Document yqJme94roN6e8bN4d1gDwm5d

Electronically Served 9/22/2017 10:33 PM Hennepin County, MN 27-CV-10-28862 Filed in Fourth Judicial District Court 11/17/2017 7:31 PM Hennepin County, MN STATE OF MINNESOTA DISTRICT COURT FOR THE COUNTY OF HENNEPIN FOURTH JUDICIAL DISTRICT CIVIL ACTION NO. 27-CV-10-28862 STATE OF MINNESOTA, et al. v. 3M COMPANY EXPERT REPORT OF PHILIPPE GRANDJEAN, MD, DMSc PREPARED ON BEHALF OF PLAINTIFF STATE OF MINNESOTA 22 September, 2017 CONFIDENTIAL - SUBJECT TO A PROTECTIVE ORDER ENTERED IN HENNEPIN COUNTY DISTRICT COURT, NO. 27-CV-10-28862 27-CV-10-28862 Filed in Fourth Judicial District Court 11/17/2017 7:31 PM Hennepin County, MN Based on the available evidence, PFCs are convincingly associated with endocrine disrupting effects that may have substantial impacts on vulnerable population groups. W hile endocrine disruption is often thought to be related to reproductive toxicity, a wide variety of hormones play a role for various physiological functions, and their disruption can cause a variety of dysfunctions and diseases. Horm ones addressed by PFC research include sex hormones, thyroxin, and insulin. The serum concentrations of some horm ones vary during the day or w ith food intake, and variability o f sampling tim es and lack o f statistical control for such factors may hide or attenuate PFC-associated changes in hormone concentrations. 1. Epidemiological evidence Serum -horm one concentrations a. Early evidence on endocrine disruption associated w ith PFC exposure originates from a doctoral thesis project, w here Frank Gilliland, M D, studied clinical pathology param eters in 111 m ale w orkers in 3 M 's C hem olite plant in C ottage G rove, M N . There w as a positive correlation betw een PFO A exposure m easured as serum total organic fluorine and estradiol (an adverse effect), and a negative correlation w ith free testosterone (also an adverse effect) w ith this association being stronger in older men. Dr. Gilliland therefore concluded that PFO A m ay affect m ale reproductive horm ones.PTM This study was not reported on its own in a scientific journal, but w as referenced in a subsequent article led by 3M authors [88]. b. This subsequent follow -up study further explored serum horm one abnorm alities in exposed workers and likewise showed a positive correlation betw een PFO A exposure and serum -estradiol (an adverse effect) [88] in 111 and 80 production w orkers studied in 1993 and 1995. The 10% increase in m ean estradiol levels observed am ong those employees with the highest serum -PFOA concentration was argued to be potentially confounded by body m ass index (although the risk o f obesity m ay be increased at higher PFC exposures, see section VILE). D espite the fact that tw o sets o f data w ere available, and 68 participated in both (and some likely were also exam ined by Dr. Gilliland), the authors chose not to conduct comparisons over time, allegedly due to variability o f the horm one analyses. The 3M authors concluded that the results provided reasonable assurance that, in this production setting, and contrary to the directionality o f Dr. G illiland's findings, there were no significant hormonal changes associated with PFO A at the serum levels measured. A m em o from Dr. G. Olsen in 1998 proposes that the horm one concentrations w ere affected by m isclassified body m ass index as a confounder.*iiii Interestingly, an anonymous reviewer who assessed the m anuscript for a m ajor occupational health journal questioned why the authors would present scatterplots for PFO A and some endpoints that w ere all non-significant, but not for the estradiol/testosterone results, w hich w ere statistically significant.jjjj c. The C8 H ealth Project exam ined 25,957 w om en aged 18-65 years regarding serum estradiol concentrations [169]. There was a significant inverse association betw een PFOS and estradiol, though not betw een PFO A and estradiol, thereby suggesting that jjjj AR226-0473. Frank Davis Gilliland, Fluorocarbons and Human health: Studies in an Occupational Cohort (October 1992) (unpublished PJ.D. thesis, University of Minnesota), with Summary. Page 003246. 11113MA00652081.Memo to file. Geary Olsen. 1/15/98. jjjj 3MA00630994. Reviewer 1, Occupational And Environmental Medicine 1997/187, page 3MA00630995. 58 CONFIDENTIAL - SUBJECT TO A PROTECTIVE ORDER ENTERED IN HENNEPIN COUNTY DISTRICT COURT, NO. 27-CV-10-28862 27-CV-10-28862 Filed in Fourth Judicial District Court 11/17/2017 7:31 PM Hennepin County, MN 75. Steenland K, D eddens J, Salvan A, Stayner L: N egative bias in exposure-response trends in occupational studies: m odeling the healthy w orkers survivor effect. A m J E pidem iol 1996, 143(2):202-210. 76. Lundin JI, A lexander BH, O lsen GW , Church TR: A m m onium perfluorooctanoate production and occupational mortality. Epidem iology 2009, 20(6):921-928. 77. G randjean P, B ellin g er D , B ergm an A, C ordier S, D avey-S m ith G, E skenazi B, G ee D, Gray K, H anson M , van den H azel P et al: The Faroes statem ent: hum an health effects o f developmental exposure to chemicals in our environment. Basic Clin Pharm acol Toxicol 2008, 102(2):73-75. 78. 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Olsen GW , Gilliland FD, B urlew M M , Burris JM, M andel JS, M andel JH: An epidem iologic investigation o f reproductive horm ones in m en with occupational exposure to perfluorooctanoic acid. J Occup E nviron M e d 1998, 40(7):614-622. 89. W en CP, Tsai SP: A natom y o f the health w orker effect - a critique o f sum m ary statistics employed in occupational epidem iology. Scand J W ork Environ H ealth 1982, 8 Suppl 1:48-52. 90. Clapp R, H oppin, P.: Perfluorooctanoic Acid. In: D efending Science. The Project on Scientific K now ledge and Public Policy; 2011. 91. Gutshall DM , Pilcher GD, Langley AE: Effect of thyroxine supplem entation on the response to perfluoro-n-decanoic acid (PFDA ) in rats. J Toxicol Environ H ealth 1988, 24(4):491-498. 128 CONFIDENTIAL - SUBJECT TO A PROTECTIVE ORDER ENTERED IN HENNEPIN COUNTY DISTRICT COURT, NO. 27-CV-10-28862