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: Millions of people across the country have been exposed to highly fluorinated chemicals (per? and polyfluoralkyl substances, including PFOA and PFOS) collectively referred to as in their drinking water supplies. 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 Taft Stettinius Hollister LLP Chicago Cincinnati Cleveland Columbus Dayton lndianapolis Northern Kentucky! Phoenix September 5, 2017 Page 2 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 in drinking water 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 drinking water 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 human health from the presence of the entire class of PFAS in drinking water, 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, 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 the entire class of PFAS chemicals through a program that could encompass and involve all affected parties, including PFAS manufacturers, PFAS users, impacted water supplies, impacted residents, 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. 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 1 See also 42 use 9604(i)(18). September 5, 2017 Page 3 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 in drinking water qualify as public health emergencies mandating immediate alternate water supplies. 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 in their drinking water 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 multiple sites were incorporated into the study. (Id. at 43.) ATSDR even listed over 100 sites identified to date across the country where PFOS and/or have been confirmed to be present in drinking water at levels above reporting limit for the chemicals under Unregulated September 5, 2017 Page 4 Contaminant Monitoring Rule 3 which could provide the needed, larger pool of study participants. (Id. at Table A.1.) 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 communities across the United States involving one or more (or a combination of) the other PFAS compounds in their drinking water, 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 greaterfinancial, scientific, and regulatory certainty. September 5, 2017 Page 5 ATSDR already has acknowledged the significance and utility of the 08 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 studies at the Pease International Tradeport, the C8 Science Panel?s/C8 Health Project?s work, which focused on human impacts from PFOA contamination in drinking water, 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 multiple PFAS compounds (including PFOA) being present in drinking water at the same time. (See Ex. at 3.) In short, the 08 Science Panel and 08 Health Project work allows ATSDR to start from what is already known and addressed by the 08 Science Panel and C8 Health Project with respect to the adverse effects of PFOA, and direct its resources toward studying the effects of having one or more (or combination) of the other PFAS materials in drinking water. Ill. 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 millions of Americans across this country. Every day, another community somewhere in the United States wakes up to news that one or more (or some combination) of an ever-expanding class of PFAS compounds (some being identified for the first time as even existing) are poisoning the drinking water that they and their families rely upon. Every day another community is being told not to drink its water or to immediately get on bottled water because the concentration of PFAS exceeds current EPA guidelines or other health benchmarks. Residents, water suppliers, local, state and national elected officials, governmental entities, NGOs, business leaders, scientists all are demanding credible, scientific answers to exactly what this mix of PFAS compounds in the water will do to people over time? especially those who have had long term exposures over many years or may be in sensitive subpopulations, such as infants, the elderly, or the infirm. Recently, the leaders of the health departments in ?ve states New York, Michigan, New Hampshire, Vermont, and Alaska all signed a joint letter specifically asking ATSDR to undertake a national PFAS health study. (Ex. I.) In the meantime, an ever?growing number of lawsuits are being filed by a variety of lawyers asserting a myriad of different claims and theories against multiple parties under varying state laws and standards. 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 PFAS contamination of the country?s drinking water supplies, including any military or other governmental entities, to pay for and/or fund such work. (See 6.9., 42 U.S.C. 9604(i)(5)(D), 9607(a)(4)(D). Given own recognition of the feasibility, importance, and need to study the effects of multiple PFAS 2 See also 42 use 9604(i)(17), 9620. September 5, 2017 Page 6 exposures in drinking water and its statutory authority and authorization to do so, continuing failure to do so provides a basis for a national class of all those negatively impacted by unstudied PFAS contamination of their drinking water supplies 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, Dr. Arlo Paul Brooks, Jr., 92 Bella Vista Drive, Vienna, West Virginia 26105 as a representative of a national class of all persons whose primary source of residential drinking water for at least one year or more has been found to contain one or more PFAS chemicals at a concentration above the Method Reporting Limit (MRL) for such PFAS chemical(s) established by EPA for purposes of UCMR-3, excluding any such water supply where the only PFAS found above such MRL is PFOA or is a water supply falling within the scope of the Leach Case settlement. ATSDR has identified in Table A1 to Exhibit attached hereto over 100 such water supplies across the country meeting this definition, including the municipal water supply for Vienna, West Virginia, which Dr. Brooks has used as his primary source of residential drinking water for many years. (See Ex. Table A1.) Dr. Brooks was one of the founding partners of Brookmar the entity that designed, managed, and implemented the highly successful CS Health Project. Dr. Brooks stands ready to share his unparalleled experience with ATSDR to help the Agency move forward with the type of national PFAS study that is now required. 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 CS Science Panel/C8 Health Project and related settlement model. (merely, - A VRobert A. Bilott RAB: Encls. (Exs. Cc: Dr. A. Paul Brooks, Jr. (w/encls.) EXHIBIT A U.S. Environmental Protection Agency 12/30/2009 Long-Chain Per?uorinated Chemicals (PFCs) I. Overview Long-chain perfluorinated chemicals 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, signi?cant adverse effects have been identi?ed in laboratory animals at 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. (J Since 2000, the Agency has taken various actions to help minimize the potential impa of PFCs 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 EPA's 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 pctential risks from long-chain PFCS. 6 63 EPA intends to consider initiating TSCA section 6 rulemaking for managing long?cha PFCs. If EPA can make certain ?ndings with respect to these chemicals (further analysis oft information will be performed as part of TSCA section 6 rulemaking), TSCA section 6 provi 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 per?uoroalkyl 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. EPA 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 5i will consider additional approaches. Long-chain PF Cs are a concern for children?s health. Studies in laboratory animals he re 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, is well as child?speci?c exposure pathways such as breast milk consumption, mouthing and ingestion of non-food items, and increased contact with the ?oor. Biomonitoring studies have found PFCs in cord blood and breast milk, and have reported that children have higher levels 3f The terms long-chain PFCs, long-chain per?uoroalkyl sulfonate (PFAS), and long-chain per?uoroalkyl carboxylate (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 thdse having shorter chain U.S. Environmental Protection Agency 12/30/2009 some PFCs compared to adults. Thus, given the pervasive exposure to PFCs, the persistence o" PFCs in the environment, and studies finding deleterious health effects, EPA will examine the potential risks to fetuses and children. II. 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 bloc persistent, bioaccumulative, and toxic characteristics; use in consumer products; production volume; and other similar factors. This Action Plan is based on initial reviex of readily available use, exposure, and hazard information4 on PFCs. EPA considered which 01 the various authorities provided under TSCA and other statutes might be appropriate to addresls potential. concerns with PFCs 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 final 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 has 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 inherent toxic effects of the polymer or exposure to dust that contains fluorinated polymers. Long-Chain Per?uoroalkyl Sulfonate (PEAS) Sub-Category The PFAS sub-category includes perfluorohexane sulfonic acid per?uorooctane sulfonic acid (PFOS) 5, 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 4Information sources customarily employed include Inventory Update Reporting (IUR) submissions; Toxic Relea Inventory (TRI) reporting; data submitted to the HPV Challenge Program; existing hazard and risk assessments performed by domestic and international authorities including but not limited to US. Federal government agencie 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 erg-(cans-soaH; CAS RN: [355-464]. 5 caravan-scan; CAS RN: [1763-23-1]. rd; 1is 65 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 established whe reviewing representative structures of the different category member compounds: a. CF 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 (PFOA) 7 and other higher hcmologues. The category also includes the acid salts and precursors. . Long-Chaln PFAC SubCategory 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; (1. CF where is any chemical moiety; and e. where non?S, non-N hetero atom and where is any chemical moiety. 7 CAS RN: [335-67-1]. l9 U.S. Environmental Protection Agency 12/30/2009 wheren>5 orm>6. IV. Uses and Substitutes 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?reiated 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 increase 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 carpet care products accounting for the next largest share in consumer product uses. Coatings, includii those for paper products, are the third largest category of consumer product uses. Fluorotelomer release sources, and consequent exposure'to fluorctelomers, can be exPlained through the examination of the life cycle of this category of chemicals: Manufacture of Monomers -) Manufacture of Polymers 9 Processing and Use 9 Product Lille The manufacture of non-polymeric chemicals (surfactants, wetting agents, cleansers, etc.) 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 conten?. Companies reporting under PFOA Stewardship Program differentiate between the amounts of PFAC precursors present in the ?nal 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 (F TBP) 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. 1g U.S. Environmental Protection Agency 12/30/2009 Uses PFCs are substances with Special properties that have thousands of important manufacturing and industrial applications. They impart valuable properties, including fire 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?chain PFAS chemicals, as defined 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 fire ?ghting 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. PFOA 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 thousands 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 PFOA. Fluorotelomers 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 - 11 even ?ow is essential, such as paints, coatings, cleaning products, and fire?fighting foams for u'se on liquid fuel ?res. luorotelomer-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. Fluorepolymers, such as polytetra?uoroethylene (PTFE), which may contain some PFAC contamination, 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 fluoropolymer market, accounting for more than 35 percent of total U.S. ?uoropolymer use. Apparel makes u] about 10 percent of total ?uoropolymer use, based on total reported production volume.- Fluoropolymers are used in a wide variety of mechanical and industrial components, such as Environmental Protection Agency 12I3OI2009 plastic gears, gaskets and sealants, pipes and tubing, O-rings, and many other products. Total US. demand for fluoropolymers in 2004 was between 50,000 and 100,000 metric tons. The United States accounted for less than 25 percent of the world consumption of PTFE in 2007, and between 25 and 50 percent of the world consumption of other ?uoropolymers. PTFE is the mo commonly used ?uoropolymer, and the United States consumed less than 50,000 metric tons of PTFE in 2008. 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 the potential risk from chemicals new to the marketplace. review of alternatives to long-chain PFCs has been ongoing since 2000 and is it i 5W consistent with the approaches to alternatives encouraged under the PFOA Stewardship Progr 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 bioaccumulatio . issues that have caused past concerns with per?uorinated substances, as well as any issues the may be raised by new chemistries (EPA, 2009b). V. Hazard Identification Summary The information used by EPA for this Action Plan includes the Organisation for Economic Co-operation and Development?s (OECD) assessments of PFOS (OECD, 2002) and PFOA (OECD, 2006), Of?ce of Pollution Prevention and Toxics? (OPPT) draft risk assessment of PFOA (EPA, 2009d), Environment Canada?s assessment (Canada, 2006), the assessment of PFOS 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 seminal plasma. 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 perfluorooctane sulfonamide (PFOSA), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid sulfonamido) acetic acid or PFOSAA), perfluoroheptanoic acid per?uorononanoate (PFNA), perfluorodecanoic acid or PFDA), per?uoroundecanoic acid (PFUA), perfluorododecanoic acid m. U.S. Environmental Protection Agency 1213012009 per?uoropentanoic acid per?uorohexanoic acid (PFHXA), and per?uorobutane sulfonate (PFBS). National Health and Nutrition Examination Survey (NHANES) data show that mean levels of PFOS, PFOA and in the general U.S. 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 reportr 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 lev: ofperfluorinated compounds are higher in children ages 3-11 years compared to adults (individual samples 2001?2002), especially for (Kato, 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 US. 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, PF OS 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 11? 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-C11 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, Cl 1, and C12) were found in fillets from bluegill in selected rivers in Minnesota and North Carolina (Delinslq 2009). In general, the highest concentrations in wildlife have been found in the livers of ?sh? eating animals close to industrialized areas. 3 :d ls u-JQ?l N. \l 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 09-011 PFAC have been found in remote Arctic region sediment ranging from 0.68 rig/kg 2.58 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/g in the Raisin, St. Clair, and Calumet Rivers (MI)(Kannan, 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/g ww and worms from the Ariake Sea in western Japan had concentrations of PFOA of 82 ng/g WW. PFAS and PFAC are Persistent, Bioaccumulative, and Toxic Persistence and Bioacczimulation in Humans and Laboratorv 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 alsr 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 1. Comparative Rates of Elimination" UW I U) :3 Serum PFOS PFOA PFNA PFDA Half-life (C6) (C8) (CS) (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 1213012009 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 '6 measured in hours to days to months in rats, mice and monkeys, but years in humans. This mes 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 rather than administered dose. Persistence and Bioaccumulatz?on 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 (Conder, 2008). Studies have found ?sh bioconcentration factor (BCF) values for C8 to C14 PFAC ranging from 4 - 40,000 in rainbow trout (Martin, 2003). Fish BCF values for C8-C11 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 (C16) in carp and BCF values from 320 to 430 for perfluorooctadecanoic 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 a smaller cross-sectional diameter as chain length increases which can lead to the ability to accumulate in organisms (NITE, 2002a, 2002b). Additional evidence that C14 and C15 PFAC bioaccumulate and are bioavailable is their presence in fish, 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 direct] related to the length of the per?uorinated chain, and PFAS are more bioaccumulative than of the same chain length (Conder, 2008). Within the PFAC and PFAS categories, the perfluorinated carboxylic and sulfonic acid. (Rf from CS to 020) are persistent chemicals that are resistant to degradation under environmental conditions. Even the reaction of precursors with hydroxyl radicals 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, JL 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 ?uorochemicals. These studies speci?cally examined PFOS or PFOA exposures and possible adverse outcomes. One occupational study of exposures to a PFNA surfactant blend was Lu :5 in i .C I-l- 11 U.S. Environmental Protection Agency 12/30/2009 undertaken. The studies on PFOS and PF 0A include mortality and cancer incidence studies, a study examining potential endocrine effects, an ?episcides-of?care? study evaluating worker insurance claims data, and worker surveillance studies examining associations between primar 1y PF OS 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 fluorochemical levels and adverse health effects has been observed. Toxicity in Laboratory Animals . PFOA The toxicity of PFOA 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 ppm: (76.5 mg/kg?day) and in male rats at doses as low as 100 (5 Studies in 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 caroinogenici1 studies in Sprague-Dawley rats, and has been shown to induce hepatocellular adenomas, Leydi cell tumors, and pancreatic acinar tumors. It has not been shown to be mutagenic in a variety assays. There is sufficient evidence to indicate that PFOA is a PPARd-agonist and that the livei? carcinogenicity (and toxicity) of PFOA is mediated by in the liver in rats. There is no evidence that the liver toxicity in nonhuman primates is due to PPARa?agonism. There is controversy over the relevance of this particular mode of action for humans. The mode of actio 1 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 immunotoxic in mice. PFOA causes thymic i and splenic atrophy, and has been shown to be immunosuppressive 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 sacrificed prior to the birth of the pups have not! shown many effects. Thus, there was no evidence of deveIOpmental toxicity after exposure to 1 doses as high as 150 mg/kg-day in an oral prenatal developmental toxicity study in rats. In a ral:T 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 rats 10 U.S. Environmental Protection Agency 12/30/2009 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 i1 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 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' 1n mammary gland differentiation 1n the da1 and stunted mammary gland development 1n the female pups. l?l .. ""33 CD 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 knockout mice have shown that the PPAROL 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 is not involved in the neonatali mortality associated with PFOS exposure. Although there is controversy over the human relevance of the PPARu?agonist hepatotoxicity observed in rodents, the role of PPARCL 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 PFAC Chemicals Although there is an extensive database for PFOA, few studies have examined the toxiciw of the shorter or longer chained PFAC. However, the data suggest that the toxicity 5 pro?le' IS quite similar to that of PFOA albeit at different dose levels presumably due to the differences' 1n elimination half?life. Although standard repeated-dose toxicity studies have not been conducted on the PFAC, with chain greater than 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 B- oxidation' 1n 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 PFOA per?uoroheptanoic acid (2006). Pennadi et al. also showed th 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 PFOA. .. . 31? ll U.S. 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 deveIOpmental 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 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 a1. (2006). Repeated-dose studies in rats and nonhuman primates 3 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 precursor of PFOS. PFOS has not been shown to be mutagenic in a variety of assays. Althougl PFOS can activate the data are not suf?cient to establish a PPARu-agonist mode of action for the live1 tumors 1 A standard prenatal developmental toxicity study in rats has shown a significant decrease in fetal body Weight and signi?cant increase in external and visceral anomalies, delayed . ossification, and skeletal variations, of 1 mg/kg-day and a LOAEL of 5 mg/kg?day 1 or developmental toxicity were indicated. In rabbits, significant reductions' 1n fetal body weight a hd signi?cant increases in delayed ossification 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/kg?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/kg?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/kg-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 BMDs ar'd BMDL5 for neonatal survival of 1.07 and 0.58 mg/kg?day in rats, respectively, and 7.02 and 3. 88 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 significant" histological and morphometric differences in the lungs of pups treated with PFOS. However, 12 U.S. Environmental Protection Agency 1213012009 subsequent studies did not ?nd 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 18 not involved in the neonatal mortality. Current research' 13 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 exposur5 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/L of PF US 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 effect has been observed with exposure to 09?011 PFAC. A ?significant induction of vitellogenin in rainbow trout was observed in a dose-dependent manner at concentrations of CID PFAC 0.025 2000 pig/g in the diet as 'well as a weak af?niw demonstrated for the hepatic estrogen receptor from PFAC. Mortality in sediment dwelling organisms such as the nematode, Caenorhabdz?tis elegai has been observed with concentrations of C9 up to 0.66 mM and subsequent effects' 1n generations were found at concentrations up to as evidence by a 70 decline' 1n fecundit 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 1n 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 2 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 e. ,p,Ka) or the fraction of the acid form present at environmentally relevant pH. PFAC and PF AS have been detected' 1n air, water, and soil samples collected throughout the world. The oceans have been suggested as the ?nal sink and route of transport for perfluorinated carboxylic and sulfonic aci 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 ov 13 I1 as Y. 1' is, U.S. Environmental Protection Agency 1213012009 long distances e. ,long?range transport) by a combination of dissolved-phase ocean and gas? phase atmospheric transport; however, determining which' re the predominant transport pathway is complicated by the uncertainty over water to atmosphere partitioning. Furthermore, there' 15 evidence that transport and subsequent oxidation of volatile alcohol precursors n?iay contribute to the levels of PFAS 1n 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 FTOH c' other chain and related chemicals in mixed microbial cultures, activated sludge and sci systems have been shown to be easily degraded to form PFOA and related per?uorinated acids. Some studies have also shown that groups can be mineralized, forming shorter chain 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 g?n 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 i fairly volatile. Based on atmospheric half-lives determined in chamber studies, FTOH can be levels of PFAC and PFAS. Data submitted by industry and in the open literature show that perfluorooctane sulfonyl fluoride (POSF) and its derivatives can be degraded under environmental conditions to form i 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 perfluoroalkyl sulfonates and carboxylic acids. Reaction of POSF (CF with methyl or ethyl amines is used to produce N-ethyl or N?methyl perfluorooctane sulfcnamidoethanols (FUSE). Similar reactions are used to make shorter and longer chain analogs to POSF and POSF i derivatives. FOSE compounds, (or where R1 and R2 can be hydrogen, methyl or longer alcohols or other organic chains), such as N?methyl and N?ethyl and perfluoroalkyl 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 number of microbial and abiotic mechanisms. Reaction with other chemical intermediates produces other FOSA derivatives, including phosphate esters, fatty acids esters, silanes, carboxylates, and polymers with acrylate, urethane and other linkages. Longer and shorter cha1' FOSEs can be degraded though a series of intermediates to form both per?uoro carboxylic acifs .d I perfluoro sulfonyl derivatives have also been produced intentionally and as unintended reactio 1 products. Based on existing data from the open literature and CB1 data, it is expected that that 1n 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 perfluorochemicals 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 poly?uoroalkyl 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 perfluorinated acids (D?eon, 2007). 14 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. In addition, preliminary research on degradation of ?uorotelomers has shown that some urethanes and acrylates biodegrade; however, half?lives and kinetics of the ?uorotelomers are not yet well-de?ned. Ongoing research by Of?ce of Research and Development research is designed to generate high quality data that will help the Agency address some key uncertainties in pathways of exposure and potential risks from PFOA (Washington, 2009). These studies have shown that the perfluorinated portion of some polymers is released as the polymer is degraded by microbial or abiotic processes to form telomer 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 degradie 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. VII. Exposure Characterization Summa? 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. Maj or 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 plants; 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. Summary of Exposure to Consumers and Children #0172 PF Cs in Indoor Environments PF Cs in Articles of Commerce EPA's 0RD has conducted research on 116 articles of commerce documenting that 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, ?oor 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 (non-detect)-3488 ng/g and ND?4640ng/ reSpectiVely; ?oor wax and sealer: 0.03-3720 ng/g; and home textiles: ND-519 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 from 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 contacts. Consumers and children may also be exposed to PFCs in apparel, home textiles, thread sealant: tape, ?oor 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. U) PF Cs in Indoor Air Another source of PFCs to the indoor environment is dust containing not only PFAC and PFAS but also ?uorotelomer 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 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 Exgosure to the General Population PFCS in. Groundwater, Freshwater, Salnvater, 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 PF OS have been measured in the Paci?c Ocean at 57,700 ng/l and in 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 love 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 in Is experience dermal, ingestion and inhalation exposures when coming into contact with freshwater 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. PFCS in Freshwater and Saltwater Fish Freshwater ?sh have been found to contain levels of PFAS and PFAC. The highest leve 16 ls . 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 F, 2006). Liver samples of bass, walleye and carp ranged from 130?6350 ng/g PFOS wet weight. Blood samples of these same ?sh ranged from PFOS levels of 136?29600 ng/ml in serum. Tot a1 PF Cs for the blood of freshwater ?sh in the same area was measured at 32248 ng/ml serum. The highest levels of PFAC for freshwater ?sh were found near the 3M Cottage Grove, MN site ar were measured for blood samples of bass, walleye, and carp in the range of 2.53-21 0 ng/ml serum. For comparison, saltwater ?sh in Danish seas had measured levels of PFOS 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 Summam 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. Final 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 that phase-cut. 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 Partie (COP) to the Stockholm Convention on POPs, held in May 2009, delegates agreed to add PPO its salts, and per?uorooctane sulfonyl fluoride (PFOSF) to Annex B, subjecting it to restriction on production and use. Parties agreed that while the ultimate goal is the elimination 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 to 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). roomy, PFAC Chemicals core strategy for working towards the elimination of PFAC chemicals has been through the PFOA Stewardship Program. Under the program, eight major companies operating 17 U.S. Environmental Protection Agency . 1213012009 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 content 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 perfluoroalkyl moieties from eligibility for the exemption? (EPA, 2006). Under this proposal, polymers containing these perfluoroalkyl moieties would need to go through the pre?manufacture noti?cation (PMN) review process so that EPA can better 1 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 longer 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 TSCA. This amendment to the polymer exemption rule is a necessary complement to the PFOA Stewardship Program and will 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 deve10p PHA values forth other PFCs. 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 used 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 level 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 prograrr 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 18 U) U.S. Environmental Protection Agency 12/30l2009 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 PFOA 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 State This is in part because companies not participating in the PFOA Stewardship Program may follow the market Opportunity presented when the eight PFOA Stewardship Program compani leave the PFAC market by 2015. This occurred with PFAS production in some Asian countrie 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' 1n PFOA Stewardship Program, resulting' 1n transboundary environmental transport to United States; 0 Articles, including imports, containing PFAC chemicals. These articles could release PFA as a result of then residual content 1n fluorotelomer-based products and/or as the fluorotelomers-based polymers 1n 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 identi?ed 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 PF Cs. EPA intends to consider initiating TSCA section 6 rulemaking for managing long-chaix of ES. 91' PFCs. If EPA can make certain ?ndings with respect to these chemicals (further analysis ofth- authority for EPA to ban or restrict the manufacture (including import), processing, and use of. information will be performed as part of TSCA section 6 rulemaking), TSCA section 6 providin?s these chemicals. A rule addressing the PFAS sub-category could expand beyond the reach of t} 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 U.S. Environmental Protection Agency 12/3012009 reach of the 2010/15 PFOA Stewardship Program beyond the eight participating companies ar 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) "prese or will present an unreasonable risk" ?ndings. If these more detailed assessments indicate that different approach to risk management is appr0priate, EPA will consider additional approache EPA will continue with the 2010/15 PFOA Stewardship Program to work with compar 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 disproportionate impact on children and other sub?populations. 20 ?1123 a . lies ue U.S. Environmental Protection Agency 12/30/2009 X. References Bossi R, R. F., Dietz R, Sonne C, Fauser P, Dam M, Vorkamp (2005). Preliminary screening ofperfluorooctane sulfonate (PFOS) and other ?uorochemicals 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 JA, Needham LL (2007). Polyfluoroalkyl chemicals in the US. Population: data from the National Health and Nutrition Examination Survey (NHANES) 20 03 --20 04 and comparisons with NHANES 1999-2000. . Environmental Health Perspective, 11501), 1596?1602. Canada (2006). Ecological Screening Assessment Report on Per?uorooctane Sulfonate, Its Salts and Its Precursors that Contain 031737802, or C3F17S02N Moiety. From list/PFOS SARIPFOS TOC.cfm> Gender JM., Hoke RA, de Wolf W, Russell MH, Buck, 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 C, Mabury SA (2007). Production of per?uorinated carboxylic acids (PFCAs) from the biotransformatior poly?uoroalkyl phOSphate surfactants (PAPs): exploring routes of human contamination. Environmental Science and Technology, 4] (13), 4799?4805. - De Silva A0 (2008). Per?uorocarboxylate 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 0 tan perfluorinated compounds in bluegill sun?sh (Lepomis macrochirns) fillets Environmental Research, 109, 97 984. Department of Health and Human Services (2005). Health Consultation 3M Chernolite, Pet?uoroohemical Rates at the SUM-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 perfluorooctanoate: relationships between serum levels and certain health parameters Journal of Occupational Environmental Medicine 48(8). EPA (2002a). Sulfonates; Significant New Use Rule. from EPA (2002b). Sulfonates; Significant New Use Rule. . from l/l5746.h1m> EPA (2006). Premanufacture Notification Exemption for Polymers; Amendment of Polymer Exemption Rule to Exclude Certain Polymers. from 07/t2152.htm> EPA (2007). Sulfonates; Significant New Use Rule. from EPA (2009a). 2010/2015 PFOA Stewardship Program from EPA (2009b). New Chemical Review of Alternatives for PFOA and Related Chemicals ?om EPA (2009c). Perfluorooctanoio Acid (PFOA) and Per?uorooctance Sulfonate (PFOS): Provisional Health Advir 21 of 5- 88.9 l> U.S. Environmental Protection Agency 12/30/2009 i information, from: OECD (2002). Perflucrooctane Sulfonate (PFOS) and related chemical products, ?om 2649 34375 23 84373 1 1 37465.00.hlm]> OECD (2006). SIDS Initial Assessment Report for Ammonium Pety?luorooctanoate and Pet?uorooctanoie Acid. Oliaei F, Kriens D, Kessler K, (2006). Investigation of pei?uorochemical (PFC) contamination in Minnesota, Phase One, Report to Senate Environment Committee - Olsen GW, Mari DC, Reagcn WK, Ellefson ME, Ehresman DJ, ButenhoffJL, Zobel LR (2007). Preliminary evidence of a decline in per?uorooctane sulfonate (PFOS) and per?uorooctanoate (PF 0A) concentrations in American Red Cross blood donors. Chemosphere 68(1), 105-111. . Olsen GW, Mari DC, Church TR, Ellefson ME, Reagen WK, Boyd TM, Herron RM, Medhdizadehkashi Z, Nobiletti JB, Rios A, Butenhoff JL, Zobel LR (2008). Decline in perfluorooctane sulfonatc and other poly?uoroalkyl chemicals in American Red Cross adult blood donors 2000-2006. Environmental Science and Technology, 42(13), 4989-4895. PaulAG, Jones. KC, Sweetman AJ. (2009). First Global Production, Emission, and Environmental Inventory fc Per?uorooctane Sulfonate. Environmental Science and Technology 43, 386-392. "1 Permadi H, Lundgren B., Anderson K, Sundberg C, DePierre (1993). Effects of per?uoro fatty acids on pcroxisome 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 (2009). Fourth Meeting of the Conference of the Parties of the Stockholm Convention Paper presented at ti Stockholm Convention on Persistent Organic Pollutants, Geneva, Switzerland (D 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 GC-MS and analysis of PFOA from large-volume samples Environmental Science and Technology, 40(20), 6405-6410. Shoeib M, Harrier 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. MJ, AB (2008). Per?ucrinated compounds in house dust from Ohio and North Carolina, USA. Environmental Science and Technology, 42(10), 3751-3 756. . Tomlin, C. (2005). sub'onamide (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 UNEP (2009b). Workshop on Managing Petj?luorinated Chemicals and Transitioning to Sayer Alternatives. from Washington W, Ellington H, Thomas MI, Evans Hoon Yoo, Hefner SC (2009). Degradability of an acrylate- 23 U.S. Environmental Protection Agency 12l30/2009 linked, ?uorotelomer polymer in soil Environmental Science and Technology, 43(17), 6617-6623. Wenya, H. (2008). PFOS related in China Paper presented at the International Conference on Chemicals Management Yamashita N, Kurunthaehalam K, Taniyasu S, Horii Y, Petrick G, Game (2005). A globai survey of per?uorinated acids in oceans. Marine Pollution Bulletin 65 8?668. 24 EXHIBIT Bilott, Robert A. From: US Environmental Protection Agency Sent: Monday, July 31, 2017 11:23 AM To: Bilott, Robert A. . Subject: EPA Adds Saint-Gobain Performance Plastics Site in Hoosick Fails, N.Y. to the Federal Superfund List - . . EPA Adds Saint-Cobain Performance Plastics Site in Hoosick Falls, N.Y. to the Federal Superfund List Contact: Elias Rodriguez, (212) 637?3664, rodriguez.eiias@epa.gov (New York, N.Y. July 31, 2017) The US. Environmental Protection Agency has added the Salnt?Gobain Performance Plastics site in the Village of Hooslck Falls, N.Y. to its Superfund National Priorities (NPL) of the country?s most hazardous waste sites. Groundwater at the Saint-Gobain Performance Plastics facility, located at 14 McCaffrey Street, and in other locatio Is in Hoosick Ealis is contaminated with Per?uorooctanoic Acid (PFOA) and Trichloroethylene (TOE). Adding the site to the federal Su .erfund list will allow the EPA to work with New York State to ensure that the contamination is cleaned up and that people's health 5 protected. I ?My goal as Administrator is to restore the Superfund program to its rightful place at the center of the agency's core mission. Today; we are adding sites to the Superfund National Priorities List to ensure they are cleaned Up for the bene?t of these 0 mmuntties," 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 1961, and had been used to manufacture circuit board laminates, polytetr ,fluoroethyier (PTFE)-coated ?berglass and other PTFE products. In 1999, Saint-Gobain Performance Plastics purchased the fa ility and begs operations there, using PFOA in its manufacturing process. PFOA belongs to a group of chemicals used to make }ousehoid anc :5 5" commercial products that resist heat and chemical reactions and repel oil, stains, grease and water. PFOA was wi ely used in stick pots and pans, stain-resistant carpets, and water-resistant outerwear. in 2006, the EPA reached a nationwide agreement Vi eight manilfacturers to phase out the production and use of PFOA. These manufacturers stopped using PFOA in 015. PFOA is persistent in the environment and can pose adverse effects to human health and the environment. TCE is a volatil organic compound widely Used as an industrial solvent. Exposure to TCE can have adverse health impacts, including liver damage and increased risk of cancer. After PFOA was disGOVered in the public drinking water supply, a carbon ?ltration system was installed on the Villa e. of Hoosic water supply wells to treat the water and protect consumers. PFOA was also discovered in private wells, and specEi systems 0 lied ?point of entry treatment systems," or POETS, have been installed on a number of private drinking water wells. Th New York 'ate Department of Environmental Consewation (NYSDEC) and Department of Health, with input from the EPA, have dverseen me to address the drinking water contamination. i 0 in January 2016, the NYSDEC added the Saint-Gobain site to New York State's Superfund list and requested that the EPA incl . de the site on federal Superfund list. I 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 frorr McCaffrey Street facility, Village baii?eids and recreational areas. 0 In June 2016, the NYSDEC entered into a legal agreement with Saint-Gobain Performance Plastics Corporation a'id Honeywell 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?Gobain Performance Plastics site to the federal Superfund list. he 1 The EPA has determined that the appropriate course of action to address contamination from the Saint?Gobain facility is to list the site on the NPL. The EPA took public comment and considered public input before ?nalizing the decision. The EPA is coorclnating all investigation and cleanup efforts with New York State. To learn more about the Saint-Gobain Performance Plastics Sup erfund site. ease visit: For Federal Register notices and supporting documents for ?nal and proposed sitesI visit: und/current- Today's 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 pg cleanup and reuse efforts by potentially responsible parties, encouraging private investment to facilitate cleanup and reuse, promotl tg 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. "he Superfund Task Force Recommendations can be viewed at Follow EPA Region 2 on Twitter at and visit our Facebook page, i 17-049 If you would rather not receive future communications from Environmental Protection Agency, let us know by clicking here. Environmental Protection Agency, 290 Broadway, New York,. NY 10007-1866 United States nited States Enwronmentai Protection h' Agency as Ing 3EPA . I NATIONAL PRIORITIES LIST (NPLJuly 2017 PERFORMACE PLASIICS Village of Hoosick Falls, New York I Rensselaer County Site Location: i The Saint-Gobain Performance Plastics (SGPP) site is located at 14 McCaffrey Street In the Village of oosick Fa ls, Rensselaer County, New York. The facility' IS situated' In the southwest corner of Hoosick Falls and along the east SI'de of the Hoosic Rive1.l A Site History: SGPP manufactures plastic materials, tapes, and foams and has operated in I-Ioosick Falls from 1999 to the present. The McCaffrey Street facility was originally built in 1961 and was used for manufacturing extruded tapes, circuit board laminates, polytetra?uoroethylene (PTFE)-coated ?berglass, and molded and extruded PTFE intermediates before SGPP began Operations. The facility used perfluorooctanoic acid (PFOA)?containing mate 'ials in their manufacturing process until they began phasing them out in 2003. I Site Contamination/Contaminants: Ground water underlying the SGPP facility and withdrawn by the public supply wells for the Village of l-Ioosick Falls is contaminated with PFOA above the Health Advisory and with chlorinated solvents, such as trichloroet 1y1ene (TC .B) and vinyl chloride. i flit Potential Impacts on Surrounding Community/Environment: The public supply wells in the Village of Hoosick Falls, which serve approximately 4,000 people as the It ain sourcelof 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): iition, PFQA Saint-Gobain Performance Plastics installed a carbon ?ltration system. Drinking water now meets all fed standards. Need for NPL Listing: eraI and st . re Ground water contaminated with PFOA 1n the public supply wells requires cleanup to protect human 1' environment. NPL listing has been determined to be the most effective approach for cleanup. The EP letter of support for placing the site on the NPL from the state of New York. [The description of the site (release) is based on information available at the time the site was evaluated with the HRS. The change as additional information is gathered on the sources and extent of contamination. See 56 FR 5 600, February 11, 199. notices. For more information about the hazardous substances identi?ed in this narrative summary, including general information regarding the to these substances on human health, please see the Agency for Toxic Substances and Disease Registry (ATSDR) ATSDR 'l?oxF. on the Internet at or by telephone at 1-800-CDC-INFO or 1-800-232-4636. .fects of expos ?g can be fo ealth and A receiver description or szIbseqz eat the a to are sad SITE SUMMARY The Saint?Gobain Performance Plastics (SGPP) site as scored consists of. soil and ground water contaminated trichloroethylene (TCE), vinyl chloride (VC), biphenyls (PCBs), and perfluorooctanoic acid (PFOA) as a result of historical releases from the SGPP facility located at 14 McCaf?ey Street in Hoosick Falls, NY. Sampling and analysis of soil and ground water by EPA in April?May 2016 document the presence of TC E3 in facility soils, and TCE, VC, and PFOA in ground water at concentrations that meet the criteria for observed rel ease by chemical analysis [see Section 3.1.1 of this HRS documentation record]. Sampling and analysis by EPA o"the Village of Hoosick Falls municipal water supply in May 2016 document Level I actual contamination of drinting water wells with VC and Level II 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 documents 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?l,2?dichloroethylene (DCE), TCE, and PCBs (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 SGPP facility soil; hows ver, due to laboratory quality control issues, the data are cpnsidered unusable and will not be evaluated in this HRS Documentation Record Package. producing extruded tapes and then circuit board laminates; prior to 1961 the property was vacant land [Ref 3 p. 23]. Oak Materials Group Oak Electronetics; a.k.a. Oak Industries) purchased the property from dge Fibers between 1969 and 1971 [Ref 39, p. 23]. Oak Industries operated the facility until 1987 when it was so to Allied Signal Fluorglas [Ref 39, p. 23]. The property was sold to Furon Company in February 1996 [Ref 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]. Fluorepolymers used to manufacture on- stick coatings are known to include PFOA [Ref 13, p. 20; 52, p. The facility that currently houses SGPP was originally built in 1961 for Dodge Fibers Corp. and was used firs? for SGPP has operated at 14 McCaf?'ey Street (Tax Map/Parcel No. Section 37.6, Block 3, Lot 1) since 1999 [Ref i? p. l; 18, p. SGPP is a Paris-based multinational corporation which manufactures a variety of polymer-based products [Ref 14, pp. The McCaffrey Street facility manufactures high-performance polymeric films and membranes, as well as foams for bonding, sealing, acoustical and vibrational damping, and thermal managemnent; the facility previously used PFOA in its manufacturing processes [Ref 4, p. 14, pp. 4, 7, The facili . is situated near the southwest corner of Hoosick Falls and along the east side of the Hoosic River [Figure 1; Ref. 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. 1; 19, p. PFOA is a man- chemical that belongs to a group of ?uorine-containing chemicals called per?uorinated chemicals (PFC) [Ref 1 p. 2; 15, p. PFOA was once widely used in nonstick cookware, in surface coatings for stain-resistant carpets and 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. 0A and related compounds are persistent in water and soil, and resistant to typical environmental degradation prose 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 so] at room temperature, and it is water-soluble and can readily migrate from soil to ground water [Ref 15, pp. discharged to the air item 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, ?lters were installed in the facility?s smokestacks in the early lEi'SOs [Ref 4, p. A former employee stated that the ?lters and other equipment contacted by the white powder ere cleaned weekly by washing them on a hillside outside the plant [Ref 4, p. Former employees of the McCaffrey Street facility describe a powder~like smoke plume that was routii?ely The Village of Hoosick Falls operates three public supply wells (Village Wells 3, 6, and the Well ?eld is loc ted 2.4.1 Hazardous Substances As discussed above, soil samples collected by SGPP in August 2015 document the presence of PFOA in faci?ity soils. Soil and ground water samples collected by EPA in April 2016 document the presence of TCE, cis-1,2-D SD- Hazardous Substan Source No. 065 and PCBs in site soils and TCE and VC in the aquifer of concern. As all of these compounds are man-m de chemicals and do not naturally occur in the environment, the data for the samples discussed above are considered for source documentation and are presented in Tables I therefore, background soil samples are used for comparison purposes. Sampling and analysis by EPA in April May 2016 showed the presence of PF 0A in soil; however, due to laboratory quality control iss the data are considered unusable and will not be evaluated in this HRS Documentation Record Package. mg The source type is contaminated :Boil; find I es, TABLE 1. BACKGROUND AND SOURCE SAMPLE INFORMATION and TCE Field Sample CLP Sample Sample Depth ID ID Date Time (feet) Solids References Back Iround Sample 301313?301 IBD371I 5/3/2016 1550 0?2 I 31.7 I Source Sam 1e seep-$30713 IBD3B1 I 4/27/2016 1710 10?12 88.7 I 22, p. 24; 23,p. 84;.49, pp. 3, 168 TABLE 2. BACKGROUND AND SOURCE SAMPLE INFORMATION PCBS Field Sample CLP Sample Sample Depth ID ID Date Time (feet) Solids References Background Sample IBD371 5/3/2016 1550 0?2 (81.7 22, p. 29; 23, p.112; 45, pp.2, 1220 Source Sam le SGPP-SO7 BD3A9 4/27/2016 I 1650 I 0?2 78.3 22, p. 24; 23,p. 84; 49, pp. 3, 1200 TABLE 3. BACKGROUND AND SOURCE CONCENTRATIONS cis-l,2-DCE and TCE Maximum Background Source Concentration Concentration Field Sample ID SGPP-SSO7B Sample Date 5/3/2016 4/27/20] 6 CLP Sample ID BD371 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, 16041, pp. 2?6, 28, 122Concentrations reported in micrograms per kilogram (pg/kg). 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 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 an through CLP, these adjusted are used in place of the HRS-de?ned sample quantitation limit (SQL) [Rc? 1.1 and 23 Contract ialyzed Sections . Hazardous Substances Released: Trichloroethylene (TOE) Vinyl chloride (VC) Per?uorooctanoic Acid (PFOA) 48 GW-Observed Rel CAS No. 79?01-6' No. 75-01-4 CAS No. 335-67- .ase EXHIBIT Overview Per?uorinated chemicals (PFCs) ATSDR age 1 of 2 ATSDR Agency for Toxic: Substances and Disease Registry Overview Per~ and Poiyfluoroaikyi 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 res, making and using these chemicals in consumer products has greatly decreased during the lal 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 anima-ls? health but are still trying to understand hon/v exposure to PFAS affects human health Over the last decade, interest in PFAS has been groLving. ATSDR and our state health partners are investigating exposure to PFAS at a number of sites. PFAS are heat, oil ?grease and water reSistant. The two best known groups of this family of chemicals are the perfluorocarboxylic acids (PF CA5), which include perfiuorooctanoic acid (PFOA, sometimes called C8), and the perfluorosulfon ates (PFSAs),which include perfiuorooctane sulfonate (PFOS). PFCAs and PFSAs do not break dc easily in the environment. They also bioaccumulate, or build up, in the blood and organs of e: 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 ti 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 2006, EPA and major companies in the PFAS industry launched the 2010/2015 PFOA Stewa Program. Companies participating in the program are working to stop producing PFOA and chemicals by 2015. These companies include Arkema, Asahi, BASF Corporation (successor tc Clariant, Daikin, 3M/Dyneon, Du Pont, and Solvay Solexis. (posed body es. in rdship elated Ciba), List of Perfiuorosuifonates and Perfiuorocarboxylic Acids and Their Abbreviation. Ul Chemical Abstracts Chemical Abbreviation Service Registry Chemical Fo Number (CAS No.) 'mula Perfiuorosuifonates (PFSAs) i 8/ 10/2017 Overview] Per?uorinated chemicals (PFCs) ATSDR age 2 of 2 Perfluoro butane sulfonate PF Bus 375-73?5 C4H F9035 Perfluorodecane sulfonate PFDS 335-77?3 F21 335 Perfluoroheptanesulfonate - 375-92-3 C7HF1503S Perfluorohexane sulfo nate 432?50-7 CGH F13035 Perfluorooc?cane sulfonate 1763-23-1 caHF?ogs Perfiuorooctanesulfonamide PFOSA 754?91-6 025 Perfluorocarboxylic acids (PFCAs) Perfluorobutanoic acid PF BA 375?2214 C4H F702 Perfluorodecanoicacid PFDA 335?76-2 Perfluorododecanoic acid 307-55-1 C12H F23 C32 Perfluoroheptanoic acid PFH pA . 375-85?9 C7HF1302 Perfluorohexanoic acid PFHXA 307-24-4 C6H F1102 Perfluorononanoic acid PF NA 375-95?1 C9H F1702 Perfluorooctanoic acid PFOA 335-674 Perfluoroundecanoic acid PFUA 205 8?94-8 C11H F21 32 A lea?ess Page last reviewed: September 18, 2015 Page last updated: May 26, 2016 Content source: Agency for Toxic Substances and Disease Registry . 10/ 2017 Health Effects of PFAS Per?uorinated chemicals (PFCS) ATSDR I age 1 of 2 ATSDR Agency for Toxlc SubstanCQs and Disease Health Effects of PFAS On this Page 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 exposure to PFAS at levels typically found in our water and food. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate and perfluorononanoic acid (PFNA) have been more widely studied than other PFAS. For the most part, laboratory animals exposed to high doses of PFOA or PFAS, including the PFAS mentioned above, have shown c: hanges in the liver, thyroid, and pancreatic function, as well as some changes in hormone levels. Because animals and humans do not always process chemicals the same way, scientific methods are sed to account for these differences and ensure their conclusions about chemicals are protective of the public. Some PFAS accumulate in the human body and the levels decrease slowly over time. The ab?n 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 lity of bout ixtures of PFAS. Further studies are needed to understand whether the same effects are caused by the same mechanism of action. f10/2017 8/ Health Effects of PFAS Per?uorinated chemicals (PF Cs) I 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 for reducing individual exposures in the general population. However if you live near known so 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. addition, research has suggested that exposure from consumer products usually low, especially when compared to the impact of exposure in contaminated drinking\ contaminated food such as fish. You can contact for updated information on this topic at FO. If you have questions or concerns about the products you use in your home, contact the Cor Product Safety Commission at (800) 638-2772. A T09 Page last reviewed: August 16, 2016 Page last updated: August 30, 2016 Content source: Agency for Toxic Substances and Disease Registry r.cdc.gov) i . . age 2 of2 levels in ly urces of 5 :0p or public 3 learn :ive 1 the )0d of is vater or sumer {10/2017 How is ATSDR involved investigating PFAS in the environment? Per?uorinated Page i of 4 ATSDR Agency for Toxic Substances and Disease Registry How is ATSDR involved investigating PFAS in the environment? ATSDR is involved at a number of PFAS-related sites, either directly orthorough assisting state and federal partners (Figure 1). As of now. most sites {are related to drinkingwater contamination connected with PFAS prodUction facilities or fire training areas where aqueous fire?ghtingfoam (AFF was regularly used. We are working with onestate partner on a site where consumlng contaminated fish is the concern. ATSDR involvement at sites with poly? and perfluoroalkyl substances (PEAS) Puluuoulh?l? ?lolni lJ-m (an: Cod,? ilmlAirli?rlmunm. Bice?i'illmv?mePA I ?realmliag?nleni I DwaiAlii'orre Eamon-sci. DE I Erpoluelmdligrfion -.. Erratum I I a I mien intone Base, bulimia?: Explanation 9 Plenum A A Dala sourceATSDH Redmlsialiand Envimnmurial lleallhl?odialiammgeminisyslem the lntaiionandsiresfmm. Hawaiian-l Punio Rim wmalimd tn ?l lh?i nup View. laslupdmd Inlao?li. Figure 1. Perfluorlnated compound (PFAS) sites with ATSDR. state health department, US Environmental Protection Agency. or Departmentof Defe involvement Examples include: Region 1 Joint Base Cape Cod, MA Military activities have contaminated soil at theJolnt Base Cape Cod facility and the aquifer below. The contaminated aquifer provides drinkingWate residents ofCape Cod. The MA Department of Health (MA DPH), under the AISIQB Coogegatiye Agreement Engcam l: .atsdr.cd 0 es ind .is evaluating whether people have been exposed to per- and polyfluoroalkyl substances (PFAS) in the water at levels high enough to cause health effects. ATS DR will provide help as needed. For more information about PFAS in drinking Water, visit the PFAS website at tt 5: .ats .cdc. ml to dex.html s: fc . MA DPH has reviewed PFAS in recreational waters. The MA DPH fact sheet about PFAS in recreational waters is at tt .mass. 0 en hs docs 0 mental invest atlons ca bcc- ec-wtr-fact?sheet. df North VT Pcakinicmllonaiiude PM, nse ;rto some ATSDR 510/2017 8/ How is ATSDR involved investigating PFAS in the environment? Per?uorinated Pa The Vermont Department of Environmental Conservation (VDEC) has found perfluorooctanoic acid (PFOA) in private well water samples collected Bennington. PFOA is one of the chemicals in theper- and poiyfiuoroaikyl substances (PFAS) family. VDEC is testing priVate Wells within a 1.5 mile ra former ChemFab site,which is the source of the PFOA. to see how widespread the contamination is. The Vermont Department of Health (VDH) ask for technical support in addressing health issues. Visit the VT DPH for more information about PFOA at - health ont. ov information about PFAS in drinking water, visit the ATSDR PFAS Website at ov envir oa.as ver 0 cl cdc. ov dex. Merrimack area ofsouthern NH The New Hampshire Department of Environmental Services (NHDES) tested public and private drinking water supplies in the Merrimack area. Som are contaminated with pertiuorooctanoic acid (PFOA). The sources of PFOA are factories in the area. The New Hampshire Department ofHealth ar Services (NH DHHS) is attending public meetings to address residents' health concerns. ATSDR is helping the NH DHHS address health issues throu Cgomta?ye Agreemgnt Program NH DES collected Water samples from public and private drinkin go 2 of4 :1 North lius of the . =or more Remains :oftheweils Human iih them ater supplies. ATSDR is evaluating the test results to determine ifdrinking the water may harm people's health and will provide the findings in a written lizport. For more information about PFAS in drinkingwater, visit the ATSDR PFAS website at Pease International Tradeport, Portsmouth. NH I The City of Portsmouth, working with the NH Department of Environmental Services and the NH Department of Health and Human Services, tested international Tradeport drinking waterwalls for chemicals in May 2014. One of three wells had eleyated levels of perfluorooctane sulfonic acid (PF of Portsmouth took theWell off-line. Other PFAS were also found in Well Water samples, and in some residential private wells located near the site. foam used at the former Pease Air Force Base is the preSUmed source of PFAS. Approximately 8,000 people Work at or visit the Pease Tradeportdai daycare centers operate on the property. The New Hampshire Department of Health and Human Services (NH DHHS), through the TSDR Co a ative A reem 0 ram asked to help them evaluate how drinkingwater contaminated with PFOS may affect health. ATSDR is workingwith NH DHHS to answar these questions and to make recommendations to protect people from further PFAS exposure. will write two reports, one evaluating PFAS exposure in water at the Pease Tradeport, and one evaluating exposure from private waterwells. The re answer the question ifdrinking PFAS contaminated Water atthese sites could harm people?s health. NH DHHS has released a report on the blood testing results. Acopv ofthe report is at .d hs . ATSDR has created a Community Assistance Panel (CAP) to receivelnpt potential ofhaving future health studies using data from the site. For more information. visit the CAP website at .atsdr. . ov sites 8 . The NH DHHS provides information about the site at tt .nh. ov vesti at 3931912 Community Water Systems (CW5) and Private Wells. Gloucester County, New Jersey The DeIaWare Rivar Keeper Network petitioned ATSDR to investigate whether residents of Gloucester County. NJ were exposed to harmful leveiso perfluorononanoic acid (PFNA) and other PFAS in their drinking water. The New Jersey Department of Health. through the rail Pro 0 states i . is and private watersampie results to see ifpeopie have been exposed to PFAS and ifthe exposure could harm their health. Focmore information abou drinking water. visit the ATS DR PFAS website at cdc. ov fc i s: atsdr.cdc. ov cle .ht Beglnn 3 Naval Air Station Joint ReserVe Base. Willow Grove. PA GroundWater at the Willow Grove Air Station Joint Reserve Base is comtaminated with per? and polyfiuoroaikyl substances (PFAS) (mainly perfluorc nearby are also contaminated with PFOS and PFOA. PFAS in the groundwater are likely a result of past use of aqueous film-forming ?refighting fee the Pease the City ?irefighting Two I eople?s INH DHHS orts will taboutthe to ca . tm esteem vingpublic QPFAS in octane in suifonic acid, PFOS for short. and perfiuorooctanoic acid. PFOA for short).\ Some publicWater supply wells in Horsham and We rrington,and some pljivate wells the area. The Department of Defense asked the Environmental Protection Agency EPA) to test private well water at the site. Pu blic Water utilities water samples from their systems. EPA asked ATSDR to evaluate PFAS water test results to see ifdrinking Water contaminated with these levels of PFAS could harm people's health. evaluating the available water test results. For more information about PFAS In drinking water visit the ATSDR PFAS Website .cdc. ov 5 ATSDR is workingwith the Mid Atlantic Center for Child ren's Health and the Environment to answar the community's health questions and to educa health professionals about possible health effects caused by to PFAS. ATSDR continUes to work with the PA Department of Health, throu - atsd r. states lnde . i to summarize available cancer statistics forthis area because com members are concerned about cancer in their community. The cancer data review forseiected zip codes ofWarminster. Warrington. and Horsham. available at it 2 a CancerDataReve ce DataRevie 508. Naval Air Warfare Center. Warminster, PA cdc. gov/ pfc/ atsdr_site s_invo 1vement.htm1 81 Ire collecting is .Ie local the AER unity IAIS 910/2017 How is ATSDR involved investigating PFAS in the environment?? Per?uorinated P2 Groundwater at the former Naval Air Warfare Center Warminster site is contaminated with per- and poiy?uoroalkyl substances (PFAS) (mainly per sulfonlc acid, PFOS for short, and perfluorooctanolc acid. PFOA for short). Some public water supply wells in and some privatewells miI contaminated with PFOS and PFOA. PFAS in thegroundwater are likely from past use ofaqueous film-forming in the area. Departmentof Defense asked EPA to test private Well samples at this site. PublicWater utilities are collecting water samples from their systems. The Environmental Protection Agency (EPA) asked ATSDR to evaluate PFAS levels in the drinking water supplies to see if eXposure to PFAS in drink? could harm people?s health.ATSDR evaluated the available off-sltewater test results. The report is available at tt .atsdr.cdc. AC a Na 3 Warfa ter Naval a are Can a 01-20-20 6 508. ATSDR is working with the Mid Atlantic Center for Children's Health and the Environment to ansWer health qUestions and to educate local health or about potential health effects caused by exposure to PFAS. in addition. ATSDR has worked with the PA Department of Health. through the A1323, ee ent Pro ra 5- states to summarize available cancer statistics for this area. The cancer data review to codes ofWarminster. Warrington. and Horsham. PA is ayallable at .atsd Dover Air Force Base, Dover, DE GroundWater at the Dover Air Forcce Base is contaminated with per- and poly?uoroalkyl substances (PFAS). but no off-base drinkingwater contami been found at this tlme.The Departmentof Defense sampled onsite and most off-site Wells. and asked EPA to test one off-site well. PFAS in the grou likely a resuitof past use ofaqueous film-forming 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 PFASWebsiteatht 5: ts .cdc. ov fci de . s: .atsd cdc. ov fc indexht Naval Auxiliary Landing Field Fentress. Chesapeake, VA The groundwater at the NaVal Landing Field Tentress site is contaminated with per? and polyfluoroalkyi substances (PFAS) and in nearby drinking waterWeils. PFAS in the. groundwater are likely a result of past use ofaqueous foams in the area. The U5. groundwater samples at this siteuorooctane arby are The 1g water erssionais selected zip nation has idWater are ater, visit l?ivate law is testing The U. 5. Navy asked ATSDR to answer health questions. ATSDR isworkingwith the VA Department ofHeaith. through the ATSDE Coopera?yg Agreement Pro a s: ov states nde and with local health departments to answer health questions from residents and health fesslonals. For more information about PFAS in drinkingwater. visit the ATSDR PFAS website at l. 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 polyfluoroalkyl 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 drinking Water. visit the ATSDR PFAS Website at l. Region at Decatur (vicinity). AL-Blological Sampling of Per- and Poly'fluoroalkyl Substances (PFAS) in the Vicinity of Lawrence, Morgan, and Limestone Alabama In 2007. a PFAS manufacturer in Decatur. AL notified the EPA that it had discharged PFAS into the Decatur Utilities wastewater treatment plant. res environmental contamination. in 2009. the Environmental Protection Agency (EPA) asked ATSDR to condUct an investigation to see if people who vicinity of Decatur. Alabama. of PFAS factories have been exposed to PFAS. In 2010, ATSDR tested residents' blood and found that some oftheir blood contained PFCs (now called PFAS). ATSDR conducted follow-up blood an testing in 2016. Information aboutATSDR's activities can be found below. a PFAS and Urine Sampling 2916 Exposure layestlgation Report ica ort 205ampling.pdf) Bloogl EEC and Health Summary, Margy]. Lawrence and Alabama information update to the ATSDR Health Consultation Exposure Investigation Report: Perfluorochemical Serum Sampling in the vicinig of Decal - Morgan, Lawrence, and leestope Counties dated April 1. 2013. For more information about PFAS. visit the ATSDR PEAS website Beskali Air Force Base. Oscoda. Mi 5. The Suntles. Its in the i i urine Elerle% ur. Alabama JAN 14.pdf) mil. {10/2017 How is ATSDR involved investigating PFAS in the environment? Per?uorinated Page 4 of 4 The Michigan Department of Health and Human Services through the ATSDB Cooperative Agreement Program is evaluating people's exposures to PFAS in the environment. Releases of PFAS from activities atth former Air Force Base haVe resulted in contamination ofgroundwater and surface water. Sampling by the Michigan Department of Environmen I al Quality and the U.S. Air Force has identified eIEVated levels of PFAS contamination in some locally caught fish and drinkingwater wells. has condu ed health education In the community, installed fish advisory signs. and helped the local health department provide an alternate water supply to the communl . More information is available at tt . 528? . i an. 5885 ~715 2945 5-2855 -- OOJ . For more information about PFAS, visit the ATSDR PFAF Website at no lSubst as an tt 5- .ats cdc. 0 de . 10 I Eteison Air Force Base, Fairbanks AK i In March 2015, Eielson Air Force Base tested the base drinking waterwells and found that some were contaminated with per- and poly?uoroelkyi substances (PFAS). The Air Force has taken the contaminated Wells offline. The Air Force continues to monitor the remaining Wells to ensure that PFAS levels lr_ the water system are not above the HA. Air Force investigations conducted in late spring and summer of 2015 determined that the PFAS moved into private drinking water wells in the Moo Creek community (north ofthe Eieison Air Force Base).TheAir Force is providing alternative drinking water to the impacted homes. The Alaska Division oflPu blic Health under the SD ative eemeni: s: .atsdr.c 0 state evaluate the test resultsto see if the past exposure may harm people's health. For more information about PFAS, visit the ATSDR PFAS website at sd .cdc. not i ht cdc. de . A TOD File Formats Help: How do I view different ?le formats (PDF, DOC, PPT, MPEG) on this site? i Page last reviewed: September 6. 2016 Page lastupdated: February 9. 2017 Contentsource: Agency forToxicSubstances and Disease Registry 8/:1 0/2017 f, 3% rig, \?lj r?C 21-: L513- ?if? I I I..-J-. is - 1 .. af?gl?la?? arr new: .3 . espon '21 i Interim Gurdance Revised on 0/2017 introduction The purpose ofthis fact sheet Is to provide interim guidance to aid physicians and other clinicians with patient consultations on perfluoroalkyl and poly?uoroalkyl substances (PFAS). it highlights what PFAS are, which if hemlcals 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. Background . What are PFAS, sometimes known as PFCs, are chemicals that do not occur naturally in the environm int. There are many different types of PFAS such as perfluorocarboxylic acids 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 matefials. Because PFAS help reduce friction, they are also used in a variety of other industries, including aerosp ace, 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 threat to 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 di5persion of these chemicals appears to be long-cange atmospheric and c'ceanic 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 lie found 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,m mobility, and bioaccumulation potential. The likelihood ofadverse 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. Ingesting food contaminated with PEAS, such as certain types offish and shellfish. Until recently, eating food packaged in materials containing PFAS g. ., popcorn bags, fast foo containers, and pizza boxes). Using PFAS compounds has been largely phased out of food packaging materials. . - . Hand-to- mouth transfer from surfaces treated with PFAS containing stain protectants, such as carpets, which thoughttOIs be most significant for infants and toddlers. . . fr? - ?Erif'fid?? a ., i. ?an fit their? h.l - Workers in industries or activities that manufacture, manipulate or use products containing PFAS may 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, carpets, 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 significant 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 sveloping fetuses can be exposed to PFAS when umbilical cord blood from their mothers crosses the placenta during pregnancht is important to note that different PFAS have varying levels of permeability to the placer tal barrier. . - Newborns can be exposed to PFAS through breast milk. The level of neonatal exposure depends on the duration of breastfeeding. Older children may be exposed to PFAS through food and water, similartoadults. In addition, young children have a higher risk of exposure to PFAS from carpet cleaners and similar largely due to time spent lying and crawling on floors in their early years. 5 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 2to eyears I PFOS 5to 6 years 8 to 9 years What are exposure limits for PFAS in drinking water? 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 noit be greaterthan 70 parts pertrillion (o.o7 parts per billion). The LTHA concentrations do not represent def nitive cut-offs between safe or unsafe conditions, but rather provide a margin of protection for individuals th ?oughout their life from possible adverse health effects. EPA health advisories are non-regulatory recbmmendat ons and 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 PFAS in their blood. The National Health and Nutrition Examination Survey (NHANES) is a program conducted by the Can pm for Disease Control and Prevention (CD C) to assess the health and nutritional status of adults and childrenliin the United States. NHANES (2011?2012) measured the concentration of PFAS in the blood of a represent tive sample ofthe US. population (12 years ofage and older). The average blood levels found were as follows: - PFOA: 2.1 parts per billion, with 95% ofthe general population at or below 5.7 parts per billion 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 and PFOS related productsjoined EPA in a global ste Nardship program to phase out production of these agents by 2015. Based on data collected from previous NHANES. How can PFAS potentially affect human health? cycle years, levels of PFOA and PFOS are generally decreasing in the blood ofthe ofthis important initiative. general population a Health Studies Studies in humans and animals are inconsistent and inconclusive but suggest that certain PFAS may ai 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 leve than those found in most people. The main health effects observed were: enlargement and changes in function ofthe liver, changes in hormone levels reduced testosterone potentiai to affe TSH levels) and adverse developmental outcomes. Developmental and reproductive effects, including birth weight, decreased gestational length, structural defects, delays in postnatal growth and develop increased neonatal mortality, and pregnancy loss have all been associated with prenatal roden PFOS and PFOA. Human Studies: C8 Health Project The C8 Health Project was a large epidemiological study conducted because drinking water in six wate across two states near Parkersburg, West Virginia were contaminated by release of PFOA (also called exposl :s a result ifect a is higher the ct T4 and reduced merit, ?ne to districts :28) from the 19505 until 2002 (when the contamination was discovered). These releases migrated and contaminated the air, parts ofthe Ohio River, and ground water. The study included 69,030 persons 318 years ofage. Th Science Panel analyzed study data and found probable links (as defined by litigation) between elevate blood levels and high cholesterol (hypercholesteremia), ulcerative colitis, thyroid function, testicular kidney cancer, preeclampsia, as well as elevated blood pressure during pregnancy. Residents in the are these releases showed 500 percent higher PFOA~c0ncentrations in blood compared to a representativ population NHANES). Table 2.: Overview of C8 and Other Human Studies cs PFOA ancen ia 'of fa us. 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 wa compared to NHANES data that is representative of the US. population. Otherstudies have found no association between PFAS exposures and the to -cholesterol levels. ter :al Uric acid and serum PFOS levels and uric acid. Significant associations were found between serum PFOA and uric acid levels at all evaluated exposure levels. Several studies have evaluated the possible association between serum 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 consistently found. A study of highly ID exposed residents demonstrated significant associations but the increase in . liver enzymes was small and not considered to be biologically significant. Cancer The International Agency for Research on Cancer (IARC) has classi?ed PFOA as possibly carcinogenic and EPA has concluded that both PFOA and PFOS are possibly carcinogenic to humans. Some studies have found increases in prostate, kidney, and testicular cancers in workers exposed to PFAS and people living neara PFOA facility. Findings from 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. Note: Additional studies have identified possible associations between ulcerative coliti pregnancy induced hypertension and higher exposure to PFAS. What health screenings were used in the C8 study? 5, thyroid disease and The C8 Medical Panel suggested health screening to evaluate the C8 study population that include a blood tests for cholesterol, uric acid, thyroid hormones and liverfunction as well as other age or situation ally appropriate screenings like blood pressure and urine protein measures. For individual patients exp ased to .PFAS who are not among the C8 study screening population, there are no official guidelines suppo [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 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 meta- 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 withiprenatal exposures to PFOS. The association between maternal PFAS level and decreased birth weight is not 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: a statistically significant association between LBW risk and PFOA. Additional effects. As a clinician, you know careful listening and patient engagement is critical for ensuring quality patient care, Patient Questions and Key Message Answers studies are needed to conclusively link the relationships between fetal PFAS exposure and health their health concerns is addressing uncertainty. If your patient has concerns about an exposure to PFAS, yoj may especially when health concerns are raised. Perhaps the most difficult challenge in speaking with patients ijout face the challenge of helping your patient cope with the uncertainty of potential health effects from a PFA exposure. Based on feedback from clinicians and from individuals who have spoken to their health care provider abouI their exposure concerns, a set of patient questions have been identified. To assist you in speaking with your 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 estIons Batl There are ?high levels of In my water. What should I do? . ?i?v 3% lgey essagg yp?pp .0 kega?y r?3f . 2 22- s22%w 232.. $232 if the water you use is above the 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 ht result in ingestion of water. Potential health effects are 3 associated with exposure to PFAS. EPA has established a lifetime health advisory for PFOA and PFOS in drinking water. This advisory . states that the concentratio S1 of PFOA and PFOS in drinking lvate'r, either individually or combir ed, should not be greater than 79 parts pertrillion. 5 There needs to be additions research to establish levels health risk, but patients may. want to reduce exPosures below the EPA health advisory level to be 0? the safe side. A home waterfiltration system can reduce the contaminant levgls in drinking water. Researchers are still clarifying how to best use me filtration for PFAS contamin: tion. installing a home filtration stem or using a pitcher-type filterlrnay reduce PFAS levels. Howev r, these filters may not reduce PFAS enough to meet the EPA Lifetime Health Advisory (LTHA) level. Three factors determine ho much PFAS are removed by filtrati, These factors are the PFAS contaminant levels, the jof filter, and how well the filteris maintained. Manufacturers fthe filtration system may be abl to make recommendations to l? optimize removal of PFAS. his may include more sophisticated media cartridges or increasirjg the frequency of exchanging filter media. I For bottled water questions how it is treated and if it is safe) cor tact the CFSAN Information Center at I r7?z?' if: . AM 43am .sea gee. . 65?a?ehs Uppf? a?w Jilfb?Ma." -1 1-888 SAFEFOOD (1-i385i-7: 3- 3355)- 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 T1, and TSH levels) - High cholesterol . Ulcerative colitis Testicular cancer - Kidney cancer - Pregnancy-induced hypertension Elevated liver enzymes - High uric acid if the patients 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 potentially 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 illr'esses and health effects will be briefly reviewed for each ofthese i lnesses or health effects. This information can be found in this fact she 81: on page 3 and 4. If your patient presents witf health concerns that might be asscl ciated with PFAS exposure, it' Is . appropriate to discuss the patient?s concerns and perform athoiough health and exposure historyiand also a physical exam relative to any reported. I Are there future health problems that might occur because of PFAS exposure? We know PFAS can cause health issues butthere 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 reoccu r. Studies in humans and anirr'als are inconsistent and inconclusive but suggest that certain PFAS can cause possible health effects. Additional research is needed to better understand health risks associated with PFAS exposure. cm I lfa MayA sfefwgm?ii?; Should ii at a blood test for ?32.th ag?g . ?glij 2%?9723?? . ii? git-13m 8.. If you 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?for treatment. The blood test results will not predict or rule?out the development of futu re health problems related to a PFAS exposure. There currently? IS no establi hed PFAS blood level at which a health effect is known nor is there level that predicts health problen?s. Most people in the US will have measureable amounts in their blood. There are no health- based screening levels for specific PFAS that clinicians can compare to concentrations measured. in blood samples. As a result, interpretation of measured concentrations in individual. i is limited in its use. The patient may be aware of blood and urine testfor PFAS being taken at other locations. These tests are used by public health officials to investigate community?wide exposure in order to understand the kinds and amounts of PFAS exposures community and how those exposures compare to those. in other populations. Serum PFAS measurements are most hel aful when they are part of a carefully designed research study. na 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 at the 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 established PFAS blood level at which a health effect is known nor is there a; level that is clearly associated with 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 his or her blood levels are.within range of the national norms or ifthe r- - 5:.4 massages.? rear wr- f? EEJ .: I??gystib?fgszi yet ants?it rit?t?t - Lats mama?s 99-32? v: .. . $341,? I . - individual's levels are high or low compared to the national background averages. 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, 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 th PFAS are not specific and can be' caused by many otherfacto?s. There are no guidelines to apport laboratory testing to monitor PFAS health concerns. However, if your patient is concerned about PFAS expc sure, discussing routine cholesterol screening can reassure the ,atient that his or her PFAS exposu :e concerns are being address Some ofthe other possible ?ealth effects can be screened for based on A parent asks: ?Should I have my child tested for any ofthe 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 foryour child. For very young children, keeping well child visits is the best plan of action to monitor your child?s According to NHLBI guidelines endorsed by the American Academy of Pediatrics, all i ildren should be screened for chol isterol levels between ages 9 and 1_ years, and again between ages 17 and 21 years, even those who are at at an increased risk of high cholesterol and heart disease. Health effects associated with PFAS are not specific and can be caused by many otherfacto is There are no guidelines to 51': use of laboratory testing to monitor PFAS health concerns. ppori: ix?? 51:; . If I ?5?3 431 ate health and watch for of illness. -- all?llessa?g es" 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 for any related do offer us a way to better understand your child?s current health status. a?g??Eff? teatime at is. at: E?ll-low-ever, if your patient pr sents with health 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 {ealth effects can be screened for based 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 w'fch PFAS are not specific and can be caused by many otherfactors. Pregnancy induced hyperte nsion occurs in many pregnancies and the specific etiology is often- unknown. ls it safe for me to breastfeed my baby? 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 benefits of breastfeeding your baby outweighs those of not breastfeeding. Extensive research has documented the broad and compelling advantages of breastfeeding for infants, families, and society. mothers, Some of the many benefits nclude immunologic advantages, z'wer obesity rates, and greater cdgnitive development for the infant as well as a variety of health advantages forthe lactating mother. I Even though a number of i environmental pollutants re adily pass to the infant through Jman milk, the advantages of ?res 5143. - )2 .-.V . .-. - saris megs. sass I: .aas?igii?iammaa ?gs? outweigh the potential risks: in nearly every circumstance. 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. There is no recommendation for repeating any vaccinations. Will I need to get my child vaccinated again? A study with 656 children has reported that elevated levels of PFOA and PFOS in serum are associated with reduced humoral immune response to some routine childhood immunizations (erella, tetanus and diphtheria) among children aged five to seven years. Studies have not suggested 'a need to re-evaluate the normal immunization schedule nor the use of an immunize boosterfor - impacted children. it is normal to be anxious about uncertain risks. haVe been very anxious about health risks from PFAS exposure. How can I deal with this Uncertainty? I am here to listen to your questions and will do my best to provide honest answers. First let's identify ways to reduce ongoing exPosures to PFAS so that overtime we can lower your health risks. 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.- Listen sympathetically and. explore the concerns ofthe patient Check for serious stress issues such as ongoing depression and ilreat accordingly. Review resou mes/references at the end of this fact sheet. 3 10 Below is a list of resources that can be helpful to clinicians. These include the Pediatric Environmental Heal Specialty Units. (PEHSU). 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 i th fd Resource Link ATSDR: PFAS Overview Toxic Substance Portal 0v fcindex.html 0v toxfa stf.as ?id=1116&tid=2 CDC: PFCS FactSheet.html C8 Science Panel C8 Medical Panel http' link.htm panel education doc.pdf EPA: PFAS foa- - chemicals 508 odf NHLBI Lipid Screening in Children 8: Adolescents Lie.- PEHSU Uncertainty and Stress in the Clinical Setting Helping Patients and Clinicians Manage Uncertainty During Clinical Care ublichealth.wustl.edu hel in - atients?and-clinicians?mana e- Navigating the Unkhown: Shared Decision-Making in the Face of Uncertain Gen intern Med. 2015 May,- 30(5): 675-578. 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): 679-678. These ational 21.1 . a p55 tzr? ?aws - . .I Hi. was); I. . 3?3: ??9ft." legit-g, - ?assesses. .. What are PFAS are a large group of man~made chemicals that have been used since the 19505. Use of some of these: chemicals has decreased in the United States over the last 10 years. People can still be exposed to PFAS because they are still present in the environment. PFAS do not break down easily in the environment. They also build up in the bodies of exposed humans and animals. Over the last decade, interest in PFAS has grown. How can i be exposed to 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. Public water systems and drinking water wells, soil, and outdoor air near industrial areas with frequent PFAS use Indoor air in spaces that contain carpets, textiles, and other consumer products treated with PFAS to resist stains a Surface water (lakes, ponds, etc.) and runoff from areas where aqueous (water?based) film-forming fire fighting 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 a Some grease-resistant paper, fast food wrappers, microwave popcorn bags, pizza boxes, and candy wrappers Nonstick cookware a Stain resistant coatings used on carpets, Upholstery, and other fabrics a Water resistant clothing . . Cleaning products a 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 with PFAS are more likely to be exposed than the general population. Workers may be exposed to PFAS by inha ing them, getting them on their skin, and swallowing them, but inhaling them is the most likely route for exposure. 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 sources of PFAS contamination you can take steps to reduce your risk of exposure to PFAS: - Some states have warnings about eating fish from bodies of water with high PFAS levels. Check with ya state public health and environmental quality 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 water. a it is safe to shower and bathe in PFAS?contaminated water. Neither routine showering or bathing are a significant source of exposure. Studies have shown very limited absorption of PFAS thmugh the skin. 3 ., ?umu??y?Heg?g?nvs 3, March 9, 2017 How can PMS affect peeple?s health? Scientists are not sure about the health effects of human exposure 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 fertility and interfere with the body?s natural hormones, increase cholesterol, affect the immune system, and even increase cancer risk. a PFAS build up and stay in the human body and the amount goes down - very slowly over time. So scientists and doctors are concerned about their effects on human health. a Some studies show that animals given PFAS have changes in the liver, thyroid, pancreas, and hormone levels. Scientists are not sure what animal data means about human health. PFAS act differently in humans than they do in animals and may be harmful in different ways. Haw can ll learn more? Contact for updated information on this topic. Contact the Consumer Product Safety Commission at (800) 638?2772 if you have questions about the products you use in your home. Visit the following websites for more information: ATSDR Websites . Environmental Protection Agency List of Common pi- and Th Perfluo sulfonate Perfluorohexane sulfonate Perfluorooctane PFOS sulfonate Perfluoroheptanoic PFH 12A acid Perfluorooctanoic acid PFOF Per?uorononanoic acid PFNA Perfluorodecanoic acid PFDA- Perfluoroundecanoic acid I Perfluorododecanoic acid Perfluorooctane PFOSA sulfonamide .: per?uorooctane AcOl- sulfonamido) acetate 2-(N-Ethyl- per?uorooctane AcOl- sulfonar'niclo) acetate Notes ?Use of trade names is for identi?cation 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 US. Department of Hea and Human Services K. .PT?K?K?IrjuifaIllrnIly tree. 'osz-jperfluoroalkyl and polyflI.II" 'ya bstances (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 spells out 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 of the 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. Per?uoro? Eli Figurei. Fa i Tree _of .. gi?i?gg perfluoroalkyl and PFAS polyfluoroalkyl . Substances l: I Fag 11 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 also an abbreviation for perfluorocarbons. Perfluorocarbons are an entirely different family of chemicals, also known as greenhouse gases. The term PFC has fallen off the family tree, but it remains in the diagram. as a reminder of past use. You may still see informational materials using theterm ?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 and chemical names. Table 1. Common PFAS: Abbreviations and Names chlemi?ca-l h-ame. .1553 -. 3. 7? ?If: . Perfluorooctane sulfonic acid .1 ?if; . t? .13 Abbrevuaqion? - -. . PFOS PFOA (aka C8) Perfluorooctanoic acid PFNA Perfluorononanoic acid PFDA Perfluorodecanoic acid PFOSA (aka FOSA) - Perfluorooctane sulfonaminde (aka 2-(N-MethyI-perfluorooctane sulfonamido) acetic ac (aka . sulfonamido acetic acid - Per?uorohexane sulfonic acid Pas?! S?wuf' H, at SDR. PUBLIC HEALTH STATEMENT sq}: werestasis-sprees? Division of Toxicology and Human Health Sciences August 2015 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 in the nation. These sites make up the National Priorities List (NFL) and are sites targeted for long-term fedieral 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 future 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 (dose), 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: perfluorooctane sulfonic acid (PFOS), per?uorooctanoic acid (PFOA), per?uorododecano'c acid per?uorodecanoic acid perfluorobutyric acid (PFBA), per?uoroheptanoic acml per?uorononanoic acid (PFNA), per?uoroundecanoic'acid (PFUA), perfluorohexane sulfonic acid per?uorobutane sulfonic acid per?uorooctane sulfonamide (PFOSA), sulfonamide) acetic acid and 2-(N-ethyl? perfiuorocctane sulfonamide) acetic acid DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry Telephone: 1?800?232-4636 NJ: DR PUBLIC HEALTH STATEMENT *?Eii?ttiiel??s?tiit?tiwces DiviSion of Toxicology and Human Health Sciences August 2:015 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-?ghting 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 perfluoroalkyl 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 BE TO Exposure to per?uoroalkyl compounds is widespread. PFOA, PFOS, PFNA, and were detecter 95?100% 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 iin DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry mvw.atsdr.cdc.gov/ Telephone: 1-800-232-4636 W??iux ?1 DR PUBLIC HEALTH STATEMENT Rh Division of Toxicology and Human Health Sciences August 2 pathways of human exposure to most of the other discussed in this toxicological pro?le. Human breast milk may contribute to the exposure of infants to since these substances have been detected in human breast milk. You may also be exposed to from treated 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 substar 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 ?om the same communities who did not work at these locations. Workplace exposure also occurred for people with jobs that required frequent handing or use ofperfluoroalkyI-treated substances, such as carpet installers. At sites where aqueous ?lm~forming foam that contained perfluoroalkyl substances was used in ?re?ghting, workers could be exposed to these substances and possibly transport them home from contaminated clothing. HOW CAN ENTER AND LEAVE MY Perfluoroalkyis can enter your body if you breathe air, eat food, or drink water containing the We do not know how much will enter your body through your lungs or your digestive tract. If ycur skin comes into contact with dusts or aerosols of per?uoroalkyl 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 leaves 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 yum Ill ith-r DR PUBLIC HEALTH STATEMENT 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 significant 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 factcr 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 people 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 2L1 increased risk for high blood pressure. There is also some evidence that PFOA and PFOS exposure In ay cause liver damage. Humans and rodents react differently to PF 0A 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 weightless 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 ngq: PUBLIC HEALTH STATEMENT 51/ DR and hearsaastaantm 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 living near a PFOA facility. These results should be interpreted cautiously because the effects were not consistent found and most studies did not control for other potential factors such as smoking. Feeding PFOA an 3? 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. Others believe that it is possible for to cause cancer in humans, and the studies in rats should not be dismissed. More research is needed to clarify this issue. The International Agency for Research on 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? '6 ?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 it an area with high PFOA levels in the water. Some studies of the general population and peeple 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 infant?s health. A study in children exposed to high levels of PFOA in drinking water found increases in bloocl? 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 the highest PFOS levels measured in workers. Oral exposure to PFOA and PFOS has resulted in early death DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry Telephone: 1-800-232?4636 y?mul- DR PUBLIC HEALTH STATEMENT rearrangements Per?u 01? 0311(3?15 Division of Toxicology and Human Health Sciences I August 1:015 and delayed development of mouse and rat pups, but this did not occur in animals exposed to PFBA ol- 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 PF OS 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 products 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 lower PFOA levels in the blood overtime by decreasing exposure to per?uoroalkyl compounds. ARE THERE MEDICAL TESTS TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO Per?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 aphysician 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 ug/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 tax. a? J) DR PUBLIC HEALTH STATEMENT Eh 1 . Division of Toxicology and Human Health Sciences I August 2015 Mid-Ohio Valley residents who had environmental exposure to PFOA from drinking water contamina by a nearby industrial facility. The range of median serum PFOA levels across several communities 121?224.] ng/mL and the mean serum PFOA concentration across all of the communities was 83.6 in 2005. Higher serum perfluoroalkyl 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, respectii Workers at another facility had serum PFOA levels of 1,000 ug/L. WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN The federal government develops regulations and recommendations to protect public health. Regulati can be enforced by law. -Federal agencies that develop regulations for toxic substances 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 proi 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 affe 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 workda 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 availab. For the mostcurrent information, check with the federal agency or organization that issued the regulation or recommendation. ted vas g/L rely. ODS ect ct vor le. DEPARTMENT of HEALTH AND HUMAN SERVICES, Public Health Service Agency for Toxic Substances and Disease Registry wmv.atsdr.cdc.gov/ .Telephone: 1-800-232-4636 4 PUBLIC HEALTH STATHMEN . 67? Division of Toxicol_ogy and Human Health Sciences August 2015 The EPA has recommended provisional drinking water health advisories of 0.4 pig/L for and 0.2 ug/L for PFOS. OSHA has not set any legal limits for perfluoroalkyl compounds in air. NIOSH as 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 Registry Division of Toxicology and Human Health Sciences 1600 Clifton Road NE Mailstop ?57 Atlanta, GA 30329?4027 Toxicological profiles 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 ?mas EHVIRONIIENTAL momma" AGENCY REGION manor: mo ARCH swam nwsa-r IOULEVARD mum PA mos sumac. IL mu 0F: . ORDER ON CONSENT . E. I. Punt chEWm I and Guam I section 1431 {21(1) ?was: - - Wam- . Washingtharh mm, 1 Rout: as: 130mm. Mam. wv 26181 AUTHORITY L'I'his Mediating Admimm? Safe 42 5 aomwm. a. Wot: No.-9-17, dam! May 114994. . 3. 0F publicmhx-aupp?u and Magnum-mum. IL DEFINITIONB 4. meman?quifer'or orwhichconuimammniuuqmn?tyaf consumption, or contains Hm: 10,900 milligram pu- lim- (mu/l) mu! 1151de Iowa. and is not an aquur. 35:40 GER. 5 . 23:91 396d mg m. 308 a-geos-a Wm: wee SST 311:: GAA001535 m. FINDINGS OF CDNMONS OF LAW 5. 3113c! Dig? ?111ng a "Person? within thumumn' noi?Sechnn' 1401 (12) 05th:: EDWA, 4! 17.3.0. 6. kumau?nwaahmm' County.WmtVir31!nh. - 7. (hctu?zr mr?mntmuDuPomhnumdinIb?mmpuMhd a 8. R?dm whavehecnz??lnacdm?uair. m?m??h Puf?n,? and 3 a oif ?rmwardirpoul km un?hadland?lh. 9. MinimCulpun?nn (ununufacbuuofCU) communal}; inm?un, contact. Shzdiulmrealsof conduc?maprdin?nmy Ad: 10. - whack, WV.P8D: 05W (11ng . n?quninrm FIdJ?meduc?nu Wells: 1.99 11M (Wall 886. 1998) 1.45 and 1999} Fndlity Drinking?th Tape 0.213% (Enildin; 5. 1999) 0.496uadt?wdlu3393. 1999) 0.135uafl (amass, Link 0H, PWSI Lawns/l (Well 1. 12/01) 2.12/01) 0.355um?l [Will 3. 12/01) 7.590 .Mcll 5, 12/01) 1.7mm Well 1. 1/02) 2.970 udl [Wall 3 1/02} 0.744143/1 Well 3. 1/03) 2 zvva'd mast awe-?haw i 9 mad mm W. '1munmm?l am: 30; wee 68: 3113. mousse we um {Well mm 11. ath?conmnhadmauhighm h? Ola-db: minimum; well MWI 34,000 0511(1998) Ola-nit: mum MVV-EA. 990 nail (1993) tummy known level: $0.031 0.045119?! and 0.0.53 uyl (duplintto ample). 1? ?Minivan-used foal-111mm Nun?vdhr Pullman: 1511:] Inbunm'on? Chum-wan. Jimmy 91.. 2002 Wu?ENVIRONmpon?sz-Dul?m ?thatWrgim sunf?u?hmd WNW 15,2001.mhedhureha winch ?ak ofC?meecondtuad nhmakuu-dm . mehna' Etuddi?ou? 14.0.8Iscunm?ynot furpmvi?mof WWI: 17oFthh Order. 16. be establidaedby 18 ?amm??ofti?s Banduof??aOnien 16. RAM What! with mm the Probation Agency and tin: Ohio Dammit-1% In con?rm that the Mammalian on whichlhil mam thli the Wand banking. OEPA. and 0131-1me dntEPA make this adim. concluded ?nial] tumult: conditions ham: been satis?ed for EPA action under Section 1431(th1) of Eh: BDWA.43 11.5.0. 5 mew). 3 :Ixsa'd 22:91 awe?um - 9 338d mg 303 - eases-u 317:311:! 01537 Et/SEl'd 2. send mg w. 303 mace?a 3mm 30. wee 661 IV. ORDER 0N comm bySe-atinnlial SDWA. 42 Ilia 5 WWI). and tn the Regional Jim-mm. Buggy the ORDERED manufhcfo?awina: l7. mmtofvn?dmd umg?ngmuluparformadm :ha?providaahunponw ?lm-nah: uses 18. Eh: G-roundwwer benign mSMg' Team pumnnt ammombym a Khadldcufimplunmn?onfurmchac?m 19. The AlmaanHng-Wml?hn . mm oranerWB anti Ohio, identi?ed - b. semiszfeuimcm?mdbyuimohms. Wham: {9:91 non-um - GAAO 3311:: 31538 . nun-- hm . Wlhn?muu mention PWB th: mp if EPA, in cpmulu?ou with WVDEP. am! W, W?a er MthmeOIdu-f Rpm. Duanma?cm?nuebomhnit {Erwin-mud. mm at: . 1h pudlailuy? a a nWWo?Im-Mbe wamdmt,? Emmy. mm, or viwpmident?afnuront in chug: ofa principal hmimu ?mntion. or my other pcrsun who performs deddon-m-king?mwm far DuPont, or (ii) the wager of the Ftdlity?fthe Facility annual tale- or mag-a have? ama-n-w-J 8 396:! WAVES 171.2. 308 3-3808-(1 SWAT 80. ??80 661 mid -.. qua?pu?w- . -- umndimn ascending 825 million (in amt! am 1980 dollm). to dOcUmenhhuhten 23. Hm 11.3. EPA Man In 1650 Amh Street . ??ll-183M PA 19103-2029 Edi-y Mom m. HA Region 7? Westjachon Badman! amp, IL 50604: An Victor Wort! DMIion of .anutmmof Mud?mmn?umm 815 0mm Shad. Suit: 418 Wumnmawm 1201 'Grecnlxiu'sm - ?312:ka 95901 OEPA: 1 MUM Division of 8r. Crowd Wm Ohio Pm?dim Am 1223mm: Fmt?haet Inn, OH 43215 ?my 1mg: aim?11w . 6 V2.2. 308 817:2? 30; 1140 881 ?oNlmId Ll ?73191 max-rpm . '25. mm 98. provisions 31. Pursuant Station 14810;) ofthc SDWA, 42113.0. 5 Bomb). violation ofany term oflhis Order, or?lihucorre?mltnoom?ywl?n this Order, 1;:de pemlty? ofupto 0mm: or Failure to cummymanm, as usual by United summniucoun. 32, When Duanlnom arlhould have. know, by lh: exercise ofduc d?igmm, arm event?zatn?a?dclay comph?on ofanylequkunmu?hh Druid, 131:1?th pmvida media: to within um (10) bu?neaa winlhe exercise oftiuc diligence, should haw harm. Cir?wt. Tinnu?ccsha?dzsaibcln detail the bail for the OT 396d mg 303 a?seoe?a ?1I?lmd??mz?1 am an; 11/.nn. GAAO EVIL-J 01541 Urn-2m {11:01pm US EPA Ill-r DIV. rm 35:1: :04 Is: 2135 mm: mm mm 2.ng. 33. mamauwmm in awashucrmm? 34. grim udmf as. Z?m'm??wh Hannahnn tin ?not . Eda-11in! SO ORDERED: 9'52? . Lima. u, 4W. - I Fmirmmr-l Pratt-dam cum 'd 5315?: mar?aw IT Baud ms 308 3?9809-0 mm 30. wee em 311:: GAAOC1542 ll .. The -. of one. Eumwt m. an . . 1 Dan-1d Dim - Region! Adminhn-ama- . 34.. 3.5. ThomuV?kimicr II US. Emimnmmul Winn Agata-y. Region Et/tt?d 31331:! 53:91 BEBE-II-H-M - FMS V2.1. 308 Win? 30. 131/GAAOC 7311:; 1543 AGREED TO: Paul Banned? Plant Mam. F-dl?g Convananmrpomtcd :1 8T Batid H.179 NJ. 308 Dammd/L?z ?002? SBIQT 1-3514 a?saos?a Wt? ao. wee set 'on' GAAO 3'1I:l 01544 are: mm. WW halowuindioued: . 1113111353; RBTURNRECEIPT Mani Lemma 7012 Raquamn immuonsm: . Wilmington. DE 1989:: Paul Baum, le Mauser DuPont Wuhihm Works Faulty Rout: 892 Wuhinpon, WV 25131 gm} 1/ I tggi/{ZM/ Maintain-hem Sadat? Maul Emma! Of?ce Emma, Compliant, mdli'mitmnumlm?m 1650mm mm PA 19103-2029 Eiftl'd 90:51 17m w. 308 a?seoe?a '"ummdmaun .stmn 30. 11/30 661 311:4 - EXHIBIT .Ll 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 For information on the PFOA risk assessment activity see: For reference materials and infomation on the C- 8 Health . "1 . Project, residents, and phys1c1ans can refer to the document available on these Website 1 odh. chic. gov/othrograms/ eh/hlth as/chemfs1.asox and epa. gov/reg1003/enforceme Stewardship Program and on the ., mit DuPont Agrees to Lower Of PFOA in Drinking Water DuPont Washington Works Parkersburg, West Virginia March 2009 A new legal agreement between US. Environmental Protection Agency and EJ. du Pont de Nemours Co. will lower the limit in drinking water for people who live near DuPont?s Washington Works fac .Iity in Parkersburg, Under terms of the agreement known as a ?consent order? DuPont will offer water treatment or bottled water to =ople on public or private water systems when the level of a chemical cal 'ed PFOA - also known as per?uorooctanoic acid or C- 8 -- in water sapplie reaches 0 40 parts per billion (ppb). i Office of Water issued a Provisional Health Advisory (P 1n January for PFOA that establishes a reasonable, health- based vallt 3 above which action should be taken to reduce exposure to 1n driliiking water. The time frame for action is short? term? meaning Weeks to mom hs. This PHA prompted the new agreement to lower the allowable conce :tration of PFOA 1n drinking water from 0.50 to 0.40 ppb' 1n communit es near the Washington Works facility. If affected homes cannot be connect cl to a publi water system or a treatment system within 30 days, DuPont mus 'offer bottle water. People who live' 1n the PFOAncontaminated water areas a . new action level may reduce their exposure by not drinking the treatment systems are installed, or they are connected to a public :water system. i u: 1?140 EPA expects a limited number of residents will be affected by th 3 new action level. Current data identities about 14 private residences that ma: need a treatment system installed or connection to a public water systeml If these residences cannot be connected to a public water system or treatment system within 14 days after the order 13 signed then DuPont must offer alternative water. In addition, there may be a small number of private drinking water Wells, installed after 2006, that need to be tested for PFOA. EPA is also assessing monitoring data and other information to determine if here are any previously untested areas that need to be surveyed. Under a 2006 consent order, all public and private water systems that had PFOA levels above 0.50 were offered alternative water or treatment, and DuPont' maintaining the alternative water or treatment at those systems today. EPA issued the 2006 order in 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 showed residents had an average PFOA level of 298 to 369 ppb' 1n their bloodstreams. More recent data gathered under a PFOA health study involving some 64, 000 people, indicates the average PFOA levels' In the bloodstreams of everyone in the affected communities to be about 28 ppb. These values are sti 1 much higher than the average 5 level found in the national populati I1n. 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, Lubeclt, 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 de?ned 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 refined 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 866?575-8543. 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. continues to conduct its risk assessment?under Technical background: What is PFOA, or Cull, is a man-made chemical that ?sists heat, water, oil, grease and stains. It has been used making common household and industrial items such pots and pans, flame resistant and water-proo non?stick clothing, wire coatings, and chemical resistant tubing. can also be formed by the breakdown of other big; ?uorinated chemicals used in stain?resistant fabrics, stain-resistant paints, ?re ?ghting foa' 'ly pets and and oil- and grease?resistant food cartons and wrapper: . PFOA does not occur naturally in the environment a 5d is highly persistent, with little or no degradation water or soil. History of legal orders ng in air, This order supersedes the Emergency Administrative Order on Consent that was issued in 2006 und'er the authority of the Safe Drinking Water Act. Section 1431 of the Act requires a ?nding that ?a contaminant is present in or is likely to enter a public water system or underground source of drinking water whit may present an imminent and substantial endangernent to the health of persons." It does not require a concl Lsive ?nding that a contaminant has, or de?nitely will, cause harm. The 2006 order contained a temporary threshold 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 acti on 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 treatment or alternate water to public and privz users in the vicinity of the facility, and the ne 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 review the existing 2006 order and have reque: assistance with this matter. I. 2006 action provide lte water action Agency the rol Act. a inant level on EPA to ted 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 of PFOA in humansis approximately 3.3 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 100 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 systems are not required to monitor for PFOA. Recent scientific information EPA ?5 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 Office of Water used in its calculation. The Of?ce of Water also applied a more advanced risk assessment . the risk assessment process. technique that resulted in an update to some of he values used to calculate the new Provisional Health A visory from those used in 2006. EPA continues to monitor 6 erging scientific information regarding PFOA in the in crest of public health. EPA and DuPont. agreed to reviseithe existing order. - . Other legal actions in 2001 DuPont, the West Virginia Department Environmental Protection and the West Virgini Department of Health and Human Resources entered into a onsent agreement. The legal order required a toxicological and human health risk assessment of be conduc ed under the supervision of a (3-8 assessment of toxicity team. Ground- water and surface-water monitoring and plume identi?cation in West Virginia and Ohio were conducted under the supervision of a ground?water investigation teani. An order issued in 2005 in response to a 2001 civil suit in Wood County, (Leach, e! a! v. DuPc?nt de Nemours Company) required collection of blood serum an health data from about 70,000 people who live near DuPont?s Washington Works facility. The collection of hi iod serum and health data is known as the Brookmar Study: It also 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 D. 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 data and blood serum levels. Then a three-member scicnc panel will assess whether there are adverse health effects to-humans associated with elevated levels of PFOA in the blood serum. Although the full results of the study are not exp . cted until about 201 l, the blood serum concentrations are a ailable to the people who participated. Ohio Department 0 Health, the federal Agency for Toxic.Substances and Disease Registry, Ohio Environmental Protection Agency, West Virginia Department of Environmental Protection and West Virginia Department of Health Human Resources wanted to have 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 pcr?uorochemicals. A formal risk assessment process is under Way. Science Advisory Board completed a review of a draft 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 final 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?evaluatcd. The Agency is funding additional research regarding the toxicity of PFOA and other perfiuorochemicals, 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 getting into the environment. In 2006 EBA i1 major companies in the industry to committ voluntary, global PFOA Stewardship Progra invited companies, including DuPont, have to the goals of the program, which include re facility emissions and product content of PF related chemicals by 95 percent 0 and toward elimination of releases and product 0 and its. icy has ivited a m. All 'ommitted ducing QA and lworking ontent of these chemicals by 2015. As of the end 01?2606, DuPont 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 0th companies are submitting reports to EPA on 'the by 99.1 rses by er their past activities and on their progress toward the Stewardship Program goals. 1! "Mr? i 1-3. REIGN it 53?, . MAR 102 :9 REGIONAL HEARING CLERK . . 0.5. surmount =1 UNITED STATES PROTECTION AG ENVIRONMENTAL PROTECTION AGENCY I 1.: u' REGION REGION l650 Arch Street 77 West Jackson Boulevard Philadelphia, PA 19103-2029 Chicago, IL 60604 IN THE MATTER OF: E.l. du Pont de Nemours and Company ORDER 0N CONSENT 1007 Market Street Wilmington, DE 19898 Proceeding under Section 143 l) 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 SDWA-05-2009-0001 l. AUTHORITY i. This Order on Consent (?Order") is issued pursuant to the authority vested in the Administrator of the United States Environmental Protection Agency by Section 1431(a)(l) of the Safe Drinking Water Act or "the Act"), 42 U.S.C. 3003(a)(l 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. 9-17, dated May 1 I, 1994. 3. Under the SDWA, Congress has authorized EPA to exercise broad authority for the protection ofpubiic health from contaminants entering a public water system or an underground source of drinking water. II. STIPULATIONS . 4. EJ. du Pont de Nemours and Company (?DuPont") consents to jurisdiction to issue this Order. DuPont does not admit to the EPA Findings in this Order. Al: NCY: l1 - a. DuPont waives any defenses it might have as to jurisdiction 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. ill. DEFINITIONS AND BACKGROUND 6. ?Contaminant? means ?an sical, chemical, biolo ice], or radiolo ical substance or matter in water." get; 42 U.S.C. {5 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 su ?icient 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 liter-total dissolwd solids, and is not an exempted aquifer. 4O C.F.R. 144.3. 8. C-8, for purposes of this Order. is per?uorooctanoic acid, CAS 3335-67-1 (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 ireatment. 12. A ?public water system," hereafter provides piped drinking water for human consumption to persons within the meaning of Section [401 (4) of the Act, 42 USS ?300f{4) and 40 CFR ?l41.2. 13. A private water system is used by individual residents, or serves less than 25 persons per . year ?'om 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. DuPont is a corporation and is therefore a ?person" within the meaning of Section 1401(12) of the SDWA, 42 U.S.C. I 2 1! i6. DuPont owns and Operates a manufacturing facility known as the Washington Works located in Washington, Wood County, West Virginia. 17. DuPont has used (2-8, in the form in its manufacturing processes at the Facility since the early_19505. 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 alia, a toxicological and human health risk assessment of 08 to be conducted under the supervision of C-8 Assessment of Toxicity 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 deveIOped a screening level of 150 for GR 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 Earn the Facility. Annual emissions to air in 2005 Were reported to be approximately 12,600 kilograms lower than annual air emissions in 2000. Annual discharges to water in 2005 were reported to be approximately 20,400 kilograms lower than annual water discharges in 2000. As of year?end 2006, DuPont had reduced annual air discharges by 99.1% and had reduced annual water discharges by 99.2% since 2000. 2 l. On November 20, 2.006, DuPont and EPA entered into an Order on Consent (?2006 Order" which requ ircd DuPont to offer. inter alto, 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 ofC?S detected in the ?nished 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 ?om (2?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 of0.4 for PFOA.2 DuPont. "Data Assessment DuPont Washington Works (OPPT-2004-01 l3 PFOA Sitc~rclated Environmental Assessment Program)" (October 2. 2008). 3 United States Environmental Protection Agency?s Of?ce ofWater, ?Provisional Health Advisories for Pcrnurooctanioic Acid (PFOA) and Pernuorooctanc Sulf?onate (2009). (including Administrative Record thereto). A vai table: 3 ?3 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. 23. Sampling conducted through the GIS Team effort since 2001, and by DuPont, has detected 08 in primate and public drinking water sources in Ohio and West Virginia at concentrations ranging ?om below the limits ol?quantitation up to 21.1 ppb.4 As set forth in more detail inparagraphs 26, 27 28, DuPont has already taken measures to address PFOA in drinking water at or above 0.50 ppb. 26. The 2006 Order achieved comprehensive identi?cation of private and public water systems in the vicinity of the Facility and ensured alternate water andlor treatment was offered, installed, and maintained at all public and private water systems that exceeded 0.50 of C-8 in their ?nished water. - 27. Prior to the 2006 Order, DuPont had offered a granular activated carbon Water treatment Treatment") at two public water systems that contained levels of (1-8 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 Wesi Virginia. Upon acceptance of the offer and completion of construction, DuPont has provided for operation and maintainence of GAG 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 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 and whose OWners have accepted DuPont ?5 offer. 29. To date, approximately four owners of' private water systems in the vicinity of the Facility with ?nished water that exceeds 0.50 of 0?8 have declined or not responded to DuPont?s offer 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 0-8 at concentrations at or above 0.40 ppb. 3 id. 4 l-lamen, Andrew 8., Project Director, DuPont, "Amended 3Q05, and 4Q05 and [(206 Residential Sampling Results, West Virginia and Ohio DuPont Washington Works, Washington, WV (EPA Docket ID Number OPPT 2004-01 l3 PFOA Site-Related Environmental Assessment Program,"suhmitted to Chad Board, West Virginia Department of Environmental Protection (April 5, 2006). 3 1. OS 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 of under the Toxic Substances Control Act 15 U.S.C. 2601 et seq. 33. DuPont has released (2?8 to the air, discharged OS to surface waters, and diaposed of residues containing (7?8 at the Facility. DuPont has also disposed of residues containing -8 to its Dry Run, Local. and Letart land?lls in West Virginia and has otherwise shipped residues containing 08 off?site for destruction and/or diSposaI. 34. The releases, discharges, and/or disposal 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 (2-8 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 C-8 at levels that may be at or above 0.40 ppb; and therefore further 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 ol?C-B at or above 0.40 in their ?nished water.5 38. Although EPA has not yet completed its risk assessment For (3-8, 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 contanu'nant 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 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 (3-8 is a contaminant present in or likely to enter a PWS or a 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 Harden A., Project Director, DuPont, concentration at or above 0.40 ug/L" (Tables 1 and 2). (dated 2/ 6/2009). 6 United States Environmental Protection Agency?s Of?ce of Water, ?Provisional Health Advisories for Per?urooctanioic Acid (PFOA) and Fertluorcoctanc Sultanate (2009). (including Administrative Record thereto). Available: 5 40. State and local authorities rely on the expertise and resources of EPA 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 in drinking Water that reduces exposure to OS 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, OEPA, and ODI-I to con?rm that the information upon which this Order is based is correct. The WVDEP, OEPA, and ODH have requested that EPA take this action. Therefore, all requisite conditions have been satis?ed for EPA action under Section 1431(a)(l )-of 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 1431(a)(l) ot? the SDWA, 42 U.S.C. 300i(a)(l), and delegated to the Regional Administrators, DuPont is ORDERED and hereby consents to the following: . a) Temporary Provision of Alternate Drinking Water. For those private water systems where existing validated data demonstrates levels of 08 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(2) or and identi?es private and public water systems where the level of (2-8 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, from the receipt of validated data. An ?alternate drinking water supply" shall mean: water from some other source, acceptable to EPA, that meets the water q?ality requirements of40 C.F.R. Part 141 and has a level ofC-S 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 fully implement the permanent remedies described fn?-a pursuant to Paragraph 42 of this Order or the resident declines the offer oris 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 ?ystems Receivm' Treatment. For private 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 replacement of carbon ?lters, until it demonstrates to the satisfaction of EPA that the source prior to GAC Treatment 6 contains less than 0.40 ol'C-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 (3-8 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 GAG 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. Action at Private Water Systems Based On Existing Data. For those private water systems where existing validated data demonstrates levels of C-8 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, OBPA, and for review, 3 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 ?ystems. 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 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 owners or operators of private and public water systems of monitoring results within 7?1 0 days after the data are ?nalized through DuPont's internal data quality controllquality assurance procedures. Newlv Activated or Permitted Water Svstems. Upon notification 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 ofC-8 in accordance with the provisions of Paragraph 42(e). On the anniversary date of the effective date of this Order and annually thereafter, DuPont shall survey the geographical areas de?ned by EPA for any new private or public water systems until DuPont demonstrates to the satisfaction that the USDWs in these geographical areas (or a subset of those areas) contain less than 0.40 of 0-8 for four consecutive quarters, or the conditions of Paragraph 46 have been met. DuPont shall monitor the ?nished and source 7 at waters of any new systems for the presence of GB in accordance with the provisions of Paragraph 42(e). g) Water Treatment Plan. If any additional private or public water systems covered by this Order contain (3-8 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 WVDEP, OEPA, and ODH for review, 21 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, MPI (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 from the owner or operator of the water source in order for DuPont to design and install the system. - h) lmlementation gt Water Treatment Plan. Following approval from EPA, DuPont shall implement the Water Treatment Plan for any additional water system whose timer 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 approvcd by EPA. If an owner or operator of a water system rejects DnPont?s offer, either through express rejection or silence, DuPont shall inform EPA of this rejection and provide documentation. DuPont?s era ion 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 7 provide for operation and maintenance of the GAC Treatment, or an altemative 7 Moody. Kwan. W.C.: Martin. Muir. D.C.G. Mabury. "Determination of Pcr?uorinalcd Surfactants in Surface Water Samples by Two Independent Analytical Techniques: Liquid Mass Spectrometry 19F Chem. vol. 73, pp. 2200~2206 (2001). Risha, Flahcny. Willa, Buck, Morandi, F. Isemura, T., ?Method for Trace [43ch Analysis ofC?S. 09, 0-10, (2?1 1, and (3-13 Pertluorocarbon Carboxy?c Acids in Cite-m.l vol. 77,1313. [503-1508 (2005). 8 approved by EPA consistent with the speci?c terms of these Agreements until it demonstrates to the satisfaction that the water system's source water prior to treatment is less than 0.40 ofC?S for four consecutive quarters, or the conditions of Paragraph 46 have been met. Follow-up Monitoring. After GAC Treatment is terminated, DuPont shall monitor annually the source Water at EPA-Speci?ed public and private water systems for a period of ?ve (5) years. 43. Progress Reports. DuPont shall submit Progress Reports as Follows: 8) C) Beginning April 1, 2009, and quarterly thereafter, DuPont shall submit to EPA, OBPA and ODH written reports summarizing all actions taken in response to Paragraph 42 herein (?Progress Reports"). This reporting requirement shall remain in effect 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 following 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 significant penalties for submitting false information, including the possibility of ?ne and imprisonment for knowing violations.? For purposes of this Order, a responsible corporate official shall be: (A) a president, secretary, treasurer, or vice-president of DuPont in charge of a principal business ?rnction, or any other person who performs similar policy or decision-making ?mctions 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. . - VI. SEENERAL PROVISIONS 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 affect the development of an MCL or other regulatory limit for 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 08 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 08, whichever comes ?rst. Notwithstanding any other provision of this Order, the EPA reserves the right to modify the Site-Specific Action Level identified 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-Specific Action Level may not he protective 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 submitted. to the following addressees: As to EPA: Roger Reinhart Groundwater and Enforcement Branch U.S. EPA Region 1650 Arch Street (3WP22) Philadelphia, PA 19103-2029 Ryan Bahr Ground Water and Drinking Water Branch U.S. EPA Region 77 West Jackson Boulevard (WG-ISJ) Chicago, IL 60604 As to Walter Ivey, Director Division of Environmental Engineering Of?ce of Environmental Health Services Dept. of Health and Human Resources Capital and Washington Streets One Davis Square, Suite 200 Charleston, WV 25301-1798 19 it. 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: M?re Baker, Chief Division of Drinking and Ground Waters Ohio EPA 122 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 I 18 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 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 DuPonl?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 beconstrued to operate in any way to .resolve any criminal liability of Du Pont. 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 of DuPont, to comply with such laws and rcgulations. 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. 300i(b), and the Adjustment of Civil Monetary Penalties for In?ation, 40 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 re?isal 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 ?rst knew, or in the exercise of due diligence, should have knoWn, of such event. The notice shall describe in detail the basis for the delay, including whether it is a force majew?e eVent, and describe the length 01", precise cause(s) of, and measures taken or to be taken to preVent or minimize such delay. If EPA agrees that such event constitutes jbrce mry?eure, EPA shall extend the time for performance of such requirement, in writing, to compensate for the delay caused by the force majeure 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, force 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. Unanticipatcd or increased costs or expenses associated with implementation of this Order and changed financial circumstances shall not, in any extent, be considered force mqjezrre 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 effective date of this Order is the date on which, after approval by the Regional Administrators. this Order is ?led with the Regional Hearing. Clerks ot?both Region and Region V, if not, then on the same day. 59. This Order shall remain in until DuPont ful?lls its obligations pursuant to Paragraphs 42 and 43 herein. submits a written request to to terminate this Order, and EPA approves such termination rcqucsl. 60. This Order constitutes ?nal agency action. SO ORDERED: 1a.: Date: Willi tun T. Wisniewski Acting Regional Administrator U.S. Environmental Protection Agency, Region Ii ?s Bharat Mathur g4 Acting Regional Administra! US. Environmental Prolec?on Region Agency, Date: 31/0207? A REED T0: . I 'Daic: ?5/5/7200? William H. Hopkins Plant Manager, Washington Works Facility EJ. du Pont dc and Company, Incorporated EXHIBIT Bilott. Robert A. From: 0.5. 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 AGENCY REGION - OFFICE OF COMMUNICATIONS GOVERNMENT RELATIONS 1650 Arch Street Philadelphia, 19103?2029 Phone - 215/814-5100 Fax - 215/814-5102 EPA Environmental News Contact; David Sternberg 215-814?5615 dandrea.michael@ epagov EPA Amends Drinking Water Order to DuPont PHILADELPHIA (January 9, 2017) - The US. Environmental Protection Agency today announced an amendment to the 2009 Safe Drinking Water Act consent order betWeen EPA and EL du Pont 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 perfluorooctanoic acid (PFOA) in drinking Water for residents in Ohio and West Virginia living near the Washington Works facility in Parker?sburg, WV. The amendment contains anew action level of .07 parts per billion (ppb) 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 of PFOA 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 PPOA in drinking water as protective of human health. lfycu would rather not receive future communicalions from Environmental Protection Agency. let us know by clicking here. Environmental Protection Agency. 1650 Arch Street. Philadelphia. PA 19103-2029 Untied states EXHIBIT EPA FACT SHEET United States Environmental Protection Agency "tease 0.. {:35 (o Health Advisories EPA has established health advisories for PFOA and PFOS based on chemicals evolves, EPA will continue to evaluate new evidence. PFOA and PFOS are fluorinate'd organic chemicals that are part of a group of chemicals referred to as perfluoroalkyl substances (PFASs) and PFOS have been the most extensively produced and studied of ture, paper packaging for food and other materials cookwarel resistant to water, grease or stains. They are also used for firefighti fields and? In a number of industrial processes. 3 Because these chemicals have been used In an array of consumer .. most people have been exposed to them. Between 2000 and 2002, gt .. was voluntarily phased out of production In the U. S. by its primary at. a. most people, drinking water can be an additional source in the smal centage of communities where these chemicals have contaminated were used forfIrefIghtIng r?m?m- iizoki?c' v. EPA develops health advisories to provide information on contaminants that can cause human healt non? regulatory and provide technical information to states agencies and other public health officials health effects, analytical methodologies, and treatment technologies associated with drinking water PFOA 8: PFOS Drinking Wa agency?s assessment of the latest peer-reviewed science to provide water system operators, and state, tribal and local officials who haI primary responsibility for overseeing these systems, with informati the health risks of these chemicals, so they can take the appropriat to protect their residents. EPA is committed to supporting states an: water systems as they determine the appropriate steps to reduce to PFOA and PFOS in drinking water. As science on health effects of' . turer. in 2006, eight major companies voluntarily agreed to phase 0 . their a, 6i global production of PFOA and PFOA-related chemicals, although th re are a limited number of ongoing uses. Scientists have found PFOA and PF Sin the blood of nearly all the people they tested, but these studies show th levels of PFOA and PFDS In blood have been decreasing. While consumer I?m products and food are a large source of exposure to these chemicals: supplies. Such contamination is typically localized and associated w? cific facility, for example, an industrial facility where these chemicals produced or used to manufacture other products or an airfield at wt and are known or anticipated to occur in drinking water. EPA's health advisories are non- enforceable . ination. in 2009, EPA published provisional health advisories for PFOA and PFOS based on the evider 'ethe anon eac?ons jdpubhc kposure gthese arger PFOA these chemicals. They have been used to make carpets, clothing, fabrics f? or furni? that are hg at air- Ioducts, PFOS Ianufac- atthe .for EPer- Water th a Spa- were ich they effects and on Icontam? ce avail? able at that time. The science has evolved since then and EPA 15 now replacing the 2009 provisional adviso? ries with new, lifetime health advisories. US Environmental Protection Agency 1 November 2016 FACT SHEET 93., :20. . .. . . ulsanes-gcon erect-"Hit"? s- -- i via-Jr To providenAmericans, including the most sensitive populations, with margin of protection fro I a life- time of exposure to PFOA and PFOS from drinking water, EPA established the health advisory levels at 70 parts per trillion. When both PFOA and PFOS are found in drinking water, the combined concentrations 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. 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 human populations that have been exposed to PFASs. These studies indicate that exposure to PFOA and PFOS over certain levels may result in adverse health effects, including developmental effects to fetuses during preg- nancy or to breastfed infants low birth weight, accelerated puberty, skeletal variations), cancejr testicular, kidney), liver effects tissue damage), immune effects-leg, antibody production anc m? 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 advisory 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. may 7A5. Svi . 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 additionalsam- 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 agency) 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 specific infor- mation on the risks to fetuses during pregnancy and breastfed and formula-fed infants from exposure to drinking water with an individual or combinedconcentration of PFOA and PFOS above health adviso- 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 waterksource, 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 8 JO-F?l?-oos FACT SHEET 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 perfIUo- roalkyl 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 ca rbor' 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 for treating PFOA and PFOS. In some communities, ertities have provided bottled water to consumers while steps to reduce or remove PFOA or PFOS from drnking 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 Standards 53 and 58 that establisf'es 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 estabiished 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/L (total of both PFOA and PFOS) and .must reduce this concentration by more than 95% to 0.07 ug/L or less (total of both PFOA and PFOS) thrijughout 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. mm- . - . skin-produ tion in the U.S. by its primary anufac? turer, 3M. EPA also issued regulations to limit future manufacturing, including importation, of PFC 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 Ibroduce 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. In 2006, EPA asked eight major companies to commit to working toward the elimination of their oduction 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 PF A, from emissions and products by the end of 2015. Additionally, PFOA is included in proposed 'Iloxic Substance Control Act?s Significant New Use Rule (SNUR) 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 81 PFOS Drinking Water Health Advisories 5 . A - N33 ablished national primary PFOA and PFOS as drinking water contaminants in accordance with the process required by the Saf 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. A water regulations for PFOS. EPA is eva 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 luating 'e Drink- a adverse levels of 3 served onkor o?ng effort are updated regularly and can be found on the publicly?available National Contaminant Occu rule#3 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. Information System (IRIS) assessment is needed. The Program identifies and characterizes the hazards of chemicals found in the environment. assessments inform the first two steps of the assessment process: hazard identification, and dose-response. As indicated in the 2015 Multi?Y found at rat? I .. ~h p- n. PEOA a pause; v-?It E??s??il?ixmln m: ?Mir-2a: shame-cu? flu-chMilt." . advi only apply to exposure scenarios involving drinking water. They are not for use, in identifying risk levels for ingestion of food sources, including: fish, meat produced fro that consumes contaminated water, or crops irrigated with contaminated water. Ii vz'rt. 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 advisories 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 wate Database (NCOD) In accordance with SDWA, EPA will consider the occurrence data from UCMR 3, along wit I the peer In addition, EPA plans to begin a separate effort to determine the range of PFAS for an integrated Risk Agenda, the IRIS Program will be working with other EPA offices to determine the range of PFAS com- pounds and the scope of assessment required to best meet Agency needs. More about this effort can be ter regu~ heakh risk ear ropriate restock breathing. ting water l, EPA _l consume low PFOA exposure. .1 US Environmental Protection Agency November 2016 EPAB DO-F-16-003 . #213,! a ll :0 . Drinking Water Health Advisories for PFOA and PFOS can be found at: . PFOA and PFOS data collected under Unregulated Contaminant Monitoring Rule are avai able: taminant-monitoring?rule stewardship program for PFAS related to TSCA: aging- chemicals?under?tsca/and . research activities on PFASs can be found at: . The Agency for Toxic Substances and Disease Registry? Perflourinated Chemicals and Your Health webpage at: 3EPA United States i . EnVImnmentai Protection Agency US Environmental Protection Agency 5 November 2015 7 EPA 00-F-16-003 EXHIBIT Brief Overview of the Feasibility Assessment for Epidemiological Studies at Pease International Tradeport' May 23, 2017 1. Introduction The Pease International Tradepcrt is located in Portsmouth, New Hampshire (NI-I) 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 peeple. 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 for perfluoroalkyl 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 per?uorooctane sulf nate (PF OS), per?ucrocctanoic acid (PFOA), and per?ucrohexane? sulfonate levels averagi 2.5 micrograms per liter 0.34 pg/L, and 0.90 pg/L, respectively. While the Environmental Protection Agency has a lifetime health advisory for PFOS and PFOA, no regulatory standards any federal agency have been promulgated for PFAS. Much lower levels of these contaminants wer found in the other two wells serving the Pease Tradeport. The Haven well was shut down in May 201 . The contamination of the drinking water wells was the result of the use of aqueous ?lm forming 0am at the former Pease Air Force Base for firefighting training and to extinguish ?ammable liquid tires. The firefighting foam contained PFAS. It was used at the base from approximately 1970 ntil the base closed in 1991. The likely leached into the soil and groundwater and migrated to the :hree drinking water supply wells that served the base and later served the Pease Tradeport. It is not it 1cwn 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 Depairtment 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 Tradeport. 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 put; ose 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 as . possible to the community?s questions and concerns. a Scienti?c importance a study should evaluate diseases and other health- related endpoints (also called ?effect Ibiomarkers?) and improve our understanding of possible health effects of PFAS exposures. - Public health signi?cance a study should provide a strong basis for determining if PFAS exposures increase the risks of 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 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 PFOA, 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 research 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 population. However, whether it is feasible to study a specific health-related endpoint depends to a great 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?s study at Pease, ATSDR took into account date when the Haven well was shut down, the length of time ?half?life?) that and remain in the blood after exposure, and the age range appropriate for the health endpoints under ied little 3 the for a ed_ the consideration. ATSDR concluded that a study is 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. uq 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 tie 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 ?lom the Pease community), and 3) not feasible to study using the Pease children population unless additio nal populations from other communities exposed to PFAS~contaminated drinking water are included 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 ?ltration rate a measure of kidney function - Insulin-like Growth Factor 1 (a measure of growth hormone deficiency) . 0 Overweight/Obesity Health-related endpoints that may be possible to study in children at Pease (although a larger sample size from the Pease community will likely be needed): 0 Mean difference'in uric acid 0 Elevated total cholesterol (hypercholesterclemia) - Elevated uric acid (hyperuricemia) IQ/neurobehavioral 0 Thyroid function 0 Sex hormones - Asthma and atopic dermatitis (Immune function) 0 Rhinitis (stuffy, runny nose) 0 Antibody response to rubella, mumps and diphtheria vaccines Health-related endpcints not feasible to studv using the Pease children population (in order t) 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 - 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 P6 ase 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 d1inking 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 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) - Elevated total cholesterol (hypercholesterolemia) - Mean difference in uric acid 0 Elevated uric acid (hyperuricemia) - Thyroid disease (uncon?rmed) 0 Cardiovascular disease 0 Hypertension - Osteoarthritis arid osteoporosis - Mean differences in serum immunoglobin and C?reactive protein (an m: of in?ammation); inc1ease in antinuclear antibodies (an indicator of autoimmune reaction); alterations 1n speci?c cytokines Health-related endpoints that may be possible to study at Pease eCaIthough a 1111 ger sample size the Pease community may be needed): 0 Liver function - Thyroid disease (confirmed) 0 Thyroid function 0 Endometriosis a Pregnancy-induced hypertension Page 4 iicator 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 nee to be included to make the study feasible): - Liver disease - Kidney disease - Ulcerative colitis . Rheumatoid arthritis - Lupus - Multiple sclerosis - 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 mortalEty 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 For Base populations, several thousands of exposed populations from military bases where ed or 33 contaminated drinking water occurred, as well as several thousands of comparison populations ?t in military bases that did not have drinking water contamination. Conclusions The feasibility assessment concluded that it is possible to evaluate some health-related endpoints a suf?cient 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 populations from other sites who were exposed to PFAS-contaminated drinking water. The feasibl assessment concluded that athird 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 lity Pease. No single study of the Pease population will provide clear answers to the community about whether 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. Whetier a Iwn study will ?nd an association between an environmental exposure and health effects cannot be kn 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 suf?cient number of study participants. The feasibility assessment is still a draft. It will be ?nalized once the Pease Community AssiStanc 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 rece The feasibility of successfully evaluating particular health-related endpoints (or effect biomarkers: change depending on ?nal study design and goals. Page 5 Lil ived. could DRAFT for Review Pnrposes Feasib?ity Assessment for Epidemiologiea] Studies at Pease International Tradeport, Portsmouth, New Hampshire May 23, 2017 The ?ndings and conclusions in this report?oresentaiion have not been formally disseminated by 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 ll 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 former Pease Air Force base . . 41 Other study designs and health-related endpoints . 42 References . 45 Tables 59 Appendix 76 Literature review 7 7 Description of sample size 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 per?uoroalkyl substan - es (PFAS), in particular per?uorooctane sulfonate (PFOS) and per?uorohexane sulfonate rom the use of aqueous ?lm-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 PF OS 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 activities 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 was concerned about cancers, elevated lipids, 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: 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 commurity?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%). . Scienti?c importance a study should evaluate biologically plausible diseases and other iealth? related endpoints (also called ?effect biomarkers?) and improve our understanding of possible health effects of PFAS exposures. . Public health signi?canCe 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 populations 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 suf?cient 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 1eviewed the epidemiological literature on PFAS exposu1 es to identify the health?relate endpoints that have been studied and current data gaps, in particular, for the effects of 'l l1te1 ature review also was used to identify adverse effect sizes observed 1n the PFAS studies for serum levels similar to those found in the Pease pOpuIation. The literature review found that most information on potential health e?'ects concerned exposur per?uorooctanoic 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 literat review found that less information was available about the potential health effects of PFOS exp 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 fill key knowledge gaps and address the community?s concerns. The literature review identi?ed many health-related endpoints evaluated in previous epidemiological studies of PFAS exposures. These included cancers, lipids, effects on thyroid and immune func developmental delays. They also included effects on kidney and liver function and sex hormone diseases such as endometriosis, ulcerative colitis and osteoporosis. Many of these health?related endpoints were also previously raised bythe community and the Pease CAP. he PFAS as to irginia sbee ire osures, Because ion, and s, and In Considering possible study designs, ATSDR focused on the methods used 1n previous epidemiological 1esea1 ch of PFAS exposures. Adopting study design methods consistent with previous research facilitate the 1nterp1etat10n and of ?ndings across studies. The literature review found most of the epidemiological studies exposures were cross?sectional and evaluated seru measurements. Some studies also evaluated cumulative PFAS serum levels that were estimated would that PFAS from modeling methods. ATS DR concluded that any study of populations exposed to the PFAS-contaminated drinking water at the Pease Tradeport should be cross?sectional and evaante 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 cons ister methods used in previous epidemiological research of PFAS exposures. Potential Study Designs A. Cross?sectional study of children The ?rst design is a cross-sectional study of children who were exposed to the PFAS-contamine 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 rang 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 3A8 methods with ted children of 4- ren aged ages 4? 16 years. The study would involve re-contacting these participants and obtaining new blood samples. To increase the sample siae, 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 duiing 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 tl the study 3 0 testing 9 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 did not work at the Pease Tradeport or have occupational exposures to PFAS, would be recruite blood samples collected. The comparison group would be sampled from the Portsmouth public 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 . evaluate PFAS serum levels and several biomarkers of effect, including lipids, thyroid function, function, immune function, and sex hormones. The children could also be assessed for neurolo parents :1 and schools 3 kidney '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 1a)! care at the Pease Tradeport. Additional sample size calculations assumed a sample size of 500 expo ed 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 detect effects found in other PFAS studies of children with serum PFAS levels similar to those ed to bserved in the Pease children population. For some health-related endpoints, there was insufficient information to conduct any sample size calculations. 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 350 exposed and 175 unexposed children), and 3) not feasible to study using the Pease children population 3: 1) :hildren less 1 additional pOpulations exposed to PFAS-contaminated drinking water from other affected comr?unities - 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) Mean difference in estimated glomerular filtration rate a measure of kidney functio Insulin-like growth factor 1 (a measure of growth hormone de?ciency) Overweight/Obesity 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) Mean difference in uric acid, a measure of kidney function Elevated total cholesterol (hypercholesterolemia) Elevated uric acid (hyperuricemia) IQ/neurobehavioral Thyroid function Sex hormones Asthma and atopic dermatitis (immune function) Rhinitis (stuffy, runny nose) Antibody responses to rubella, mumps and diphtheria vaccines 4 (D 1? 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 0 Delayed puberty - Thyroid disease 0 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 :18 - 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. In the 2015 blood testing program at Pease, 1,182 adults aged years particip 1,083 adults reported that they last worked at Pease during 2008?20 14: 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 p0p 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 (hypercholesterolemia) 0 Mean difference in uric acid, a measure of kidney function 0 Elevated uric acid (hyperuricemia) - Thyroid disease (unconfirmed) - Cardiovascular disease 0 Hypertension .- Osteoarthritis and osteOporosis vould 16 acular ated, and the Pease iexposed ther ulation. s: 1) :l and :litional Draft for Review Purposes Do Not Cite'or Quote 0 Mean differences in serum immunoglobin (lgA, 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 studv in adults at Pease (although a larger size from the. Pease community may be needed) 0 Liver function - Thyroid disease (confirmed) - Thyroid function 0 Endometriosis Pregnancy-induced hypertension ndicator sample Health 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 in to evaluate these health-related endpoints) - Liver disease . Kidney disease 0 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 quartiles based on thei1 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 A third study design that was considered would evaluate mortality and cancer incidence among military service and civilian worker personnel at the former Pease Air Fo1ce 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 identi?ed that had no PFAS?ccntaminated dri1 water or drinking water contamination from other chemicals above the U.S. Environmental Prot Agency?s maximum contaminant levels (MCLs). Personal identifier information Social 8 number, name, date of birth, sex) necessary for data linkage with the national death index and st federal cancer registries could be obtained from the Defense Manpdwer 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 eluded Jr the former tary 311(ng ection ecurity ate and not a 10 were Draft for Review Purposes Do Not Cite or Quote stationed or worked at the Pease Air Foree Base. Such a study would require, in addition to the Air Force Base populations, several thousands of exposed populations from military bases whei contaminated drinking water occurred, as well as several thousands of comparison pepulations 1 military bases that did not have drinking water contamination. Conclusions The feasibility assessment concluded that it is possible to evaluate some health?related endpoints suf?cient number of children and adults from the Pease population participate. Other health~re12 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 forms 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 thecommunity about their exposures to the PFAS~contaminated drinking water caused their health problems. All epidemiological studies of environmental exposures and health outcomes have limitationsand 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 popul p1 owde useful information will depend to a great extent on the success of recruiting suf?cient 11 study participants. - Pease PFAS- Trom if a Lted of ibility at Pease. Whether health ation to umber of The feasibility assessment is still a draft. It will be finalized once the Pease Community Assistance Panel (CAP) and the larger Pease Tradeport community have the opportunity to review and mak 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 biomaike change depending on ?nal study design and goals. 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 and Disease Registry?s feasibility assessment of possible drinking water epidemiological studies at the Pease International Tradeport (?Pease?), Portsmouth, New Hampshire. The purpose of th feasibility assessment was to determine whether epidemiological studies are reasonable to conda ct at Pease and whether data exist to conduct scienti?cally credible epidemiological studies. This dr feasibility assessment report for possible future studies at Pease International Tradeport is bein 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 news. The report is a DRAFT document that may be edited based on CAP input; it is not intended to be a protocol or systematic literature review. The ?nal study design, including sample size, the health endpoints that can be considered and the deveIOpment 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 feasibility assessment does not represent a commitment by ATSDR to conduct research at Pease International Tradeport, given that funding and staf?ng to conduct the described research are not available at this time. . Three criteria were used to determine whether epidemiological studies are warranted at Pease: l. Meaningful and credible results study should have suf?cient validity and precision, be capable of detecting health?related effects, and be as responsive as possible to the comm unity?s questionsand 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%). To achieve suf?cient validity, a study should minimize biases such as selection bias and confounding bias. Suf?cient precision can be achieved by a sample size that has at least 80% statistical power to detect health-related effect sizes observed in other 51 udies for PFAS serum levels similar to those in the Pease population. . Scientific importance a study should evaluate biologically plausible diseases and otF er health-related endpoints (also called ?effect biotnarkers?) and improve our understanding of possible health effects of PFAS exposures and ?ll 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 health? related endpoints evaluated in these studies and the data gaps that exist on the health effects of and PFOS. . Public health signi?cance a study should provide a basis for determining if PFAS exposures increase the risks for specific adverse health effects, and if so, what public health actions are necessary to reduce the risks. In particular, the study should provide a basis for early medical intervention for health outcomes that are not routinely evaluated in physical exams. The study should also be relevant to other populations with similar exposures. 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. Is there a complete exposure pathway, well-defined exposed population, and ability to a? levels of exposure with adequate accuracy? Is there justi?cation for studying the specific 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?ng 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 note compile total enrollment statistics, but its capacity is 220 children, they usually enroll about 18C :ion bias status.) ssign is there 50 3 ?xed that asily ?1 95 children at a time, and they have been operating for almost 7 years. As of July 2015, the estima ed population of Portsmouth was 21,530 62900). 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. Additionally, 51.5% of the population were female, 91.5% were white, and 95.6% of persons 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 Base. In October 1989, 3,465 military personnel were assigned to the base, accompanied by 4,7 dependents. The Air Force estimated that 537 civilian employees worked on?base at that time (.1 1999). During 1970?1990, an average of 3,000 personnel and their families were assigned to the 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 Harrison 1 Before 1981, the wells fed directly into the distribution system so that a particular area of base a cs 25 Tes 6?1 7 iorce 46 base at vells. would - p1imarily 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 d1 inking water to the Pease Tradeport after it opened. In 1977, water from the base wells was found to contain trichloroethylene (TOE). Two of the th serving the base were contaminated. The maximum concentrations of TCE measured in the Hay ided ree wells en and Harrison supply wells were 391 micrograms per lite1 (pg/L) and 28. 5 pig/L, respectively. After- discovery of the contamination, those wells were shut down and the city of Portsmouth suppIie d1inking water to the base during 1977?1978. In the fall of 1978, the wells were back' 1n operati n. TCE levels in the Haven well ?uctuated between 50 ug/L and 115 ug/L f1om the fall of 1978 througl January 9 Draft for Review Purposes Do Not Cite or Quote 1980, then fell below 50 pg/L, with an occasional spike above 50 ug/L through October 1980. November 1980 through July 1981, TCE levels averaged about 30 jig/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 pg/L until January 1986 (ATSDR 1999). The base of?cially closed. in October 1991, and most of the property was transferred to the Pear i?rom llg/L atly VICL) in 3 Development Authority (PDA). During 1993, the business and aviation industrial park began Operation. The City of Portsmouth entered into a long?term lease and operation agreement with the PDA to operate and maintain the public water system serving the Tradeport. From approximately 1970 until the base closed, aqueous ?lm-forming foam was used t3 at the extinguish and prevent flammable liquid ?res. was also used during ?re?ghting training base. Through 2001, perfluorcalkyl substances (PFAS) were used in the manufacturing including per?uorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and per?uorohexane sulfonate (PF HXS). containing PFAS likely leached into the sci-l and groundwater and migrated to the three supply wells serving the Pease Tradeport. It is not known when these Wells were contaminated 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 When the 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 Tradeport, with the Smith well providing 44% and the Harrison well out of service. In 2000-20 1, the Works. Up through 1999, the Haven well on average provided about 56% of the total water supfly at the Haven well supplied 88% of the supply and the Smith well supplied 12%. From 2003 until itw out of service in May 2014, the Haven well on average supplied about half the water supply. the Harrison well was back in service and the Smith and Harrison wells together supplied on av about half of the water supply at the Tradeport. After May 2014, the Smith and Harrison wells 5 56% of the Tradeport water supply and the City of Portsmouth provided the other 44%. In 2009, EPA established provisional health advisory levels for PP OS and PFOA of 0.2 pg/L ar pg/L, respectively EPA 2009]. In 2013, sampling of monitoring wells at the former Pease Air Force Base ?re 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 combined concentrations of PFOS and PFOA in drinking water should not exceed 0.07 ug/L 2016a]. No drinking water health advisory level has been established for or other PFAS 3 taken 2006, . erage upplied [Cl 0.4 levels. EPA chemicals. While the EPA has a lifetime health advisory for PF OS and PFOA, no federal regulatory standards for these contaminants have been issued. In April and May 2014, the three 'supply wells serving the Tradeport were sampled for PFAS. In the April sampling, the Haven well had PFOS, PFOA, and levels of 2.5 ug/L, 0.35 ug/L, 0.83 pg/L, respectively. In the May sampling, the Haven well had PFOS, PFOA, and levels 2.4 pg/L, 0.32 pg/L, and 0.96 pg/L. Other PFASs were also detected in the Haven well. The Harris 11 well had much lower levels of these contaminants with maximum PROS, PFOA, and levels 0.048 pg/L, 0.009 lug/L, and 0.036 pg/L, respectively. The Smith well had maximum levels nd of 0.018 pg/L and 0.013 pg/L, respectively, with an estimated level of PFOA of about 0.004 its/L. 10 -- Draft for Review Purposes Do Not Cite or Quote No samples of the Pease Tradeport distribution system for PFAS are available from the period 1 Haven well was in operation. We can use a simple mixing model to estimate the PFAS levels it 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 totai demand, and the concentrations of PFAS 'in the wells during the April and May 2014 sampling. this simple approach, the estimated levels PF 0A, and in the Pease Tradeport distribution system in April 2014 would be approximately 1.4 pg/L, 0.2 [lg/L, and 0.5 pg/L,. 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 beti 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 conducted 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 report of its activities on December 21, 2015. Among the recommendations of the CAB in its fi report were the following: when the the Jughout 1 water Using . PFAS Neen the by NH 3CAB final ma] 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 Tradepdrt. 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 February 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 review 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 would pi 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 peeple have been exposed to hazardous substances, and inform ATSDR about ways to involve the corn The ?rst public meeting of the CAP was held in May 2016 in Portsmouth. The second public 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 definh information regarding the possible health effects of PFC [perflucrinated 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 expos ?these risks might be manifested.? In an email sent to ATSDR in November 2015, the CAB asked that ATSDR consider the follon question: ?What, if any, long?term health?effects, such as specific cancers, elevated blood lipids 11 for to the ase ving the of the 'ovide with night - munity. eeting =ive mains a better ure ing thyroid reduced. activities 5 . . Draft for Review Purposes Do Not Cite or Quote function, immune function and developmental delays, are associated with the PFC exposure at case? This question should be broken down with regard to speci?c populations including children, nursing/pregnant women, ?re?ghters, and adult exposed workers.? This'questi on was reiterate lat the first 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 ?re?ghters who were exposed to contaminated drinking water at Pease and also irectly to as part of their ?refighting duties. CAP members expressed their desire for a longitudina approach (compared to a cross-sectional approach) to evaluate short-term and long?term health conditions, including cancers. 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 April?May 2014 sampling reflect 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 Force base, including accidental 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 of PFAS 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. blood testing program conducted during April?October 2015. A person was eligible for this pro ram if Another important source of information on exposures at the Pease Tradeport was the NH PFAS he or she had worked at, lived on, or attended childcare at the Pease Tradeport or Pease Air For Base, or lived in a home near the Pease Tradeport that was served by a PFAS-contaminated private we total of 1,578 persons volunteered to submit a blood sample for PFASs testing DHHS 2016 Was a convenience (or volunteer) sample, not a statistically based sample. Nevertheless, the test program provided important information on the extent and magnitude of exposures to the PFAS contaminated drinking water at the Pease Tradeport. A This ng Table 1 shows the serum concentrations of PF OS, 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 checter 2012] and California (Wu 2015). Data from the National Health a 12 1d . . . 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 blcoc from 68 .children ages 2?8 years for PFAS analyses during December 2007?No'vember 2009. parents of the children had higher education levels than the general population. The Texas study 16 [Schecter 2012] analyzed serum samples collected from 300 children ages 512 years at a children?s 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 compai 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 PFOA level for persons aged E12 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 ug/L in the 2013?2014 cycle. also de but more gradually, from 2.1 pg/L during the 1999?2000 cycle to 1.3 pg/L in the 2013?2014 cy the NHANES 2013?2014 cycle, children ages 12?19 years had geometric mean PFOA, PFOS, serum levels of 1.66 pg/L, 3.54 pg/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 PF OS, 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 at l? the median and geometric mean serum levels of 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 NHANES 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 0.15, marginal effect Geometric mean PFOS and PFOA serum levels were also hig among persons who drank 24 cups of water per day compared with those who drank <4 cups pe DHHS 2016]. Linear trends were observed for geometric mean serum levels of PFOS, PFC and increasing time Spent at the Pease Tradeport. The trend was strongest for PFOS and DHHS 2016]. . 13 at for of children en in the ?aws s. e, in the was 5.2 arply. clined, cle. In .nd ly cipants 014 (the ease, BIC can ons who ierum ar, water 0.31, SE 161' day A, and a study - 1 samples . 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 st and the data gaps that exist, in particular, for the effects of and PF OS. The literature rev was used to identify adverse effect sizes observed in the PFAS studies for PFAS serum levels si those found in the Pease population. The Appendix has a listing of the epidemiological literature on PFAS exposures and adult canoe adult diseases, and adverse outcomes in children. Tables 3 and 4 provide a summary. In these ta udied ew also milar to .rs, other bles, a indicates that at least one study had a ?nding for a speci?c 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 tes that the findings from studies have not suggested an increased risk for an adverse outcome al 1 i ratios or risk ratios are <1.20) but the information is too limited to conclude that there is no ass ciation between the PFAS exposure and the adverse outcome. These tables are for illustrative purposes, to indicate where data gaps exist and therefore additio alt research may be needed. Tables 3 and 4, and the tables and descriptions of the studies in the ap endix, should not be interpreted as implying causation or as an assessment of the weight of evidence an association. Currently, epidemiological research on the health effects of PFAS exposures is at a. early stage. This is particularly true for in addition to PFAS chemicals other than PF 0A and However, even for PFOA and PF OS, 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 OS. itioned ss ted or diseases adult 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 PF 0A 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 i 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; Bach 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 3 - etermine etus size 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 PPAS 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 associated with ADHD, but ?ndings have not been consistent across studies. Evaluating the evi ence for PFAS exposures and neurobehavioral outcomes isdif?cult for several reasons: 1) the studies us different methods to measure the outcomes, 2) studies are inconsistent in the outcomes evaluate and 3) too few studies have been conducted. A few studies have found associations between PFAS ex osures function in older children. A few studies have found elevated uric acid with PFAS exposures, 13? rubella). In SUmmary, there are considerable data gaps concerning ?re health effects in chi PFAS exposures. This is because of the small number of studies conducted, inconsistencies in 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. and a decline in antibody response to speci?c vaccines, but only two studies evaluated the samj?vaccine 1 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, bl weight, preterm birth, and gestational age. Although the birth certi?cate has a checklist for song 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 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 are collected 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) diabetes, previous preterm birth, parity and gravidity, cigarette smoking before and during pregr principal source of payment for the delivery (a measure of socio?economic status), date of last 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, names and address, mother?s marital status, labor and delivery complications, and whether the ii I rancy, ren. of ethods imes, ?cate are 9rth en ital hire ege, ent birth 3. 1 of rarents? ifant is being breastfed at discharge. The New Hampshire Division of Vital Records Administration col information on births in New Hampshire from hospitals and midwives, birth certi?cates, and in exchange agreements for births occurring out-of?state to New Hampshire residents ects erstate Mortality information is available from the National Death Index (NDI) operated by the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention. Currently, 2014 data complete and available for searches. ?Early release data? for 2015 are 290% complete (98% cor for New Hampshire) and also available for searches. NDI ?plus? provides information on cause 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. Draft for Review Purposes Do Not Cite or Quote New Hampshire death certi?cate data are available from the New Hampshire Division of Vital Records Administration, which collects information on deaths of New Hampshire residents and deaths occurring in New Hampshire Information on deaths of New Hampshire residents that occur out-of-state is captured through interstate exchange agree ents. Information on underlying cause of death and up to 14 contributing causes of death is collecte 1. Complete data are available approximately 24?48 months after the close of a calendar year. Population-based cancer registries exist in all 50 states and Washington, DC. The New Hamps Iire State Cancer Registry .is a statewide, population?based cancer surveillance program that collected incidence data on all cancer cases diagnosed or treated in the state since 1985 which is contracted to the Geisel School of . edicine at Dartmouth College, currently collects data from the larger hospitals in the state. NI-IS CR alslg?lreceives case reports from physician practices, free standing radiation oncology centers, pathology labo Etories and other sources. NHS CR staff assist hospitals with fewer than 100 cases per year with reporti g. Through interstate data exchange agreements, also receives case reports for New Hampshire residents who are diagnosed outside the state. The New Hampshire Uniform Hospital Discharge Data Set (UHDDS) collects discharge data from all 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, Massachusetts, and Vermont hospitals for New Hampshire residents are included in the UHDDS via interstate data exchange agreements. The dataset includes transfers of NH residents. Chronic diseases such as asthma, chronic obstructive pulmonary disease, angina, hypeitension, congestive heart failure, hypoglycemia, and diabetes are included in the UHDDS. Limitations of this dataset are that discharges are not e- duplicated and one person with multiple admissions might falsely increase the number ofperso hospitalized. Additionally, state law requires health care professionals to report information on thronic health conditions relating to children, infectious diseases, immunizations, and autism to NH topics). To ascertain autism or ADHD reliably, a review of school special education records and medica records from providers that conduct developmental evaluations of children or provide treatment is neces- ary. In Portsmouth, records are available from three elementary schools (serving grades one mid le school (serving grades and one high school (serving grades 9?12). Projected enrollment fo the 2016?17 school year Was 988 students in the elementary schools, 516 students in the middle 01, and 1,183 students in the high school In school year 2015?2016, the Portsmouth Public Schools provided special education services to 4 6 students. Among those students, 121 had an orthopedic impairment, 36 had a speech/language impairment, 32 had a developmental delay, 25 had autism, 17 (4 had an emotional disturbance, 11 had some other disability, and 174 were classi red as having a ?specific learning disability.? Various studies have focused on West Virginia and Ohio residents and workers exposed to PFO from a chemical plant (the studies) [Frisbee 2009]. In a 08 study that evaluated ADHD, affected ersons were identi?ed via questionnaire, which included a question requesting information on medicati ns used [Stein 2011]. For chronic diseases, the C8 studies relied primarily on self-reported information from questionnaires with attempted con?rmation of self-reports by obtaining medical records. 16 . I Draft for. Review Purposes Do Not Cite or Quote Sources of exposure data An important source of exposure information is PFAS biomonitoring. Measuring serum levels of PFAS chemicals provides information on the amount of these chemicals that has entered the body fro a all sources. At Pease, 1,578 persons volunteered to submit blood samples for PFAS analyses durin the NH DHHS biomonitoring program in 2015. In the CS study, blood samples for PFAS analyses wer obtained from 66,899 persons during the 13-month baseline period, 2005?2006 [Frisbee 2009]. Biomonitoring for PFAS is useful in estimating past exposures, given the long half-lives of PF .3 (approximately 5.4 years) and (approximately 8.5 years). Although bi01nonitoringintegi'rates PFAS exposures from all sources, including diet and consumer products, PFAS levels in serum om populations exposed to PFAS?contaminated drinking Water will mostly re?ect the drinking wat 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 limitati is the issue of ?reverse causation,? in Which the disease under investigation kidney disease or ki ney function) affects the elimination of PFAS in the body, causinghigher serum levels of PFAS. Qt. er problems include potential confounding by a factor that is both a risk factor for the disease of in?rest and a factor in?uencing serum PFAS levels parity in the evaluation of adverse birth outco es). Another limitation is that biomonitoring results, by themselves, might not provide suf?cient information to estimate historical exposures. Estimating historical exposures is necessary to assess cumulative exposure and to characterize periods of special vulnerability to PFAS exposures, such as prenatal or 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 absorption, 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 current PFOA serum levels [Shin 2011]. Researchers have also been able to simulate PFOS serum levels using information on drinking water levels and PBPK modeling [Loccisano 2011]. Therefore, reconstruction of historical PFOS serum levels is also feasible. However, reconstruction of PFOA and PFOS serum levels is limited by various uncertainties. These include lack of accurate information on individt al consumption of drinking water and length of time exposed and limited information on factors th at produce inter?individual variability gender, age) and pre-existing' medical conditions compromised renal function) [Loccisano 2011]. Nevertheless, the ability to predict serum PFOS and 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 prevalences of nonfatal diseases, in particular, diseases with no clear point of onset [Checkoway 2004]. However, if the cross?sectional study concurrently measures the exposure and the outcome the disease or effect biomarker), then it might be dif?cult to determine whether the exposure caused the outcome or whether the outcome influenced the measured exposure level [Flanders 1992, 2016]. For example, as discussed above, the concurrent measurement of serum PFAS levels and kidney function biomarkers might raise 17 Dra? for Review Purposes Do Not Cite or Quote the question of ?reverse causation? because kidney function can affect the levels of PFAS in ser PFAS levels. In addition, it might be possible to estimate exposures during critical vulnerable in utero exposure) through the modeling of historical serum PFAS levels. However, the of historical PFAS serum levels is subject to uncertainties and data limitations, as discussed abo published methods are available only to model serum levels of PFOA and PFOS. issue can be addressed by estimating exposures based on the historical reconstruction modelingEf serum Other issues concerning cross-sectional study designs are similar to those that confront other observational study designs, such as cohort studies. These issues include: I) the ability to clearl: enumerate and recruit (without introducing selection bias) the exposed and comparison populati the comparability of the exposed and comparison populations on risk factors other than the PFA ascertainment of diseases. exposures, 3) accurate exposure assessment, and 4) accurate measurement of effect bicmarkers and um. This =riods deling ve, and .1 define, ans, 2) Based on its review of the literature, ATSDR concludes that several health-related endpoints could be considered for studies of the Pease population. It is also clear that exposures to the PFAS?conta. drinking water have occurred in the Pease pepulation, as documented by the observed serum PF levels in the NH DHHS PFAS blood teeting program. Therefore, it is reasonable to conduct epidemiological studies of the Pease population. However, whether it is feasible to study a speci health~related endpoint depends to a great extent on the size of the exposed population that can recruited into a study. The usual approach to determine the necessary size of the study populatic 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 find an association between an environmental exposure and effects cannot be known prior to conducting the study. No single study of the Pease population minated AS fie )e . in for [Cl health will provide de?nitive 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 useful information will depend to a great extent on the success of recruiting a sufficient number participants. Feasibility of an epidemiological study of children at the Pease Tradepor The first population that ATSDR considered for an epidemiological study was the children who the two day-care centers at the Pease Tradeport. One reason to focus on children is that they are 1 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 effect children from the drinking water exposures, which was conveyed to ATSDR by the Pease CAP. a study of children who attended daycare at the Pease Tradeport is the most feasible epidemiolo 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 l) the possibilit early intervention if early signs of adverse health effects, including developmental delays, are ob and 2) the relevance of a study at Pease for other populations exposed to drinking water primaril: 18 wide 3f study attended nore sto inally, ical yof terved Draft for Review Purposes Do Not Cite or Quote contaminated with PF OS and A study of children at Pease would have scienti?c impo ance because of key data gaps concerning PFAS eprsure effects on sex hormones and on neurobeh vicral, immunological, and thyroid function. Animal studies'support the biological plausibility of immune effects. Animal data also suggest that PFAS might be developmental neurotoxicants that can alter 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 statistica' power) to provide meaningful and credible results for some of the adverse outcomes of interest. However, a study limited to the population of children who attended the Pease Tradeport day?care centers would likely not be sufficiently large for some of the possible adverse outcomes of interest higher prevalences of rare diseases or very subtle changes in biomarkers of effect that have been observed in research conducted elsewhere). A. Study population The population of interest could be persons who attended day care at the Pease Tradeport before June 2014 and are in the age range of 4-16 years at the start ofthe study. The end of the period was selected because the Haven well was taken out of service in May 2014. Because PFAS?contaminated dri . king water exposures could occur to children in uteroand during breastfeeding if the mother worked the Pease Tradepoit, the study would include these additional children if the exposures began prior 0 June 2014 and their ages are 4 16 years at the time the study begins. . The age range for the Pease children study was determined by taking into account the age range 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 ta limitations no PFAS serum data for those aged <12 years), the studies that used NHANES ata evaluated those aged 12?1 8 years or 12?19 years. Some of the CS studies limited participant ag to those <12 years; other C8 studies included persons up to 18 years of age. The upper age limit fo .many of the Taiwan children studies of PFAS was 15 years. An age range of 4?16 years would overla the age ranges in these studies. The chosen age range also re?ected the focus of the study children exposed to the PFAS- contaminated drinking water while attending daycare at the Pease Tradeport). The younger age 1 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 231d Dif?culties Questionnaire (SDQ), a behavioral screening questionnaire used in a Faroes study lulhote 2016], a Taiwan study [Lien 2016] and a Danish study [Pei 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. - 2. The IQ and SDQ testing instruments for children have an upper age limit of 16 years. 3. Children aged >16 years would have been last exposed last attended daycare) more than 10 years ago. 19 Draft for Review Purposes Do Not Cite or Quote Table 5 provides the data on serum PFOS, PFOA, and for the 370 children who particip the 2015 NH DI-IHs 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 i was 3.80 ug/L, approximately three times higher than the serum levels reported in the Texas 2012] and California [Wu 2015] studies and in the NHANES data for 2013?2014. ated in draw. zhildren ehecter I We currently do not know how many children attended daycare at the Pease Tradeport before June 2014 and who would be in the 4-16 years age range in 2018. The Discovery Child Enrichment Cente located at the Pease Tradeport and began operation in 1994. Its yearly enrollment is approximat 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 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 512 years. Assuming that most of the chi enrolled would be 55 years of age, and that most of the children attend daycare for 4 years, aboL 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 reerui 175 children in the same age range from the public schools in Portsmouth, NH, who were unexp the PFAS?contaminated drinking water at the Pease Tradeport and whose parents did not work a Pease Tradeport or have occupational exposures to PFAS. It is reasonable to assume that particir 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 cemmunity. If the actual number of children who attended the two day?care centers prior to Jun: and would be aged 4 16 years in 2018 is in the range of 650 750, then as many as 500 ohildre 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 samp used in the Faroes study [Grandjean 2012, 2016] and in a CS study of 320 exposed children [Stei 2014b]. However, the sample size of 35.0 exposed and 1.75 unexposed would be conSiderably sm. is ely 149 695 018. ne 2014 10. Its dren 300 years in re June 6, it at least used to the ration when a 3 2014 could the le sizes 'n 2013, aller than most of the 08 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 13.. Study Hypotheses As indicated in the literature review summary, the scienti?c literature has little information on the health effects of exposures to PF is a key contaminant associated with the use of AFF 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 exposed to drinking water contaminated by from the use of In addition, few studies have been conducted to evaluate possible associations between childhood exposures to PFASs and effects thyroid function, uric acid and sex hormone levels, delays in reaching puberty, IQ, and immune 311 function. Inconsistent ?ndings have been observed for most of these endpoints, likely in part bceause of differences in exposures drinking water and other sources, such as diet) and PFAS levels of exposure, study population-differences 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 choleste density lipoprotein, and triglycerides, and higher prevalence of hypercholesterolemia. rol, low- I-Iigher serum levels of PF 0A, PF 08, or are associated with differences in thyroid stimulating hormone (TSH), T'l?4, and TTS, and a higher prevalence of hypothyroidism. 3. Higher serum levels of PFOA, PF OS, or are associated with a higher level of uric acid and a higher prevalence of hyperuricemia. . 4. Higher serum levels of PFOA, PFOS, or are associated with differences in testos:erone, estradiol, and sex hormone?binding globulin (SHBG). 5. Higher serum levels of PFOA, PF 08, or are associated with delayed puberty, 6. Higher serum levels of PF 0A, PF OS, or are associated with lower IQ. 7. Higher serum levels of PFOA, PF OS, or are associated with ADHD behaviors and learning problems. 8. Higher serum levels of PFOA, PFOS, or are associated with a higher prevalences of hypersensitivity?related outcomes asthma, rhinitis infectious diseases). 9. Higher serum levels of PF 0A, PF OS, or are associated with lower antibody responses to rubella, mumps, and diphtheria vaccines. C. Recruitment and Consent Based on sample size calculations (see Appendix), a minimum of 350 exposed children aged 4?4 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 -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 the contaminated drinking water while attending the two day-care centers could be recruited via outreach to the two day-care centers at Pease, the Portsmouth public schools, media, and community organizations in the Portsmouth area. The Pease CAP has also offered to assist in recruitment, and CAP involvement 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 cc inpation that involved PFAS exposure) during the pregnancy and breastfeeding of the child would he rec uited from the Portsmouth, NH, public schools. Before enrollment in the study, the child?s mother wo Id be interviewed to determine whether the child is eligible for the study. Recruitment would involve utreach 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 help with the recruitment effort. The total enrollment of Portsmouth?s elementary, middle, and high 5 chools is projected to be 2,687 in 2016?17. To encourage participation of exposed and unexposed children, an appropriate incentive would be provided. The Pease blood testing program?s consent form was strictly limited to the use of the participant s. blood sample for PFAS analyses o_nly. The participant also consented to complete a brief questionnaire at the time of blood draw concerning demographic information, time at Pease TradepOrt, and consumption of drinking water. The consent form did not mention the use of the blood sample for research purpc see or the possibility of re?contacting the participant for future studies. Moreover, the amount of blood drawn from the children was only suf?cient for the PFAS analyses. Therefore, ATSDR cannot directly contact the participants in the Pease blood testing program to recruit them for a children?s study. In addition, these participants must sign a new consent form to participate in a research study. I A parent of each child would be asked to sign a parental permission form requesting a blood sarrple (about 4 teaspoons or 20 mL) from the child for the analyses of PFASS and the effect biomarkers lipids, uric acid, sex hormones, and immune function parameters). The consent form would also ask that the child be administered the Wechsler Abbreviated Scale of Intelligence (IQ) tests if aged 6 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. 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 (orin 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 22 Draft for Review Purposes Do Not Cite or Quote Speci?c questions could be included in the questionnaire that addresshealth outcomes of intere based on the ?nal study design. For example, for ADHD, the questionnaire could ask, ?Has a doctor 0 health professional ever told your child that your child has/had ADD or If the answer is ?yes a second question could ask for a list of medications being used for the condition. Parents would 150 be asked if the child had learning or behavioral problems, and if so, the type of problem and the tre tment being used. Questions would be included for the hypersensitivity-related outcomes, asthma, ato uic 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 ?rst 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 Iipoprotein, 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 0 Immuno globulin and antibodies to measles, mumps, rubella, tetanus, and diphtheria Approximately 4 teaspoons of blood (20 mL) could be drawn from each participant to be analyze for the standard panel of PFAS compounds and the effect biomarkers. An attempt would be made to obtain an 8-hour fasting blood sample. The parents could be asked how long the child fasted before the alood 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 ered to 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, school records, including special education records could be reviewed to identify learning-problems and 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 DI-II-IS 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 23 Draft for Review Purposes Do Not Cite or Quote Geometric mean PFOS 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 2016]. 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 PFAS-contaminated drinking water at the Pease Tradeport was a complete exposure pathway. Study participants could submit blood samples for PFAS and biomarker analyses during 2018. 3r those who participated in the 2015 blood testingprogram, these measurements would be used to assess their exposures. For those who did not participate in the 2015 blood testing program but who attended daycare at the Pease Tradeport during January 200 S?May 2014, the .PFAS serum levels obtained in 2018 could be used to estimate serum levels during 2015 by adjusting for PFAS elimination rates and taking into account background PFAS exposures. For those who consumed drinking water from the Pease Tradeport after 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 before 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 2014 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 drinking water contamination could be combined using PBPK modeling with information from the questionnaires on 1) the dates and length of time the child attended daycare at the Tradeport and the child?s consumption of drinking water at the daycare and 2) whether the child?s mother worked at the Pease Tradeport during pregnancy and during the period of breastfeeding and the length of the period when the child was breastfed. PBPK modeling estimates would also incorporate information fro? 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 ates of the mother?s serum levels during the pregnancy and breastfeeding of the child would be needed. if the mother participated in the 2015 blood testing program at Pease, her measured PFAS serum levels could be used in the modeling. Children?s serum levels from the 2015 NH DHHS Pease blood testing program 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 coefficients for serum and serum PFOS and PFOA were quite high among persons ages 2?14 years who particir the 2015 testing (Pearson correlation for was 0.75, and for PFOS and PFOA was 0.73). ated in Therefore, it might be possible to predict historical scram levels of based on histdrical estimates for serum PFOA and PFOS. G. Sample Size The sample size for the Pease children study should include at a minimum 350 exposed children. It should also include a minimum of 175 unexposed children randomly sampled from the Portsmou}:l public schools with frequency matching to the exposed children on age, sex, and race. This mini sample size is based on several considerations. First, 370 children ages 1?13 years participated in 24 um 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 500 children attended daycare at Pease and would be in that age range in 2015. It should be possible tc not participate in the 2015 blood testing would have to be recruited, as well as a high percentage those recruit a similar percentage of the children who attended daycare at Pease. However, children whi did who did participate. Second, some studies conducted of PFAS exposure and children had similar 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 study), but had suf?cient statistical power to observed ?n to achieve statistical significance. 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 (a errc false positive error) and type 2 error error, false negative error, or 1 statistical power): 1. Type 1 error 0.05 (corresponds to atwo-tail hypothesis test using a p-value cutoff of 0.C 95% con?dence interval, to determine statistical signi?cance) 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 (corre3ponds to a one-tail hypothesis test using a p-value cutoff of 0.0 90% con?dence interval, to determine statistical significance) 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 negativ: 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 of and type 2 errors. Table 6b also includes the minimum effect sizes that can be detected with a sam size of 500 exposed and 250 unexposed. These minimum effect sizes assume a simple comparisor between the exposed and unexpcised children that is not adjusted for possible confounding risk fao strati?ed 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 ?float? instead of the minimum detectable effect. However, this approach is problematic bec?auset are few studies of PFAS exposures and the childhood outcomes being considered for the Pease chi 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 so of children exposed to PFAS drinking water contamination as a result of use. Therefore, the 25 1' and oral :lin gs ed, equal 5 that 31? or or a 5,.or a 0% as and 1 ple tors or those 3 to here ldren 30?: higher 1dies 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 PFOA 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 suf?cient statistical power. However, the observed PFOA OR'of 1.2 for hypercholesterolemia wo uld have required a sample size of over 1,700 per stratum with atype 1 error of 0.10 and 80% power (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 hypercholesterolemia. The serum levels of PF 0A and PFOS among the children at Pease would put them in the ?rst qua ile the reference level) if they had been in the C8 study (Frisbee 2010). In the lower PFOA and F08 quartiles, the 0R5 for hypercholesterolemia were between 1.2 and 1.3, requiring sample sizes of 00 1660 per stratum with type 1 error of 0.10 and 80% power (using the prevalence of 1 . hypercholesterolemia in this study of The strongest findings in this study for total cholest rol were observed for the top quintile of PFOS serum levels. When the top quintile PF 03 serum leve 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 - with suf?cient statistical power in a Pease study with 350 exposed and 175 unexposed children. However, the tOp quintile for PP OS 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] observed a mean difference in total cholesterol of 4.7 mg/dL for the 2??1 tertile serum levels of PFOA compared with the reference lev The 2nd tertile serum levels of PFOA in this study correspond to the PF 0A 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. With type 1 error of 0.10 and 80% power, the sample size required to detect a mean difference of 4.7 mg/dL would be 439 per stratum (or with an exposed to unexposed ratio of 2, as suggested for the Pease children study, 660 exposed and 330 unexposed would be required). In the NHANES study, the 2nd tertile PFOS 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 of 0.10 and 80% power. U) In the NHANES study, the ORs for hypercholesterolemia corresponding to serum PFOA and PFO levels among children at Pease were 1.49 and 1.35, respectively. To detect an OR of 1.49 with CD 1?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 NHANES 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 compared with the 1St quartile reference level was ?6.6 mL/min/1.73 m2, which would be in the range detectable, with sufficient 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, 398 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 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 mg, which would be in the range detectable with suf?cient statistical power by the Pease study sample size of 350 exposed and 175 unexposed chi dren. Howevel, the mean diffelence in uric acid was 0.05 mg/dL which would requi1e 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 sufficient 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 seru levels much lower than observed among the Pease children. A sample size of 350 exposed and 175 unexposed children would be suf?cient to detect this OR with suf?cient statistical power. Attention Deficit/Hyperactivity Disorder (ADHD) and other neurobehavioral endpoints In a CS study of ADHD (Stein 2011), the ?rst quartile or reference level for PFOA and PFOS wo 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 3rd quartile level in the C8 study. For the 3rd quartile of the OR for ADI-ID was 1 .43 and with current medications, the OR was 1.55. The prevalence of ADI-ID was 12. and with current medications, To detect an OR of 1.43 'th a 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 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 coefficient in the 10 fstic model). To detect this OR, a sample size of 540 per stratum would be required for type 1 error of 0.10 and 80% power. For PFOA, the serum levels corresponding to the top 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 ADI-ID. For this OR, the requi sample size would be 390 per stratum (or 596 exposed and 298 unexposed children) for a typejl 0.10 and 80% power. 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 PF 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 suf?cient statistical power would requir sample sizes of over 1,600 exposed and 1,600 unexposed. Sex hormones and delayed puberty In the C8 study of sex hormones [Lopez?Espinosa 2016], the serum levels of PFOA, PFOS, and were considerably higher than among the children at Pease. For PF 08, the natural log estradiol pe difference in boys off-4% (per interquartile range of the natural log of PFOS) would require at lea 1,154 per stratum for type 1 error of 0.10 and 80% power. The strongest ?nding in this study was decrease in testosterone among girls associated with PFOS. The natural 10 testosterone percent difference in girls was 6.6% per interquartile range of the natural log of PFOS. To detect a percnejit 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 to make sample size calculations for the endpoint, delayed pub The C8 study that evaluated this endpoint in included thousands of boys and girls [Lopez?Espinos 201 Growth hormone In the C8 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 log of respectively. To detect these differences suf?cient statistical power, a sample size of 350 exp?osed and 175 unexposed children would be sufficient. Thyroid disease and function A C8 study [prez-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 a? OR 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 red rror of ed LU rcent st the. m, or erty. ted and - with n. To dren. Draft for Review Purposes Do Not Cite or Quote In the O8 study of thyroid function [Lopez-Espinosa 2012], the largest percent difference for natural log TSH was and 2.3% for TT4. These percent changes were for PFOA and PFOS serum levels considerably higher than the serum levels among the children at Pease. To detect a 2.3% change in TT4 would require a sample size of at least 850 per stratum (type 1 error 0.10 and 80% power). To detect 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 was 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 0.35 respectively, for the >90th percentile serum PFOA compaied 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 mi imum proposed for the Pease children study 350 exposed and 175 unexposed children), and two 3 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. dies Buser For asthma, the ORS observed in the NI-IANES 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: sufficient statistical power. However, a Taiwan study [Dong 2013] obtained ORs for asthma between 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 suf?cient to detect these with suf?cient statistical power. ORs Only one study [Stein 2016a] evaluated rhinitis and observed an OR. of 1.35 for serum PFOA. Tia-detect 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 finding in this study. Other health-related endpoints A NHANES study [Geiger 2014b] evaluated PF OS and PFOA serum levels and hypertension and of 1.5 obtained ORs 1.0. Since there is no evidence so far of an association between PFAS serum lev Is and hypertension in children, this endpoint is not considered further. A study conducted in the Faroes [Karlsen 2016] evaluated serum levels of PFOA, PF 08 and PF x8 and ?overweight/obesity in children. At age 5 years, the ORs for overweight/obesity and the third tert le serum levels of PFOA, PFOS and were 1.88, 0.94, and 1.22. The serum levels of the PF 3 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 nationah 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 ?ndings 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 sufficient 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 concerns 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 'ldren. 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 ding 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 Tradeport 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 0 350 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 ha suf?cient statistical power to obtain effect estimates that achieved statistical significance had sa sizes within the range suggested as a minimum for the Pease children study. 1e When the effect sizes seen in previous PFAS studies are considered, the suggested minimum sami 1e size for the Pease children study could be suf?cient for several endpoints, such as mean differences in lipids, and For other outcomes, such as uric acid mean difference, the sex hormones testosterone and estradiol, and thyroid function, the sample size of a study limited to the Pease children population 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 endpoints are grouped below into three categories: 1) feasible to study, 2) possible to study (but might require 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 1? case children population, unless additional populations exposed to PFAS-contaminated drinking water are included in the study. Health endpoints feasible to studv in children at Pease - Mean difference in lipids (total cholesterol, LDL, HDL, triglycerides) - Mean difference in estimated glomerular ?ltration rate R), a measure of kidney function I Insulin-like growth factor?1 a measure of growth hormone de?ciency) It Overweight/Obesity Health endpoints that might be possible to study in children at Pease (although a larger sample size may be needed) 0 Mean difference in uric acid, a measure of kidney function - Elevated total cholesterol (hypercholesterolemia) - Elevated uric acid (hyperuricemia) IQ/neurobehavioral . Thyroid function 0 Sex hormones - Asthma and atopic dermatitis (immune function) - Rhinitis (stuffy, runny nose) . - 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) 0 Attention deficit/hyperactivity disorder (ADHD) - 0 Autism spectrum disorder - Delayed puberty Thyroid disease 0 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 exposr 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 (untransformed and natural log transformed) PFAS serum levels and categorized PFAS serum law and logistic regression of categorized effect biomarkers hypercholesterolemia) or disease prevalence on continuous (untransformed and natural log transformed) and categorical PFAS ser 31 'en rtiles re 1uous rels, 1m ?u n?m 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 PF if an historical reconstruction modeling method becomes available), estimated cumulative serum levels and estimated serum levels during critical vulnerability periods in utero exposure) could be evaluated. In summary, a study limited to the Pease children population will likely have a suf?cient sample size for some of the candidate endpoints if 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 aints, 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 PFAS?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 adults who participated 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 leve ?s were also elevated among the adults who participated in the NH DHHS blood testing program. Althou considerably more studies found evaluated PFOS exposures and adult health effects, there remain data gaps and inconsistencies in the ?ndings for liver function, kidney function and kidney disease, th yroid disease and thyroid function, autoimmune diseases and immune function, osteoporosis/osteoar?thritis, endometriosis, and most cancers. The public health signi?cance of conducting a study of adults at Pease is that the study will be rel event to other adult populations exposed to drinking water primarily contaminated with PF OS and A study might also provide an opportunity for early medical intervention for certain health endpoin 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 that rations because it potentially could help to ?ll critical data gaps mentioned above concerning the health effects 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 parties that could lead to alterations in thyroid ?mction. However, few epidemiological studies have evaluated or PFOS 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 speci?c chronic diseases). A. Study hypotheses Based on the literature review, the following hypotheses could be evaluated: 1. Higher serum levels of PFOA, PFOS, or are associated with higher total cholester density lipoprotein. and triglycerides, and a higher prevalence of hypercholesterolemia. 32 some study erse 91, low- .. Dra? for Review Purposes Do Not Cite or Quote 2. Higher serum levels of PF 0A, PFOS, or are associated with higher prevalences coronary artery disease and hypertension. 3. Higher serum levels of PFOA, PFOS, or are associated with differences in thyroic 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 and a higher prevalence of hyperuricernia. 5. Higher serum levels of PF OA, PFOS, or are associated with a lower estimated glomerular ?ltration rate and a higher prevalence of kidney disease. 6. Higher serum levels of PFOA, PFOS, 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, PF OS, or are associated with higher prevalences of osteoarthritis and osteoporosis. 8. Higher serum levels of PFOA, PFOS, or are associated with a higher prevalence endometr-iosis. 9. Higher serum levels of PF 0A, PFOS, or are associated with higher prevalences of autoimmune diseases such as ulcerative colitis, rheumatoid arthritis, lupus, and multiple sclerosis. 10. Higher serum levels of PFOA, PF OS or are associated with differences in serum of reactive protein (CRP), and antinuclear antibodies (ANA) and alterations 1n specific cytokines. A study of adults could include the collection of new blood samples to analyze PFAS serum leve blood samples would also be analyzed for lipids and biomarkers of'kidney, liver, thyroid, and im1 function. A questionnaire could be used to ascertain kidney disease, liver disease, cardiovascular disease, hypertension, thyroid disease, autoimmune diseases, osteoporosis, osteoarthritis, pregnar induced hypertension, and endometriosis. Diseases ascertained via questionnaire would be confir: using medical records 13. Study population According to the census, Portsmouth has 21,530 residents. About 67.5 are adults aged 19?64 and another 15.9% are aged 65 years and older. This would mean that there are about 14,500 adu 18?64 years and about 3,400 aged 65 years and over. Although the actual number is unknown, so 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 pm In the 2015 blood testing program at Pease, 1,182 adults aged 218 years participated. Table 5 pro PFAS se1 um data for the 1,190 participants in the 2015 Pease blood testing program who will be >18 years in 2018. 33 1-1, 1 acid 1?1- 1?13 levels 8. The nune cy? ned ears ts aged me of sons. vides age 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. 1i ited to use of the participant?s blood sample for PFAS analyses oily. 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 ?re?ghter, and consumption of drinking water. The consen - 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 A SDR cannot directly contact the participants in the Pease blood testing program to recruit them for a st dy. 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) ?'om the adult for analyses of PFAS's 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 001an te a . questionnaire covering demogr aphics, water consumption, dates and length of time working at ase, occupational history, lifestyle and health behaviors, diseases diagnosed by a physician or other alth provider and provider contact information. To 1ec1uit adult study participants, NH 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 ?rms on their mailing lists. TA 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: 0 Total cholesterol, low density lipoprotein, high density lipoprotein, total triglycerides - - Thyroxine (T4), T3, thyroid stimulating hormone (TSH) - Uric acid, creatinine 0 Alanine transaminase (ALT), (GGT) and direct bilirubin - Immunoglobulin and reactive protein, and antinuclear antibodies (ANA), and alterations in speci?c cytokines. E. Exposure assessment Exposure assessment could be based on the serum PFAS levels obtained in the study supplement by the serum PFAS levels for those who participated in the 2015 NH DHHS Pease blood testing program. Using historical estimates of the PFAS contaminant levels in the drinking water at the Pease Tra?d?eport (based on water modeling methods), PBPK modeling can be used to estimate historical serum 1e ls of PFOA and FPO S, combining information from the questionnaire on water consumption and date and length of time employed at Pease Tradeport, and information on background PFAS serum levels om NHANBS and from a comparison group unexposed to PFAS?contaminated drinking water or occupationally exposed to PFAS or Serum levels from the 2015 NH DHHS Pease bloodt sting 34 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, historicalestimates of serum can be based on historical estimates for serum PFCA and PFOS, because serum levels of and PFOS were highly correlated among the Pease adults who participated in the 2015 blood testing program (Pearson correlation coef?cient 0.73). F. Sample size considerations 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 PFAS- contaminated drinking water or occupationally exposed to PFAS or Another key problem will be recruiting a suf?cient number of participants to achieve reasonable statistical power and precision of effect estimates. Studies conducted of the adult C8 population included tens of thousands of participants. For example, studies of thyroid disease [Winquist 2014a], cardiovascular disease and lipids [Winquist 2014b], kidney 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 l,l81?4,333 adults Table 7a indicates the minimum detectable effects for a study that included 1, 500 participants pet stiatum. For a simple comparison between exposed and unexposed, this would require a total of- ?1 ,000 participants, i. 1, 500 exposed and 1500 unexposed. If the study population were divided into quartiles of PFAS serum levels, with the ?rst 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 combinations of type 1 error (01 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 signi?cance, or using a 95% confidence interval. A type 1 error of 0.10 corresponds to a one-tail hypothesis test 1 sing 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 the minimum detectable effects to the effect sizes observed in previous studies for similar levels of exposure select the type 1 and type 2 error rates, and allow the sample size to ??oat? instead of minimum detectable effect. However, this approach 13 problematic because there are few studies PFAS exposures and the adult outcomes being considered for the Pease adult study. In sOme inst noes, studies evaluating similar PFAS serum levels obtained very different effect sizes for 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. Moreoventhere are no studies of adults exposed to PAS drinking water contamination as a result of use. Therefore, there is much uncertainty about the effect size for each health?related endpoint that would be expected for PFAS serum levels observ-d 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 I . Lipids In the lipid study conducted of the C8 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 study was 11?12 To detect a difference of 11 mg/dL, a sample size in the range of 200?3 00 per stratum 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 than the Pease pepulaticn, 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 wi1h sufficient statistical power with a sample size of 1,5 00 per stratum. Kidney disease/function, and uric acid 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 1.3 6. 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 observed among the adult participants in the Pease blood testing program resulted in a difference of 0.14 g/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?600 per stratum. Table 7a indicates that much lower differences in uric acid could be detected with reasonable statistical power using a sample size of 1,500 per stratum. In the CS study, the OR for hyperuricemia for PF OA serum levels similar to those at Pease equaled 1.02. 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 cf450?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. 1 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. Based on sample size calculations, an OR of 1.90 can be detected with reasonable statistical power using sample size of about 240 per stratum. - Liver function For liver function, to detect the very subtle changes observed in the CS studies [Gallo 2012; Darrow a 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 2?:1 quintile of serum PFOA. The quintile of serum PFOA in the CS study is higher than the serum levels at Pease. To detect an OR of 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 function biomarkers 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 biomarlcers with a total sample size of 2,216 persons. This study also evaluated quartiles, so each stratum had a sample size of about 554 persons. Cardiovascular disease The C8 study that evaluated coronary artery, disease did not find an elevation in risk [Winquist 201 However, a study that used NI-IANES data [Shankar 2012] obtained an OR of 2.01 for cardiovascular disease for the 4?1 quartile PFOA serum levels. These PF OA serum levels, 26 ng/mL, would correspond to the 5th quintile of PFOA serum levels among Pease adults. The prevalence of cardiovascular d'sease in this study was 13%. To detect an OR of 2.01, a sample size of about 250/stratum would probab be suf?cient. Hypertension One study evaluated hypertension in a community population and observed an OR <1.0 [Winquis 2014b]. The prevalence of hypertension in this study was about 38%. With a sample size of 1,50 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 PF DA levels similar to those at Pease per the hazard ratios were in 'the range of For all self?reported thyroid disease (prevalence 11.3 Ma), a sample size of about 2,100 per stratum would probably be suf?cient to detect a hazard ratio of 1.3 prevalence for con?rmed disease was so that a sample size of about 3,500 per stratum would probably be necessary to detect an HR of A study that used NHANES data evaluated thyroid disease [Melzer 2010]. For confirmed thyroid The disease (prevalence 2.4% in this study), the ORs were above 1.1 for PFOS and PFOA se rum levels similar to those at Pease. To detect this OR would require a sample size equivalent to the 37 Draft for Review Purposes Do Not Cite or Quote population. The highest OR observed was 1. 89 among men in the top quartile of PFOS and PFOA. detect this odds ratio, a sample size of about 1,400 per stratum would probably be suf?cient. To The CS 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 13 ower. On the other hand, a study that used NHANES data [Wen 2013] to evaluate thyroid function observed Iaiger changes that could be detected with a total sample size of 200 (or <3 00 pm quartile stratum). Immune function and autoimmune diseases Only one published study [Stein 2016b] evaluated serum immune biomarkers at baseline cross- sectionally) and PFAS serum levels. The study evaluated deridenti?ed archived blood samples m75 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 findings were observed but the con?dence intervals for these ?ndings were extremely wide indica 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 ting evaluation of PFAS serum levels and Immune biomarkers 1n a Pease adult study could provide important infonnation 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 3 As indicated in Table 7a, ORs 2.0 cannot be detected with suf?cient statistical power for these endpoints with a sample size of 1,500 per stratum. For lupus and multiple sclerosis, ORs <35 cannot be detected with suf?cient statistical power with a sample size of 1,505 stratum. Osteoarthritis and Osteoporosis Two studies evaluated osteoarthritis. In a CS study [lnnes 2011], an OR of about-1.4 was observe- serum PF DA levels considerably higher than those at Pease. However, 1n an NHANES study [Uh 2013], an OR of 1.5 was observed f01 serum PFOA levels Similar to those at Pease. Table 7a indic that 1n the range of 1.4? 1.6 can be detected with suf?cient statistical power with a sample131 1,500 per stratum. An NHANES study evaluated osteoporosis in women [Khalil 2016] and obtained an 10 for levels lower than those at Pease. With 750 women per stratum, an OR of 1.58 can be deter with suf?cient statistical power. Endometriosis An NHANES study [Campbell 2016] obtained ORs of 1.47 and 2.86 for serum and PFOA respectively. The serum levels for these two PFAS were similar to those in the Pease population. 7a indicates that with a sample siZe of 750 per stratum, ORs in the range of 1.55 1.85 can be dot with sufficient statistical power. 38 per for ates ze of serum :ted 5 Table acted Draft for Review Purposes Do Not Cite or Quote Pregnancy?induced hypertension Several 08 studies evaluated pregnancy?induced hypertension. One study observed an OR of 1.6 serum PF OS. However, the PFOS serum leVels in the CS study were higher than those at Pease. . 7a indicates that ORs in the range of 1.6 1.9 can be detected with sufficient statistical power for 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 with a sample size of 1,500 per stratum. Even for a cancer with a much higher prevalence than cancer, e. prostate cancer, ORs 2.0 cannot be detected with sufficient statistical power with a size of 750 men per stratum. F. Conclusion A sample size of about 1,500 per stratum (or a total sample size of 6,000 if quartiles are evaluatec for Table a power dney sample 1) 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 suf?cient. For 0th 611' 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 (hyperuricemi?a) I Thyroid disease (uncon?rmed) - Cardiovascular disease - Hypertension - - Osteoarthritis and osteoporosis - Mean differences in serumimmunoglobin(1gA, 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 0 Thyroid disease (con?rmed) i Thyroid function - EndometrioSis Pregnancy-induced hypertension Health endpoints not feasible to study using the Pease adult population (in order to address these health endpoints, populations from other sites with PFAS-contamina'ted drinking water would nee included along with the Pease adult population) 0 Liver disease Kidney disease - Ulcerative colitis - Rheumatoid arthritis 0 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 dto be quartiles based on their serum PFAS levels. For some of the candidate health endpoints that are li sted abOVe as feasible to study or possible to study, the Pease adult population that can be recruited to statistical power for 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 i: participate will not be large enough to be split into exposure tertiles or quartiles and still have suf?cient mple necessary to recruit 4,500 adults (aged 2:18 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 am. from the Portsmouth area who were not exposed at Pease. Data analyses similar to those used in the CS studies would be used. The methods include linear regression of continuous (untransformed and natural log-transformed) effect biomarkers on contir. (untransformed and natural log-transformed) PFAS serum leiIels 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 uous els; levels. Restricted cubic Splines for linear and logistic regression would be conducted to obtain flexible, 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 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 unexpose group. Recruitment of at least 1,5 00 adults from Pease should be feasible, given thatthe 2015 bloc testing program at Pease was able to recruit at least 1,182 adults aged >18 years who worked at PE 40 for )d ase. Draft for Review Purposes Do Not Cite or Quote However, a study limited to the Pease adult pOpulation might not have a suf?cient 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. Sufficient variability in PFAS serum levels might be achieved by including other populations withresidential exposures to PEAS-contaminated drinking water. Feasibility of an epidemiological study of former military service and civilian 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 ?ammable liquid fires. 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 ed to be followed for a suf?cient number of years to account for the long induction periods of most cancers and to have suf?cient statistical power. For example, the Camp'Lejeune mortality study of U.S. 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 cohort, ATSDR will conduct follow-up using state and federal cancer registries for the period 1996?2016 (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 of 29,993 from San Francisco, Chicago, or Philadelphia from 1985 through 2009, for a total of 403,1 52 person-years [Daniels 2014]. A CS study of cancer incidence that relied on self?reported cancers that were con?rmed 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 5 37 civilian employees Were employed on base at that time 1990]. From 1970 to 1990, an average of 3,000 personnel and their families were aSngned 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 'n a cancer incidence and mortality study is that drinking water at the base was also contaminated by TEE from the Haven well during some of the years the base operated. Service personnel and civilian rkers 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 evaluateeancers with suf?cient statistical power. Because of the relatively small numbers of assigned to Pease Air Force Base, We conclude that it is not feasible to conduct a study of cancer incidence and mortality that is limited to the Pease military service personnel and civilian worker cohorts stationed at the base from 1986 41 Draft for Review Purposes Do Not Cite or Quote onward. For a study to be feasible, it would require a larger population size, for example, by including service personnel and civilian workers from other military bases with PFAS-contaminated drinking water as a result of the use of Exposures to other drinking water contaminants, such as TCE, other chlorinated organic chemicals, and benzene, must also be taken into account when considering candidate military bases and de?ning the cohorts. maintained at the Defense Manpower Data Center. Personnel data are available from 1971 altho gh information on military unit, which rs needed to determine the base where the individual was stat oned, does not begin until the second quarter of 1975 For civilian wor,kers data are available starting 1 the last quarter of 1972, with data missing for the first quarter of 1973. The data contain the location the workplace (codes for state, city, and ZIP code). The Defense Manpower Data Center data contai Social Security number, name, date of birth, and sex to facilitate follow-up. Cohorts of service pe1sonnel and civilian workers can be identified at military bases from personrl data Military service personnel constitute a highly mobile population after their tours of duty are com leted. For a mortality study, this' IS not a problem, because the rs available to obtain information 0 causes of death. However, there is no national cancer registry to ascertain cancer incidence. Therefore, a study of military service personnel and civilian workers would require gaining the participation of all ot most of the state cancer registries and the Department of Veterans Affairs Central Cancer Registry CV CCR). The Camp Lej eune Cancer Incidence Study' rs one model for such a study. This study rs 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 identi?cation 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 PF AS 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, fires, 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 malformations with sufficient statistical power, several thousand births should be studied. For example, to detect an OR of 1.5 for SGA (5th percentile) with 80% power would require 1,775 births per stratum. For SGA (10th 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 detect an OR of 2.0 would require about 15,000 births per stratum. 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 adverse birth outcome study is not feasible at Pease because there were too few births to moths rs Who worked at the Tradeport during their pregnancy. The most appropriate candidate populations for a study of adverse birth outcomes would be one or more large municipalities with residential exposr res to PFAS?contaminated drinking water where a simple mixing model could be used to estimate contaminant levels throughout the distribution system, a system that is not complex but instead has relatively 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, unex; 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, alth osed individuals will drop out over time, resulting in interpretation dif?culties selection bias resulting from loss to follow-up). In any event, before a registry or longitudinal study can be contemplated, an 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 pepulations at the Pease Tradepo the former Pease Air Force Base we1e of insufficient size for some of the health-1e1ated endpoints interest to the community. Moreover, Pease CAP members have expressed interest 1n linking the rt and sof 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 large systems (serving >10,000 retail customers) and a small sample of small systems (11 800 or 0.5% of a total of 144,165 systems serving <10,000 retail customers) via the Third Unregulated Contaminan Monitoring Rule database maintained by the EPA EPA 2016b]. monitoring for PFAS is required at the entry point to the distribution system for each 1 and at any interconnection that is in operation. Water utilities had to sample twice during a 12?month period 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 ut1lities ranked by the maximum level of combined PFOS and detected in the system. The highest 1 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 in 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 in Massachu Suffolk County Water Authority 1n 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 evel ter ter setts; ealth d, the lity Draft for Review Purposes Do Not Cite or Quote contaminant levels in a supply well) and generally do not represent the levels of contamination reaching particular residences served by the utility. To estimate the population receiving contamir. ated drinking water and the'levels of PFAS in their drinking water, the UCMR data must be supplemented with information on the con?guration and operation of the utility?s system. For a system that mixe its sources of water before to entering the distribution system, a simple mixing model can be 'used 5 all to estimate the contaminant levels in the drinking water serving the residences by taking into account the contaminant levels in each sou1ce and the contribution of each source to the total supply. This is t- situation at the Pease Tradeport, where water from each of the supply wells 13 mixed at the treatm nt 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 in 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 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 suf?cient number of oh and adults from the Pease population pa1ticipate. Other health~related endpoints would require lar extent ildren ger were exposed to PEAS-contaminated drinking water. The feasibility assessment concluded that a hird numbers of eXposed individuals and would require the inclusion of populations from other sites ?To study design, a mortality and cancer incidence study of former military service and civilian worke personnel, would not be feasible solely with the. population at Pease. . The feasibility assessment is still a draft. It will be ?nalized once the Pease Community Assistano 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 recc The feasibility of successfully evaluating particular health?related endpoints (or effect biomaikers change depending on ?nal study design and goals. 44 U) .ived. could Draft for Review Purposes 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 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 RRZ 1.20) no studies were conducted (for liver cancer and PFOS, and multiple myeloma and PFOA, there were too few deaths to evaluate). inconclusive? the findings 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 Thyroid function Thyroid disease I Uric acid 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 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 PFAS?contaminated drinking water while attending daycare at the Pease Tradeport can be estimated, thereis a lack of information on the number of children potentially exposed in utero to the PFAS?contaminated drinking water bec?use 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 Draft for Review Purposes Do Not Cite or Quote Table 6a. Minimum detectable effects for a Pease children study with 350 exposed and 175 unexposedf Endpoint on and 8= .05 or .05, 13:20 a and [3 .10 .10, 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 Uric 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?! OR 2.47 OR 2.09 OR 2.13 OR 1.94 ADHD meds'? OR 3 .50 - OR 2.80 OR 2.89 OR 2.52 Atopic dermatitis OR 2.49 OR 2.10 OR 2.15 OR 1.95 Asthma OR 2.56 OR 2.16 OR 2.21 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 1.62 Table 6b. Minimum detectable effects for a Pease children study with 500 exposed and 250 unexposedf Endpoint or. and 8= .05 o. .05, [3:20 a and 8= .10 .10, 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)# 1.85 1.90 1.73 ADHD meds'? OR 2.98 OR 2.40 OR 2.48 2.19 Atopic dermatitis OR 2.20 OR 1.86 - OR 1.91 OR 1.74 Asthma OR 2.26 OR 1.91 1.96 OR 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 Oveiweight/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 thyroid function, see the appendix for a description of the assumptions used in the sample size calculations and the resulting calculations. 1" mL/min/l.73 rn2 .64 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 2011) was 12.4%. In this study, the prevalence of an ADI-ID diagnosis reported by a study participant who a so reported currently using a medication commonly used to treat ADI-ID was 65 Table 60. Summary of information used to categorize the feasibility iof 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 PFOA serum levels similar to Pease. Feasible to study at Pease Estimated glomerular ?ltration rate 5.5 mL/min/1.73 m2 A NHANES study (Kataria 2015) observed a mean difference of 6.6 mL/min/ 1.73 m2 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 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. ercholesterolemia 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 PF 0A serum levels similar to Pease. However, for PFOS, the mean difference was 0.05 Ing/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 PFOA 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 ofSZ 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 <1.5 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 250unexposed would be necessary. Sex hormones See appendix for sample size calculations and assumptions required for the calculations. At PF OS serum levels much higher than at Pease, a CS study (Lopez-Espinosa 2016) observed reductions in estradiol that would require a sample size of over a thousand of exposed to achieve suf?cient 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, a 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 evalriat?d atopic dermatitis Possible to study at Pease. Asthma Two NHANES 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 PFOA similar to those at Pease. To detect this OR would require over a thousand exposed. However, ORs 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 0R5 that are reasonable to detect and fall within the 95% CI for the ?nding in the NHANES study. Possible to study at Pease 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 (Granurn 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 Detectahle Effect Size Other Sample Size Considerations Conclusion Attention deficit/hyperactivity disorder (ADI-1D) 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 ADI-ID confirmed by current medications) Autism spectrum disorder (ASD) ORs 4.0 One study (Li'ew 2015) obtained an OR of 1.3 for serum 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 C8 study (Lopez-Espinosa 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 8.0- 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 population 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 is on 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 of 280%) by a'sample size achievable at Pease, a sample size of 350 exposed children at Pease and 175 children unexposed to the PFAS-contaminated 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 of <10 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 PFAS?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 a and .05 ct .05, 3=.20 0t and .10 u. .10, [i=.20 Chronic kidney disease Thyroid disease, uncon?rmed 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 Uric acid (mean difference) 0.21 mg/dL 0.17 mg/dL 0.18 mg/dL 0.15 mg/dL Hyperuricemia .28 .24 Elevated ALT (>45 men; >34 women) ElevatedGGT (>55 men; >38 women) Elevated direct bilirubin (>003 mg/dL) ALT (mean difference) 2.65 2.06 2.15 1.83 GGT (mean difference) 4.60 4.80 4.09 Direct bilirubin (mean 0.079 mg/dL 0.060 mg/dL 0.064 m?g/dL 0.055 mg/dL difference) Liver disease Cardiovascular disease Hypertension Ulcerative colitis Rheumatoid arthritis Lupus Multiple Sclerosis 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 information 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 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 CS study (Steenland 2009) observed a 3 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 Hyperuricemia ANHANES 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 (unconfirmed) A C8 study (Winquist 2014a), hazard ratios 51.3 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 A NHANES 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 PFOA (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 (Uh12013) obtained an OR of 1.5 for serum PFOA levels similar. to those at Pease. Feasible to study at Pease Osteoporosis A NHANES study (Khalil 2016) obtained an 10 among women, for serum PF 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 ?lnction in humans. Feasible to study at Pease Liver function: Elevated ALT Elevated GGT Elevated direct bilirubin .33 6 A NHANES study (Gleason 2015) evaluated PFAS serum levels similar to those at Pease. For elevated ALT, ORs betweenl.2 and 1.5 were obtained. For elevated GGT, 0R3 between 1.0 and 1.3 were obtained. For elevated direct bilirubin, ORs between 1.1 and 1.7 were obtained. 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 CS study (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, 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 PFOA, 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 CS study (Stein 2009, Darrow 2013) obtained an OR 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 C3 study (Darrow 2016) and study (Melzer 2010) observed no elevation in liver disease. However, the CB 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 0R5 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 serum PFOA levels, considerably higher than those at Pease. At lower PFOA serum levels, the RRs were <2.2 Not feasible to study using the Pease population alone. Rheumatoid arthritis 1 0 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 population alone. Multiple sclerosis .50 A CS study (Steenland 2013) observed RRS between 1.1 Not feasible to study using the and 1.6 for serum PFOA Pease population alone. 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 CS 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 Hooking 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 1,500 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 1n other PFAS studies. Where possible, the focus 1s on adverse effect sizes in the PFAS studies observed for PFAS serum levels similar to those among the Pease adults. An endpoint 13 considered feasible to study at Pease if an adverse effect size observed in PFAS study can be detected with sufficient statistical power statistical power of 280%) by a sample size of 1,500 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 (RR). 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 1n 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-3 Table shows the maximum combined levels of and In any sample taken from each utility. Only utilities with detectable levels of either or PFOS are listed. The data are from the 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 Distr serving Colorado Springs, the Horsham Water Sewer (PA), the Warminster Municipal Authority tesian (PA), the Oatman Water Company (AZ), the Issaquah Water System (WA), the Hyannis Water Syitem (MA), the Suffolk County Water Authority (NY) and the Walrington Township Water 85 Sewer (P A). Three of the top 10 utilities are located near each othe1 1n the vicinity of Philadelphia, PA: Horsham, Warminster, and Wa1rington.ATSDRis currently considering whether it is feasible to include children and adults fiom these towns in studies that would also evaluate the Pease populations. Willow Grove Naval Air Station/Air Reserve Station Naval Air Station Joint Reserve ass and Air Force Reserve Station), Montgomery County, The Naval Air Station Joint Reserve Base (NASJRB) and Air Reserve Station (ARS) at Wi low Grove (?Willow Grove?) are two separate, but co-located military facilities in Montgomery Coun The Navy acquired site in 1942 and beganjet training there in 1949; the air force ba began operations in 195 8. 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 on-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 tu1 over to Horsham Township for redeveIOpment. 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 abm EPA Provisional Health Advisory Level (PHAL) for PFOS and were taken out of service. PFOS 1e were the following: Well 1 (0.21 rig/L), Well 2 (1.6 ug/L), and Well 6' (1.3 jig/L). Although the we 3, 993 1116131 V6 there to Gove 'ned stern re the vels 11s pump directly into the distribution system, wells 1, 2, and 6 are blended together at a tank and ente distribution system at one point. These wells constituted about 30% of the supply. Well the I?ln the northeast area of the eastern section, and well 9, which is centrally located in the eastern sectio had very low levels of contamination. Using currently available water distribution system information, ATSDR determined that f- ?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 3: received water containing PFOA and PFOS, 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 containing 1 00 lstem ory PFOA Draft for Review Purposes Do Not Cite or Quote and PFOS concentrations above the EPA LTHA. The southeastern part of the eastern section ofthe. system received water containing PFOA and PFOS concentrations up to 10 times the EPA LTHA. detailed analyses of the water?distribution system need to be conducted to estimate historical PFAS 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 weste1n section of the Warrington system is supplied by water purchased from North 1? Water Authority and' IS not contaminated with PFAS. However, there 13 an interconnection betweei eastern and western sections of the system which IS used when there 13 a need 1n the eastern sectior Warrington Township Water and Sewer Department UCMR 2014-2015 data* More ution Vales 1 the l. Well PFOS (pg/L) (pig/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 1s served by 15 wells as well as interconnections with other nea1by water utilit BS. The water system is separated into two pressure zones, ?high? and ?low,? with the wells' In each zone pumping to fill 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 with Aqua Southeastern Division. (N ote: the Aqua system had 0.009 rig/L of PFOS and .C 05 [lg/L PFOA during sampling in 4/16. There are now samples from 7/16 which measured 0.0068 ug/L for PF OS and 0.0065 ug/L for PFOA.). June 2014 drinking water sample results indic ated that PFAS contamination was solely in the low pressure zone which serves the majority of the service area. Prior to 1996 the system did not have pressure zones which means customers located in the high pressure zone may have received water from wells in the low pressure zone. Generally, dema Jrrent id is met using water from the storage tanks. There are three elevated tanks, and each tank generally sup plies a certain area of the system. Each tank will have different PF AS concentrations depending on which wells are supplying water to them. However, it is possible that a property in close proximity to a well which has a demand at the same time the well is pumping will have a higher percentage of water from 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 g1 eater than the EPA PI-IAL 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 UCMR 3 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 confidence report 1?01 the HWSA, the average level PFOS reported was 0.06 ppb, the average level of was 0.037 ppb, and PFOA was not detec. The two contaminated wells generally supplied about 25% of the water Jfor the system; however, tl 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 #26 :led ervice of 'ed. ere was 1A, 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 fo ?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 PF 0A 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 custc consumption information in more detail. In addition to the five 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 70 the 1? 3 1) ns, the liner ti?ed parts per trillion (ppt). The Navy is providing bottle water to these private well owners. Horsham Water and Sewer Authority (HWSA) UCMR 2014 data* Well PFOS (pg/L) (pg/L) PFOA (pg/L) PFNA Well 10 0.05 0.04 0.03 Well 17 0.10 0.05 0.03 - Well 21 0.14 0.08 Well Well 40 1. 00 0. 59 0.06 *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 300 for TCE. After contamination was detected, the well with the highest levels of contamination used mainly for ?re protection. Additionally, the Navy installed an air stripper to treat groundwate was 1' prior to distribution, and monitoring of treated water between 1996 and 1998 found no contaminants above 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 the supply wells 820). VOC contami in off-site wells has .not been attributed to the base, and the local water authorities (I-IWSA and treat the water for YOCs before distribution (ATSDR 2002a). nation Naval Air Warfare Center (a/k/a Naval Air Development Center), Warminster Township, Bucks County, The former Naval Air Warfare Center (NAWC) is located in Warminster Township. The b: operated from 1944 until its closure' 1n September 1996. In 1994, approximately 1, 850 civilians ant 1,000 military personnel 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 ?136 Draft for Review Purposes Do Not Cite or Quote Approximately 800 to 1,000 military personnel and their families stationed at nearby Willo Grove Naval Air Station lived in two on-base housing areas at NAWC while as many as six famili BS 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 A1ea C, provided housing for the base? 3 commanding of?cer and second-in-comrnand (ATSDR 2002b). Four out of eighteen of the Warminster Municipal Authority (WMA) public water supply 11 are in close proximity to the former NAWC site. The WMA provides water to approximately 40,000 peOple. The water supplied to the customers is from water supply wells in the WMA system and 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 tells ay be yto 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 receive more water from that well than users located further away (ATSDR 2016). AFF was used for decades at the base for ?re?ghting training activities. PFAS were ?rst for in groundwater as emerging contaminants in preparation for the CERCLA 2012 Five Year Re 'kely ested 'ew for this site. In summer 2013, PFOS levels above the EPA PHAL were ?rst discovered in ground ater 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 con ucted sampling in November 2013 and May 2014 for all wells and conducted sampling in November 20 3 and February, May, and August 2014 for the interconnection with NWWA (ATSDR 2016). Samples taken in the WMA system detected levels of PFOS, PF 0A, and/or . The source of the contamination was the use of at NAWC. In November 2013, three WMA pub ic water wells had levels at or above PHAL for PFOS. In this sampling event, 17 samples cov 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 4 44. Water from these two Wells is combined for treatment and samples are taken after treatment at entry point to the distribution system. PFOS was detected in 6 public wells and PFOA was detecte public wells. PFOS was detected in Well 26 at 0.791 ug/L, more than three times the 0.2 ug/L PHAL value. Wells 10 and 13 had PFOS concentrations of 0. 193 and 0. 16 pg/L that can be rounde 0.2 ug/L. None of the PFOA detections exceeded the PFOA PHAL 1n the WMA wells. Well 26 be highest detections f01 PFOA and PFOS. In summer 2014, PFOS was detected' 1n four public wells. highest concentrations were in Well 26 at 1.09 ug/L, more than ?ve times the 0.2 PFOS PHI4 value, and in Well 10 at 0.176 ug/L. PF 0A was detected 111 four wells, including Well 26 at 0.349 close to the 0.4 ug/L PHAL for PFOA. Wells 13 and 26 were shut down' 1n June 2014. Well 10 we down in September 2014. On May 19, 2016, wells 2,14 and 15 were removed from service due to EPA new lifetime health advisory level for PF (ATSDR 2016). PFOS 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 samp within an approximate 1?3 mile radius of the site. At least one PFAS was detected in the majority out of 100) of these private water wells. 0f the 94 residential private water wells, ?ve were non-dc and PFOS, 18 had detections of PFOA only, and 71 had both PFOA and PFOS. Eleven exceeded the PFOS PHAL, ranging from 0.152 ug/L to 0.729 ug/L. The PFOS PHAL exceedance 103 ering the The lug/L, shut the ed 93 tect 3 are 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 ldeation is in the area of York Road and Street. Six residential wells with PFOS levels that range from 0.102 to 0.109 ug/L (50% of the PHAL) are located at the Jacksonville/East Bristol Roads intersection (ATSDR 2016). The Navy and EPA provided a limited number of residents whose private well water was at or above EPA's 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) 1g and ?present day? conditions, the southWestern part of the Warminster system typically received water that Using currently available water-distribution system information, ATSDR determined that tier did not contain PFOA and PF OS 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 PFOA and PFOS .d concentrations at or below the EPA LTHA. Some areas in the eastern parts of the Warminster system received water containing PFOA and PFOS concentrations at levels up to three times the EPA LTlid A. 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 specific housing areas. These analyses would involve looking at the water-distribution 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 contain 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 data* Well PFOS (pg/L) (pig/L) PFOA (ug/L) PFNA (pg/L) Well 2 0.06 0.03 0.03 Well 10 0.19 0.10 0.09 - W611 13 0.16 0.09 0.12 Well 14 0.06 - . 0.03 0.02 - 'Well 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 Samples taken in 1979 showed maximum levels of contamination in on-site supply wells 0 3h 1?36 for PCB and 293 for TCE. These wells were closed in 1979. Contamination levels in samples taken from off-site municipal supply wells found 17 for PCE and 67.8 for past off-b ase residents may have been exposed to these VOCs between 1974, when the well ?rst began supplyir water, until it was closed in 1979. Sampling of VOCs in off?site private wells detected PCE at 31 ppb; as 104 Draft for Review Purposes Do Not Cite or Quote a result, affected homes were connected to municipal water supplies or groundwater treatment systems were installed (ATSDR 200%). 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 be 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 Speci?c 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 specific data pertinent to each water system?s operations needs to be obtained from site visits to the water utilities. 105 Draft 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 Water Utility Name State Size 8: PFOS sum Commonwealth Utilities Corp. (Saipan) MP 8.60 Artesian Water Company - DE . 2.48 Security WSD CO 1.89 Horsham Water Sewer Authority PA 1.59 Warminster Municipal Authority PA 1.479 Oatman Water Company AZ 1.03 Warrington Township Water Sewer Department PA 0.91047 lssaquah Water System . WA 0.841 Hyannis Water System MA 0.7 Suffolk County Water Authority NY 0.67 United Water PA PA 0.572 Emerald Coast Utilities Authority FL 0.56 GU Waterworks Authority Northern System GU . 0.55 Wide?eld WSD CO 0.54 Oakdale MN 0.4913 City of Tucson AZ 0.476 City of Cleveland Heights OH 0.4 Sanford Water District ME 0.4 Wright?Patterson AFB Area OH 0.36 Liberty Water LPSCO AZ 0.33 Westfield Water Department MA 0.33 City of FL 0.32 Bemidji . 0.32 City of Fountain - CO 0.29 FL U.LDU .J 107 Draft for Review Purposes Do Not Cite or Quote Water Utility 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 Martinsburg Dyer Water Department Atlantic City MUA West Morgan East Lawrence Water Authority City of Greensboro Rome Dover Water Department CA Water Service Chico Moore County Public Utilities - Pinehurst Rhinelander Water 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 Size 8: PFOS sum 0.245 0.241 0.24 0.212 0.202 0.1935 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 City of Lathrop Northeast Alabama Water System City of Anaheim Fair Lawn Water Department City of Orange Montebello Land Water Company Vienna Chatsworth Bethany City of Pico Rivera Water Department Camp Pendleton (South) Montgomery County Water Services #2 Rainbow City Utilities Board Florence Water?Wastewater Department Plainfield Township Pendleton County Water District til/South City of Miami Beach Ridgewood Water Woodbury Montgomery County Water Services #1 CA Water Service - East Los Angeles Town of Nashville Metropolitan DWID City of Downey Water Department Pierre Park Water Company Beilflower/Norwalk Washington Township MUA State 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 State Size PFOS sum Colbert County Rural Water System AL 0.05 Gadsden Waterworks Sewer Board AL 0.05 Southside Waterworks AL 0.05 City of North Miami FL 0.05 Kennebunk; Kennebunkport 0; Wells WD ME 0.05 Bell Arthur Water Corp. . NC 0.05 City of Garden Grove CA 0.0496 City of Lauderhill FL 0.049- FKAA FL 0.049 Yorba Linda Water District c4 0.0474 City of Miramar FL 0.047 Miami international Airport FL 0.047 City of Corona CA 0.046 Orchard Dale Water District CA 0.045 Lima City Water OH 0.045 Pico Water District CA 0.044 Golden State Water Co. - Norwalk CA 0.043 MDWASA - Main System I FL 0.043 . Ann Arbor MI 0.043 City of Fullerton . CA 0.0412 Cliffdale West NC 0.041 Central ASG AS . 0.04 City of DeFu niak Springs Water System FL 0.04 Cottage Grove MN 0.0381 City of Great Bend KS 0.037 City of Pieasanton CA 0.036 Sacramento Suburban Water District CA 0.035 110 Draft for Review Purposes Do Not Cite or Quote Water Utility Name State Size 8: PFOS sum Mashpee Water District MA 0.033 Belvidere IL 0.03167 L=large system (serves >10,000); S=small system (serves <10,000) Tribal nation located in Arizona 111 EXHIBIT I Department OPPORTUNITY. of Health ANDREW M. CUOMO HOWARD A. ZUCKER, M.D., J.D. SALLY DRESLIN, M.S., R.N. Governor - Commissioner Executive Deputy Commissioner August 24, 2017 Brenda Fitzgerald, MD. Director . Center for Disease Control and Prevention - Administrator, Agency for Toxic Substances and Disease Registry US Department of Health Human Services 1600 Clifton Road Atlanta, Georgia 30329-4027 Dear Dr. Fitzgerald: The presence of periluoroalkyi substances (PFAS) in drinking water is a growing national issue, with the number of affected water systems identified throughout the US. increasing rapidly. As Health Commissioners and Directors in states that have identified PFAS, including perfluorooctanoic acid (PFOA) and perfiuorooctane sulfonate (PFOS), in local water systems, we request that ATSDR undertakes a longitudinal. national health "effects study of communities impacted by PFAS across the country. Our state health departments, along with other states in the northeastern United States, have been working to 'address PFAS contamination since 2015, by minimizing exposure to PFAS in drinking water and some states are offering blood testing for affected residents. These efforts are supported by fact sheets, online tools and resources, and assistance with blood testing from the Centers for Disease Control and Prevention's (CDC) National Center for Environmental Health (NCEH) and Agency for Toxic Substances and Disease Registry (ATSDR). ATSDR recently releaSed a draft document, "Feasibility Assessment for Epidemiological Studies at Pease International Tradeport in Portsmouth, New Hampshire,? documenting an approach to appropriate follow-up health studies for children and adults as well as highlighting population?size related issues that our states would be confronted with if we conducted these studies individually. - Our communities are familiar to your staff? Hoosick Falls, Petersburgh, and Newburgh in New York; Portsmouth, New Hampshire; North Bennington, Vermont; Warminster and Willow Grove, Oscoda and Graying, Michigan. We welcome the opportunity to share additional information about our affected populations as part of a national effort to develop a plan to study health outcomes in multiple PFAS-affected communities. Empire State Plaza. Corning Tower, Albany. NY 12237] healih.ny.gov Through prior communication between the CDC, our departments, and Senators Gillibrand and Schumer, we understand that ATSDR and NCEH are determining if a long?term community health study would answer some questions about the health effects of exposure to PFAS. This letter is our of?cial request for ATSDR to move quickly to launch a longitudinal study of health outcomes in communities affected by PFAS from legacy industrial sources and from ?refighting foams used by the military and others. Sincerely .Howwn?i %M}cu Md). Howard A. Zucker, MD, JD Commissioner of Health Jay Butler, MD Director of Public Health Alaska NickLyon Director, Department of Health and Human Services Michigan Lisa Morris, MSSW Director, Division of Public Health Service New Hampshire Rachel Levine, MD Secretary of Health 2% 46/ Mark A. Levine, MD Commissioner of Health Vermont