Fluomchemical Steeling Commillee Members Jeff MandeL M.D., 333-8670 (220-3W-O5) Papers/Dr. Gilliland December 7, 1~ ¯ These are two additional papers that a~e being prepered by Dr. Gill=land_ They need ou~ inpul/appmval before being su~itted for publication. The papers are negative for lhe.mos! part, We’re workirg with him regarding some of the wo~ding. We’re operaSng under the pre~nise Ihat these s0Hs of topics need 3M suppod. Please send you~ ~,omments back !o me by the end of Ihe monlh so I can communJc~e with IDr_ Gitlilat~l. JHM/vtk 3MA00323875 Exhibit 1409 State of Minnesota v, 3M Co,, Court File No, 27-CV-10-28862 CONFIDENTIAL - SUBJECT TO A PROTECTIVE ORDER ENTERED IN HENNEPIN COUNTY DISTRICT COURT, NO, 27-CV-10-28862 1409.0001 3M MN00051484 Peripheral Blood Lymph~T~e Coun¢ in Men Occupationally Exposed to Perfluomoctanoic Acid Prank D. GiRiland, M~D., Ph.D. Jack S. Mandel PKD. Affiliations: Division of Environmental and Occupational Health, School of Public Health, University of Mirmesota, Minneapolis (F.D.G); and Department o~ Internal Medicine, Occupational a~d ]~nvivonmei~tal Medic~e Section, St_Paul Ramsey Medica~ Center, SuPaRI0 M~nnesota (F.D.G.) Reprint requests should be addressed to F~-n~ir D. (~il!i!~d, Univers~W of New Me~xic~ Sclmol of Me~e, New ~ T~or ~, ~ C~mi~ de Salud ~, ~buque~ue, ~ 87131. Tetep~ (~5) 277-~41, F~ 277-7041. This study was supported in part by NIOSH Grant T150h07098-16 and 31v£ Medical Departmen~ Running title: Lymphocyte count and PFOA " 3MA00323~7~ CONFIDENTIAL - SUBJECT TO A PROTECTIVE ORDER ENTERED IN HENNEPIN COUNTY DISTRICT COURT, NO. 27-CV-10-28862 1409.0002 3M MN00051485 ABSTRACT Studies in Rhesus monkeys suggest thac perfluoroocta~oic acid (PFOA) has immua0toxie effects on the coil-mediated immune system in pximates. The predominant histopathological lesion in PFOA-treated monkeyswas diffuse atrophy of lymph nodes and splenic germinal centers. Although PFOA acmunts for the majority of fluorine presen~ in the serum of the general population and in occupationally exposed worker~0 little information is available concerning human responses to PFOA exposure. To as~ss whether PFOA exposure is associated with effects on the human ~ll-mediated immune system, we examined the cross-sectional associations between peripheral bk~l lymphocyte courts and PFOA in 115 workers employed at- a PFOA production planh Total serum fluorine was ur~ as a surrogate measure for sex~.un PFOA levels. Peripheral blood lymphocyte cotmt was sig~facanrly ass~L~e~_ with total serum JQ~oride level; however, the magnitude and direction of the ~elationship was dependent on smoking, alcohol use, and obesity status. For example, for nolI-smokers and moderate drinkers, an ~ncrease of 10 ppm in/~! serum fluoride w~s associated with a decrease in lymphocyte count of 1~40 ce)]s in non-obese (BM]=25 l~g/m2) worker~ and by 925 cell in obese workers (BMI=35 kg/m2). ]’I~OA is s~iated with alterations in peripheral blo~ lymphocyte numbers ha PFOA pro~iuc~ion workers, suggesting ~hat cel].media~i immurd~y may be affected ~ PFOA. WORDS perlluorooctanoic acid, epidemiology, immune toxicity, CONFIDENTIAL - SUBJECT TO A PROTECTIVE ORDER ENTERED IN HENNEPIN COUNTY DISTRICT COURT, NO. 27-CV-10-28862 1409.0003 3M MN00051486 Perfiuorooctanoie acid (PFOA) is widely used in industrial proce~3es and consumer produet~ a~ a reset ofit~ unique chemleal properties and potent surface activity (Ot~fith, 1980). Because PFOA has s long biological half-life, small ~quent do~es can ac~lmulate to appreciable levels (Ube], 1980). As a result, PFOA ha~ been found in the serum of all human population studied, and accounl~ for the majority of fluorine pre~ent in the ~rum ofp~pul~i~n$ in industrialized countries1"7. Little i~ known abou~ the toxic potential of PFOA in human~; however, studie~ have suggested that the celIomediated immu~e system may be a site of tuxicity in primates. Rhesus monkeys treated with oral PFOA developed histologle ehange~ in ~p~eeu and lymph nodes. The primary histopathologic lesion was atrophy in lymph node and splezfic gex~ninal centers1. The immune system o~rodent species bee not been rei~orted to undergo histvpathologie changes in subacute and chronic feeding studies !. No data available concerning immunotox~c~y in human~. Becatt~e PFOA ~s present in the ~erum ofexpo~ed worker~ and in the general population ~-7, it is a matter of concern whether the finding~ in monkeys indicate the potential rot human immunotexicity. To assess whether PFOA could affect the cell-media~ed immune system in humans, we studied the a~ciation of PFOA. as measured by total serum fluorine, wi~h peripheral b~ lymphocyte count (PBL) in 115 occupationally exposed emp]oyee~ at_ a plant l:hat produces B~L-kTERL-~L~ AArD ~THODS ;3MA(}0323878 CONFIDENTIAL - SUBJECT TO A PROTECTIVE ORDER ENTERED IN HENNEPIN COUNTY DISTRICT COURT, NO. 27-CV-10-28862 1409.0004 3M MN00051487 All current workers employed in PFOA production over the 5 previous years and a sample of workers in jobs with no apparent PFOA e~posure for the previous ~ years were invited to participate. Participants had vi£a! paxameters measured in the.plant medical department by an occupational health nurse, c~mpleted a medical history questionnaire, and underwent venipunc~me. Blood was drawn foz assays ofperipheral lymphocyte count. A fluorine-L,-ev 15 ml va~tainer was used to ~Hect blo~i for total serum fluorine dete~r~_i~Ation. Total serum fluorine was used as the measure of PFOA in this eccupatieual g~oup, Total sexttm fluorine was determined using the sodium biphenyl extraction and atomic absorption spectrometry s, RESULTS Pax~icipant charac~ezistics are displayed in Table L Total serttm fluorine values ranged f~m 0 and 26 ppm with a mean of 3.3 ppm. Twenty-three 3MA00323879 CONFIDENTIAL - SUBJECT TO A PROTECTIVE ORDER ENTERED IN HENNEPIN COUNTY DISTRICT COURT, NO. 27-CV-10-28862 1409.0005 3M MN00051488 (20.0%) par~cipants bad ~erum values less than I ppm. 6 (5.2%} had values between t0 and 15 ppm, and 5 (4.456) had values greater than 15 ppm_ Table 2 presents the o~rdation coefficients between PIlL and total serum fluori~e, age, BMI, akohol use, and cigarette co~umption. Peripheral blood lymphocyte count was significantly correlated with total ~erum fluorine (r=.19, p=,04). The fin~] regression model for PBL, which adjusted for age, BMI, cigarette use, and alcohol use. included data for Ill workers; 4 of the 115 workers had miss~g assay values and were excluded from the analysi~ (Table 3). Total serum fluorine was inversely associated with PBL; however, the relationship was complex, with si~ut interactions bel~ween total serum fluorine and BMI0 ~iRarette use, mud alcohol use. Table 4 illustrates t~e rela~onship for a 10 ppm chan~e in total s~rum fluor~e for comb~uations ofsmokingo alcohol consumption, and BMI st~tu~. In moderate ~h~;-ker~ (1o 3oz ~kohol per day), PBL decrea~d in the categar~es of ~moking an~ of obesity; ~n light drinkers (