection Agency US Environmental Protection Agency 5 November 2016 EXHIBIT Brief Overview of the Feasibility Assessment for Epidemiological . Studies at Pease International Tradeport? May 23, 2017 1. Introduction I The Pease International Tradeport is located in Portsmouth, New Hampshire (NH) on land that was formerly the Pease Air Force Base. In 1993, companies began to operate at the Tradeport. It contains over 250 companies employing more than 9,525 people. Two day care centers are located at the Tradeport. In April and May 2014, the three drinking water supply wells serving the Pease Tradeport were iampled for per?uoroalkyl substances (PFAS). The Haven Well, which supplied about half of the total inking water at the Pease Tradeport at the time of the sampling, was found to have perfluorooctane sulfbnate (PF OS), perfluorooctanoic acid (PFOA), and perfluorohexane? sulfonate levels averagir 2.5 micrograms per liter 0.34 pig/L, and 0.90 gig/L, respectively. While the Environmental Protection Agency has a lifetime health advisory for PFOS and PFOA, no regulatory standards by any federal agency have been promulgated for PFAS. Much lower levels of these contaminants were found in the other two wells serving the Pease Tradeport. The Haven Well was shut down in May 2014. The contamination of the drinking water wells was the result of the use of aqueous ?lm forming foam at the former Pease Air Force Base for ?re?ghting training and to extinguish ?ammable liquid ?res. The ?refighting foam contained PFAS. It was used at the base from approximately 1970 until the base closed in l991. The likely leached into the soil and groundwater and migrated to the three drinking water supply wells that served the base and later served the Pease Tradeport. It is not k10Wl?1 when these wells were contaminated with PFAS. However, it is possible that the contamination began when the base was still in operation and prior to the opening of the Tradeport in 1993. During April October 2015,_a blood testing program for PFAS was conducted by the NH Department of Health and Human Services. The program was for those who may have been exposed to the contaminated drinking water at the Pease Tradeport or those who consumed water from contaminated private wells adjacent to the Tradepmt. A total of 1,578 individuals volunteered to submit a blood sample. A report of the program found that the average levels of PFOS, PFOA and in the blood of those tested were higher than national averages for these chemicals The Agency for Toxic Substances and Disease Registry (ATSDR) evaluated the feasibility of conducting epidemiological studies of the populations at the Pease Tradeport. This assessment was in response to community health concerns and the community?s request for health studies. The purpose of the assessment was to determine whether studies are feasible to conduct at Pease given the size of the exposed populations, and whether data exist to conduct scienti?cally credible studies. . 2. Approach ATSDR used three criteria to determine whether health studies were feasible: - Meaningful and credible results - a study should have suf?cient validity and precision, be capable of detecting moderate as well as large health-related effects, and be as responsive possible to the community?s questions and concerns. - Scienti?c importance a study should evaluate diseases and other as ealth- related endpoints Ealso called ?effect biomarkers?) and improve our understanding of possible health effects of PEAS exposures. - Public health signi?cance - a study should provide a strong basis for determining if PFAS exposures increase the risks of speci?c adve1se health effects and if so, what public health actions are necessary to reduce the risks. The study should also be relevant to other popule with similar exposures. tions Feasibility was also assessed in terms of whether suf?cient participation (sample size) could be obtained from within the Pease community, or whether the study would need to be expanded to other - communities beyond the Pease population. ATSDR reviewed published health studies to identify health-related endpoints that have been stuc and the data gaps that exist. The review found that most information on potential health effects concerned exposures to PF OA, much less information was available for PFOS exposures, and ver information was available for exposures. In general, there was limited information on the human health effects of PFAS exposures because research IS still at an early stage. Because of thi resea1ch gap, health studies of the Pease population might contribute to scienti?c knowledge abou health effects of PFAS exposure, in particular, PF OS and exposure. Based on its review, ATSDR concluded that several health?related endpoints could be considered studies 'of the Pease p0pulation. However, whether it is feasible to study a specific health?related endpoint depends to a g1 eat extent on the size of the exposed population that can be recruited into study. In order to determine the size of the exposed population required to study each health-relat endpoint effectively, sample size calculations were made. 3. Feasibility of Possible Studies at Pease - a. Feasibility of a Children?s Health Study at Pease To determine the population appropriate for a children? study at Pease, ATSDR. took into account date when the Haven well was shut down, the length of t1me g. ., ?half-life?) that and remain in the blood after exposure, and the age range appropliate for the health endpoints under ied little 3 the for (D the consideration. ATSDR concluded that a study 18 feasible of children who attended a day care center at Page 2 Pease any time prior to June 2014 and who will be aged 4 16 years at the time the study begins. Because PFAS~contaminated drinking water exposures could occur to children in utero and durin breastfeeding if the mother worked at the Pease Tradeport, the study would include these additional children if the exposures began prior to June 2014 and their ages are 4 16 years at the time the study - begins. UN The sample size calculations indicated that at least 350 exposed children were needed to be included in a study. The study would also require a comparison group of at least 175 children unexposed to 1e contaminated drinking water at the Pease Tradeport. Based on this sample size, health-related endpoints were grouped into three categories: 1) feasible to study, 2) possible to study in children at Pease (out likely will require recruiting a larger sample size than 350 exposed and 175 unexposed children cm the Pease community), and 3) not feasible to study using the Pease children population unless additioll'ral populations from other communities exposed to PFAS?contaminated drinking water are included 11 the study. Health-related endpoints feasible to study in children at Pease: Mean difference in lipids (total cholesterol, LDL, HDL, triglycerides) Mean difference in estimated glomerular filtration rate a measure of kidney function Insulin?like Growth actor? I (a measure of growth hormone de?ciency) Overweight/Obesity Health-related endpoints that may be possible to study in children at Pease (althorjgh a larger sample size from the Pease community will likely be needed): 0 Mean difference'in uric acid 0 Elevated total cholesterol (hypercholesterolemia) - Elevated uric acid (hyperuricemia) - IQ/neurobehavioral 0 Thyroid function 0 Sex hormones - Asthma and atopic dermatitis (Immune function) - Rhinitis (stuffy, runny nose) - Antibody response to rubella, mumps and diphtheria vaccines Health?related endpoints not feasible to study using the Pease children population (in orderta address these health endpoints, populations from other sites beyond the Pease community with contaminated drinking water would need to be included along with the Pease children population). 0 Attention de?cit/hyperactivity disorder (ADHD) - Autism spectrum disorder 0 Delayed puberty 0 Thyroid disease 0 Childhood cancers Page 3 b. Feasibility of an Adult Health Study at Pease Based on the date when the Haven Well was shut down and the length of time ?half-life?) that and PFOS remain in the blood after exposure, ATSDR concluded that an adult study at PE ass of adults aged 218 years who worked anytime at the Pease Tradeport during January 2008 ?'May 2014 is feasible. The sample size calculations indicated that at least 1,500 exposed adults needed to be included in a study. The study would also require a comparison group of at least 1,500 adults unexposed to the contaminated drinking water at the Pease Tradeport. Based on this sample size, health-related eniipoints were grouped into three categories: I) feasible to study, 2) possible to study at Pease (but likely ill require recruiting a larger sample size than 1,500 exposed and 1,500 unexposed adults from the Pease community), and 3) not feasible to study using the Pease adult population unless additional populations from other communities exposed to PFAS-contaminated drinking water are included in the study. Health-related endpoints feasible to study at Pease: - Mean difference in lipids (total cholesterol, LDL, HDL, triglycerides) 0 Elevated total cholesterol (hypercholesterolemia) - Mean difference in uric acid 0 Elevated uric acid (hyperuricemia) Thyroid disease (uncon?rmed) - Cardiovascular disease 0 Hypertension - Osteoarthritis and osteoporosis - Mean differences in serum immunoglobin and C-reactive protein (an indicator of inflammation); increase in antinuclear antibodies (an indicator of autoimmune reaction); alterations in speci?c cytokines Health-related endpoints that may be possible to studv at Pease (although a larger sample size the Pease community may be needed): .0 Liver function - Thyroid disease (con?rmed) 0 Thyroid function I Endometriosis Pregnancy?induced hypertension Page 4 from Health-related endpoints not feasible to study using the Pease adult population populations from other sites beyond the Pease community with PFAS~contaminated drinking water would need to be included to make the study feasible): 0 Liver disease - Kidney disease 0 Ulcerative colitis Rheumatoid arthritis - Lupus 7 Multiple sclerosis 0 Kidney cancer (and other adult cancers) c. Study of former military service and civilian workers at the Pease Air Force Base Based on sample size considerations, ATSDR concluded that it is not feasible to conduct a morta 'ty or cancer incidence study that is limited to the military service and civilian workers who were static worked at the Pease Air Force Base. Such studies would require, in addition to the Pease Air Force Base populations, several thousands of exposed populations from military bases where contaminated drinking water occurred, as well as several thousands of comparison pepulations military bases that did not have drinking water contamination. 4. Conclusions The feasibility assessment concluded that it is possible to evaluate some health-related endpoints sufficient number of children and adults from the Pease population participate. Other health?relate endpoints would require larger numbers of exposed individuals and would require the inclusion of ed or fa populations from other sites who were exposed to PFAS-contaminated drinking water. The feasibility assessment concluded that a third study design, a mortality and cancer incidence study of former military service and civilian worker personnel, would not be feasible solely with the population at No single study of the Pease pOpulation will provide clear answers to the community about wheth= exposures to the PFAS-contaminated drinking water caused their health problems. All epidemiolo Pease. 4? their gical studies of environmental exposures and health outcomes have limitations and uncertainties. Whether a study will ?nd an association between an environmental exposure and health effects cannot be kn an prior to conducting the study. The ability of a study of the Pease population to provide useful information will depend to a great extent on the success of recruiting sufficient number of study participants. The feasibility assessment is still a draft. It will be ?nalized once the Pease Community Assi?tanc Panel (CAP) and the larger Pease Tradeport community have the opportunity to review and make comments on the assessment. ATSDR will then revise the assessment based on the comments recs The feasibility of successfully evaluating particular health-related endpoints (or effect biomarkers: change depending on ?nal study design and goals. Page 5 ived. could DRAFT for Review Pnrposes Feasibility Assessment for Epidemiologicai Studies at Peas-e International Tradeport, Portsmouth, New Hampshire May 23, 2017 The ?ndings and conclusions in this report?oresentation have not been formally disseminated the Agency for Toxic Substances and Disease Registry and should not be construed to represent any agency determination or policy. 'Draft for Review Purposes Do Not Cite or Quote Contents Summary . 2 Introduction . . . 8 Site history 9 Community concerns -. 1 1 Exposure 12 Summary of literature review 14 Adult cancers and other adult diseases .. . . 14 Health effects in children . .. 14 Sources of adverse outcome data for the Pease population . .. . . 15 Sources of exposure data . . 17 Feasibility of an epidemiological study of children- at the Pease Tradeport 18 Feasibility of an epidemiological study of adults at the Pease 32 Feasibility of an epidemiological study of former military service and civilian workers at the form Pease Air Force base .. . . . .. 41 Other study designs and health?related endpoints . . 42 References i 45 . 59 Appendix 76 Literature review 77 Description of sample size calculations . 93 Other sites with PFAS~contaminated drinking water from the . 100 106 Appendix tables Draft for Review Purposes Do Not Cite or Quote Summary This report describes the activities and the conclusions of feasibility assessment of pos ible future drinking water epidemiological studies at the Pease International Tradeport, Portsmouth, ew Hampshire (?Pease?). The drinking water at Pease was contaminated with perfluoroalkyl substan es (PFAS), in particular per?uorooctane sulfonate (PFOS) and per?uorohexane sulfonate rom the use of aqueous film-forming foam at the former Pease Air Force Base. The base used . for ?re?ghting training and to extinguish ?ammable liquid fires. In 2015, the New Hampshire Department of Health and Human Services (NH DHHS) established a PFAS blood testing progra- at Pease. A total of 1,578 persons submitted a blood sample for analysis. The results from the blood testing program indicated that the exposed population had higher serum levels of PFOS and than did the US. population. - In March 2016, ATSDR established a community assistance panel (CAP) as a mechanism for'the community to voice its concerns and provide input on decisions concerning potential health activi ies at Pease. A key concern expressed by the community was the lack of information on the possible short- term and long-term health effects to children and adults exposed to the PFAS contaminants in the drinking water at Pease. Speci?cally, the community was concerned about cancers, elevated lipid: effects on thyroid and immune function, and developmental delays in children. ATSDR then assessed whether epidemiological studies focusing on populations at Pease were feasible and whether such studies could answer the concerns of the community. When evaluating whether an epidemiological study would be scienti?cally feasible, ATSDR used three main criteria: 1. Meaningful and credible results a study should'have suf?cient validity and precision, be capable of detecting health-related effects, and beas responsive as possible to the commur ity?s questions and concerns. Ideally, a study should also be capable of detecting health?related effects, for example a 20% to 100% increase in risk with suf?cient statistical power statistical power 280%). 2. Scientific importance a study should evaluate biologically plausible diseases and other 1eaIth- related endpoints (also called ?effect biomarkers?) and improve our understanding of possible health effects of PFAS exposures. 3. Public health significanoe a study should provide a basis for determining if PFAS exposures increase the risks for speci?c adverse health effects, and if so, what public health actions are necessary to reduce the risks. The study should also be relevant to other pepulations with similar exposures. The feasibility assessment is guided by these three criteria and does not address considerations of ?nancial or operational feasibility. Feasibility was also assessed in terms of Whether suf?cient participation (sample size) could be'obtained from within the Pease community to achieve sufficient statistical power for the health-related endpoints being considered, or whether the study would need to be expanded to other communities beyond the Pease population. - Draft for Review Purposes Do Not Cite or Quote ATSDR reviewed the epidemiological literature on PFAS exposures to identify the health-relate endpoints that have been studied and current data gaps, in particular, for the effects of literature review also was used to identify adverse effect sizes observed in the PFAS studies for serum levels similar to those found in the Pease population. The literature review found that most information on potential health effects concerned exposur perquorooctanoic acid (PFOA). In particular, numerous studies have been conducted of West and Ohio residents and workers exposed to PF CA from a chemical plant (the studies) [Fri 2009]. Studies of other workforces also were primarily focused on PFOA exposures. The Iiterat review found that less information was available about the potential health effects of PF OS eXpr and very little information Was available on the potential health effects of exposures to the primary contaminants in the drinking water at thePease Tradeport were PFOS and epidemiological studies of the Pease populations have the potential to ?ll key knowledge gaps aind address the community?s concerns. The literature review identi?ed many health-related endpoints evaluated in previous epidemiol 0 studies of PFAS exposures. These included cancers, lipids, effects on thyroid and immune functiigon, and developmental delays. They also included effects on kidney and liver ?mction and sex hormone diseases such as endometriosis, ulcerative colitis and osteoporosis. Many of these health-related. endpoints were also previously raised by the community and the Pease CAP. In Considering possible study designs, ATSDR focused on the methods used in previous epidemiological research of PFAS exposures. Adopting study design methods consistent with previous research facilitate the interpretation and of ?ndings across studies. The literature review found most of the epidemiological studies of PFAS exposures were cross?sectional and evaluated seru measurements. Some studies also evaluated cumulative PFAS serum levels that were estimated modeling methods. ATSDR concluded that any study of populations exposed to the PFAS-cont: drinking water at the Pease Tradeport should be cross?sectional and evaluate measured serum Pl measurements as well as estimated cumulative PFAS serum levels. ATSDR also concluded that used to evaluate health?related endpoints in the Pease Tradeport populations should be consister methods used in previous epidemiological research of PFAS exposures. Potential Studv Designs A. Cross-sectional study of children The first design is a cross?sectional study of children who were exposed to the PEAS?contamina drinking water while attending the two day-care centers at Pease. Inclusion would be limited to who attended the day-care centers any time before June 2014, and who would be in the age range of 4? 16 years at the time the study begins. During the 2015 blood testing program at Pease, 370 chilc 1?13 years contributed blood samples. If a study were to begin in 2018, these children would be 16 years. The study would involve. re?contacting these participants and obtaining new blood sa increase the sample size, the study would also recruit and obtain blood samples from children attended the day-care centers at Pease, but who did not participate in the New Hampshire blood program. Because PFAS-contaminated drinking water exposures could occur to children in uter during breastfeeding if the mother worked at the Pease Tradeport, the study would include these additional children if the exposures began prior to June 2014 and their ages are 4 16 years at the study begins. - 3 triples. To ?he PFAS as to irginia sbee ire asures, Because ical s, and would that PFAS from uninated 2AS methods with ted children ren aged ages 4- 0 testing 3 and 1e time Draft for Review Purposes Do Not Cite or Quote A comparison group of children, who did not attend day care at the Pease Tradeport and whose parents did not work at the Pease Tradeport or have occupational exposures to PFAS, would be recruited and blood samples collected. The comparison group would be sampled from the Portsmouth public schools and selected to have similar demographics as the Pease children. Based on the health?related endpoints included in the ?nal study, blood samples could be used to . evaluate PFAS serum levels and several biomarkers of effect, including lipids, thyroid function, kidney function, immune function, and sex hormones. The children could also be assessed for neurolo 'cal endpoints such as intelligence quotient (IQ), learning problems, and ty disorder (ADHD) behaviors. Calculations were conducted assuming a sample size of 350 exposed children who attended da care at the Pease Tradeport and 175 unexposed children from the Portsmouth area who did not attend ay care at the Pease Tradeport. Additional sample size calculations assumed a sample size of 500 expocged children and 250 unexposed children. The sample size calculations also assumed a simple comparison of exposed versus unexposed children. A second approach was to determine the sample sizes nee ed to detect effects found in other PFAS studies of children with serum PFAS levels similar to those bserved in the Pease children population. For some health-related endpoints, there was insufficient info mation to conduct any sample size calculations. Based on sample size considerations, health-related endpoints were grouped into three categori s: 1) feasible to study, 2) possible to study (but would require a larger sample size than 350 exposed -hildren and 175 unexposed children), and 3) not feasible to study using the Pease children population 11 . less additional pupulations eXposed to PFAS?contaminated drinking water from other affected comrEunities are included in the study. . Health?related endpoints feasible to study in children at Pease 0 Mean difference in lipids (total cholesterol, LDL, HDL, triglycerides) 0 Mean difference in estimated glomerular ?ltration rate a measure of kidney function - Insulin-like grOwth factor ?1 (a measure of growth hormone deficiency) 0 Overweight/Obesity (D Health?related endpoints that may be possible to study in children at Pease (although a larg sample size from the Pease 'community will likely be needed) 1' 0 Mean difference in uric acid, a measure of kidney function 0 Elevated total cholesterol (hypercholesterolemia) - Elevated uric acid (hyperuricemia) IQ/neurobehavioral - Thyroid function - Sex hormones 0 Asthma and atopic dermatitis (immune function) I Rhinitis (stuffy, runny nose) . I Antibody responses to rubella, mumps and diphtheria vaccines 4 Draft for Review Purposes Do Not Cite or Quote Health-related endpoints not feasible to study using the Pease children population (in orde address these health endpoints, populations from other sites beyond the Pease community with contaminated drinking water would need to be included along with the Pease children populatio Attention de?cit/hyperactivity disorder (ADHD) Autism spectrum disorder Delayed puberty Thyroid disease Childhood cancers To evaluate exposure?response trends, the study participants would need to be split into tertiles quartiles based on their serum PFAS levels. This might require a larger sample size for some of health-related endpoints listed as feasible to study. B. Cross-sectional study of adults to n) or the The second cross?sectional study design would involve obtaining blood samples from adults aged 218 - years who worked anytime at the Pease Tradeport during January 2008?May 2014. This study evaluate PFAS- serum levels, lipids, thyroid function, liver function, kidney function, and immui function. The'study would also evaluate diseases such as kidney disease, liver disease, cardiova disease, thyroid disease, ulcerative colitis, rheumatoid arthritis, osteoporosis, osteoarthritis, and endometriosis. 1n the 2015 blood testing pro gram at Pease, 1,182 adults aged years particip 1,083 adults reported that they last worked at Pease Calculations Were conducted assuming a sample size of 1,500 adults exposed while employed a Pease Tradeport and 1,500 unexposed adults from the Portsmouth area who never Worked at the Tradeport. The sample size calculations also assumed a simple comparison of exposed versus 111 adults. A second approach was to determine the sample sizes-needed to detect effects found in PFAS studies of adults with serum PFAS levels similar to those observed in the Pease adult pop .Based on sample size considerations, health-related endpoints were grouped into three categorie feasible to study, 2) possible to study (but would require a larger sample size than 1,500 expose 1,500 unexposed adults), and 3) not feasible to study using the Pease adult population unless ad populations exposed to PFAS?contaminated drinking water are included in the study. Health?related endpoints feasible to study in adults at Pease Mean difference in lipids (total cholesterol, LDL, HDL, triglycerides) Elevated total cholesterol (hypercholcsterolemia) Mean difference in uric acid, a measure of kidney function Elevated uric acid (hyperuricemia) Thyroid disease (uncon?rmed) Cardiovascular disease Hypertension Osteoarthritis and osteoporosis Jould 1e acular ited, and the Pease 1eXposed ther ulation. s: 1) :land iitional Draft for Review Purposes Do Not Cite'or Quote 0 Mean differences in serum immunoglobin lgE, and C-reactive protein (an of in?ammation); increase in antinuclear antibodies (an indicator of autoimmune reaction); alterations in Speci?c cytokines Health-related endpoints that may be possible to study In adults at Pease (although a large1 size from the. Pease community may be needed) 0 Liver function Thyroid disease (confirmed) 0 Thyroid function - Endometriosis - Pregnancy-induced hypertension Health endpoints not feasible to study using the Pease adult population e. ,populations ndicator sample other sites beyond the Pease community with PFAS contaminated drinking water would need to be in cluded to evaluate these health?related endpoints) '7 'Liver disease 0 Kidney disease - Ulcerative colitis Rheumatoid arthritis . . Lupus - Multiple sclerosis 0 Kidney cancer (and other adult cancers) To evaluate exposure?response trends, the study participants would need to be Split into tertiles 3r quartiles based on their serum PFAS levels. This might require a larger sample size for some of health endpoints listed as feasible to study. C. Mortality study of former military service and civilian worker personnel the A third study design that Was considered would evaluate mortality and cancer incidence among former military service and civilian worker personnel at the former Pease Air Force Base and other mil bases where drinking water was contaminated with PFOS and from the use of Comparison military bases would also need to be identified that had no PFAS-contaminated drii water or drinking water contamination from other chemicals above the U. S. Environmental Prot Agency 3 maximum contaminant levels (MCLs). Personal identifier information Social tary aking ection scurity number, name date of birth, sex) necessary for data linkage with the national death index and state and federal cancer registries could be obtained from the Defense ManpOwer Data Center. However, based on sample size considerations, ATSDR concluded that it is not feasible to cond mortality or cancer incidence study that is limited to the military service and civilian workers 6 uct a ?10 were Draft for Review Purposes Do Not Cite or Quote stationed or worked at the Pease Air Force Base. Such a study would require, in addition to the Air Force Base populations, several thousands of exposed populations from military bases wher contaminated drinking water occurred, as well as several thousands of comparison populations 1 military bases that did not have drinking water contamination. Conclusions The feasibility assessment concluded that it is possible to evaluate some health-related endpoint suf?cient number of children and adults from the Pease population participate. Other health-relr endpoints would require larger numbers of exposed individuals and would require the inclusion populations from other sites who were exposed to PFAS?contaminated drinking water. The feas assessment concluded that a third study design, a mortality and cancer incidence study of forme military service and civilian worker personnel, would not be feasible solely with the population No single study of the Pease population will provide de?nitive answers to the community about their exposures to the PFAS-contaminated drinking water caused their health problems. All epidemiological studies of environmental eXposures and health outcomes have limitations and uncertainties. Whether a study will find an association between an environmental exposure and effects cannot be known prior to conducting the study. The ability of a study of the Pease popu] provide useful information will depend to a great extent on the success of recruiting suf?cient study participants. - The feasibility assessment is still a draft. It will be finalized once the Pease Community Assistaliice Panel (CAP) and the larger Pease Tradeport community have the opportunity to review and ma comments on the assessment. ATSDR will then revise the assessment based on the comments re The feasibility of successfully evaluating particular health~related endpoints (or effect biomarke change depending on ?nal study design and goals. Pease PFAS- Trom if a Lted of Lbility at Pease. whether thealth 'ation to umber of ?e ceived. rs) could Draft for Review Purposes Do Not Cite or Quote - Introduction This draft report describes the approach and the conclusions of the Agency for Toxic Substance Disease Registry?s feasibility assessment of possible drinking water epidemiologics at the Pease International Tradeport (?Pease?), Portsmouth, New Hampshire. The purpose of the and 1 studies feasibility assessment was to determine whether epidemiologicalstudies are reasonable to condi?pt at Pease and whether data exist to conduct scienti?cally credible epidemiological studies. This dra feasibility assessment report for possible future studies at Pease International Tradeport is being distributed to the Pease Community Assistance Panel (CAP) for members? review and input. Input from the CAP is intended to help ATSDR ensure the proposed research is relevant to community con The report is a DRAFT document that may be edited based on CAP input; it is not intended to l: protocol or systematic literature review. The ?nal study design, including sample size, the healt endpoints that can be considered and the development of the study protocol itself, including the statistical analysis approach have yet to be determined. The Pease CAP will have an opportunity review and provide input on a draft of the study design before it is ?nalized. The draft feasibilitj assessment does not represent a commitment by ATSDR to conduct research at Pease Internatio Tradeport, given that funding and staffing to conduct the described research are not available at time. - Three criteria were used to determine whether epidemiological studies are warranted at Pease: serns. a 1 to nal this 1. Meaningful and credible results study should have suf?cient validity and precisiot, be capable of detecting health-related effects, and be as responsive as possible to the damn nity?s questionsand concerns. Ideally, a study should also be capable of detecting health?relat effects, for example a 20% to 100% increase in risk with suf?cient statistical power statistical power 280%). To achieve suf?cient validity, a study should minimize biases ch as selection bias and confounding bias. Suf?cient precision can be achieved by a sample sihe that has at least 80% statistical power to detect health-related effect sizes observed in other 5 nudies for PFAS serum levels similar to those in the Pease population. 2. Scientific importance?? a study should evaluate biologically plausible diseases and ot er health-related endpoints (also called ?effect biomarkers?) and improve our understandin of possible health effects of PFAS exposures and fill important data gaps. Evidence for the biological plausibility of a health-related endpoint can come from animal studies of PF eXposures, information on how PFAS exposures cause adverse effects mechanistic information), and epidemiological studies. Since and PFOS serum levels were el vated in the'Pease population compared to national data, a Pease study should focus on data gaps concerning the health effects of exposures to these chemicals. The feasibility assessmen- included a literature search of epidemiological studies of PFAS exposures to identify the related endpoints evaluated in these studies and the data gaps that exist on the health eff: and PFOS. 3. Public health signi?cance a study should provide a basis for determining if PFAS e} increase the risks for speci?c adverse health effects, and if so, what public health actions necessary to reduce the risks. In particular, the study should provide a basis for early me intervention for health outcomes that are not routinely evaluated in physical exams. The should also be relevant to other populations with similar exposures. . health- of .posures are :lical study Draft for Review Purposes Do Not Cite or Quote In addition to the above criteria, a feasibility assessment must address specific questions: 1. Can the study population be enumerated and selected to minimize selection bias? (Selec occurs when the probability of selection is related both to exposure status and to disease 2. Is there an appropriate comparison population? 3 levels of exposure with adequate accuracy? Is there justi?cation for studying the speci?c health outcome(s) being considered? suggestive biological evidence? A ?nding in a previous study?) Can the health effect(s) be validly ascertained or measured? Is the exposed population suf?ciently large so that risks can be estimated with precision Can information be obtained on other risk factors that need to be taken into account? Can a study answer the questions of concern to the Pease community? 9?99.? Site history The Pease International Tradeport is located in Portsmouth, New Hampshire. It contains over 21 companies employing more than 9,525 people. In 1993, companies began to operate at the Peas Tradeport. Two day?care centers are located at the Tradeport. One of the day?care centers estim. about 695 children attended the center during 1996?2016. The other day-care center could not compile total enrollment statistics, but its capacity is 220 children, they usually enroll about 180 :i-on bias status.) . Is there a complete exposure pathway, well-defined exposed population, and ability to assign is there 30 a 3.th that asily children at a time, and they have been operating for almost 7 years. As of July 2015, the estima population of Portsmouth was 21,530 ://Www.census. ov/ According to the 2010 census, 4.7% were children younger than 5 years, 11.9% were children years, 67.5% were adults ages 18?64 years, and 15.9% were adults ages 65 years and older. uickfacts/table/PST045215/3 62900 . ed Additionally, 51.5% of the population were female, 91.5% were white, and 95.6% of persons a es 25 years and older were high school graduates. The area on which the Tradeport is located was originally built in 1951 as part of the Pease Air orce Base. In October 1989, 3,465 military personnel were assigned to the base, accompanied by 4,7 6 dependents. The Air Force estimated that 537 civilian employees worked on?base at that time TSDR 1999). During 1970?1990, an average of 3,000 personnel and their families were assigned to th any one time. Before 1970, the base supported a maximum of 5,000 personnel (ATSDR 1999). Three major supply wells provided drinking water to the base: the Haven, Smith, and Harrisom Before 1981, the wells fed directly into the distribution system so that a particular area of base base at yells. rould primarily receive water from the nearest well. After 1981, the water from the three wells were mixed together and treated before entering the distribution system. These same three supply wells prov drinking water to the Pease Tradeport after it opened. In 1977', water from the base wells was found to contain Two of the th ided :ee wells serving the base were contaminated. The maximum concentrations of TOE measured in the Haven and Harrison supply wells were 391 micrograms per liter (pg/L) and 28.5 pg/L,? respectively. After the discovery of the contamination, those wells were shut down and the city of Portsmouth suppliec drinking water to the base during 1977?1978. In the fall of 1978, the wells were back in operath TCE levels in the Haven well fluctuated between 50, pg/L and 115 rig/L from the fall of 1978 through January 9 Draft for Review Purposes - Do Not Cite or Quote 1980, then fell below 50 ug/L, with an occasional Spike above 50 ug/L through October 1980. November 1980 through July 1981, TCE levels averaged about 30 ug/L, then fell to around 10 from August 1981 through May 1983. Levels continued to decline, but did not remain consiste. below the current US. Environmental Protection Agency (EPA) maximum contaminant level drinking water of 5 ug/L until January 1986 (ATSDR 1999). The base of?cially closed in October 1991, and most of the property was transferred to the Pea EB Development Authority (PDA). During 1993, the business and aviation industrial park began 01 The City of Portsmouth entered into a long-term lease and operation agreement with the PDA and maintain the public water system serving the Tradeport. From approximately 1970 until the base closed, aqueous ?lm-forming foam was usedt extinguish and prevent ?ammable liquid ?res. was also used during ?re?ghting training base. Through 2001, perfluoroalkyl substances (PEAS) were used in the manufacturing of AFFZ including per?uorooctanoic acid (PFOA), per?uorooctane sulfonate (PFOS), and per?uorohexi sulfonate containing PFAS likely leached into the soil and groundwater and mi the three supply wells serving the Pease Tradeport. It is not known when these wells were conte with PFAS, but it is possible that the contamination began before the opening of the Tradeport, Air Force base was still in operation. . The Haven, Smith and Harrison wells have also served the Tradeport. In addition, the City of From rig/L tly .VICL) in eration. 3 operate 3 at the 5 me agrated to .minated 4U Portsmouth has the capability to supply water to the Tradeport via its main distribution system. pumping records for the three wells were provided by the City of Portsmouth, Department of Public Works. Up through 1999, the Haven well on average provided about 56% of the total water sup ly at the Tradeport, with the Smith well providing 44% and the Harrison well out of service. In 2000?20 1, the Haven well supplied 88% of the supply and the Smith well supplied 12%. From 2003 until itw 3 taken out of service in May 2014, the Haven well on average supplied about half the water supply. 2006, the Harrison well was back in service and the Smith and Harrison wells together supplied on av rage about half of the water supply atthe Tradeport. After May 2014, the Smith and Harrison wells applied 56% of the Tradeport water supply and the City of Portsmouth provided the other 44%. In 2009, EPA established provisional health advisory levels for PE OS and PFOA of 0.2 ug/L a 0.4 pg/L, respectively EPA 2009]. In2013, sampling of monitoring wells at the former Pease Base fire training areas detected PFOS and PFOA above these EPA provisional health advisory In May 2016, EPA established a new lifetime health advisory ?for PFOS and PFOA that said the ir Force levels. combined concentrations of PFOS and PFOA in drinking water should not exceed 0.07 ug/L EPA 2016a]. No drinking water health advisory level has been established for or other PFAS chemicals. While the EPA has a lifetime health advisory for PFOS and PFOA, no federal regula standards for these contaminants have been iSSUed. In April and May 2014, the three supply wells serving the Tradeport were sampled for PFAS. Ir April sampling, the Haven well had PFOS, PFOA, and levels of 2.5 pg/L, 0.35 ug/L, an ug/L, respectively. In the May sampling, the Haven well had PFOS, PFOA, and levels pg/L, 0.32 ug/L, and 0.96 pg/L. Other PFASs were also detected in the Haven well. The Harris had much lower levels of these contaminants with maximum PFOS, PFOA, and levels tory [the 0.83 2.4 in well 0.048 ng/L, 0.009 ug/L, and 0.036 ug/L, respectively. The Smith well had maximum levels of PFOS and of 0.018 ug/L and 0.013 ug/L, respectively, with an estimated level of PFOA of about 0 vg/L- 10 .004 when the Draft for Review Purposes Do Not Cite or Quote No samples of the Pease Tradeport distribution system for PFAS are available from the period irvhen the Haven well was in operation. We can use a simple mixing model to estimate the PFAS levels in the distribution system, assuming that contamination concentrations are approximately uniform the system. The model takes into account the pumping rates for each of the three wells, the tota demand, and the concentrations of PFAS "in the Wells during the April and May 2014 sampling. this simple approach, the estimated levels of PFOS, PFOA, and in the Pease Tradeport distribution system in April 2014 would be approximately 1.4 ug/L, 0.2 ug/L, and 0.5 respectively. In April 2015, the City of Portsmouth created a community advisory board (CAB) to address th contamination in the Tradeport drinking water. The CAB was established to act as a liaison bet? affected community and the New Hampshire Department of Health and Human Services (NH I to represent the diverse views of the affected community, to review the blood testing conducte DHHS, and to provide input into future direction of the blood testing program (CAB 2015). Th held 14 public meetings during May through December 1, 2015, and disbanded after issuing its oughout water Using 6 PFAS ween the by NH CAB ?nal report of its activities on December 21, 2015. Among the recommendations of the CAB in its final report were the following: 1. Establish a community body to coordinate ongoing issues with ATSDR, NH DHHS, and the'U.S. Air Force?s Restoration Advisory Board at Pease and to provide an effective mechanism communication with all persons working or cared for at the Pease Tradeport. 2. A new community body should, along with its partner agencies, provide health educatio public regarding environmental chemical exposures and how exposures and risks can be In Februaiy 2016, ATSDR began recruiting community volunteers to serve as members of a Pe community assistance panel (CAP). Technical advisers who could help CAP members in re'vieir scienti?c information on PFAS and proposed health activities were also recruited. The purpose CAP was to provide a mechanism for the community to participate directly in health related to the exposures to the contaminated drinking water at the Tradeport. The CAP wouid p1 input concerning possible health activities proposed by ATSDR. CAP members would also w01 ATSDR to gather and review community health concerns, provide information on how people have been exposed to hazardous substances, and inform ATS-DR about ways to involve the com The ?rst public meeting of the CAP was held in May 2016 in Portsmouth. The second public 1n was held in September 2016. ATSDR has also convened calls with the CAP. Community concerns The ?nal report of the CAB, issued on December 21, 2015, noted that . .the lack of any de?nir' information regarding the pessible health effects of PFC [perfluorinated compound] exposure re, source of frustration and concern.? 2015] The report concluded, ?There is a great need to understand what if any health effects might result for PFC exposure, and at what levels of expo: these risks might be manifested.? In an email sent to ATSDR in November 2015, the CAB asked that ATSDR consider the follou question: ?What, if any, long-term health effects, such as specific cancers, elevated blood lipids 11' for to the ase ving the of the evide with night - munity. eeting Ive mains a better ure ing thyroid reduced. 3 activities 5 Draft for Review Purposes Do Not Cite or Quote i This question should be broken down with regard to speci?c populations including children, nursing/pregnant women, fire?ghters, and adult eXposed workers.? This'question was reiterate lat the ?rst in?person CAP meeting in May 2016. Some CAP members, as parents, were very concern about the health of their children who were exposed at a critical, early age of development while atte ding the two day-care centers at the Pease Tradeport. They noted the lack of pediatric studies associated with PFAS exposure and wanted ATSDR to consider testing the exposed children for health endpoi such as lipids. CAP members also voiced concern about the exposed adult population, especially for er military service personnel and civilian workers at the former Pease Air Force Base. Concern also expressed for firefighters who were exposed to contaminated drinking water at Pease and also irectly to AFF as part of their ?re?ghting duties. CAP members expressed their desire for a longitudinal. approach (compared to a cross-sectional approach) to evaluate short-term and long?term health conditions, including cancers. I function, immune function and developmental delays, are associated with the PFC exposure at $32136? Exposure assessment Using the information currently available On PFAS concentrations in the supply wells during April and May 2014, supply well pumping data, the total demand-in the system, and assuming that PFAS concentrations in the supply wells during the Apriln-May 2014 sampling re?ect historical concentrations (given the persistence of these chemicals in the environment), a simple but crude assessment of PFAS drinking water exposures could be conducted. However, to' accurately estimate historical PFAS concentrations in the Haven,- Harrison, and Smith supply wells and the distribution system they served, both during the operation of the Air Force base and the Tradeport, would require the following steps: 1. Obtain information on the locations and use of at the Air oroe base, including ac sidental releases. 2. Model the migration of contaminants from the soil Where was used or released to the groundwater and then to the supply wells. 3. Model the PFAS concentrations throughout the distribution system. Historical reconstruction concentrations in the drinking water distribution system would be needed to assess exposures to service personnel and civilian employees who were at the Air Force base during its, operations, and to workers and day-care attendees at the Tradeport. . Another important source of information on exposures at the Pease Tradeport was the NH PFAS blood testing program conducted during April?October 2015. A person was eligible for this pro ram if he or she had worked at, lived on, or attended childcare at the Pease Tradeport or Pease Air For - 6 Base, or lived in a home near the Pease Tradeport that was served by a PFAS?contaminated private .11. A total of 1,578 persons volunteered to submit a blood sample for PFASs testing mH DHHS 2016]. This was a convenience (or volunteer) sample, not a statistically based sample. Nevertheless, the test ng program provided important information on the extent and magnitude of exposures to the PFAS - contaminated drinking water at the Pease Tradeport. Table 1 shows the serum concentrations of PFOS, PFOA, and per?uorononanoic acid (PFNA) for the 366 children younger than 12 years at the time of testing and comparison values from studies conducted in Texas [Schecter 2012] and California (Wu 2015). Data from the National Health and 12 . .. Draft for Review Purposes Do Not Cite or Quote Nutrition Examination Survey (NHANES) are not available for children younger than 12 years. NHANES testing for serum PFAS was restricted to those ages 12 years and older. The Californ [Wu 2015] conducted a random sample of households in northern California and obtained blooc from 68 children ages 2?8 years for PFAS analyses during December 2007?November 2009. parents 'of the children had higher education levels than the general population. The Texas stud} [Schecter 2012] analyzed serum samples collected from 300 children ages 312 years at a childrc hospital during 2009. Whether the children in the Texas study were healthy or receiving treatme illness was not reported. None of the California and Texas children were known to be exposed contaminated drinking Water. The children in both studies were considered to be representative general population exposures to PFAS via diet and consumer products. Table 1 shows that the median and geometric mean serum and PFOS levels in the Pease (ages <12 years) are considerably higher than background median and geometric mean levels se Texas and California studies. For PFOA, the Pease children have higher levels than the reference group in the Texas study, but lower than in the California study. However, the compal with Texas and California results might not be appropriate given the difference in sampling year . Nationally, serum levels of PFOS and PFOA have been declining sharply over time. For examp 1999?2000 NHANES cycle, the geometric mean serum PF 0A level for persons aged 212 years pg/L. By the 2013?2014 cycle, it had declined to 1.9 rig/L. Serum PFOS declined even more sh from 30.4 ug/L during the 1999?2000 cycle to 5.0 rig/L in the 2013?2014 cycle. also de but more gradually, from 2.1 pg/L during the 1999?2000 cycle to 1.3 ug/L in the 2013?2014 cy the NHANES 2013?2014 cycle, children ages 12?19 years had geometric mean PFOA, PFOS, 2 serum levels of 1.66 ug/L, 3.54 ug/L, and 1.27 ug/L, reSpectively. Therefore, the most appropriate PFAS comparison values for the Pease blood testing program would be serum level.- obtained near in time to the Pease sampling 2015). Such comparison values are not current available. Table 2 shows the serum concentrations of PFOS, PFOA, and PFNA for the 1,212 parti ages 12 years and older at the time of testing and comparison values from NHANES for 2013-2 . most recent years data are currently available). Table 2 indicates that, similar to the children atI the median and geometric mean serum levels of PFI-IXS and PF OS among those ages 212 years considerably higher than those in the NHANES 2013?2014 cycle. The median and geometric serum PFOA among those at Pease were also elevated compared with NI-IANES results. In analyses conducted by NH DHHS, geometric mean serum levels were higher for pers drank 24 cups of water per day compared to those who drank <4 cups per day. Of all the PFAS levels measured, water consumption had the strongest effect on serum levels. In particul consumption had the highest effect on serum levels among persons aged 519 years (0 0.15, marginal effect Geometric mean PFOS and PFOA serum levels were also higl among persons who drank 24 cups of water per day compared with those who drank <4 cups pe 1 samples 1e :n?s nt for of children en in the risons U: le, in the was 5.2 arply, clined, ole. In .nd 1r cipants 014 (the ease, are ean ons who serum ar, water 0.31, SE 1er day DHHS 2016]. Linear trends were observed for geometric mean serum levels of PF OS, PFC A, and and increasing time spent at the Pease Tradeport. The trend was strongest for PF OS and DHHS 2016]. 13 a study Draft for Review Purposes Do Not Cite or Quote Summary of literature review ATSDR reviewed published health studies to identify health-related endpoints that have been 3 and the data gaps that exist, in particular, for the effects of and PF OS. The literature rev udied ew also was used to identify adverse effect sizes observed in the PFAS studies for PFAS serum levels similar to those found in the Pease pepulation. The Appendix has a listing of the epidemiological literature on PFAS exposures and adult cance adult diseases, and adverse outcomes in children. Tables 3 and 4 provide a summary. In these ta indicates that at least one study had a ?nding for a specific PFAS chemical that suggests an increased risk of an adverse outcome an odds ratio or risk ratio of 21 .20), and indicates that no study has been conducted for that PFAS chemical. In these tables, an indie. the findings from studies have not suggested an increased risk for an adverse outcome all ratios or risk ratios are <1.20) but the information is too limited to conclude that there is no asso between the PFAS exposure and the adverse outcome. These tables are for illustrative purposes, to indicate where data gaps exist and therefore additio research may be needed. Tables 3 and 4, and the tables and descriptions of the studies in the app should not be interpreted as implying causation or as an assessment of the weight of evidence fc rs, other bles, a crap? tes that adds ciation 1al endix, an association. Currently, epidemiological research on the health effects of PFAS exposures is at an early stage. This is particularly true for in addition to PFAS chemicals other than PF 0A and I However, even for PFOA and PFOS, additional research on all the health?related endpoints me in these tables will be needed to provide suf?cient evidence for causal assessments and to addre community health concerns. - Adult .cancers and other adult diseases Based on its assessment of the epidemiological literature, ATSDR concluded that there was limi no information concerning associations with PFAS exposures and most cancers and other adult (Table 3). In particular, very few studies have evaluated exposures and cancers and othe diseases. Although more information is available for PFOS exposures and cancers and other adL FOS. itioned ss ted or 7 diseases adult 1t diseases than for exposures, the information is still very limited and therefore inadequate to determine whether PFOS exposures increase the risk for most of the adult diseases evaluated. A more information is available on PFOA exposure, the information is still too limited to determir whether a causal association exists between PFOA and speci?c cancers and other adult disease. Therefore, additional research on the effects of PFOS, and PFOA would be needed to whether exposures increase the risk for many adult cancers and non-cancer diseases. Health effects in children There is some evidence that PFAS exposures are associated with decreased birth Weight, small iietus size for gestational age, measures of intrauterine growth retardation, and preterm birth. In particular, meta?analyses have found an overall decrease in birthweight associated with PFOA and PFOS 2015; Each 2015]. However, the ?ndings across studies are inconsistent for these outcomes and other adverse birth outcomes, and few studies have evaluated Several studies of infants 14 [though 6 etermine two Verner for have . -. .. Draft for Review Purposes Do Not Cite or Quote found that prenatal PFAS exposures affect thyroid function, but only two studies have evaluated thyroid the possibility of reverse causation cannot be ruled out. Four studies of PFAS exposures and testost rone and other sex hormones have been conducted. However, the ?ndings have not been consistent a ross studies and further research is needed. Three of the studies did ?ndthat PFAS exposures decrea ed testosterone in boys or girls. There is some evidence from four studies that PFAS exposures mi ht be function in older children. A few studies have found elevated uric acid with PFAS exposures, bEt associated with ADHD, but ?ndings have not been consistent across studies. Evaluating the evi PFAS exposures and neurobehavioral outcomes is dif?cult for several reasons: 1) the studies us different methods to measure the outcomes, 2) studies are inconsistent in the outcomes evaluate too few studies have been conducted. A few studies have found associations between PFAS exp and a decline in antibody response to speci?c vaccines, but only two studies evaluated the same rubella). In summary, there are considerable data gaps concerning the health effects in chil ed and 3) osures vaccine dren of PFAS exposures. This is because of the small number of studies conducted, inconsistencies in methods and ?ndings across studies, and limited sample sizes in some studies. As for other adverse outcc few studies have evaluated the effects on children of exposures. Sources of adverse outcome data for the Pease population The adverse outcomes of interest for PFAS exposure that can be ascertained from the birth certi pregnancy-induced hypertension, diabetes, small for gestational age (SGA), low birth weight, b1 weight, preterm birth, and gestational age. Although the birth certi?cate has a checklist for cong anomalies, the most reliable data on birth defects are provided by population-based birth defect registries. Birth defects registries exist in 41 states, including New Hampshire. The New Hamps Birth Conditions Program (NHB CP), based at the Geisel School of Medicine at Dartmouth-Coll began collecting data on births occurring in~state to New Hampshire residents in 2003 Data reported on 46 differ defects are ascertained for infants aged 51 year arecollected through active surveillance methoc Congenital hypothyroidism data can be obtained from the newborn screening program. Newbor screening for congenital hypothyroidism is conducted in every state, including New Hampshire. The birth certi?cate has information on sex of the child, plurality, gestational and pre-pregnanc). imes, ?cate are enital hire 336, ent birth SI 1 diabetes, previous preterm birth, parity and gravidity, cigarette smoking before and during pregnancy, principal source of payment for the delivery (a measure of socio?economic status), date of last of pregnancy, date of last normal menses, date of ?rst and last prenatal care visit and total number prenatal care visits, race/ethnicity of the mother and father, education of the mother and father, arents? names and address, mother?s marital status, labor and delivery complications, and whether the i% fant is i being breastfed at discharge. The New Hampshire Division of Vital Records Administration col ects information on births in New Hampshire from liOSpitaIs and midwives, birth certi?cates, and int exchange agreements for births occurring out~of~state to New Hampshire residents Mortality information is available from the National Death Index (NDI) operated by the Nations for Health Statistics (NCHS), Centers for Disease Control and Prevention. Currently, 2014 data complete and available for searches. ?Early release data? for 2015 are 2.90% complete (98% cor for New Hampshire) and also available for searches. NDI ?plus? provides information on cause erstate 11 Center are nplete of death (underlying, contributing and all other causes of death listed on the death certi?cate) and date and state of death based on death certi?cate data provided by the states. The NDI has data starting from 1 1'5 979. ence for .. .-. Draft for Review Purposes 7 Do Not Cite or Quote New Hampshire death certi?cate data are availabl Administration, which collects information on de in New Hampshire from the New Hampshire Division of Vital aths of New Hampshire residents and deaths Information on deat Information on underlying cause of death and up to 14 contributing causes of death is collected. Complete data are available approximately 24?48 months after the close of a calendar year. Population-based cancer registries exist in all 50 st Cancer Registry .is a statewide, populati collected incidence data on all cancer cases diagnos NHS CR, . at Dartmouth College, currently collects data from the larger hospitals in the state. als case reports from physician practices, free standing radiation oncology centers, pathology labc and other sources. staff assist hospitals with fewer than 100 cases per year with reporti Through interstate data exchange agreements, residents who are diagnosed outside the state. ates and Washington, DC. The New Hamps- ed or treated in the state since 1985 The New Hampshire Uniform Heepital Discharge Data Set (UHDDS) collects discharge data fr health care facilities in the state (acute care hospitals, specialty hospitals, freestanding hospital emergency facilities, and walk-in urgent care centers), as required by law Discharge data from Maine, Massachi and Vermont hospitals for New Hampshire residents are included in the UI-IDDS via interstate exchange agreements. The dataset includes transfers of NH residents. Chronic diseases such as chronic obstructive pulmonary disease, angina, hypertension, and diabetes are included in the UHDDS. Limitations of this duplicated and one person with multiple admissions might falsely increase the number of persor hospitalized. Additionally, state law requires health care professionals to report information on health conditions relating to children, infectious diseases, immunizations, and autism to NH DH topic_s). 1 congestive heart failure, hypoglyc dataset are that discharges are not I To ascertain autism or ADI-ID reliably, a review of school special education records and medica from providers that conduct developmental evaluations of children or provide treatment is neces Portsmouth, records are available from three elementary schools (serving grades one middle school (serving grades and one high school (serving grades 9?12). Projected enrollment fo'r the the elementary schools, 516 students in the middle 2016?17 school year Was 988 students i 1,183 students in the high school school year 2015?2016, the Portsmouth Public Schools provided special education services to 4 students. Among those students, 121 had an orthopedic impairment, 36 had a speech/language impairment, 32 had a had an emotional disturbance, 11 had having a ?speci?c learning disability.? ome other disability, and 174 Were classi Various studies have focused on West Virginia and Ohio residents and workers exposed to studies) [Frisbee 2009]. In a C8 study that evaluated ADI-ID, affected chemical plant (the were identi?ed via questi [Stein 2011]. For chronic questionnaires with attempted confirmation of self-reports by obtaining medical records. onnaire, which included a question requesting information on medicati 16 Records hs of New Hampshire residents that occur cut-of-state is captured through interstate exchange agreements. on-based cancer surveillance program that which is contracted to the Geisel School of Medicine i. Eg also receives case reports for New Ham] shire am all Jsetts, developmental delay, 25 had autism, 17 (4 diseases, the C8 studies relied primarily on self-reported information f1 ccurring ire State receives cries ata isthma, emia, le? UJ :hronic HS records sary. In 301tied as I from a ersons ns used om Draft for Review Purposes Do Not Cite or Quote Sources of exposure data An important source of exposure information is PFAS bio?monitoring. Measuring serum levels chemicals provides information on the amount of these chemicals that has entered the body from PFAS a all sources. At Pease, 1,578 persons volunteered to submit blood samples for PFAS analyses during the NH DHHS biomonitoring program in 2015. In the CS study, blood samples for PFAS analyses were obtained from 66,899 persons during the 13-month baseline period, 2005?2006 [Frisbee 2009]. Biomonitoring for PFAS is use?il in estimating past exposures, given the long half-lives of PF (approximately 5.4 years) and (approximately 8.5 years). Although biomonitoring inteo ates PFAS exposures from all sources, including diet and consumer products, PFAS levels in serum pepulations exposed to PFAS?contaminated drinking water will mostly reflect the drinking wate exposures, unless the person is or was also exposed occupationally ?re?ghters, PFAS manufacturing workers). The use of PFAS biomonitoring in epidemiological studies has some limitations. A key limitatic issue of ?reverse causation,? in which the disease under investigation kidney disease or kit from is the lney function) affects the elimination of PFAS in the body, causing higher serum levels of PFAS. Other problems include potential confounding by a factor that is both a risk factor for the disease of in terest and a factor in?uencing serum PFAS levels parity in the evaluation of adverse birth outcomes). Another limitation is that biomonitoring results, by themselves, might not provide sufficient inf: to estimate historical exposures. Estimating historical exposures is necessary to assess cumulatii exposure and to characterize periods of special vulnerability to PFAS exposures, such as prenatr early childhood exposures. Modeling methods are used to reconstruct historical PFAS serum levels. The results of PFAS biomonitoring can be used to validate estimates of PFAS serum levels obtained from modeling. C8 researchers have successfully used physiologically based pharmacokinetic modeling of abso distribution, metabolism, and excretion of PFOA in the body in conjunction with drinking water contaminant levels, estimates of water intake, and residential history to predict historical and our PFOA serum levels [Shin 2011]. Researchers have also been able to simulate PFOS serum level information 'on drinking water levels and PBPK modeling [Loccisano 201 Therefore, reconstr of historical PFOS serum levels is also feasible. However, reconstruction of PFOA and PFOS se levels is limited by various uncertainties. These include lack of accurate information on individt consumption of drinking water and length of time exposed and limited information on factors th produce inter-individual variability gender, age) and pre?existing medical conditions compromised renal function) [Loccisano 2011]. Nevertheless, the ability to predict serum PFOS PFOA levels based on drinking water contamination levels can substitute for, and enhance, the information provided by PFAS biomonitoring. Issues concerning cross-sectional study designs Cross?sectional studies are especially suitable for assessing effect biomarkers and the prevalence nonfatal diseases, in particular, diseases with no clear point of onset [Checkoway 2004]. Howev cross-sectional study concurrently measures the exposure and the outcome the disease or e1 biomarker), then it might be dif?cult to determine whether the exposure caused the outcome or i the outcome influenced the measured exposure level [Flanders 1992, 2016]. For example, as dis above, the concurrent measurement of serum PFAS levels and kidney function biomarkers migh 17 *rmation A re L1 01? ?ption, rent 3 using uction rum the fect vhether cussed raise Draft for Review Purposes Do Not Cite or Quote the question of ?reverse causation?. because kidney function can affect the levels of PFAS in serum. This issue can be addressed by estimating exposures based on the historical reconstruction modeling of serum PFAS levels. In addition, it might be possible to estimate exposures during critical vulnerable =riods in utero exposure) through the modeling of historical serum PFAS levels. However, the deling of historical PFAS serum levels is subject to uncertainties and data limitations, as discussed aboive, and published methods are available only to model serum levels of PFOA and PFOS. Other issues concerning cross-sectional study designs are similar to those that confront other observational study designs, such as cohort studies. These issues include: 1) the ability to clearl define, enumerate and recruit (without introducing selection bias) the exposed and comparison populati ns, 2) the comparability of the exposed and comparison populations on risk factors other than the PF exposures, 3) accurate exposure assessment, and 4) accurate measurement of effect biomarkers nd ascertainment of diseases. - Based on its review of the literature, ATSDR concludes that several health-related endpoints coild be considered for studies of the Pease population. It is also clear that exposures to the PFAS-contaminated drinking water have occurred in the Pease population, as documented by the observed serum PF AS levels in the NH DHHS PFAS blood testing program. Therefore, it is reasonable to conduct if epidemiological studies of the Pease pepulation. However, whether it is feasible to study a Speci rc health-related endpoint depends to a great extent on the size of the exposed population that can be . recruited into a study. The usual approach to determine the necessary size of the study population for each health-related endpoint is to conduct sample size calculations. All epidemiological studies of environmental exposures and health outcomes have limitations ar uncertainties. Whether a study will ?nd an association between an environmental exposure and health effects cannot be known prior to conducting the study. No single study of the Pease population will provide definitive answers to the community about whether their exposures to the PFAS?contaminated drinking water caused their health problems. The ability of a study of the Pease population to provide useful information will depend to a great extent on the success of recruiting a suf?cient number of study participants. I'l? Feasibility of an epidemiological study of children at the Pease Tradepor The ?rst population that ATSDR considered for an epidemiological study was the children who 1ttended the two day-care centers at the Pease Tradeport. One reason to focus on children is that they are more vulnerable to environmental exposures, in particular exposures to potential endocrine-disrupting chemicals. In addition, there is serious concern in the community about the possible health effects to children from the drinking water exposures, which was conveyed to ATSDR by the Pease CAP. inally, a study of children who attended daycare at the Pease Tradeport is the most feasible epidemiolo ical study to conduct. The population is less transient than an adult population and the adverse health endpoints of interest do not require as large a sample size as adult chronic conditions. The public health significance of conducting a study of these children consists of 1) the possibility of early intervention if early signs of adverse health effects, including developmental delays, are observed and 2) the relevance of a study at Pease for other populations exposed to drinking water primarily 18 Draft for Review Purposes Do Not Cite or Quote contaminated with PFOS and A study of children at Pease would have scientific impo because of key data gaps concerning PFAS exposure effects on sex hormones and on neurobeh ance vioral, immunological, and thyroid function. Animal studies support the biological plausibility of immune effects. Animal data also suggest that PFAS might be deveIOpmental neurotoxicants that can alt 31' cognitive function and reduce learning ability. PFAS also have endocrine?disruptive properties and could interfere?with thyroid function and sex hormones. A study of children at Pease would be responsive to the community?s concerns and has the potential (from the perspective of statistical to provide meaningful and credible results for some of the adverse outcomes of interest. Howev study limited to the population of children who attended the Pease Tradeport day-care centers likely not be suf?ciently large for some of the possible adverse outcomes of interest highe prevalences of rare diseases or very subtle changes in biomarkers of effect that have been obseri research conducted elsewhere). A. Study population power) er, a ould red in The population of interest could be persons who attended day care at the Pease Tradeport beforeaJune' 2014 and are in the age range of 4?16 years at the start ofthe study. The end of the period was elected because the Haven well was taken out of service in May 2014. Because PFAS?contaminated drinking water exposures could occur to children in uteroand during breastfeeding if the mother worked Pease Tradeport, the study would include these additional children if the exposures began prior 2014 and their ages are 4 16 years at the time the study begins. at the 1io June The age range for the Pease children study was determined by taking into account the age ranges in previous PFAS studies and the age range appropriate for the candidate endpoints. Previous epidemiological studies of children exposed to PFAS included varying age ranges. Because of d, 1ta limitations no PFAS serum data for those aged <12 years), the studies that used NHANES data evaluated those aged 12?1 8 years or 12?19 years. Some of the CS studies limited participant age those <12 years; other C8 studies included persons up to 18 years of age. The upper age limit for of the Taiwan children studies of PFAS was 15 years. An age range of 4?1 6 years would overlap ranges in these studies. The chosen age range also reflected the focus of the study children exposed to the contaminated drinking water while attending daycare at the Pease Tradeport). The younger age 1 to many the age mit of 4 years was chosen because intelligence quotient (IQ) testing is available for those aged 4 years a older. (For example, the Wechsler Preschool and Primary Scale of Intelligence test has an age band of years to 7 years, 7 months that overlaps the Wechsler test for those aged 6?16 years.) The and Difficulties Questionnaire (SDQ), a behavioral screening questionnaire used in a Faroes study ulhote 2016], a Taiwan study [Lien 2016] and a Danish study [Fei 2011] has an age range of 4 16 years. The upper age limit of 16 years was chosen for three reasons: 1. Age at puberty was a candidate endpoint and virtually all of the children in a C8 study achieved puberty by age 16 years. The IQ and SDQ testing instruments for children have an upper age limit of 16 years. years ago. 1 9 Children aged >16 years would have been last exposed last attended daycare).rnore ihan 10 Draft for Review Purposes Do Not Cite or Quote Table 5 provides the data on serum PFOS, PF 0A, and for the 370 children who participated in the 2015 NH DHHs testing program at Pease and who were aged 1?13 years at the time of bloo These children would be aged 4?16 years in 2018. The geometric mean serum in these was 3.80 [lg/L, approximately three times higher than the serum levels reported in the Texas [3 2012] and California [Wu 2015] studies and in the NHANES data for 2013?20 14. We currently do not know how many children attended daycare at the Pease Tradeport before .1 draw. :hildren 3hecter ne 2014 and who would be in the 4?16 years age range in 2018. The Discovery Child Enrichment Cente is located at the Pease Tradeport and began operation in 1994. Its yearly enrollment is approximat 1y 149 children ages 6 weeks to 5 years. Computerized records at this day?care center start in 1996. A preliminary records search by the director of the Discovery Child Enrichment Center identi?ed 95 children who attended the daycare during 1996?2015 and who would be aged of 6?1 8 years in 2 Based on the results of this search, the number of children who attended this day care prior to and would be between the ages of 4 and 16 years in 2018 could be within the range of 250 45 individuals. The Great Bay Kids? Company is also located at the Pease Tradeport and began operation in 20 annual enrollment is approximately 270 children aged 312 years. Assuming that most of the chi enrolled would be years of age, and that most of the children attend daycare for 4 years, abet children might have attended this daycare during the period of interest and would be aged 4?16 201 8. Assuming that a minimum of about 500 children attended the two day~care centers at Pease befc 2014 and would be aged 4~16 years in 2018, and assuming a reasonable participation rate of 709 Would be possible to recruit 350 Pease children into the study. It would also be feasible to recrui 175 children in the same age range from the public schOols in Portsmouth, NH, who Were unexp 018. me 2014 l0. Its dren 300 years in re June it at least osed to the PFAS?contaminated drinking water at the Pease Tradeport and whose parents did not work at the Pease Tradeport or have occupational exposures to PFAS. It is reasonable to assume that partici rates would be high because of strong interest in the community concerning the Pease Tradeport situation. Moreover, the Pease CAP members have pledged to support recruitment efforts if and study is to be conducted. Pease CAP members have strong ties and are active in the Portsmouth community. If the actual number of children who attended the two day-care centers prior to um and would be aged 4 16 years in 2018 is in the range of 650 750, then as many as 500 childre be recruited from the Pease population. It should also be possible to recruit at least 250 children same age range from the Portsmouth public schools for the unexposed group. A sample size of 350 exposed children and 175 unexposed children would be similar to the sam}: used in the Faroes study [Grandjean 2012, 2016] and in a C8 study of 320 exposed children [Stei 2014b]. However, the sample size of 35.0 exposed and 175 unexposed would be considerably sm. ation when a a 2014 could the .le sizes '11 2013, aller than most of the C8 children studies and some 'of the other epidemiological studies of children exposed to PFAS. Therefore, atotal of 525 children, 350 exposed and 175 uneXposed, should be consider minimum sample size, and attempts should be made to recruit a higher number of exposed and unexposed children to improve the statistical power of the study. 20 eda Draft for Review Purposes Do Not Cite or Quote B. Study Hypotheses As indicated in the literature review summary, the scienti?c literature has little information on the health effects of exposures to is a key contaminant associated with the use for ?re?ghting training and extinguishing ?ammable liquid ?res. The study would be an important contribution in ?lling this data gap and would generate knowledge relevant to other populations to drinking water contaminated by from the use of In addition, few studies have conducted to evaluate possible associations between childhood exposures to PFASs and effects thyroid function, uric acid and sex hormone levels, delays' 1n reaching puberty, IQ, and Immune exposed een 911 function. Inconsistent findings have been observed for most of these endpoints, likely' 1n part because of differences' 1n exposm es g. ., drinking water and other sources, such as diet) and PFAS levels of exposure, study population differences g. age differences), and differences In methods. More over, few studies have evaluated the same neurobehavioral or immune endpoint. The study would address these issues by using methods and evaluating health effects similar to those used in previous studies of PFAS exposures in children, in particular, methods used in the C8 studies. Based on the literature review, the following hypotheses could be evaluated: 1. Higher serum levels of PFOA, PFOS, or are associated with higher-total cholesterol, low- density Iipcprotein, and triglycerides, and higher prevalence of hypercholesterolemia. Higher serum levels PFOS, or are associated with differences in thyroi stimulating hormone (TSH), TT4, and TT3, and a higher prevalence of hypothyroidism. CL 3. Higher se1u1n levels of PFOA, PFOS, or are associated with a higher level of uric acid and a higher prevalence of hype1urice1nia. Higher serum levels of PFOA, PFOS, or are associated with differences in testes estradiol, and sex hormone?binding globulin (SHBG). . Higher serum levels of PF 0A, PF OS, or are associated with delayed puberty, Higher serum levels of PF 0A, PF OS, or are associated with lower IQ. Higher serum levels of PFOA, PFOS, or are associated with ADI-ID behaviors an learning problems. 8. Higher serum levels of PFOA, PFOS, or are associated with a higher prevalences hypersensitivity?related outcomes g. ., asthma, rhinitis infectious diseases). Highe1 se1 um levels of PF 0A PFOS, or are associated with lower antibody respc rubella, mumps, and diphthe1ia vaccines. C. Recruitment and Consent Based on sample size calculations (see Appendix), a minimum of 350 exposed children aged who attended the day?care centers at Pease before June 2014 would need to be recruited. To recr children who participated in the blood testing program, NH DHHS would have to send letters to 21 :erone, of inses to 6 years uit the the . Draft for Review Purposes Do Not Cite or Quote parents to ask that their child participate in the study. Additional children who were exposed to be contaminated drinking water while attending the two day-care centers could be recruited via on each to the two day?care centers at Pease, the Portsmouth public schools, media, and community organi? ations in the Portsmouth area?. The Pease CAP has also offered to assist in recruitment, and CAP invol ement will be crucial in achieving high participation rates. A minimum of 175 children aged 4?16 years, who were unexposed to the PFAS-contaminated 'rinking water at the Pease Tradeport and whose mother did not work at the Pease Tradeport (or in an 00 that involved PFAS exposure) during the pregnancy and breastfeeding of the child would be rec from the Portsmouth, NH, public schools. Before enrollment in the study, the child?s mother wo interviewed to determine whether the child is eligible for the study. Recruitment would involve to the eight day?care centers in Portsmouth that were located outside the Pease Tradeport, the Portsmouth public schools, media, and community organizations. The Pease CAP has offered to with the recruitment effort. The total enrollment of Portsmouth?s elementary, middle, and high is projected to be 2,687 in 2016?17. To encourage participation of exposed and unexposed child appropriate incentive would be provided. The Pease blood testing program?s consent form was strictly limited to the use of the participant sample for PFAS analyses duly. The participant also consented to complete a brief questionnaire time of blood draw concerning demographic information, time at Pease Tradeport, and consump drinking water. The consent form did not mention the use of the blood sample for research purpc .upation ?uited uld be outreach help chools ten, an 5. blood at the ion of ses or :lrawn contact ion, the possibility of re-contacting the participant for future studies. Moreover, the amount of blood from the children was only suf?cient for the PFAS analyses. Therefore, ATSDR cannot directly . the participants in the Pease blood testing program to recruit them for a children?s study. In addit these participants must sign a new consent form to participate in a research study. A parent of each child would be asked to sign a parental permission form requesting a blood 3am (about 4 teaspoons or 20 mL) from the child for the analyses of PFASS and the effect biomarkers lipids, TSI-I, uric acid, sex hormones, and immune function parameters). The consent form woulc ask that the child be administered the Wechsler Abbreviated Scale of Intelligence (IQ) tests if ag years or older or the Wechsler Preschool and Primary Scale of Intelligence for children younger than 6 years. The consent form would ask permission to access the child?s school records, including special education records. The parent would be asked to sign a consent form to complete a questionnaire. Children ages 7 years and older would be asked to give their assent to participate in the study. ple 1 also 3d 6 D. Questionnaire The parents of the child participant could be asked to complete the questionnaire. The questionn could obtain demographic information, medical history of the parents and child, the child?s medi -ations, the dates the child?s mother worked at the Pease Tradeport (or in other occupations involving PF . exposures) and her reproductive history, the dates the child attended daycare at the Pease Tradep rt, water consumption of the mother and child while at Pease Tradeport (including use of water for ormula, juices, etc.) if applicable, bottled water consumption by the mother and child, length of time the hild was breastfed, parental information education, primary occupation, maternal age at birth of the participating child), the child?s height and weight, and whether the child regularly exercises, curr ntly smokes (and the number of cigarettes/day), or consumes alcohol (and the number of drinks/week . 2.2 Draft for Review Purposes Do Not Cite or Quote Speci?c questions could be included in the questionnaire that address health outcomes of intere? on the ?nal study design. For example, for ADHD, the questionnaire could ask, ?Has a doctor 0 professional ever told your child that your child has/had ADD or If the answer is ?yes l? 3! based health a second question could ask for a list of medications being used for the condition. Parents would also be asked if the child had learning or behavioral problems, and if so, the type of problem and the treatment being used. Questions would be included for the hypersensitivity-related outcomes, asthma, ate} ic dermatitis (or atopic eczema), and allergies. Information on the child?s vaccination history would also be requested from the parents. The parents would also be asked when the female child first began to menstruate. E. Biomarkers of exposure and effect The following biomarkers of lipids, thyroid function, kidney function, sex hormones, and immune function could be analyzed in the serum: 0 Total cholesterol, low density lipoprotein, high density lipoprotein, total triglycerides - Thyroxine (T4), T3, thyroid stimulating hormone (TSH) - Uric acid, creatinine Testosterone, estradiol, sex hormone-binding globulin (SHBG), follicle stimulating hormone, insulin?like growth factor - Immune globulin and antibodies to measles, mumps, rubella, tetanus, diphtheria Approximately4 teaspoons of blood (20 mL) could be drawn from each participant to be analyze the standard panel of PFAS compounds and the effect biomarkers. An attempt would be made to .an 8-hour fasting blood sample. The parents could be asked how long the child fasted before the and for obtain blood draw. The cut points of 50 ng/dL of total testosterone and 20 pg/mL of estradiol would be used to identify sexual maturation in boys and girls, respectively. antibodies for measles, rubella, and diphtheria would be analyzed to determine vaccine responses. Allergen-speci?c (mold, dust nites, dog, cat, cow?s milk, peanut, hen?s egg, and birch) could be analyzed. Serum levels of thyroid. stimulating hormone (TSH) and total T4 could be analyzed separately and also used to determine clinical and subclinical hypothyroidism. Uric acid, total cholesterol, low-density and high-density lipoprotein, and triglycerides could be analyzed. For children older than 6 years, the Wechsler Abbreviated Scale of Intelligence could be adminisr the child to assess verbal IQ, performance IQ, and full?scale IQ. For children aged 4?6 years, the Wechsler Preschool and Primary Scale of Intelligence would be administered. For each child, records, including special education records could be reviewed to identify learning-problems and ered to col behavioral problems. The SDQ could be administered to parents to assess emotional, conduct, and peer relationship problems as well as problems with hyperactivity and inattention. F. Exposure Assessment As stated earlier, the analyses by NH DHHS of the data from the blood testing program at Pease indicated that geometric mean serum levels were higher for persons who drank 24 cups oi'water per day than for those who drank <4 cups per day. The strongest ?nding was for serum in participants aged 0?19 years and water consumption 0.31, marginal effecF36.4%) 23 Draft for Review Purposes Do Not Cite or Quote Geometric mean PF OS and PFOA serum levels .were also higher among those who, while at the Tradeport, drank 24 cups of water per day than for those who drank <4 cups per day DHHS Although these ?ndings are based on a ?convenience sample? (or a ?volunteer sample," not a statistically-based sample), it is clear from these results that consumption of PEAS-contaminated drinking water at the Pease Tradeport was a complete exposure pathway. 2016]. Study participants could submit blood samples for PFAS and biomarker analyses during 2018. those who participated in the 2015 blood testing program, these measurements would be used to assess exposures. For those who did not participate in the 2015 blood testing program but who attended daycare at the Pease T1 adeport during January 200 S?May 2014, the PFAS serum levels obtained could be used to estimate serum levels during 2015 by adjusting for PFAS elimination rates and 1 into account background PFAS exposures For those who consumed drinking water from the Pease their 1n 2018 aking Tradeport a?er the Haven well was taken out of service, the adjustment could also take into account the PFAS levels in the drinking water after May 2014. The 2015 (estimated or measured) PFAS serum levels and 2018 measured PFAS serum levels would be used in the analyses. No water samples from the Pease Tradeport distribution system for PFAS testing are available be :fore 2014. Using a simple mixing model that takes into account the pumping rates for each of the three wells, the total water demand, and the concentrations of PFAS in the wells during the April and May 20 sampling, we can estimate historical PFAS levels in the distribution system, assuming that contamination concentrations are approximately uniform throughout the distribution system and assuming that the contamination was present at least from 2008 through May 2014. To estimate serum levels of PFOA and PFOS over the child?s life, the historical estimates of the questionnaires on 1) the dates and length of time the child attended daycare at the Tradeport and ?14 drinking water contamination could be combined using PBPK modeling with information from child?s consumption of drinking water at the daycare and 2) whether the child?s mother worked Pease Tradeport during p1 egnancy and during the period of breastfeeding and the length of the pd when the child was breastfed. PBPK modeling estimates would also incorporate information fret; driod NHANES and from the PFAS serum levels of the unexposed comparison group to estimate back round levels of PFAS in serum. For those children whose mothers worked at the Pease Tradeport, estim the mother?s serum levels during the pregnancy and breastfeeding of the child would be needed. 1 mother participated in the 2015 blood testing program at Pease, her measured PFAS serum levels be used in the modeling. Children?s serum levels from the 2015 NH DHHS Pease blood testing and serum levels obtained for this study would be used to calibrate the PBPK models. 'No human PBPK model for is currently available. However, correlation coef?cients for and serum PFOS and PFOA were quite high among persons ages 2?14 years who particip the 2015 testing (Pearson correlation for was 0.75, and for PFOS and PFOA was 0.73). Therefore, it might be possible to predict historical serum levels of based on historical est for serum PFOA and PFOS. G. Sample Size The sample size for the Pease children study should include at a minimum 350 exposed children. should also include a minimum of 175 unexposed children randomly sampled from the Portsmow ates of the could rogram erum ated in imates It :h public schools with frequency matching to the exposed children on age, sex, and race. This minimum sample size is based on several considerations. First, 370 children ages 1?13 years participated in 24 the Draft for Review Purposes Do Not Cite or Quote 2015 blood testing at Pease. That would be a 75% participation rate, assuming that a minimum of children attended daycare at Pease and would be in that age range in 2015. It should be possible t( 500 recruit a similar percentage of the children who attended daycare at Pease. However, children who) did not participate in the 2015 blood testing would have to be recruited, as well as a high percentage who did participate. Second, some studies conducted of PFAS exposure and children had similar I smaller sample sizes than the 350 exposed and 175 unexposed children at Pease Zeng [2015 Qin [2016] in Taiwan, Grandjean [2012] in the Faroes, Stein [2013] in a C8 study of neurobehavi effects, Hoffman [2010] in a NHANES study), but had suf?cient statistical power to observed ?n to achieve statistical signi?cance. Finally, sample size calculations conducted for this feasibility assessment indicated that at least some of the health-related endpoints of interest could be evaluat with suf?cient statistical power statistical power 280%) to detect effects of exposure that are to or greater than those listed in Tables 6a and 6b as well as effects observed in other PFAS studie occurred at PFAS serum levels similar to those in the Pease children population. . Sample size calculations were conducted using four different combinations for type 1 error (at. cm false positive error) and type 2 error error, false negative error, or 1 statistical power): 1. Type 1 error 0.05 (corresponds to a two-tail hypothesis test using a p?value cutoff of 95% con?dence interval, to determine statistical significance) and a type 2 error 0.05 (corresponding to statistical power of 2. Type 1 error 0.05 and type 2 error 0.20 (80% power). 3. Type 1 error 0.10 (corresponds to a one-tail hypothesis test using a p-value cutoff of 0.0 90% con?dence interval, to determine statistical signi?cance) and a type 2 error 0.10 (9 power). 4. Type 1 error 0.10 and type 2 error 0.20 (80% power). (Note: Setting the type 1 and type 2 errors to be equal indicates an equal concern for false negatiw false positives and could bejusti?ed from a public health perspective.) Table 6a indicates the minimum effect sizes that can be detected with a sample size of 350 Pease children and 175 unexposed children from the Portsmouth area using the four combinations oftyp and type 2 errors. Table 6b also includes the minimum effect sizes that can be detected with a cam size of 500 exposed and 250 unexposed. These minimum effect sizes assume a simple comparisor between the exposed and unexpdsed children that is not adjusted for possible confounding risk fac stratified into smaller exposure groupings low, medium, and high exposure). Another approach to sample size calculations that might be informative was to ?x the minimum detectable effects to the effect Sizes observed in previous studies for PFAS serum levels similar to observed in the Pease population, select the type 1 and type 2 error rates, and allow the sample siz ??oat? instead of the minimum detectable effect. However, this approach is problematic because are few studies of PFAS exposures and the childhood outcomes being considered for the Pease Ch] study. In some instances, studies evaluating similar PFAS serumlevels obtained very different eff sizes for the same outcome. In other instances, a'study with a lower PFAS serum level obtained a] effect size for an outcome than a study with a higher PFAS serum level. Moreover, there are no st] of children exposed to PFAS drinking water contamination as a result of use. Therefore, the 25 if those 3r and oral :lin gs ed, . equal 3 that for or a 5,-or a 0% as and 1 ple tors or those 3 to tere ldren 'ect higher dies re is Draft for Review Purposes Do Not Cite or Quote much uncertainty about the effect size for each health?related endpoint that would be expected for PFAS serum levels observed among the Pease children. With these caveats, the following sample size per stratum calculations use the ?ndings from studies of PFAS?exposed children. (Note: a sample size of 500 per stratum means that the study would need 500 exposed and 500 unexposed children. If the goal is to compare an outcome by exposure quartiles, then each quartile would need 500 children. Also, a 2:1 ratio of exposed to unexposed requires a larger total sample size than a 1:1 ratio of exposed to unexposed.) Table 60 provides a summary of the sample size considerations for each health-related endpoint. . Lipids Mean Total Cholesterol, LDL, HDL, triglycerides: In the Taiwan study of lipids (Zeng 2015), the sample size of 225 children aged 12-15 was sufficient to detect total cholesterol and LDL differences of 11-12 mg/dL for PF OA serum levels similar to Pease. Table 6 indicates that with a sample size of 350 exposed and 175 unexposed, much lower mean differences in total cholesterol could be detected with sufficient statistical power. However, the observed PFOA OR of 1.2 for hypercholesterolemia would have required a sample size of over 1,700 per stratum with a type 1 error of 0.10 and 80% power l?using the prevalence of hypercholesterolemia in this study of Using a lower type 1 error and/or higher 'statistical power would require even larger sample sizes to detect an OR of 1.2 for hypercholesterelemia. The serum levels of PF 0A and PFOS among the children at Pease would put them in the ?rst qua ile (1.6., the reference level) if they had been in the C8 study (Frisbee 2010). In the lower PFOA and F03 quartiles, the ORs for hypercholesterolemia were between 1.2 and 1. 3, requiring sample sizes of 00 1660 pe1 stratum with type 1 error of 0.10 and 80% power (using the prevalence of 8L. hypercholesterolemia 1n this study of 34. The strongest findings 1n this study for total cholest rol Were observed for the top quintile of PF OS serum levels. When the top quintile PFOS serum level was compared with the reference level, the mean difference in? total cholesterol was 8.5 mg/dL and the OR for hypercholesterolemia was 1.6. Both of these ?ndings are within the range that could be detect - cl with suf?cient statistical power in a Pease study with 350 exposed and 175 unexposed children. However, the tip quintile for PFOS in the C8 study contained serum levels several times higher than serum levels in the top quintile of the Pease children. A study using NHANES data for 1999?2008 [Geiger 2014] obse1ved a mean difference 1n total cholesterol of 4. 7 mg/dL for the 2nd tertile serum levels of PFOA compared with the reference leve l. The 2??l tertile serum levels of PFOA 1n this study correspond to the PFOA serum levels among children at Pease. To calculate a sample size to detect this mean difference, a standard deviation of 28 mg/dL (similar to the standard deviations for total cholesterol in the Taiwan and C8 study) was used. Wit type 1 error of 0.10 and 80% power, the sample size required to detect a mean difference of 4.7 mg/dL ould be 439 per stratum (or with an exposed to unexposed ratio of 2, as suggested for the Pease childre study, 660 exposed and 330 unexposed would be required). In the study, the 2nd tertile .FOS serum levels correSponded to the PFOS serum levels among Pease children. The mean difference total cholesterol for this tertile was 3 .4 mg/dL, which would require 630 per stratum with type 1 error 0 O. 10 and 80% powe1. In the NHANES study, the ORs for hypercholesterolemia corresponding to serum PFOA and PFOIS levels among children at Pease were 1.49 and 1.35, respectively. To detect an OR of 1.49 with type 1 26 Draft for Review Purposes Do Not Cite or Quote error of 0.10 and 80% power would require 358 per stratum (or with an exposed to unexposed ratio of 2, 540 exposed and 270 unexposed). Kidney function and uric acid In a study of adolescents (aged 12?1 9 years) and kidney function using NI-IANES data for 2003?201 0 [Kataria 2015], the top quartile for serum PFOA would correspond to the top quartile for serum PFOA among the Pease children. The mean difference in the estimated glomerular ?ltration for the top quartile of PFOA compared with the 1St quartile reference level mL/min/1.73 m2, which would be in the range detectable, with suf?cient statistical power, by the Pease study sample size of 350 exposed and 175 unexposed children. In this study,.the serum uric acid mean difference of 0.21 mg/dL_was observed, comparing the top quartile PFOA to the reference level. To detect this difference with a type 1 error of 0.10 and 80?? power would require a sample size larger than that projected for the Pease children study, 390 per stratum (or for an exposed to uneXposed ratio of two, 596 exposed and 298 unexposed children). The serum PFOS levels in the 3rd quartile of the NHANES study would correspond to the top qu tile for serum PF OS among the Pease children. The mean difference in for the 3rd quartile PFOS level compared to the reference level was ~7.2 mL/min/1.73 m2, which would be in the range detectable with suf?cient statistical power by the Pease study sample size of 350 exposed and 175 unexposed children. However, the mean difference in uric acid was 0.05 mg/dL which would require a sample size of more than 5,000 per stratum. In a Taiwan study of uric acid [Qin 2016], the sample size of 225 children aged 12?15 years was suf?cient to obtain a statistically signi?cant OR for hyperuricemia of 1.65 for at serum levels much lower than among the Pease children. For PFOA, the OR for hyperuricemia was 2.2 at serum levels much lower than observed among the Pease children. A sample size of 350 exposed and 175 unexposed children would be sufficient to detect this OR with sufficient statistical power. Attention De?cit/Hyperactivity Disorder (ADI-ID) and other neurobehavioral endpoints In a C8 study of ADHD (Stein 2011), the ?rst quartile or reference level for PFOA and PF OS we uld correspond to the serum PFOA and PFOS levels among the children at Pease. For the serum levels among the children at Pease would correspond to the 31rd quartile level in the C8 study. or lthe 3rd quartile of the ORfor ADI-ID was 1.43, and with current medications, the OR was 1.55. he prevalence of ADHD was 12.4%, and with current medications, To detect an OR of 1.43 prevalence of 12.4 the required sample size for atype 1 error of 0.10 and 80% power would - 829 per stratum. To detect an OR of 1.55 with a prevalence of 5.1 the required sample size for a ty 1 error of 0.10 and 80% power would be 1,179 per stratum. In a study that used NHANES data for 1999?2004 [Hoffman 2010], the serum levels wer about half the levels among the children at Pease. For serum levels corresponding to the top quintile lev 1 among the Pease children, the OR for ADHD was 1.67 (using the regression coef?cient in the 10 istic model). To detect this OR, a sample size of 540 per stratum would be required for type I error of 0.10 and 80% power. .F or PFOA, the serum levels corresponding to the t0p quintile level among the ildren 27 Draft for Review Purposes Do Not Cite or Quote at Pease in the NHANES population would have an OR of 1.82 for ADHD. For this OR, the requi sample size would be 390 per stratum (or 596 exposed and 298 unexposed children) for a type?l 0.10 and 80% power. red rror of For neurobehavioral outcomes other than ADHD, some of the neurobehavioral outcome studies Stein [2013, 2014b]; Wang [2015], Lien [2016]) were also in the range of the minimum sample size suggested for the Pease children study. IQ differences in the range of 3 to 4 points could be detect with reasonable statistical power with a sample size of 350 exposed and 175 unexposed children. One study [Liew 2015] evaluated autism Spectrum disorder and obtained an OR of 1.3 for serUm With a prevalence of about a sample size of several thousand children Would be necessary to detect this OR. To detect an OR of 2.0 with sufficient statistical pOWer would require sample sizes of over 1,600 exposed and 1,600 unexposed. Sex hormones and delayed puberty ed In the 08' study of sex hormones [Lopez-Espinosa 2016], the serum levels of PFOA, PFOS, and were considerably higher than among the children at Pease. For PFOS, the natural log estradiol pe difference in boys of (per interquartile range of the natural log of PFOS) would require at least rcent 1,154 per stratum for type 1 error of 0.10 and 80% power. The strongest ?nding in this study was the decrease in testosterone among girls associated with PFOS. The natural log testosterone percent difference in girls was per interquartile range of the natural log of PFOS. To detect a percteJit difference this large with type 1 error of 0.10 and 80% power would require at least 290 per stra 434 exposed and 217 unexposed children. There was insuf?cient information tomake sample size calculations for the endpoint, delayed pul: The C8 study that evaluated this endpoint in included thousands of boys and girls [Lopez?Espinos 2011]. Growth hormone 1n the CB study that evaluated sex hormones, insulin?like growth factor-1 was also evalua [Lopez?Espinosa 2016]. The difference in the natural log among boys and girls was 2.1% per interquartile range of the natural 10g of respectively. To detect these differences sufficient statistical power, a sample size of 350 exposed and 175 unexposed children would be suf?cient. Thyroid disease and function A C8 study [Lopez-Espinosa 2012] evaluated thyroid disease among children. The prevalence of participant?reported thyroid disease among children in this study was very low, about 0.6% and at of 1.44 was obtained for PFOA serum levels considerably higher than those in the Pease populati detect this OR with 80% statistical power would require a sample size of over 10,000 exposed chi 28 m, or CD rty. p: ted and - with OR n. To dren. Draft for Review Purposes ?-Do Not Cite or Quote- In the C8 study of thyroid function [Lopez-Espinosa 2012], the largest percent difference for mat - ral log TSH was and 2.3% for TT4. These percent changes were for PFOA and PFOS serum level considerably higher than the serum levels among the children at Pease. To detect a 2.3% change in would require a sample size of at least 850 per stratum (type 1 error 0.10 and 80% power). To etect a 3.1% change in natural log TSH would require a sample size of at least 8,545 per stratum (type 1 error 0.10 and 80% power). In the Taiwan study of thyroid function [Lin 2013], the sample size for those aged 12-19 years vs as 212. The geometric means for serum PFOA and PFOS were lower than the geometric mean serum levels among the children at Pease. For males and females, the natural log TSH declined by 0.5 and 0.3 5 respectively, for the >90th percentile serum PFOA compared with the reference level. To detect either of these differences with suf?cient statistical power, a sample size of 350 exposed and 175 unexposed children would be suf?cient. Immune function and diseases related to immune function For immune function, one study [Grandjean 2012] had a similar sample size (N 532) as the minimum proposed for the Pease children study 350 exposed and 175 unexposed children), and two studies had somewhat larger sample sizes that might be achievable at Pease (Stein [2016a], 640; am: [2016], 637). The? data reported in these studies were insuf?cient to conduct sample size calculations. - Buser For asthma, the ORs observed in the NHANES studies [Humblet 2014, Stein 2016a] were in the range of 1.2 1.3 and would require much larger sample sizes than can be recruited at Pease to achieve. suf?cient statistical power. However, 21 Taiwan study [Dong 2013] obtained ORs for asthma betizveen 3.8 and 4.0 for and PFOA serum levels lower than those observed in the Pease children population. A sample size of 350 exposed and 175 unexposed would be sufficient to detect these: with suf?cient statistical power. Only one study [Stein 2016a] evaluated rhinitis and observed an OR of 1.35 for serum PFOA. To an OR this low with sufficient statistical power would require a ?sample size larger than could be recruited from the Pease population. However, with suf?cient statistical power, ORs in the range 1.6 could be detected in a study of the Pease population with a sample size of 500 exposed and 250 uneXposed children. These ORs would fall within the 95% CI for the ?nding in this study. Other health-related endpoints A NHANES study [Geiger 2014b] evaluated PF OS and PF OA serum levels and hypertension and ORs - detect of 1.5 obtained ORs 1.0. Since there is no evidence so far of an association between PFAS serum le els and hypertension in children, this endpoint is not considered further. . A study conducted in the Faroes [Karlsen 2016] evaluated serum levels of PFOA, PFOS and and overweight/obesity in children. At age 5 years, the ORs for overweight/obesity and the third ten": serum levels of PFOA, PF 03 and were 1.88, 0.94, and 1.22. The serum levels of the PF chemicals were considerably lower than at Pease. An OR of 1.62 could be detected with 80% st tistical power with a sample size of 350 exposed and 175 unexposed children. 29 Draft for Review Purposes Do Not Cite or Quote Childhood cancers For childhood cancers such as leukemias, the incidence and prevalence is very low, requiring large sample sizes. For example, the probability of getting a leukemia at 515 years is 0.08% or 8 per 10,000. For ages 520 years, the probability is 0.09% or 9 per 10,000. At ages 514 years, the incidence rate for leukemias is 5.5 per 100,000 person-years. A study that attempted to evaluate leukemias or other childhood cancers would have to be multi-site or national. H. Conclusion Very little is known about the health effects from exposure to a PFAS that was considerably elevated in the serum of children tested at Pease. More information is available on the health effects of PFOS exposure, which was also elevated in the serum of children at Pease. However, there are still major data gaps and inconsistencies in the findings concerning the health effects of PF OS exposure, particularly effects on immune, thyroid and kidney function, neurobehavioral endpoints, sex hormones, and age at puberty. Based on sample size calculations, a study of children at Pease could haVe suf?cient statistical power to evaluate several health-related endpoints. The study could also meet the criteria of public health signi?cance and scienti?c importance, and could address some of the health concer ns voiced by the Pease CAP and the previous CAB. The study population can be enumerated and selection bias can be minimized if recruitment is carefully done to avoid selection bias selection that is associated with exposure and disease status). A sample of Portsmouth public school students would be an appropriate comparison group for the Pease There is a complete exposure pathway and a well-de?ned exposed population. The health?relate endpoints under consideration have been evaluated in at least one epidemiological study of PFA exposures to children, and these endpoints can be measured accurately. Information on potential confounding factors can be obtained via questionnaire. The issue of reverse causation and confo from the use of measured serum PFAS levels can be avoided by predicting serum levels using PK modeling. Therefore, a children?s study at Pease could provide meaningful and credible results. A key issue is Whether a study limited to the children exposed at the Pease Tradepo1t would have suf?cient statistical power and precision for some of the endpoints under consideration. A minim sample size of 350 exposed Pease children and 175 unexposed children from the Portsmouth are would be suf?cient for several outcomes of interest. For example, Table 6 indicates that a sample size 0 1 350 exposed and 175 unexposed children is suf?cient to detect effects of reasonable size for most oft endpoints listed in the table. In addition, some of the immune and neurobehavioral studies that had suf?cient statistical powe1 to obtain effect estimates that achieved statistical significance had sa sizes within the range suggested as a minimum for the Pease children study. le When the effect?sizes seen in previous PFAS studies are considered, the suggested minimum 3am] 1e size for the Pease children study could be sufficient for several endpoints, such as mean differences i lipids, and IGF-1. For other outcomes, such as uric acid mean difference, the sex hormones testo tercne and estradiol, and thyroid function, the sample size of a study limited to the Pease children p'opul tion might not be suf?cient. Based on sample size calculations assuming 350 Pease children and 175 unexposed children, and assuming a simple comparison of exposed versus unexposed, health end oints are grouped below into three categories: 1) feasible to study, 2) possible to study (but might requi 'e a 30 Draft for Review Purposes Do Not Cite or Quote larger sample size, e.g. 500 exposed and 250 unexposed), and 3) not feasible to study using the ease children population, unless additional populations exposed to PFAS-contaminated drinking water are included in the study. Health endpoints feasible to study in children at Pease I Mean difference in lipids (total cholesterol, LDL, HDL, triglycerides) I Mean difference in estimated glomer?ular ?ltration rate a measure of kidney function I Insulin?like growth factor-1 a measure of growth hormone de?ciency) I Overweight/Obesity Health endpoints that might be possible to study in children at Pease (although a larger sample size may be needed) I Mean difference in uric acid, a measure of kidney function I Elevated total cholesterol (hypercholesterolemia) I Elevated uric acid (hyperuricemia) I IQ/neurobehavioral I Thyroid function I Sex hormones I Asthma and atopic dermatitis (immune function) I Rhinitis (stuffy, runny nose) . I Antibody responses to rubella, mumps, and diphtheria vaccines Health endpoints not feasible to study using the Pease children population (to address these health endpoints, populations from other sites with PFAS-contaminated drinking water would need to be included, along with the Pease children population) I Attention deficit/hyperactivity disorder (ADHD) I. Autism spectrum disorder I Delayed puberty I Thyroid disease I Childhood cancers 'To evaluate exposure response relationships, more than two strata are necessary. For some of the candidate outcomes that are listed above as feasible to study or possible to study, the Pease child] population that can be recruited to participate will not be large enough to be split into exposure tr or quartiles and still have sufficient statistical power for comparisons between each of the expOSL strata and a reference (unexposed) stratum. Data analyses similar to those used in the C8 studies could be used. The methods include linear regression of continuous (untransformed and natural log transformed) effect biomarkers on contii fen rtiles re 11.10118 (untransformed and natural log transformed) PFAS serum levels and categorized PFAS serum levels, and logistic regression of categorized effect biomarkers hypercholesterolemia) or disease prevalence on continuous (untransformed and natural log transformed) and categorical PFAS serum 31 . _n Draft for Review Purposes Do Not Cite or Quote levels. Restricted cubic Splines for'linear and logistic regression would be conducted to obtain ?exible, smoothed exposure?response curves. Measured PFAS serum levels would be evaluated. In addition, for PFOS and PFOA (and possibly if an historical reconstruction modeling method becomes available), estimated cumulative serum levels and estimated serum levels during critical vulneral: periods in utero exposure) could be evaluated. - ility In summary, a study limited to the Pease children population will likely have a suf?cient sample size for some of the candidate endpoints ii the comparisons are simply between an exposed and unexposed group. For some of the candidate endpoints, the sample size will be insufficient for even a simple comparison between an exposed an unexposed group. Moreover, for many of the candidate endp Dints, the Pease children population will be of insuf?cient size to split into tertiles or quartiles to evaluate exposure?response trends. Therefore, the inclusion of other sites with PEAS?contaminated drinking water could be considered. Feasibility of an epidemiological study of adults at the Pease Tradeport Compared with NHANES data, serum levels were elevated among participate in the 2015 NH DHHS blood testing program. However, the literature review indicated that very few studies have been conducted that evaluated exposures and adult health effects. PFOS serum level also elevated among the adults who participated in the NH DHHS blood testing program. Although considerably more studies found evaluated PFOS exPosures and adult health effects, there remair gaps and inconsistencies in the ?ndings for liver function, kidney function and kidney disease, th disease and thyroid function, autoimmune diseases and immune function, osteoporosis/osteoar?thr endometriosis, and most cancers. The public health signi?cance of conducting a study of adults at Pease is that the study will be re: to other adult populations exposed to drinking water primarily contaminated with PFOS and PF were . data yroid itis, event x3. A that study might also provide an opportunity for early medical intervention for certain health endpoint might be associated with PFAS exposure but not evaluated in routine physical exams, such as alt in thyroid, liver, and kidney function. A study of adults at Pease would have scienti?c importanc rations because it potentially could help to ?ll critical data gaps mentioned above concerning the health ffects of and PFOS exposures. Based on animal studies, there is biological plausibility that PF exposures could result in alterations of immune function and might have endocrine-disruptive pr perties that could lead to alterations in thyroid function. However, few epidemiological studies have evaluated or PF OS exposures and these health endpoints. Finally, a study of adults at Pease has the potential to provide meaningful and credible results (from the perspective of statistical power) for of the adverse outcomes of interest and would be responsive to community concerns. However, a limited to Pease adults would likely not be suf?ciently large to associate exposures and some adv health outcomes rare diseases such as Speci?c cancers and specific chronic diseases). A. Study hypotheses Based on the literature review, the following hypotheses could be evaluated: 801116 study erse 1. Higher serum levels of PFOA, PFOS, or are associated with higher total cholesterel, low? density lipoprotein and triglycerides, and a higher prevalence of hypercholesterolemia. 32 Draft for Review Purposes Do Not Cite or Quote 2. Higher serum levels of PFOA, PF OS, or are associated with higher'prevalences cf coronary artery disease and hypertension. 3. Higher serum levels of PFOA, PFOS, or are associated with differences in thyroid stimulating hormone (TSH), TT4, and TT3, and a higher prevalence of hypothyroidism. 4. Higher serum levels of PFOA, PFOS, or are associated with a higher level of uric acid and a higher prevalence of hyperuricemia. 5. Higher serum levels of PFOA, PF OS, or are associated with a lower estimated glomerular filtration rate and a higher prevalence of kidney disease. 6. Higher serum levels of PFOA, PF OS, or are associated with higher levels of liver function biomarkers alanine transaminase (ALT), (GGT), and direc bilirubin and a higher prevalence of liver disease. 7. Higher serum levels of PFOA, PFOS, or are associated with higher prevalences of osteoarthritis and osteOporosis. 8. Higher serum levels of PFOA, PF OS, or are associated with a higher prevalence cf endometriosis. - Higher serum levels of PFOA, PFOS, or are associated with higher prevalences of autoimmune diseases such as ulcerative colitis, rheumatoid arthritis, lupus, and multiple sclerosis. Fl- 10. Higher serum levels of PFOA, PF OS, or are associated with differences in serum levels of reactive protein (CRP), and antinuclear antibodies (ANA) and alterations in speci?c cytokines. A study of adults could include the collection of new blood samples to analyze PFAS serum love 3. The blood samples would also be analyzed for lipids and biomarkers of kidney, liver, thyroid, and immune function. A questionnaire could be used to ascertain kidney disease, liver disease, cardiovascular disease, hypertension, thyroid disease, autoimmune diseases, osteoporosis, osteoarthritis, pregnar cy? induced hypertension, and endometriosis. Diseases ascertained via questionnaire would be con?rmed using medical records B. Study population According to the census, Portsmouth has 21,530 residents. About 67.5 are adults aged 19?64 years and another 15.9% are aged 65 years and older. This would mean that there are about 14,500 adu ts aged 18?64 years and about 3,400 aged 65 years and over. Although the actual number is unknown, some of the workers at the Pease Tradeport live in New Hampshire towns other than Portsmouth or in the bordering states of Massachusetts and Maine. The Pease Tradeport has a workforce of >9,000 persons. In the 2015 blood testing program at Pease, 1,182 adults aged 218 years participated. Table 5 pro vides PFAS serum data for the 1,190 participants in the 2015 Pease blood testing program who will be age 218 years in 2018. 33 Draft for Review Purposes Do Not Cite or Quote C. Recruitment and consent As stated previously, the NH DHHS Pease blood testing program?s consent form was strictly limli use of the participant?s blood sample for PFAS analyses gm. The participant also consented to complete a brief questionnaire atthe time of blood draw concerning demographics, time at Pease Tradeport, whether the worker was a fire?ghter, and consumption of drinking water. The consent ted to form did not mention the use of the blood sample for research purposes or the possibility of re?contact ng the participant for future studies. Therefore, the blood samples were not stored for future use, and ATSDR cannot directly contact the participants in the Pease blood testing program to recruit them for a study. Adults would need to sign a new consent form to participate. The consent form would request a blood sample (about 35 mL or 1.2 ounces) from the adult for tie analyses of PFASs and the effect biomarkers. (Note: 35 mL was the maximum amount of blood obtained from adults in the C8 studies.) The consent form could also ask the participant to complete a . questionnaire covering demographics, water consumption, dates and length of time working at P6 ase, occupational history, lifestyle and health behaviors, diseases diagnosed by a physician or other he provider, and provider contact information. alth To recruit adult study participants, NH DHHS would have to contact those who participated in the 2015 blood testing program. Another approach is to work with the Tenants Association at Pease (TAP). and the Pease International Development Authority (PDA) to contact firms on their mailing lists. TAP sends newsletters and email notices to subscribing ?rms at the Tradeport. The FDA list, with mailing addresses and email addresses of all ?rms at the Pease Tradeport, was provided to ATSDR to hel . recruit members to the Pease CAP. This list could be used to conduct outreach to recruit adult study participants. Other methods of outreach include contacting community groups and the media. D. Biomarkers of effect The following biomarkers would be analyzed in the serum: - Total cholesterol, low density lipoprotein, high density lipoprotein, total triglycerides - - Thyroxine (T4), T3, thyroid stimulating hormone (TSH) I Uric acid, creatin'ine 0' Alanine transaminase (ALT), (GGT) and direct bilirubin I Immunoglobulin and reactive protein, and antinuclear antibodie (ANA), and alterations in specific cytokines. E. Exposure assessment Exposure assessment could be based on the serum PFAS levels obtained in the study supplement: the serum PFAS levels for those who participated in the 2015 NH DI-IHS Pease blood testing pro; Using historical estimates of the PFAS contaminant levels in the drinking. water at the Pease Traj (based on water modeling methods), PBPK modeling can be used to estimate historical serum le PFOA and FPO S, combining information from the questionnaire on water consumption and dates ad by gram. eport els of and length of time employed at Pease Tradeport, and information on background PFAS serum levels from NHANES and from a comparison group unexposed to PFAS-contaminated drinking water or occupationally exposed to PFAS or Serum levels from the 2015 NH DHI-IS Pease blood te 34' sting Draft for Review Purposes Do Not Cite or Quote program and serum levels obtained for this study would be used to calibrate the PBPK models. It feasible, historical estimates of serum can be based on historical estimates for serum PFC PFOS, because serum levels and PFOS were highly correlated among the Pease adults participated in the 2015 blood testing program (Pearson correlation coef?cient 0.73). F. Sample size considerations A and who A key problem for an adult study at Pease will be identifying an appropriate comparison pOpulation of workers from the Portsmouth area with similar occupations as the Pease workforce and who were not exposed to PEAS-contaminated drinking water or occupationally exposed to PFAS or Another key problem will be recruiting a suf?cient number of participants to achieve reasonable statistica and precision of effect estimates. . power Studies conducted of the adult CS population included tens of thousands of participants. For example, studies of thyroid disease [Winquist 2014a], cardiovascular disease and lipids [Winquist 2014b], ikidney disease [Dhingra 2016], and liver function [Darrow 2016] included 28,541 community members and 3,713 workers at the DuPont plant. Smaller studies using NHANES data Wen [2013], Webster [2016], Shankar [2011], Gleason [2015], and Lin [2010]) had sample sizes of 1,181?4,333 adults Table 7a indicates the minimum detectable effects for a study that included 1,5 00 participants per stratum. For a simple comparison between exposed and unexposed, this would require a total of 3 ,000 participants, 1,500 exposed and 1,500 unexposed. If the study population were divided into quartiles of PFAS serum levels, with the first quartile being the reference exposure level, then this would result in atotal sample size of 6,000 persons 4,500 exposed and 1,500 unexposed). Four combination sof type 1 error (or error) and type 2 error error) are used in the table. A type 1 error of 0.05 to a two-tailed hypothesis test using a p?value cutoff of 0.05 to determine statistical significance, or using a 95% con?dence interval. A type 1 error of 0.10 corresPonds to a one-tail hypothesis test using a p-value cutoff of 0.05 to determine statistical signi?cance, or using a 90% con?dence interval. A type 2 errors of 0.05, 0.10, and 0.20 correspond to statistical power of 95%, 90% and 80%, respectively. Another possible approach to sample size calculations that might be informative would be to ?x minimum detectable effects to the effect sizes observed in previous studies for similar levels of 6 exposure, select the type 1 and type 2 error rates, and allow the sample size to ??oat? instead oft 6 minimum detectable'effect. However, this approach is problematic because there are few studies PFAS exposures and the adult outcomes being considered for the Pease adult study. In some inst nces, studies evaluating similar PFAS serum levels obtained very different effect sizes fer the same on come. In other instances, a study with a lower PEAS serum level obtained a higher effect size for an out - ome than a study with a higher PFAS serum level. Moreover, there are no studies of adults exposed to drinking water contamination as a result use. Therefore, there is much uncertainty about effect size for each health?related endpoint that would be expected for PFAS serum levels observe PFAS the among the Pease adults. With these caveats, the following sample size per stratum calculations use the ?ndings from studiesof PFAS-exposed adults. Table 7b provides a summary of the sample size considerations for each health~related endpoint. 35 Draft for Review Purposes Do Not Cite or Quote Lipids In the lipid study conducted of the CS adult population [Steenland 2009], PFOS serum levels corresponding to the PFOS serum levels among adults who participated in the Pease blood testing program would result in a 3?4 mg/dL change in total cholesterol and in LDL. Table 7a indicates that detecting a difference of about 4 mg/dL in total cholesterol would require a sample size of about 1,500 per stratum. To detect a difference of 3 mg/dL would require a larger sample size. For LDL, a sample size of 1,500 per stratum would be suf?cient for mean differences in the 3?4 mg/dL range. The predicted increase in total cholesterol at the highest decile for PFOA and PFOS in the C8 stu 11?12 mg/dL. To detect a difference of 11 mg/dL, a sample size in the range of 200?300 per stra -ywas I?l?l would probably be suf?cient. However, the highest decile for PFOA and PFOS in the C8 population is considerably higher than the serum levels observed for the adult participants in the Pease 2015 blood testing. In a C8 study [Steenland 2009] and a Canadian study [Fisher 2013], ORs in the range of 1.35 1.6 were observed for hypercholesterolemia. Although PFAS serum levels were higher in the C8 populatic the Pease population, the PFAS serum levels in the Canadian study were lower than in the Pease population. Table 7a indicates that ORs in this range for hypercholesterolemia can be detected wi1 suf?cient statistical power with a sample size of 1,5 00 per stratum. Kidney disease/function. and uric acid than In the C8 study of chronic kidney disease [Dhingra 2016], the highest hazard ratio (HR) was observed for the lowest quintile of exposure (compared with the reference level) and was equal to 1.36. To detect this HR, given the low prevalence of the disease (approximately would require a sample size of at least 8,600 per stratum. In the C8 study of uric acid [Steenland 2010], serum PFOS levels that correspond to those observ- (1 among the adult participants in the Pease blood testing program resulted in a difference of 0.14 /dL. To detect this difference would require a sample size in the range of 1,600?2,100 per stratum. The largest differences in uric acid observed in this study was 0.28 mg/dL for PFOA serum levels 2188.7 ng/mL and 0.22 mg/dL for PFOS serum levels 240.5 ng/mL. These serum levels are considerably higher than those observed for the adults at Pease. Based on sample size calculations a uric acid difference of 0.28 mg/dL could 'be detected with-reasonable statistical power and a sample size in the range of 500?6 00 per stratum. Table 7a indicates that much lower differences in uric acid coul detected with reasonable statistical power using a sample size of 1,500 per stratum. In the C8 study, the OR for hyperuricemia for PF OA serum levels similar to those at Pease equale For the top quintile of serum PFOA in the CS population, the OR was 1.47. Based on sample size calculations, a sample size in the range of 450?600 would be sufficient to detect an OR of 1.47 with reasonable statistical power. However, the top quintile serum PFOA level in the C8 study was considerably higher than observed in the Pease population. dbe 1.02. In a study using NHANES data [Shankar 2011], a change in uric acid of 0.40 mg/dL was observed for serum PFOA levels similar to those observed for Pease. Based on sample size calculations, this difference could be detected with reasonable statistical power using a sample size of about 300 per 36 Draft for Review Purposes Do Not Cite or Quote stratum. For hyperuricemia, an OR of 1.90 was observed for serum PFOA levels similar to Pease. on sample size calculations, an OR of 1.90 can be detected with reasonable statistical power using a sample size of about 240 per stratum. Liver function For liver function, to detect the very subtle changes observed in the (38 studies [Gallo 2012; Darrow Based 2016] would require a sample size as large as the C8 study itself. The same is true for liver disease. In the Darrow 2016 study, the highest OR observed was 1.19 for the 2nd quintile of serum PFOA. Tb quintile of serum PF 0A in the C8 study is higher than the serum levels at Pease. To detect an OR 1.19 would require a sample size of at least 20,000 per stratum. A study using NHANES data [Gleason 2015] was able to detect associations with uric acid and liver 3 2nd of function biomarlcers at serum PFAS levels similar to those observed at Pease and with a total sample size of 4,333 persons. This study evaluated quartiles of serum PFAS, so each stratum had a sample size of about 1,083 persons. Another study that used NHANES data [Lin 2010] also was able to detect associations with liver function biomarkers with a total sample size of 2,216 persons. This study a evaluated quartiles, so each stratum had a sample size of about 554 persons. Cardiovascular disease 130 The C8 study that evaluated coronary artery, disease did not find an elevation in risk [Winquist 2014b]. However, a study that used NHANES data [Shankar 2012] obtained an OR of 2.01 for cardiovascular disease for the quartile PFOA serum levels. These PFOA serum levels, 26 ng/mL, would correspond to the 5th quintile of PF OA serum levels among Pease adults. The prevalence of cardiovascular disease in this study was 13%. To detect an OR of 2.01, a sample size of about 250/stratum would probably be suf?cient. I Hypertension One study evaluated hypertension in a community population and observed an OR <1.0 [Winquisr 2014b]. The prevalence of hypertension in this study was about 38%. With a sample size of 1,50(l per stratum and a prevalence of 38%, ORs between 1.21 and 1.31 could be detected with suf?cient statistical power. Thyroid disease/function For thyroid disease, the CS study evaluated self-reported disease and self?reported disease that was confirmed by medical records [Winquist 2014a]. For serum PFOA levels similar to those at Pease hazard ratios were in'the range of 1.2?1.3. For all self?reported thyroid disease (prevalence 11.3 sample size of about 2,100 per stratum would probably be suf?cient to detect a hazard ratio of 1.3 prevalence for confirmed disease was so that a sample size of about 3,500 per stratum woul probably be necessary to detect an HR of 1.3. A study that used NHANES data evaluated thyroid disease [Melzer 2010]. For con?rmed thyroid disease (prevalence 2.4% in this study), the ORs were above 1.1 for PP OS and PFOA se levels similar to those at Pease. To detect this OR would require a sample size equivalent to the CE 37 the M3), a The rum 3 Draft for Review Purposes -- Do Not Cite or Quote population. The highest OR observed was 189 among men in the top quartile of PFOS and PF 0A. To detect this odds ratio, a sample size of about 1,400 per stratum would probably be suf?cient. The C8 study that evaluated thyroid function biomarkers [Knox 2011] observed very subtle changes that would require a study of equivalent size (52,296) to detect associations with suf?cient statistical power. On the other hand, a study that used NHANES data [Wen 2013] to evaluate thyroid function observed larger changes that couldbe detected with a total sample size of <1,200 (or <3 00 per quartile stratum). Immune function and autoimmune diseases Only one published study [Stein 2016b] evaluated serum immune biomarlcers at baseline cross- sectionally) and PFAS serum levels. The study evaluated deridenti?ed archived blood samples 75 adults aged 21-49. Given the very small sample size, this should be considered a pilot study. The serum levels in this study were considerably lower than in the Pease adult population and a few positive ?ndings were observed but the confidence intervals for these ?ndings were extremely wide indicating little precision and a high degree of uncertainty in the effect estimates. Given the strong animal evidence of effects on the immune system from PFAS exposures 2016], a cross-sectional . 7 evaluation of PFAS serum levels and immune biomarkers' in a Pease adult study could provide important information on the effects of PFAS exposures on immune function in humans. The prevalences of ulcerative colitis, rheumatoid arthritis, lupus, and multiple sclerosis in a (38 study [Steenland 2013] were 5 As indicated in Table 7a, ORs 2.0 cannot be detected with suf?cient statistical power for these endpoints with a sample size of 1,5 00 per stratum. For lupus and multiple sclerosis, ORs <3.5 cannot be detected with sufficient statistical power with a sample size of 1,500 per stratum. osteoarthritis and Osteoporosis Two studies evaluated osteoarthritis. in a C8 study [Innes 2011], an OR of about. 1 .4 was observed for serum PF DA levels considerably higher than those at Pease. However, in an NHANES study [Uhl 2013], an OR of 1.5 was observed for serum PFOA levels similar to those at Pease. Table 7a indicates that ORs in the range of 1.4 1.6 can be detected with sufficient statistical power with a sample Size of 1,500 per stratum. An NHANES study evaluated osteoporosis in women [Khalil 2016] and obtained an 10 for serum levels lower than those at Pease. With 750 women per stratum, an OR of 1.58 can be detected with suf?cient statistical power. Endometriosis An NHANES study [Campbell 2016] obtained ORs of 1.47 and 2.86 for serum and respectively. The serum levels for these two PFAS were similar to those in the Pease pOpulation. Table 7a indicates that with a sample size of 750 per stratum, ORs in the range of 1.55 1.85 can be detected with sufficient statistical power. 38 Draft for Review Purposes Do Not Cite or Quote Pregnancy-induced hypertension Several C8 studies evaluated pregnancy~induced hypertension. One study observed an OR of 1.6 for serum PF OS. However, the PFOS serum levels in the C8 study were higher than those at Pease. Table 7a indicates that ORs in the range of 1.6 1.9 can be detected with sufficient statistical power for a sample size of 750 pregnancies per stratum. Cancer incidence For kidney cancer, Table 7a indicates that ORs <3.8 cannot be detected with suf?cient statistical power with a sample size of 1,5 00 per stratum. Even for a cancer with a much higher prevalence than dney cancer, prostate cancer, ORs 2.0 cannot be detected with suf?cient statistical power with a sample size of 750 men per stratum. F. Conclusion A sample size of about 1,500 per stratum (or atotal sample size of 6,000 if quartiles are evaluated) would have suf?cient statistical power to detect several of the health-related endpoints, as indicated by Tables 7a and 7b. For some endpoints, such as mean difference in uric acid, hyperuricemia, and cardiovascular disease, smaller sample sizes of about 500 per stratum might be sufficient. For other endpoints, such as ulcerative colitis, rheumatoid arthritis, and chronic kidney and liver disease, sample sizes larger than 1,500 per stratum would be necessary. Based on the sample size calculations that assume a sample size of 1,500 adults employed at the Pease Tradeport and 1,500 adults from the Portsmouth area who were never employed at the Pease Tradeport, and assuming a simple comparison of exposed versus unexposed, health endpoints are grouped below into three categories: 1) feasib to study, 2) possible to study (but might require a larger sample size from the Pease population), and 3) not feasible to study using the Pease adult population unless additional populations exposed to PFAS- contaminated drinking water are included in the study. Health endpoints feasible to study in adults at Pease - Mean difference in lipids (total cholesterol, LDL, HDL, triglycerides) - Elevated total cholesterol (hypercholesterolemia) - Mean difference in uric acid, a measure of kidney function 0 Elevated uric acid (hyperuricerni?a) - Thyroid disease (uncon?rmed) - Cardiovascular disease 0 Hypertension - Osteoarthritis and osteoporosis 0 Mean differences in serum immunoglobin (lgA, and C-reactive protein (an indicator of in?ammation); increase in antinuclear antibodies (an indicator of autoimmune reaction); alterations in speci?c cytokines 39 Draft for Review Purposes Do Not Cite or Quote Health endpoints that may be possible to studv in adults at Pease (although a larger sample size may be needed) 0 Liver function - Thyroid disease (con?rmed) - Thyroid function - - Endometriosis Pregnancy-induced hypertension Health endpoints not feasible to study using the Pease adult population (in order to address th 686 health endpoints, populations from other sites with PFAS-contamina'ted drinking water would nee to be included along with the Pease adult population) 0 Liver disease 0- Kidney disease - Ulcerative colitis - Rheumatoid arthritis - Lupus - Multiple sclerosis - Kidney cancer (and other adult cancers) To evaluate exposure-response trends, the study participants would need to be split into tertiles or quartiles based on their serum PFAS levels. For some of the candidate health endpoints that are liLted above as feasible to study or possible to study, the Pease adult population that can be recruited to statistical power fer comparisons between each of the exposure strata and a reference (unexposed, stratum. For example, if the study population is to be divided into quartiles, and assuming that a 3 size of 1,500 per stratum would be suf?cient for many of the endpoints of interest, then it would l: participate will not be large enough to be split into exposure tertiles or quartiles and still have sufficient mple necessary to recruit 4,500 adults (aged 218 years at the start of the study) from the Pease workforce and a representative group employed in similar occupations as the Pease workforce) of 1,500 ad from the Portsmouth area who were not exposed at Pease. Data analyses similar to those used in the C8 studies would be used. The methods include linear Its regression of continuous (untransformed and natural log-transformed) effect biomarkers on continuous (untransformed and natural log-transformed) PFAS serum leirels and categorized PFAS serum lev and logistic regression of categorized effect biomarkers hypercholesterolemia) or disease prevalence on continuous (untransformed and natural log?transformed) and categorical PFAS serum els; levels. Restricted cubic splines for linear and logistic regression would be conducted to obtain ?exible, smoothed exposure-response curves. Measured PFAS serum levels Would be evaluated. In additio PFOS and PFOA (and possibly if an historical reconstruction modeling method becomes available), estimated cumulative serum levels would be evaluated. In summary, a study limited to the Pease adult population could likely have a sufficient sample sir. some of the candidate endpoints the comparisons are-simply between an exposed and unexposed group. Recruitment of at least 1,500 adults from Pease should be feasible, given that the 2015 blor testing program at Pease was able to recruit at least 1,182 adults aged >18 years who worked at PE 40 n, for for )Cl age. Draft for Review Purposes Do Not Cite or Quote However, a study limited to the Pease adult pOpulation might not have a sufficient sample size to evaluate exposure?response relationships. Moreover, a study limited to the Pease worker population might not have suf?cient variability in serum PFAS levels to evaluate exposure?response trends . effectively. Suf?cient variability in PFAS serum levels might be achieved by including other populations withresidential exposures to PFAS?contaminated drinking water. Feasibility of an epidemiological study of former military service and civrlian workers at the former Pease Air Force base Drinking water contamination at a military base involves potential residential eXposures to those living and training at the base and potential exposures to those working at the base. At the former Pease Air Force Base, starting in the 1970s, foam was used for ?re training and to extinguish flammable liquid ?res. The PFAS contamination in the Haven well water supply likely occurred sometime during the period from the start of usage and the closing of the base and would have resulted in exposures to those living and working at the base. To evaluate the incidence and mortality of speci?c cancers, a large population of adults would ne ad to be followed for a- suf?cient number of years to account for the long induction periods of most cancers and to have sufficient statistical power. For example, the Camp'Lejeune mortality study of US. Marines and Navy personnel followed a cohort of 154,932 from 1979 to 2008 for a total of over-4 million person? years [Bove 2014]. To evaluate cancer incidence for the Camp Lej eune cohert, ATSDR will conduct follow-up using state and federal cancer registries for the period 1996?201 6 (1996 is the earliest ate that >90% of the state registries were in operation), for a total of over 3 million person-years. For the civilian worker cohort at Camp Lej eune, 8,085 workers will be followed over the period 1996?2016 for cancer incidence, for a total of 121,875 person-years. This is similar in size to a study of cancer incidence among workers at a PFAS manufacturing plant [Raleigh 2014]. A recent study of ?re?ghters followed a pooled cohort of29,993 from San Francisco, Chicago, or Philadelphia from 1985 through 2009, for a total of 403,1 52 person?years [Daniels 2014]. A C8 study of cancer incidence that relied on self?repelted cancers that were confirmed by medical records and cancer registry review included 32,254 who contributed over 1 million person-years of follow?up [Barry 2013]. In October 1989, 3,465 military personnel were assigned to Pease Air Force Base, accompanied by 4,746 dependents. The Air Force estimates that 537 civilian employees were employed on base at that time 1990]. From 1970 to 1990, an average of 3,000 personnel and their families were assigned to the base at any one time. Before 1970, the base supported a maximum of 5,000 personnel 1994]. One important consideration about including Pease service personnel and civilian workers 'na from the Haven well during some of the years the base operated. Service personnel and civilian rkers cancer incidence and mortality study is that drinking water at the base was also contaminated by GEE stationed at the base before 1986 should not be included because of this contamination. Because base closed by 1991, the number of service personnel and civilian workers at Pease AFB that could be included in a study would be insuf?cient to evaluate cancers with sufficient statistical power. Because of the relatively small numbers of personnel assigned to Pease Air Force Base, we conclude that it is not feasible to conduct a study of cancer incidence and mortality that is lit to the Pease military service personnel and civilian worker cohorts stationed at the base fron 41 nited 1 1986 Draft for Review Purposes Do Not Cite or Quote onward. F01 a study to be feasible, it would require a larger population size, for example, by incl ding service personnel and civilian workers from other military bases with contaminated drinki water as a result of the use of Exposuies to other drinking water contaminants, such as E, other chlorinated o1gan1c chemicals, and benzene, must also be taken into account when conside ng candidate military bases and de?ning the cohorts. Cohorts of service personnel and civilian workers can be identi?ed at military bases from person el data maintained at the Defense Manpower Data Center. Personnel data are available from 1971, altho gh information on military unit, which is needed to determine the base where the individual was stat oned, does not begin until the second quarter of 1975. For civilian workers, data are available starting in last quarter of 1972, with data missing for the ?rst quarter of 1973. The data contain the location 0 the the workplace (codes for state, city, and ZIP code). The Defense Manpower Data Center data contain: Social Security number, name, date of birth, and sex to facilitate follow-up. Military service personnel constitute a highly mobile population afte1 their tours of duty are com; leted. For a mortality study, this 15 not a problem, because the 13 available to obtain information on causes of death. However, there IS no national cancer 1egistry to ascertain cancer incidence. Therefore, a study of military service personnel and civilian workers would require gaining the participation of all or most of the state cancer registries and the Department of Veterans Affairs Central Cancer Registry CCR). The Camp Lej eune Cancer Incidence? Study is one model for such a study. This study is attempti to recruit at least two?thirds of the state cancer registries and VACCR to cover >90% of the Camp ejeune and Camp Pendleton cohorts. The study will send the personal identi?ers for each cohort member to each registry for matching with the registry?s data. For any matches that occur, the registry will send to ATSDR the cancer information that is linked to personal identifier Social Security number or a unique identification number linked to the Social Security number). This will allow assessment of exposures and other covariates and cancers at the individual level. The most appropriate military sites for inclusion would be those with water systems that are not complex so that simple mixing models can be used to estimate contaminant levels throughout the distribution system. In addition, candidate sites should have information on the history of use at the base including major incidents such as spills, tires, etc. Other study designs and health-related endpoints 1. Adverse birth outcomes To evaluate adverse birth outcomes such as SGA, preterm birth, and specific congenital malfonnations with suf?cient statistical power, several thousand births should be studied. For example, to detect of 1.5 for SGA (5th percentile) with 80% power would require 1,775 births per stratum. For SGA an OR (1 01h percentile) and preterm birth, with 80% powerdetected with a sample size of about 960?990 births per stratum. For rare birth defects, such as neural tube defects, to detect an OR of 2.5 with 80% power would require a sample size of about 22,000 births per stratum. For oral clefts, tc an OR of 2.0 would require about 15,000 births per stratum. ete ct Birth weight, SGA and preterm birth can be evaluated using birth certi?cate data. For birth defects, a population-based registry must be used to identify cases. 42 Draft for Review Purposes Do Not Cite or Quote An adve1se birth outcome study is not feasible at Pease because them were too few births to mothe who worked at the Tradeport during their pregnancy. The most app1opriate candidate populations study of adverse birth outcomes would be one or more large municipalities with residential exposr rs for a res to PFAS- contaminated d1 1nk1ng water where a simple mixing model could be used to estimate contaminant levels thioughout the d1st11but10n system, i. e. ,a system that 1s not complex but instead has relative uniform contaminant levels throughout the distribution system. 2. Registry Creating a registry of exposed children and adults at the Pease Tradeport involves following the he status over a period of time and is similar to an epidemiological, longitudinal study of an exposed cohort. The difference is that an epidemiological study would usually include a comparison, unexr cohort. A registry, like a longitudinal epidemiological study, can be resource-intensive. A decision would also have to be made concerning the length of the follow-up. As in any longitudinal effort, individuals will drOp out over time, resulting in interpretation dif?culties selection bias read from loss to follow-up). In any event, before a registry or longitudinal study can be contemplated, initial cross?sectional study must ?rst be conducted, similar to the children?s study and adult study discussed above. 3. Multi?site studies The results of sample size calculations indicated that the exposed populations at the Pease Tradepc the former Pease Air Force Base were of insuf?cient size for some of the health-related endpoints interest to the community. Moreover, Pease CAP members have expressed interest in linking the 1y alth osed ting an rt and of ease communities with other communities that have been exposed to PFAS-contaminated drinking water. A national database exists that can be used to identify other communities with PFAS-contaminated drinking water. Data on PFAS contamination of public drinking water supplies are available for la systems (serving >10, 000 1etail customers) and a small sample of small systems 800 or 0.5% total of 144,165 systems serving <10, 000 retail custome1s) via the Third Unregulated Contaminani Monitoring Rule database maintained by the EPA EPA 2016b]. UCMR-3 monitoring for PFAS is required at the entry point to the distribution system for each we at any interconnection that is in operation. Water utilities had to sample twice during a 12-month from 2013?201 5 with sampling events occurring 5?7 months apart. The UCMR dataset contains sampling data from January 2,2013 through March 1,2016. Table A1 in the Appendix lists the at lanked by the maximum level of combined PFOS and detected In the system. The h1ghest was detected in the system serving the Mariana Islands. Among the U. S. water systems, the top 10 systems for combined PFOS and were Artesian Water Company 1n Delaware; Security We System in Colorado Springs, Horsham and Warminster systems in Oatman Wa Company in Arizona; Issaquah Water System in Washington; Hyannis Water System' 1n Massachu Suffolk County Water Authority in New York; Warrington Township Water 1n and United Water 1n which serves various municipalities. Although the UCMR database can be used to identify potential sites for further consideration for studies, it has several limitations. First, most small systems are not included in the database. Seco data represent levels of contamination at the entry points to the distribution system of the water ut1 43 "ge of a ll and eriod lities evel ter ter setts; ealth d, the lity Draft for Review Purposes Do Not Cite or Quote g. ., contaminant levels 1n a supply well) and genei ally do not represent the levels of contamination reaching particular residences served by the utiliw. To estimate the population receiving contamir ated drinking water and the levels of 1n their drinking water, the UCMR data must be supplemented with information on the con?guration and opeiation of the utility? system- For a system that miXe its sources of wate1 before to entering the distribution system, a simple mixing model can be used to all estimate the contaminant levels' 1n the drinking water serving the residences by taking into account the contaminant levels 1n each sou1 ce and the contribution of each source to the total supply. This' 15 the situation at the Pease Tr,adeport where water from each of the supply wells 1s mixed at the plant before entering the distribution system. However, many utilities have more complex system which each of the supply wells (or surface water sources) primarily serve particular areas of the 111' distribution system. For these systems, additional information is needed (for example, on the operation of the supply wells, tank levels, and the water demand in each area of the distribution. system), and complex modeling methods must be used. Conclusions The ability of a study of the Pease population to provide useful information will depend to a great extent on the successof recruiting suf?cient number of study participants. The feasibility assessment concluded that it is possible to evaluate some health?related endpoints if a sufficient number of oh1 ldren and adults from the Pease population participate. Other health?related endpoints would require larger numbers of exposed individuals and would require the inclusion of pOpulations from other sites who were exposed to PEAS-contaminated drinking water. The feasibility assessment concluded that a t??rd study design, a mortality and cancer incidence study of former military service and civilian worke personnel, would not be feasible solely with thepOpulation at Pease. The feasibility assessment is still a draft. It will be ?nalized once the Pease Community Assistance Panel (CAP) and the larger Pease Tradeport community have the opportunity to review and make comments on the assessment. ATSDR will then revise the assessment based on the comments received. The feasibility of successfully evaluating particular health?related endpoints (or effect biomarkers) could change depending on ?nal study design and goals. 44 Draft for Review Purpo'ses Do Not Cite or Quote Table 3. Summary of the PFAS literature on adults. PFOS PFOA Cancer Prostate Bladder Colorectal I Breast I I Pancreatic I Testicular Kidney Thyroid Liver i? Leukemia non?Hodgkin Multiple myeloma Ovarian Other diseases Kidney disease/kidney function Hyperuricemia I Liver disease/liver function Cardiovascular Disease, hypertension, hypercholesterolemia Thyroid disease/function Autoimmune diseases Osteoarthritis, osteOporosis and bone mineral density Immune response Reproductive outcomes - - One or more studies suggesting increased risk of an adverse outcome OR or RR: 1.20) no studies were conducted (for liver cancer and PFOS, and multiple myeloma and PFOA, there were too few deaths (52) to evaluate). inconclusive the ?ndings have not suggested an increased risk an OR or RR <1 .20) 61 Draft for Review Purposes ?Do Not Cite or Quote Table 4. Summary of the PFAS literature on children. PFOS PFOA Adverse birth outcomes - - Lipids I Thyroid function Thyroid disease I ?t Uric acid a Sex hormones Delay in reaching puberty I Neurobehavioral outcomes Immune function Hypertension I I Adiposity/BMI/Overweight One or more studies suggesting increased risk of an adverse outcome OR or RR 2 1.20) no studies were conducted. inconclusive the ?ndings have not suggested an increased risk an OR or <1.20) Note: adverse birth outcomes are not included in this table because these outcomes are not feasible to study at Pease. Although the number of children potentially exposed to the PEAS?contaminated drinking water while attending daycare at the Pease Tradeport can be estimated, there. is a lack of informatii- on the number of children potentially exposed in utero to the PFAS?contaminated drinking water becguse their mothers were employed at the Pease Tradeport during the pregnancy. To evaluate adverse outcomes with suf?cient statistical power would require the inclusion of several hundreds of expo sed births. 62 uu? . - Draft for Review Purposes Do Not Cite or Quote Table 6a. Minimum detectable effects for a Pease children study with 350 exposed and 175 unexposed.?k - Endpoint or and B: ;05 at .05, [3:20 or and 13 .10 on .10, [3=.20 Total cholesterol 9.8 mg/dL 7.6 mg/dL 8.0 mg/dL 6.8 mg/dL (mean difference) Hypercholesterolemia OR 2.00 OR 1.73 OR 1.77 OR =1 .63 Hyperuricemia OR 2.30 OR 1.96 OR 2.00 . OR 1.83 Urio acid (mean 0.40 mg/dL 0.31 mg/dL 0.33 mg/dL 0.28 mg/dL difference) (mean 8.0 6.2 6.5 5.5 difference)ll OR 2.47 OR 2.09 OR =,2.13 OR 1.94 ADHD rnedsll 3.50 - 2.80 Atopic dermatitis . OR 2.49 OR 2.10 OR 2.15 OR 1.95 Asthma OR 2.56 OR 2.16 OR 2.21 OR 2.00 Rhinitis OR 2.08 OR 1.79 OR 1.83 OR 1.69 Hypertension OR 2.12 OR 1.80 OR 1.85 OR 1.69 Overweight/Obese OR 2.00 OR 1.72 OR 1.76 OR 1.62 Table 613. Minimum detectable effects for a Peasechildren study With 500 exposed and 250 unexposed.* Endpoint on and .05 .05, [3=.20 0L and .10 or .10, [i=.20 Total cholesterol 8.2 mg/dL 6.4 mg/dL 6.7 mg/dL 5.7 mg/dL (mean difference) Hypercholesterolemia OR 1.78 OR 1.57 OR 1.60 OR =1 .50 Hyperuricemia OR 2.04 OR 1.75 OR 1.79 OR 1.65 Uric acid (mean 0.34 mg/dL 0.26 mg/dL 0.27 mg/dL 0.23 mg/dL difference) ?(mean 6.7 5.2 . 5 .4 4.6 difference)it 1.85 1.90 ADHD medsll OR 2.98 OR 2.40 OR 2.48 OR 2.19 Atopic dermatitis OR 2.20 OR 1.86 - OR 1.91 OR 1 .74 - Asthma OR 2.26 OR 1.91 1.78 Rhinitis OR 1.85 OR 1.62 OR 1.65 OR 1.54 Hypertension OR 1.88 OR 1.64 OR 1.68 OR 1.56 Ovemeight/Obese OR 1.79 OR 1.58 OR 1.61 OR 1.50 Some health?related endpoints are not included in the table because there was insuf?cient information to calculate minimum detectable effects. For sex hormones, insulin-like growth factor 1,'and th function, see the appendix for a description of the assumptions used in the sample size calculation the resulting calculations. ?1 mL/min/1.73 m2 _64 yroid and Draft for Review Purposes Do Not Cite or Quote- 1? The prevalence of an ADHD diagnosis reported by a study participant in the CS study (Stein 201 12.4%. In this study, the prevalence of an ADHD diagnosis reported by a study participant who a? reported currently using a medication commonly used to treat ADI-ID was 65 1) was so Table 60. Summary of information used to categorize the feasibility 'of studying health-related endpoints for a Pease children study. Health?related Endpoint Minimum Detectable Effect Size: 350 exposed, 175 unexposed Other Sample Size Considerations Conclusion Lipids (total cholesterol) 6.8 mg/dL A Taiwan study (Zeng 2015) obtained mean differences of 11?12 mg/dL for total cholesterol and low density lipoprotein at PF 0A serum levels similar to Pease. Feasible to study at Pease Estimated glomerular ?ltration rate R) 5.5 mL/min/l.73 m2 A NHANES study (Kataria 2015) observed a mean difference of 6.6 mL/min/ 1.73 In2 for PFOA serum levels similar to those at Pease. For PFOS, the mean difference was 7.2 mL/min/1.73 m2 . Feasible to study at Pease Insulin?like growth hormone?1 See appendix for sample size calculations and assumptions required for the calculations. A CS study (Lopez?Espinosa 2016) observed a reduction of IGF -1 for serum levels similar to those at Pease that could be detected with suf?cient power by. a sample size of 350 exposed and 175 unexposed. Feasible to study at Pease. Overweight/ Obesity A Faroes study (Karlsen 2016) observed and OR of 1.88 for PFOA serum levels below those at Pease. This OR could be detected with a sample size of 350 exposed and 175 unexposed children. Feasible to study at Pease. Hypercholesterolemia ANHANES study (Geiger-2014) obtained 0R3 of 1.49 and 1.35 for serum PFOA and PF OS levels similar to those at Pease. To detect an OR of 1.49 With 80% power requires a minimum of 540 exposed and 270 unexposed Possible to study at Pease although a sample size of at least 500 exposed and 250 unexposed would be necessary (see table 6b). Uric acid 0.28 mg/dL A NHANES study (Kataria 2015) obtained a mean difference of 0.21 mg/dL for PFOA serum levels similar . to Pease. However, for PFOS, the mean difference was 0.05 mg/dL. Possible to study at Pease although a larger sample size than 500 exposed and 250 unexposed would be necessary. 66 Draft for Review Purposes Do Not Cite or Quote Health-related Endpoint Minimum Detectable Effect Size Other Sample Size Considerations Conclusion Hyperuricemia A Taiwan study (Qin 2016) obtained an OR of 1.65 for serum levels much lower than at Pease. For PFQA serum levels lower than at Pease, an OR of 2.2 was obtained. Possible to study at Pease although a sample size of at least 500 exposed and 250 exposed may be necessary to evaluate the effect of serum (For serum PFOA, the Pease sample size of 350 exposed and 175 unexposed may be suf?cient) IQ 3 point mean difference A Taiwan study (Wang 2015) obtained IQ mean differences of 52' points for PFOS serum levels higher than at Pease. A C8 study (Stein 2013) did not find a decrease in IQ with PFOA exposure and did not evaluate PFOS or Possible to study at Pease although a sample size larger than 500 exposed and 250 unexposed would be necessary. Neurobehavioral Could not be calculated due to insufficient information Some studies had sample sizes achievable at Pease while others had much larger sample sizes. The effects observed were not large an OR for learning problems was 1.2 for and lower for the other PFAS, and ORs for hyperactivity and coordination problems were <15 for each of the PFAS). The few studies that have been conducted evaluated different neurobehavioral tests. Similar conclusion as for IQ: Possible to study at Pease although a sample size larger than 500 exposed and 25 Ounexposed would be necessary. Sex hormones See appendix for sample size calculations and assumptions required for the calculations. At PFOS serum levels much higher than at Pease, a C8 study (Lopez-ESpinosa 2016) observed reductions in estradiol that would require a sample size of over a thousand of exposed to achieve sufficient statistical pOWer. However, the observed reductions in testosterone would require a sample size of between 500 and 1,000 exposed. Possible to study at Pease although a sample size larger than 500 exposed and 250 unexposed would be necessary. 67 Draft for Review Purposes Do Not Cite or Quote Health-related Endpoint Minimum Detectable Effect Size Other Sample Size Considerations Conclusion Thyroid function See appendix for sample size calculations and assumptions required for the calculations. A CS study (Lopez?Espinosa 2012) observed small differences for PFOS and PFOA serum levels considerably higher than at Pease. To detect these differences would require a sample size of over a thousand exposed. On the other hand, 21 Taiwan study (Lin 2013) observed differences that could be detected with suf?cient power with a sample size of 350 exPosed and 175 unexposed. Possible to study at Pease. . AtOpic dermatitis A Taiwan study (Wang 2011) obtained an OR of 2.19 for PFOS serum levels similar to Pease. However, the study evaluated children aged 2 years. No other PFAS study evaluated atopic dermatitis Possible to study at Pease. Asthma 0 0 Two NIELANES studies (Humblet 2014, Stein 2016) observed ORs between 1.2 and 1.3 which would require a sample size of over 2,000 exposed. However, a Taiwan study (Dong 2013) obtained ORs between 3.8 and 4.0 for and PFOA serum levels lower than at Pease. Possible to study at Pease. Rhinitis A NHANES study (Stein 2016a) evaluated rhinitis and obtained an OR of 1.35 for serum PF 0A similar to those at Pease. To detect this OR would require over a thousand exposed. However, 0R5 between 1.5 and 1.6 could be detected with suf?cient statistical power with a sample size of 500 exposed and 250 unexposed. These are ORs that are reasonable to detect and fall within the 95% CI for the ?nding in the NHANES study. Possible to study at Pea'se Antibody response to childhood vaccines Could not be calculated due to insuf?cient information Three studies that have been conducted of these endpoints had sample sizes that could be achievable at Pease. Only two studies (Granum 2013, Stein 2016) have evaluated the same endpoint rubella. Possible to study at Pease although a sample size larger than 500 exposed and 250 exposed may be necessary. 68 Draft for Review Purposes Do Not Cite or Quote Health-related Endpoint Minimum Detectable Effect Size Other Sample Size Considerations Conclusion Attention de?cit/hyperactivity disorder (ADHD) 0R5: 1.9 2.5 A C8 study (Stein 2011) obtained an OR of 1.55 (ADHD meds) for serum levels similar to Pease. A NHANES study (Hoffman 2010) observed an OR of 1.67 for serum levels similar to Pease. Not feasible to study using the Pease population alone.(for ADHD confirmed by current medications) Autism spectrum disorder (ASD) ORs 4.0 One study (Li'ew 2015) obtained an OR of 1.3 for serum PF levels lower than at Pease. To detect this OR would require >10,000 exposed. Not feasible to study using the Pease population alone. Delayed puberty Could not be calculated due to insufficient information Only one study evaluated delayed puberty among children. This was a CS study (LopezeEspinosa 2011) that evaluated several thousand children. It is likely that sample sizes much larger than at Pease would be necessary. Not feasible to study using the Pease population alone. Thyroid disease A C8 study (Lopez-Espinosa 2012) obtained an OR of 1.44 for PFOA serum levels considerably higher than those in the Pease population. To detect this OR with 80% statistical power would require a sample size of over 10,000 exposed children. Not feasible to study using the Pease population alone. Childhood cancers No PFAS study has evaluated childhood cancers. Given the incidence and prevalence of cancers such as leukemia, a sample size of many thousands of exposed would be necessary. Not feasible to study using the Pease pepulation alone. The minimum detectable effect size is based on a sample size of 350 children exposed and 175 children unexposed, and specifying statistical power of 80% (or a type 2 or error of .20) and a type 1 error of .10 (see table 6a). This minimum detectable effect size is compared to the adverse effect sizes observed in other PFAS studies. Where possible, the focus ison adverse effect sizes in the PFAS studies observed for PFAS serum levels similar to those among the Pease children. An endpoint is considered feasible to study at Pease if an adverse effect size observed in PFAS study can be detected with suf?cient statistical power statistical power of280%) by a'sample size achievable at Pease, a sample size of 350 exposed children at Pease and 175 children unexposed to the PFAS?contarninated drinking water at Pease. If only one PFAS study has been conducted on a health-related endpoint, then the endpoint was considered feasible to study at Pease if an odds ratio could be detected with statistical power of 80%. 69 Draft for Review Purposes Do Not Cite or Quote Note: The studies mentioned in the column of the table labeled ?Other Sample Size Considerations? are included only to give a sense of the adverse effect sizes that might occur in a Pease study. Due to the paucity of studies for each health-related endpoint, there is considerable uncertainty concerning the effect sizes that might be expected to occur in a Pease study. OR: Odds ratio. The odds ratio roughly approximates the risk ratio, The risk ratio is the proportion of the exposed population with a disease divided by the proportion of the unexposed population with a disease. Note: Hypertension is not included in this table because there is no evidence so far of an association between PFAS serum levels and hypertension in children. Adverse birth outcomes are not included in this table because these outcomes are not feasible to study at Pease. Although the number of children potentially exposed to the PEAS-contaminated drinking water while attending daycare at the Pease Tradeport can be estimated, there is a lack of information on the number of children potentially exposed in utero to the PFAS?contaminated drinking water because their mothers were employed at the Pease Tradeport during the pregnancy. To evaluate adverse birth outcomes with suf?cient statistical power would require the inclusion of several hundreds of exposed births. Note: The health-related endpoints listed in this table satisfy the criteria of scienti?c importance and public health signi?cance as discussed on page 8 of the text. 70 Table 7a. Minimum detectable effects for an adult epidemiological study, 1,500 per stratum.* Endpoint or and I3 .05 or, .05, a and .10 a .10, 0=.20 Chronic kidney disease Thyroid disease, unconfirmed Thyroid disease, con?rmed Total cholesterol (mean 5.5 mg/dL 4.3 mg/dL 4.5 mg/dL 3.8 mg/dL difference) LDL (mean difference) 4.5 mg/dL 3.5 mg/dL- 3.7 mg/dL 3.1 mg/dL Hypercholesterolemia .42 Uric acid (mean difference) 0.21 mg/dL 0.17 mg/dL 0.18 mg/dL 0.15 mg/dL Hyperuricemia Elevated ALT (>45 men; >34 women) Elevated. GGT (>55 men; >3 8 women) Elevated direct bilirubin (>003 mg/dL) . ALT (mean difference) 2.65 2.15 1.83 GGT (mean difference) 5.92 4.60 4.80 4.09 Direct bilirubin (mean 0.079 mg/dL 0.060 mg/dL 0.064 m'g/dL 0.055 rug/dis difference) Liver disease Cardiovascular disease Hypertension Ulcerative colitis .24 .3 8 Rheumatoid arthritis Lupus I Multiple Sclerosis .50 Osteoporosis 8 Osteoarthritis Endometriosis (750 per stratum) Pregnancy?induced hypertension (750 per stratum) 'Kidney cancer Some health?related endpoints are not included in the table because there was insufficient infor to calculate minimum detectable effects. For thyroid function, see the appendix for a description assumptions used in the sample size calculations and the resulting calculations. 71 . ation of the Table 7b. Summary of information used to categorize the feasibility of studying health-related endpoints for a Pease adult study. Health-related Endpoint Minimum Detectable Effect Size: 1,500 exposed and 1,500 unexposed Other Sample Size Considerations Conclusion Lipids (total cholesterol) 3.8 mg/dL A C8 study (Steenland 2009) observed a 3 4 mg/dL change in total cholesterol and LDL for PFOS serum levels similar to those at Pease. Feasible to study at Pease Hypercholesterolemia A Canadian study (Fisher 2013) obtained an OR of 1.57 for serum levels similar to those at Pease. Feasible to study at Pease Uric acid 0.15 mg/dL A NHANES study (Shankar 2011) observed a mean difference of 0.40 mg/dL for serum PF 0A levels similar to those at Pease. Feasible to study at Pease eruricemia A NHANES study (Shankar 2011) obtained an OR of 1.90 for serum PFOA levels similar to those at Pease. Feasible to study at Pease Thyroid disease (uncon?rmed) A C8 study (Winquist 2014a), hazard ratios 31.3 were obtained for PFOA Serum levels similar to those at Pease. (Only PFOA was evaluated in this study.) Feasible to study at Pease Cardiovascular disease ANHANES study (Shankar 2012) obtained an OR of 2.01 for PFOA serum levels similar to those at Pease. Feasible to study at Pease Hypertension Only one community study (a CS study, Winquist 2014b), evaluated hypertension and obtained an OR 1.0 for serum PF 0A (the only PFAS evaluated). However, the sample size achievable at Pease is capable of detecting very low ORs with suf?cient statistical power. Feasible to study at Pease Osteoarthritis A NHANES study (Uhl 2013) obtained an OR of1.5 for) serum PF DA levels similar to those at Pease. Feasible to study at Pease Osteoporosis A NHANES study (Khalil 2016) obtained an on 10 among women, for serum levels lower than those at Pease- Feasible to study at Pease 72 Draft for Review Purposes Do Not Cite or QuOte Health-related . Endpoint Minimum Detectable Effect Size Other Sample Size Considerations Conclusion Serum Immune . Biomarkers Could not be calculated due to insuf?cient information Only one published study (Stein 2016b) has been conducted that evaluated serum immune biomarkers at baseline crosslsectionally). This study had a sample size of 75 adults. A cross-sectional evaluation of PFAS serum levels and immune biomarkers in a Pease adult study could provide important information on the effects of PFAS exposures on immune function in humans. Feasible to study at Pease Liver ?mction: Elevated ALT Elevated GGT Elevated direct bilirubin 0R=l.29 A NHANES study (Gleason 2015) evaluated PFAS serum levels similar to those at Peas e. For elevated ALT, ORS betweenLZ and 1.5 were obtained. For elevated GGT, ORs between 1.0 and 1.3 were obtained. For elevated direct bilirubin, ORs between 1.1 and 1.7 were obtained. I Possible to study at Pease, but may require a larger sample size than 1,500 exposed and 1,500 unexposed to evaluate PFOS and serum levels and ALT and GGT. Direct bilirubin is probably not feasible to study using the Pease population alone. Thyroid disease (continued) A C8 study (W inquist 2014a), hazard ratios 51.3 were obtained for PFOA serum levels similar to those at Pease. (Only PFOA was evaluated in this study.) Possible to study at Pease, but will require a larger sample size than 1,500 exposed and 1,500 unexposed. Thyroid function See appendix for sample size calculations and assumptions required for the calculations. A C8 study (Knox 2011) observed very subtle changes that would require a study of equivalent size (52,296) to detect associations with sufficient statistical power. On the other hand, a NHANES study (Wen 2013) observed larger changes (at PFAS serum levels similar to those at Pease) that could be detected with a sample size achievable at Pease. Possible to study at Pease. 73 Draft for Review Purposes Do Not Cite or Quote Health-related Endpoint Minimum Detectable Effect Size Other Sample Size Considerations Conclusion Endometriosis (750 exposed 750 unexposed) A NHANES study (Campbell 2016) obtained ORs of 1.47 and 2.86 for serum and PF 0A, respectively. The serum levels for these two PFAS were similar to those in the Pease population. Possible to study at Pease if suf?cient numbers of women can be recruited. Pregnancy-induced hypertension (750 exposed pregnancies and 750 unexposed pregnancies A C8 study (Stein 2009, Darrow 2013) obtained an of 1.6 for serum PFOS levels higher than at Pease. Possible to study at PEase but may require a larger sample size than 1,500 exposed and 1,500 unexposed in order to achieve a suf?cient number of pregnancies. Liver disease A CS study (Darrow 2016) and study (Melzer 2010) observed no elevation in liver disease. However, the C8 study evaluated only PFOA and the NHANES study evaluated PFOA and PFOS but not Not feasible to study using the Pease population alone. Kidney disease A C8 study (Dhingra 2016a) evaluated only PFOA and obtained ORsof 1.26 and 1.36 for the retrospective and prospective analyses, respectively, at the second quintile PFOA serum level. (Smaller ORs were observed at higher PFOA serum levels.) Not feasible to study using the Pease population alone. Ulcerative colitis A C8 study (Steenland 2013) observed RRs between 2.8 and 3.1 at the highest serumPFOA levels, considerably higher than those at Pease. At lower PFOA serum levels, the Rs were <22 Not feasible to study using the Pease population alone. Rheumatoid arthritis A C8 study (Steenland 2013) observed RRs between 1.3 and 1.7 for serum PFOA. Not feasible to study using the Pease population alone. Lupus A C8 study (Steenland 2013) observed RRs <1.3 for serum PFOA. Not feasible to study using the Pease pepulation alone. Multiple sclerosis .5 0 Not feasible to study using the A 08 study (Steenland 2013) observed RRs between 1.1 Pease population alone. and 1.6 for serum PFOA 74 . Draft for Review Purposes Do Not Cite or Quote Health?related Minimum Other Sample Size Considerations Conclusion Endpoint Detectable Effect Size Kidney cancer for kidney A C8 study of a community population (Vieira 2013) Not feasible to study using the cancer observed an of 1-70 for those served by the Little Pease population alone. (Due to the Hocking water system. very low background prevalences - of other adult cancers, it is not feasible to study cancers using the Pease population alone.) The minimum detectable effect size is based on a sample size of 1,5 00 adults exposed and 1,500 adults unexposed, and specifying statistical power of 80% (or a type 2 or error of .20) and a type 1 error of .10 (see table 6a). This minimum detectable effect size is compared to the adverse effect sizes observed in other PFAS studies. Where possible, the focus is on adverse effect sizes in the PFAS studies observed for PFAS serum levels similar to those among the Pease adults. An endpoint is considered feasible to study at Pease if an adverse effect size observed in PFAS study can be detected with suf?cient statistical power statistical power of 280%) by a sample size of 1,5 00 exposed and 1,500 unexposed. If only one PFAS study has been conducted on a health-related endpoint, then the endpoint was considered feasible to study at Pease if an odds ratio of <2.0 could be detected with statistical power of 80%. Note: the studies mentioned in the column of the table labeled ?Other Sample Size Considerations? are included only to give a sense of the adverse effect sizes that might occur in a Pease study. Due to the paucity of studies for each health-related endpoint, there is Considerable uncertainty concerning the effect sizes that might be expected to occur in a Pease study. OR: odds ratio. The odds ratio roughly approximates the risk ratio (R). The risk ratio is the proportion of the exposed pepulation with a disease divided by the proportion of the unexposed population with a disease. A hazard ratio can be interpreted in the same way as a risk ratio. Note: The health-related endpoints listed in this table satisfy the criteria of scienti?c importance and public health signi?cance as discussed on page 8 of the text. 75 Draft for Review Purposes Do Not Cite or Quote Other sites with PFAS?contaminated drinking water. from the UCMR-B Table A1 shows the maximum combined levels of and PFOS in any sample taken from eac utility. Only utilities with detectable levels of either or PF OS are listed. The data are from the UCMR-3 database as of July 2016 (US EPA 2016b). The ten utilities with the highest PF levels in a sample are the Commonwealth Utilities Corporation serving the Mariana Islands, the A1 Water Company serving portions of the state of Delaware, the Security Water and Sanitation Distri serving Colorado Springs, the Horsham Water Sewer (PA), the Warminster Municipal Authority tesian ?cts (PA), the Oatman Water Company (AZ), the Issaquah Water System (WA), the Hyannis Water System (MA), the Suffolk County Water Authority (NY) and the Warrington Township Water Sewer (PA). Three of the top 10 utilities are located near each other in the vicinity of Philadelphia, PA: Horsham, Warminster, and Warrington. ATSDR is currently considering whether it is feasible to include chi]. and adults from these towns in studies that would also evaluate the Pease populations. dren Willow Grove Naval Air Station/Air Reserve Station Naval Air Station Joint Reserve Base and Air Force Reserve Station), Montgomery County, The Naval Air Station Joint Reserve Base (NASJRB) and Air Reserve Station (ARS) at Wi llow Grove (?Willow Grove?) are two separate, but co-located military facilities in Montgomery Count? 9 The Navy acquired site in 1942 and beganjet training there in 1949; the air force ha began operations in 1958. In 2001, the Willow Grove bases employed 1,571 active-duty individua members of the National Guard, 3,500 members of the Reserves, and 778 civilians with approximc 1,700 staff err?station daily. About 230 people resided on the bases year-round: less than 30 people resided in single family dwellings and less than 200 resided in barracks. Additionally, there were of?cer family units, 200 enlisted family units, and 250 unaccompanied enlisted units as well as a daycare center on base for 96 children. The Willow Grove Branch Medical Clinic was also located and provided primary care, medical support, preventive medicine, and occupational health services 20,000 active duty, reserve, retired personnel, and their family members (ATSDR 2002a). Willow became an Air National Guard Base in September 2011. The surplus land with the runways was tu over to Horsham Township for redevelopment. AFF used on the Willow Grove bases resultedin PFAS contamination of two nearby wate systems the Warrington Township Water'and Sewer Department which served the ea portion of Warrington and the Horsham Water and Sewer Authority (HWSA). In late October 2014, three of eight wells in the southern portion of the were abox EPA Provisional Health Advisory Level (PHAL) for PFOS and were taken out of service. PFOS le were the following: Well 1 (0.21 pig/L), Well 2 (1.6 pig/L), and Well 6' (1.3 lag/L). Although the we pump directly into the distribution system, wells 1, 2, and 6 are blended together at a tank and ente s, 993 iter VB there to Gove ?ned stern re the vels the distribution system at one point. These wells constituted about 30% of the supply. Well 2 the northeast area of the eastern section, and well 9, which is centrally located in the eastern sectior very low levels of contamination. Using currently available water distribution system information, ATSDR determined that fr ?present-day? conditions, the northern part of the eastern section of the system generally received Water that did not contain PF 0A and PFOS. If any customers in the northern part of the 33 received water containing PFOA and PF OS, it was at levels below the EPA Lifetime Health Advis (LTHA). The central part of the eastern section of the system may have received water. containinglstem Dry PFOA Draft 'for Review Purposes Do Not Cite or Quote and PFOS concentrations above the EPA LTHA. The southeastern part of the eastern section of the system received water containing PF OA and PFOS concentrations up to 10 times the EPA LTHA. detailed analyses of the water-distribution system need to be conducted to estimate historical PFAE concentrations at speci?c housing areas. These analyses would involve looking at the water-distrib system operating conditions, historical Well pumping records, and customer consumption information in more detail. The western section of the Warrington system is supplied by water purchased from North Water Authority and is not contaminated with PFAS. However, there is an interconnection betweei eastern and western sections of the system which is used when there is a need in the eastern sectior Warrington Township Water and Sewer Department UCMR 2014-2015 data* Well PFOS (ug/L) (pg/L) PFOA (pg/L) PFNA (pg/L) Wells 1, 2, 6 0.67 0.24 0.12 - Well 3 0.06 0.04 0.02 - Well 9 0.09 0.06 0.03 - *Wells 1, 2, 3, and 6 were sample 11/11/2014; Well 9 was sampled 5/11/2015 The HWSA is served by 15 wells as well as interconnections with other nearby water utilit The water system is separated into two pressure zones, ?high? and ?low,? with the wells in each 20 pumping to ?ll storage tanks. The high zone has two storage tanks supplied by three wells and two interconnections. The low zone has three storage tanks served by 11 wells and an interconnection 1 Aqua Southeastern Division. (Note: the Aqua system had 0.009 ug/L of PFOS and . ug/L PF 0A during sampling in 4/16. There are now samples from 7/16 which measured 0.0068 ug/L for PFOS and 0.0065 ug/L for June 2014 drinking water sample results indic that PFAS contamination was solely in the low pressure zone which serves the majority of the serv area. Prior to 1996 the system did not have pressure zones which means customers located in the 0 high pressure zone may have received water from wells in the low pressure zone. Generally, dema met using water from the storage tanks. There are three elevated tanks, and each tank generally sup a certain area of the system. Each tank will- have different PFAS concentrations depending on whic wells are supplying water to them. However, it is possible that a property in close proximity to a which has a demand at the same time the well is pumping will have a higher percentage of water ft the nearby well than other areas. In June 2014, HWSA wells were tested for PFAS as part of the Two wells, well and well #40, had levels of PFOS greater than the EPA PHAL of 0.2 ug/l, and well #26 also excee the EPA HAL of 0.4 ug/l for PFOA. The PFAS contamination levels from the for the Horsham supply wells are shown in the table below. Both wells #26 and #40 were removed from in July 2014. According to the 2014 consumer con?dence report for the HWSA, the average level PFOS reported was 0.06 ppb, the average level of was 0.037 ppb, and PFOA was not deters The two contaminated wells generally supplied about 25% of the water for the system; however, t} were times that the two contaminated wells supplied as much as 35% of the water for the system. In May 2016 subsequent to the EPA announcement of its lifetime health advisory for wells 10, 17, and 21 were immediately taken out of service. One of these three wells Shut down to comply with the new LTHA. The other two wells, which tested below the 101 605 v/ell More i ution ales 1 the 1. BS. 113 vith ated ice .ll?ant 1d is plies om #26 ?ed ervice of :ed. ere was 12A, {a Draft for Review Purposes Do Not Cite or Quote were shut down as a precaution. The other nine wells that now supply public drinking water across township have tested below the EPA lifetime health advisory levels. ATSDR used currently available water-distribution system information to determine that fc ?present?day? conditions, some areas in the southern and Southeastern part of the low pressure zon received water containing PFOA and PFOS concentrations up to 9 times the EPA LTHA. The northeastern part of the low pressure zone received water containing PFOA and PFOS concentratic less than the EPA LTHA. More detailed analyses of the system need to be conducted to estimate historical PFAS concentrations at speci?c housing areas. These analyses would involve looking at water?distribution system operating conditions, historical well pumping records, and eustc consumption information inmore detail. In addition to the ?ve total public wells that HWSA shut down, the Navy and the EPA iden approximately 40 additional private wells in Horsham that are at or above the EPA guidance of 7 0 per trillion (ppt). The Navy is providing bottle water to these private well owners. Horsham Water and Sewer Authority (HWSA) UCMR 2014 data* the "t \Iv? he mer tified parts . Well PFOS (pg/L) (pg/L) PFOA (pg/L) PFNA (pg/L) Well 10 0.05 0.04 0.03 Well 17 0.10 0.05 0.03 Well 21 0.14 0.08 - - Well Well *Wells 10 and 17 were sampled 12/9/2014; Wells 21,26, and 40 were sampled 6/24/2014 Other drinking water contaminants Supply wells on 'base contained volatile organic compounds (VOC) and metals. Maximum - detected levels in supply wells from sampling conducted in 1979-1984 were 91 for PCB and 3 for TCE. After contamination was detected, the well with the highest levels of contaminationi used mainly for ?re protection. Additionally, the Navy installed an air stripper to treat groundwate to distribution, and monitoring of treated water between 1996 and 1998 found no contaminants abc Maximum Contaminant Levels (MCLs) (ATSDR 2002a). According to the EPA, over 800 employees at the two facilities may have drank or come into contact with treated water from theN supply wells 820). VOC contami in off~site wells has .not been attributed to the base, and the local water authorities (HWSA and treat the water for V0 Cs before distribution (ATSDR 2002a). Naval Air Warfare Center (a/k/a Naval Air Development Center), Warminster Township, B1 County, The former Naval Air Warfare Center (NAWC) is located in Warminster Township. The bise Operated from 1944 until its closure' in September 1996. In 1994, approximately 1850 civilians an 1,000 military peisonnel were stationed or employed on base. At its peak, the base employed 2, 80( civilians, 200 military personnel, and up to 300 daily contractors (ATSDR 2002b). 102 00 was prior ivy nation leS 1 Draft for Review Purposes Do Not Cite or Quote Approximately 800 to 1,000 military personnel and their families stationed at nearby Willow Grove Naval Air Station lived in two on-base housing areas at NAWC while as many as six families may have resided in of?cer housing. Between 450?550 enlisted personnel and their families lived at the Shenandoah Woods housing complex. Site 5, a former land?ll, was located in Shenandoah Woods Quarters A and B, located within Area C, provided housing for the base?s commanding of?cer and- second-in-command (ATSDR 2002b). Four out of eighteen of the Warminster Municipal Authority (WMA) public water supply wells are in close proximity to the former NAWC site. The WMA provides water to approximately 40,310 people. The water supplied to the customers is from water supply wells in the WMA system and ay be purchased from the North Wales Water Authority (NWWA) as well as the Upper Southampton Municipal Authority on an emergency basis. WMA's water supply wells are conneCted individuall to the distribution network and are subsequently blended within the distribution system in tanks and standpipes. Therefore, customers located geographically closest to a given water supply well will 'kely receive more water from that well than users located fuither away (ATSDR 2016). - was used for decades at the base for ?re?ghting training activities. PFAS were ?rst 1ested for in groundwater as emerging contaminants in preparation for the CERCLA 2012 Five Year Review for this site. In summer 2013, PFOS levels above the EPA PHAL were first discovered in groundwater on the former Navy property. As part of the EPA's UCMR-B, sampling for six PFAS in the WMA ?rst occurred in November 2013. monitoring for PFAS is required at the entry point to the distribution system for each well and at any interconnection in operation. Accordingly, WMA conducted sampling in November 2013 and May 2014 for all wells and conducted sampling in November 20il3 and February, May, and August 2014 for the interconnection with NWWA (ATSDR 2016). Samples taken in the WMA system detected levels of PFOS, PFOA, and/or The source of the contamination was the use at NAWC. In November 2013, three WMA public water wells had levels at or above PHAL for In this sampling event, 17 samples covering 17 wells in the WMA and one sample of the NWWA interconnection were taken and analyzed for PFAS. One of the 17 WMA samples represents the combined water extracted from WMA Wells 43 and 44. Water from these two Wells is combined for treatment and samples are taken after treatment at the entry point to the distribution system. PFOS was detected in 6 public wells and PFOA was detecte :l in 8 public wells. PFOS was detected in Well 26 at 0.791 gig/L, more than three times the 0.2 ug/L PFOS PHAL value. Wells 10 and 13 had PFOS concentrations of 0.193 and 0.16 pg/L that can be rounded to 0.2 ug/L. None of the PF OA detections exceeded the PF 0A PHAL in the WMA wells. Well 26 had the highest detections for PF 0A and PFOS. In summer 2014, PFOS was detected in four public wells. The highest concentrations were in Well 26 at 1.09 ug/L, more than ?ve times the 0.2 ug/L PF OS PHAL value, and in Well 10 at 0.176 ug/L. PFOA was detected in four wells, including Well 26 at 0.349 ug/L, close to the 0.4 ug/L PHAL for PF OA. Wells 13 and 26 were shut down in June 2014. Well 10 was shut down in September 2014. On May 19, 2016, wells 2, 14 and 15 were removed from service due to the EPA new lifetime health advisory level for (ATSDR 2016). PF OS levels above the PHAL were also detected in private drinking water samples. As of September 2015, 100 private wells (94 residential and 6 non-residential) were identi?ed and sampl ed within an approximate 1-3 mile radius of the site. At least one PFAS was detected in the majority (93 out of 100) of these private water wells. Of the 94 residential private water wells, ?ve were non-detect and PFOS, 18 had detections of PFOA only, and 71 had both PFOA and PF OS. Eleven exceeded the PF OS PHAL, ranging from 0.152 ug/L to 0.729 ug/L. The PF OS PHAL exceedance; are 103 Draft for Review Purposes Do Not Cite or Quote in two general locations: one location is south of the Jacksonville Road and East Bristol Road intersection and the other lecation is in the area of York Road and Street. Six residential wells *1 PFOS levels that range from 0.102 to 0.109 pg/L (50% of the PHAL) are located at the aeksonville/East Bristol Roads intersection (ATSDR 2016). vith The Navy and EPA provided a limited number of residents whose private well water was at or above PHAL (with rounding up to one signi?cant digit) with bottled water to use for drinki cooking water, and is currently working to connect these locations to public water (ATSDR 2016) ?present day? conditions, the southwestern part of the Warminster system typically received Water that Using currently available water?distribution system information, ATSDR determined that [fr did not contain PFOA and PFOS concentrations. If any customers in this part of the system receiv water containing PFOA and PFOS concentrations, it was at levels below the EPA LTHA. The northwestern part of the Warminster system typically received water containing PF OA and PFOS concentrations at or below the EPA LTHA. Some areas in the eastern parts of the Warminster received water containingPFOA and PFOS concentrations at levels up to three times the EPA LT and areas in the central part received water containing concentrations at level up to 15 times the EPA LTHA. More detailed analyses of the system need to be conducted to estimate historical PFAS concentrations at speci?c housing areas. These analyses would involve looking at the water-distrit system Operating conditions, historical well pumping records, and customer consumption information in more detail. Although some WMA customers received the majority of their water from one of the contaminated wells, the majority of water customers likely received water that either did not conta PFAS or had levels less than the PHALs (but levels may be higher than the EPA LTHA for If one assumes that all the wells supply a similar amount of water to the system (ea well typically supplied 5?10% of the water to the system), then the number of customers potential] exposed to elevated PFAS in their drinking water could be approximately 7,000. Warminster Municipal Authority (WMA) UCMR 2013?2014 6616* Well PFOS (pg/L) (pg/L) PFOA (pg/L) PFNA (pg/L) Well 2 0.06 0.03 0.03 Well 10 0.19 0.10 0.09 Well 13 0.16 0.09 0.12 W611 14 0.06 - . 0.03 0.02 - 'Well 15 0.06 0.04 0.02 Well 26 1.09 0.39 0.35 *Wells 2, 10, 13, 14, and 15 were sampled 11/19/2013; Well 26, was sampled 6/9/2014 Other drinking water contaminants 6d em 3 11.112101] in ch ?36 Samples taken in 1979 showed maximum levels of contamination in on?site supply wells 0 for PCB and 293 for TCE. These wells were closed in 1979. Contamination levels in sam les taken from off?site municipal supply wells found 17 for PCB and 67.8 for past off- ase residents may have been exposed to these VOCs between 1974, when the well first began supplyi water, until it was closed in 1979. Sampling of VOCs in off?site private wells detected PCE at 31 104 pb; as Draft for Review Purposes Do Not Cite or Quote a result, affected homes were connected to municipal water supplies or groundwater treatment were installed (ATSDR 2002b). Because the TCE- and PCB-contaminated wells were shut down in 1979, military service personnel and DOD civilian workers who began service/employment at NAWC after 1979 might tems 36 eligible for a PFAS study. More information is needed to determine when the water supply may have been contaminated with PFAS. More detailed analyses will help determine which specific housing areas received water containing PFOA and PFOS from the NASJRB and ARS at Willow Grove and the NAWC in Warminster. To conduct more detailed analyses, including modeling, additional information and 8 data pertinent to each water system?s operations needs to be obtained from site visits to the water utilities. 105 peeific Dra?: for Review Purposes -- Do Not Cite or Quote Appendix tables 106 Draft for Review Purposes Do Not Cite or Quote Table A1. Maximum levels (parts per billion) of combined and PFOS from the US Third Unregulated Contaminant Monitoring Rule (UCMR-S) Water Utility Name State iz Commonwealth Utilities Corp.? (Saipan) MP Artesian Water Company DE Security WS CO Horsham Water Sewer Authority PA Warminster Municipal Authority Oatman Water Company AZ - Warrington Township Water Sewer Department I PA Issaquah Water System . WA Hyannis Water System MA Suffolk County Water Authority I NY United Water PA PA Emerald Coast Utilities Authority - FL GU Waterworks Authority - Northern System GU Widefield wso . co 0a kdale I MN City of Tucson - AZ City of Cleveland Heights OH Sanford Water District . . ME Wright-Patterson AFB Area OH Liberty Water LPSCO - AZ Westfielcl Water Department MA City of FL Bemidji . MN City of Fountain - CO A FL 8; PFOS sum 8.60 2.48 1.89 1.59 1.479 1.03 0.91047 0.841 0.7 0.67 0.572 0.56 . 0.55 0.54 0.4913 0.476 0.4 0.4 0.36 0.33 0.33 0.32 0.32 0.29 'u-n OJ -J 107 Draft for Review Purposes Do Not Cite or Quote Water Utilit Name City of Tempe CA American Water Co. Suburban City of Newburgh' CA Water Service Visalia Eastern Municipal Water District New Windsor Consolidated Water District VAW Water System, Inc. Freeport La Crosse Waterworks Salt River Public Works City of Ma rtinsburg Dyer Water Department Atlantic City UA West Morgan - East Lawrence Water Authority City of Greensboro Rome Dover Water Department CA Water Service Chico Moore County Public Utilities - Pinehurst Rhinelander Water 8: Wastewater Bayleaf Master- City of Ocala NJ American Water Co. Raritan Mahwah. Water Department City of Abilene West Lawrence Water Co?op Hampton Bays Water District Fort Drum 108 State PFOS sum 0.245 0.241 0.24 0.212 0.202 0.1936 0.18 0.18 0.172 0.166 0.157 0.1437 0-142 0.13 0.124 0.12 0.12 0.118 0.118 0.1173 0.11 0.104 0.103 0.098 0.09781 0.09 0.082 0.08 Draft for Review Purposes Do Not Cite or Quote Water Utilit Name State City of Lathrop . I CA Northeast Alabama Water System AL City of Anaheim CA Fair Lawn Water Department . NJ City of Orange CA Montebello Land Water Company CA Vienna WV Chatsworth GA Bethany OK City of Pico Rivera Water Department CA Camp Pendleton (South) CA Montgomery County Water Services #2 0H Rainbow City Utilities Board AL Florence Water-Wastewater Department AL Plainfield Township A Ml Pendleton County Water District #1/South KY City of Miami Beach . FL Ridgewood Water NJ Woodbury - MN Montgomery County Water Services #1 OH CA Water Service East Los Angeles CA Town of Nashville NC Metropolitan AZ City of Downey Water Department CA Pierre . SD Park Water Company Bellflower/Norwalk CA Washington Township MUA I - NJ In .5 8; PFOS sum 0.076 0.07 . 0.07 0.06603 0.0659 0.065 0.0641 0.06303 0.063 0.062 0.062 0.061 0.06 0.06 0.06 0.05853 0.058 0.058 0.0577 0.0542 0.054 0.05312 0.053 0.053 0.053 0.051 0.0503 109 Draft for Review Purposes Do Not Cite or Quote Water Utility Name Colbert County Rural Water System Gadsden Waterworks Sewer Board Southside Waterworks City of North Miami Kennebunk; Kennebunkport 8L Wells WD Bell Arthur Water Corp. City of Garden Grove City of Lauderhill FKAA Yorba Linda Water District City of Miramar Miami international Airport City of Corona Orchard Dale Water District Lima City Water Pico Water District Golden State Water Co. - Norwalk MDWASA - Main System Ann Arbor City of Fullerton Cliffdale West Central ASG City of DeFuniak Springs Water System Cottage Grove City of Great Bend City of Pleasanton Sacramento Suburban Water District 110 State AL AL AL FL lVlE PFOS sum 0.05 0.05 0.05 0.05 0.05 0.05 0.0496 0.049' 0.049 0.0474 0.047 0.047 0.046 0.045 0.045 0.044 0.043 0.043 . 0.043 0.0412 0.041 0.04 0.04 0.0381 0.037 0.036 0.035 Draft for Review Purposes Do Not Cite or Quote Water Utility Name Mashpee Water District Belvidere L=large system (serves >10,000); S=small system (serves <10,000) Tribal nation located in Arizona State MA ml .5 .J.A 8: PFOS sum 0.033 0.03167 111 EXHIBIT Cancer risk among ?re?ghters: a review and meta?analysis of 32 studies. PubMed NCBI Pag ;elof2 CS Occup Environ Med. 2006 Walters K- Cancer risk among firefighters: a review and meta-analysis oi" 32 studies. LeMasters Genaidv AM. Succop P. Deddens J. Sobeih T. Barriera-Vlruet H. Dunninq K. Lock (D Author information Abstract . OBJECTIVE: The objective of this study was to review 32 studies on firefighters and tc quantitatively and qualitatively determine the cancer risk using a meta?analysis. METHODS: A comprehensiVe search of computerized databases and bibliographies fro identified articles was performed. Three criteria used to assess the probable, possible, :r I unlikely risk for 21 cancers included pattern of meta-relative risks, study type, and heterogeneity testing. RESULTS: The findings indicated that firefighters had a probable cancer risk for multiale myeloma with a summary risk estimate (SRE) of 1.53 and 95% confidence interval (Cl) 1.21?1.94, non?Hodgkin (SRE 1.51, 95% Cl and prostate (SFKEI 1.28; 95% CI Testicular cancer was upgraded toprobable because it had highest summary risk estimate (SRE 2.02; 95% CI Eight additional canc were listed as having a "possible" association with firefighting. CONCLUSIONS: Our results confirm previous findings of an elevated metarelative riskl multiple myeloma among firefighters. In addition, a probable association with non?Hod prostate, and testicular cancer was demonstrated. PMID: 17099456 [indexed for Publication types, terms of the ?s . gkin 709945 6 8/ 14/2017? Cancer incidence among male Massachusetts ?re?ghters, 1987?2003. - PubMed NCBI Page PubMed . -. . .. . .. a; Format: Abstract I Full text links Am ind Med. 2008 doi: 10.1002/ajim.20549. Cancer incidence among male Massachusetts firefighters, 1987-2003. Kano D1, Davis LK, Hunt P. Kriebel D. Author information Abstract . BACKGROUND: Firefighters are known to be exposed to recognized or probable carcinogens. Previous studies have found elevated risks of several types of cancers in firefighters. METHODS: Standardized morbidity odds ratio (SMORs) were used to evaluate the can :er risk in white, male ?refighters compared to police and all other occupations In the Massachusetts Cancer Registry from 1986 to 2003. Firefighters and police were ident by text search of the usual occupation field All other occupations included cases with identifiable usual occupations not police or firefighter. Control cancers were those not - associated with firefighters in previous studies. RESULTS: Risks were moderately elevated among firefighters for colon cancer (SMOR 1.36, 95% Cl: and brain cancer (SMOR 1.90, 95% Cl: Weake: evidence of increased risk was observed for bladder cancer (SMOR 1. 22, 95% Cl: 0 kidney cancer 1. 34, 95% Cl: 0. 90-2. 01), and Hodgkin's 95% Cl: 0. 72-4. 53). CONCLUSIONS: These findings are compatible with previous reports, adding to the evidence that firefighters are at increased risk of a number of types of cancer. (0) 2008 Wiley?Lies, Inc. PMID: 18306327 . DOI: 10.1002/aiim.20549 [indexed for n, -L'uu! -m . .u Irv-7? l?of2 ed 1' 06327 8/ 14/2012 Mortality and cancer incidence in a pooled cohort of US ?re?ghters from San Francisco, Page 1 of 2 . i ["l1uu . - . . . . . .. . -. .. . . mi. . .1 Format: Abstract Full text links 4 I E3133 5 . 0::ch Environ Med. 2014 doi: . ?Text JEMJC Mortality and cancer incidence in a pooled cohort of US firefighters from San Francisco, Chicago and Philadelphia (1950-2009). - Daniels Kubale TL Yiin JH. Dahm MM. Hales TR. Baris D, Zahm SH Beaumont JJ. Waters .- Pinkerton LE. Author information Abstract i OBJECTIVES: To examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009. METHODS: Mortality and cancer incidence were evaluated by life table methods with tt US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focus ad on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias. RESULTS: Person-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses respectively. All- -cause mortality was at expectation 99, 95% Cl 0.97 to 1.01, n=12 028). There was ?excess cancer mortality 14, 95% Cl 1.10to1.18, n=3285) and incidence 09, 95% CH. 08 to 1.12, n=4481) comprised mainly of digestive 95% Cl 1.18to1.34, 17, 95% Cl 1.10to1.,25 n=930) and. respiratory (SMR 1.10, 95% CH. 04to1. 17, n=1098; 18, 95% Cl 1. 08 to124 n=?813) cancers. Consistent with previous reports, modest elevations were observed In several solid cancers; however, evidence. of excess or haematopoietic canceIs was lacking. This study is the ?rst to report excess malignant mesothelioma 95% Cl 1.03 to 95% CI 1.60 to 3.19, n=35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques. CONCLUSIONS: Our results provide evidence of a relation between fire?ghting and car The new ?nding of excess malignant mesothelioma' Is noteworthy, given that asbestos - exposure is a known hazard of firefighting. KEYWORDS: Longitudinal studies Methodology, speciality 8/t4 1 er. /2017 Risk of cancer among ?re?ghters in California, 198 8-2007. - PubMed - NCBI Page PubMed Am Med. 2015 doi: 10. 1002/ajim. 22466. Epub I Format: Abstract . Full text links 91' In} lof2 Risk of cancer among firefighters in California 1988-2007. LuckhauptSE1 Sohumacher P1 Cress R023 Deepen DM, Calvert out. I Author information Abstract BACKGROUND: Most studies of refIghter cancer risks were conducted prior to 1990 do not reflect risk from advances' In building materials. METHODS: A case?control study using California Cancer Registry data (1988?2007) was conducted to evaluate the risk of cancer among firefighters stratlt" ed by race RESULTS: This study identified 3,996 male firefighters with cancer. Firefighters were found to have a significantly elevated risk for melanoma (odds ratio 1. 8; 95% confidence interval [Cl] 1 ..4-2 1), multiple myeloma (OR 1 95%Cl 1. 1. 8), acute mye o' leukemia (OR 1 95%0] 1. 0-2. 0), and cancers ofthe esophagus (OR 1 95%Cl 1 2.-. Z. prostate (0R1. 5; 95%Cl 1. 3- 1 .7), brain (0R1. 5; 95%Cl 1. 2-2. 0), and kidney (0R1. 3' 95 Cl 1. 0-1. 6). CONCLUSIONS: In addition to observing cancer ?ndings consistent with previous research this study generated novel findings for firefighters with race/ethnicity other than white. it provides additional evidenCe to support the association between firefighting and severe specific cancers. 2015 This article has been contributed to by US Government employees and their work' Is in the public domain' In the KEYWORDS: cancer; firefighters; occupation; registry; risk PMID: 25943908 PMCID: PMC4527530 [Indexed for Free PMC Article Publication types, terms, Grant support gov/pubmed/25943 908 I 8/14/2017 Novel ?ucrinated surfactants tentatively identi?ed in ?re?ghters using Page ur. ham Format: Abstract - Full text links Wans; 9me atoms? Enwron Sci Technol. 2015 Feb doi: 10.1021/e5503653n. Epub 2015 Feb 6. Novel fluorinated surfactants tentatively identified. in firefighters using liquid chromatography quadrupole time-of-- flight tandem mass spectrometry and a case-control approach. Rotander A1, Karrman A. Toms LM, Kay M, Mueller JF. Gomez Ramos MJ. Author information Abstract Fluorinated surfactant-based aqueous film-forming foams are made up of per? a polyfluorinated alkyl substances (PFAS) and are used to extinguish fires involving highly flammable liquids. The use of periluorooctanesulfonic acid and other perfluoroalkyl acids (PFAAs) in some formulations has been linked to substantial environmenta contamination. Recent studies have identi?ed a large number of novel and infrequently reported fluorinated surfactants in different formulations. In this study, a strategy based on a case?control approach using quadrupole time?of?flight tandem, mass 1di spectrometry and advanced statistical methods has been used to extr and identify known and unknown PFAS in human serum associated with AF FF-exposed ?refighters. Two target sulfonic acids and perfluorohexanesulfonic acid three non?target acids [perfluoropentanesulfonic acid perfluoroheptanesulfonic acid and perfluorononanesulfonic acid and four unknown sulfonic ac ics ketone~PFOS, and were exclusively or significantly more frequently detected at higher levels in firefighters compared to controls. The application of this strategy has allowed for identification of previously unreported fluorinated chemicals in a timely and cost-efficient way. 25611076 10.1021/es503653n [l ndexed for Publication type, terms, Substances 8/ . 0017' Per?uoroalkyl acids including per?uorcoctanc sulfonate and per?uorohcxane sulfonate Pagi [Fell of2 Formati Abstra ct,? Full text lin <5 Waite-rs Occup Environ Med. 2011 doi: in war! Perflucroalkyl acids including perfluorooctane sulfonate and perfluorohexane sulfonate in firefighters. Jin Sun Y, lslam A, Qian Y, Ducatman A. Author information Abstract OBJECTIVE: Fire?ghters were likely exposed to perfluorooctane sulfonate since it Was component of extinguishing foams and perfluorohexane sulfonate a surfacta - coating carpet and other building materials, during ?refighting. The objective of the stud to evaluate serum concentrations of periluoroalkyl acids (PFAAs) in firefighters. METHODS: A total of 8826 male adults, including 37 firefighters, were analyzed. Multivc analysis was conducted byvusing a general linear model. The least square mean of sen PFAAs was obtained after adjustment for demographic and socioeconomic variables. RESULTS: Serum concentration of was statistically higher in ?refighters both be and after adjustment. Perfluorobctane sulfonate and perfluorononanoic acid were also higher in fire?ghters, though not statistically significant. CONCLUSIONS: The study suggests that fighting ?re can be a risk of exposure to speci?cally - 21346631 cor: 10.1097/JOM.0b013e31820d1314 [indexed for Publication type, terms, Substances LinkOut -. more resources is riate m? i fore ound gov/pubmcd/2134663 1 8/ 14(2017 EXHIBIT .. The FluoroCouncil is a global membership organization 0 1.0 CO I. representing the world 's leading manufacturers of @3 l0 a! in U512 ry C0 ii (:11 fluoropolymers. fluorotelomers, and other fluorinated surfactants and surface property modification agents. between life and death for first responders, whether through its use in safety gear or . 7 firefighting foams. The low surface tension' and positive spreading coefficient of fluorinated surfactants make them ideal ingredients in the production of firefighting foam, used to fight Class flammable liquid fires and provide both shorter extinguishment times and critical burnback resistance. Clothing utilizing FluoroTechnology offers life- e? saving protection to first responders, whether by helping to deflect bullets or by maintaining performance of protective gear in the extreme environment of a fire. The use of FluoroTechnology in the emergency services industry supports more than 1,000 jobs in the U.S. and more than 9,000 jobs in Europe. Globally, FluoroTechnology materials and products specific to the emergency services industry generate a total of $15.1 billion in economic output.1 High-Performance First Responder Safety Applications 0 Firefighter Turnout Gear 0 Chemical Protective Suits . Bulletproof Vests . Firefighting Foams . Outdoor Clothing and Equipment FluoroCouncil?s Commitment to Sustainability FluoroCouncil andits members are working with regulatory authorities and other stakeholders worldwide to innovate and drive increasingly sustainable FluoroTechnology solutions, including the global transition from long-chain PFAS.2 to alternatives such as short-chain fluorochemicals. Short- chain fluorochemicals are alternatives to the long-chain PFAS that provide the same valuable properties, but with improved environmental and human health profiles. All FluoroCouncil companies are charter members of the 2010/2015 PFOA Stewardship Program, a global partnership with U.S. Environmental Protection Agency (EPA) based on goals to eliminate perfluorooctanoic acid (PFOA) and related chemicals from facility emissions and product content by the end of 2015. Similar programs are in place with Environment and Health Canada. A significant volume of data has been developed and rigorously evaluated by industry and regulators, supporting the conclusion that the short-chai alternative substances offer equivalent performance with improved environmental and human health profiles. According to the U.S. EPA, ?data indicate that [shorter-chain chemicals] have substantially shorter half-lives in these animals than PFOA and are less toxic than long-chain PFAC chemicals. 1 Based on preliminary estimates of 2013 data by the American Chemistry Council. 2 PFAS per- and polyfluoroalkyl substances THE FLUOROCOUNCIL MEMBERS ARE: Archroma Management LLC, Arkema France, Asahi Glass Co., Ltd., Daikin industries, Ltd, Solvay Specialty Polymers and The Chemours Company LLC. {a FluoroCouncil 2015