Document dnrNOV1pRyGBJ406516D0mdDQ

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 a disease, such as prostate cancer, occurs at a different (lower) rate in the background population o f M innesota, as com pared to the country as a whole. In addition, deficits in m ortality or m orbidity should not necessarily be interpreted as a sign that PFC exposure is beneficial to health, but rather that the exposed population, at least at the tim e o f first hire, w as in a better health condition and with better longevity prospects than the background population, which includes the non-working population, some of whom may suffer from chronic disease or otherwise have an increased m ortality risk. Such selection bias is well established. A lthough it does not affect all health outcom es uniform ly, the healthy w orker effect dem ands critical assessm ent o f relative risks, not ju st those that m ay show a statistically significant excess, but all outcom es [75]. A 1989 letter w ith detailed tables from Dr. Jack M andel to 3M 's Dr. Larry Zobel em phasized that deaths among form er Chem ical D ivision and Chem olite em ployees occurred in 41 states.z B oth total cancer and prostate cancer w ere elevated in the tw o groups w hen com pared to M innesota rates. The findings are sim ilar to an article by Drs. Gilliland and M andel published in 1993 [72]. Partial adjustm ent may be achieved by using occupational comparison groups that have not been exposed to PFCs or other hazards. A nother local occupational group m ight avoid "healthy w orker" selection bias and geographical differences, but one m ust then m ake sure that the com parison group is not exposed to some other toxicants. Exactly this issue was relevant in regard to the control group o f 3M w orkers from St. Paul that does not appear to have been u n exposed,aa as further discussed below . A s an optim al com parison group m ay not be available, it may be preferable to show the results from the exposed population in comparison with more than one reference population and to identify the strengths and w eaknesses o f the comparisons. 3M 's Drs Geary Olsen and Larry Zobel were clearly aware of these issues when they com m ented, in 2006, on Dr. B ruce A lexander's draft version o f a m anuscript that w as later published w ith a revised title, w ith Dr. O lsen as a co-author [76]. The 3M colleagues criticized the use o f "non-exposed" 3M workers as a control group (with a very low cancer m ortality) and emphasized the im portance of the general population, although the healthy w orker effects would bias the results.bb T ables w ere produced to show the im pact o f using different com parison g roups.cc In the end, the published article highlighted the com parison w ith general population rates but also included the internal com parison group w ith several caveats [76]. As a further concern, m ortality statistics are lim ited by num bers o f deaths and provide little inform ation about diseases that are rare, occur m ainly in the elderly or that are not reflected w ell by m ortality data that m ay not include all contributing conditions at the tim e of death. As an alternative, some studies use clinical pathology tests or other diagnostic means obtained at a particular point in time, to uniform ly establish disease or risk markers, although such data may sometimes be complex to interpret in term s of long-term health implications. 2. General population studies*2 z 3MA00632313 Letter of April 6 , 1989 from Dr. Jack Mandel to Dr. Larry Zobel. aa 3MA00058525. Memo to Clifford W. Hanson from F.A. Ubel. April 3, 1978. bb 3MA02557490. Letter to Dr. Bruce Alexander, July 14, 2006. cc 3MA00632317 and 3MA00632315 prepared Dr. Jack Mandel and sent to Dr. Larry Zobel on April 6 , 1989. 22 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 Prostate cancer Both prostate cancer and bladder cancer are diagnoses that m ay not necessarily appear on a death certificate, as the patient may die from some other disease, rather than the cancer, because the cancer is often curable or may not be fatal for several years. In addition, cancer risks in these types o f studies often are calculated on the basis o f small num bers o f cases and may therefore not deviate w ith statistical significance from expectation. Thus, although the risk may not be significantly elevated, the upper confidence lim it could be 5 or higher, suggesting that, at the same tim e, a 5-fold increased risk or greater cannot be ruled out. How ever, based on published evidence, neither the C8 Panel nor the IARC considered prostate cancer a probable risk in regard to PFC exposure. o. In a follow -up to 3 M 's 1989 m ortality study carried out by D r. M andel, involving alm ost 3,000 m ale 3M workers at Cottage Grove from 1947 to 1983, ten years of em ploym ent in exposed jobs was associated w ith a statistically significant increase in prostate cancer mortality (more than three-fold). Still, this calculation w as based on four cases among the exposed w orkers [72]. U nfortunately, com parisons w ith the general population o f M innesota probably biased the results o f this study tow ard underestim ated risks. p. In 1993, Dr. G illiland and Dr. M andel o f 3M published a paper based on the new m ortality study included in G illiland's thesis.' r * There were m ostly null findings, except, as before, for prostate cancer (a 3.3-fold increase in mortality). Again, the num ber of cases w as small (n = 6 ). The paper sought to explain the observed prostate cancer deaths as due to a purported higher prevalence o f prostate cancer in M innesota than the U.S. (control group) and/or as a chance finding.P JJj How ever, subsequent analyses provided to 3M by the author indicated that prostate cancer w as actually less prevalent in M innesota than in the U.S., suggesting an even greater excess am ong 3M w orkers.ppppp q. In a m ortality study o f alm ost 4,000 em ployees exposed to PFOA, no clear tendencies were found for liver, pancreatic or testicular cancer. An increased standardized m ortality ratio, how ever, w as found fo r prostate cancer, and a 6 .6 -fold increased risk w as found in workers w ith definite exposure. I note that the statistical significance relied upon tw o cases am ong the w orkers w ith know n high exposure [76]. r. T he m o st recent update is from a thesis com pleted in 2 0 13.qqqqq U sin g air m onitoring results (and ignoring non-respiratory intakes), this study o f 9,000 w orkers hired after 1947 com pared deaths at C ottage G rove w ith those at the unexposed St. Paul plant th rough to 2002. W hen dividing the w orkers into six different exposure groups, a dose-dependent risk appeared for prostate cancer, although not statistically significant. The author concluded that the results supported previous findings o f a prostate cancer risk. How ever, in the published report mmnnAR226226-0472.pdf, Frank S. Gilliland & Jack S. Mandel, Mortality Among Employees of a Perfluorooctanoic Acid Production plant, 35 JOM 950-954 (September 1993), with Summary of study. Page 003166. oooo AR226-0471. Jack S. Mandel & Leonard M. Schuman, "Mortality Study at the 3M Chemolite Plant" (January 1989), with Summary of study. Pages 003148-003149. ppppp 3MA00632313. Letter from Jack S. Mandel to Larry Zobel (Apr. 6 , 1989); 3MA00632314. Table 5 (attachment to Mandel letter to Zobel) (Apr. 6 , 1989). qqqqq3 M MN03059185. Cancer mortality in 3M chemical workers (PhD thesis by Katherine Koehler Raleigh). 81 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 concentrations in Am erican Red Cross adult blood donors, 2000-2010. Environ Sci Technol 2012, 46(11):6330-6338. 61. Genuis SJ, Liu Y, Genuis QI, M artin JW: Phlebotom y treatm ent for elim ination o f perfluoroalkyl acids in a highly exposed family: a retrospective case-series. P L oS One 2014, 9(12):e114295. 62. Lorber M, Eaglesham GE, Hobson P, Toms LM , M ueller JF, Thom pson JS: The effect of ongoing blood loss on hum an serum concentrations o f perfluorinated acids. Chemosphere 2015, 118:170-177. 63. M innesota Departm ent of Health: Environm ental Public Health Tracking & Biom onitoring. In: R eport to the M innesota Legislature. St.Paul, MN: M innesota D epartm ent of Health; 2011. 64. M innesota D epartm ent o f H ealth: E ast M etro PFC3 B iom onitoring Project. In. St. Paul, MN: Environm ental Public Health Tracking and Biomonitoring, M innesota Departm ent of Health; 2015. 65. Em m ett EA, Shofer FS, Zhang H, Freem an D, Desai C, Shaw LM: Com m unity exposure to perfluorooctanoate: relationships betw een serum concentrations and exposure sources. J Occup Environ M ed 2006, 48(8):759-770. 6 6 . Olsen GW , Burris JM, Burlew M M , M andel JH: Plasm a cholecystokinin and hepatic enzymes, cholesterol and lipoproteins in amm onium perfluorooctanoate production workers. D rug Chem Toxicol 2000, 23(4):603-620. 67. Chang SC, Das K, Ehresm an DJ, Ellefson M E, Gorm an GS, H art JA, N oker PE, Tan YM , L ieder PH , Lau C et al: C om parative pharm acokinetics o f perfluorobutyrate in rats, mice, m onkeys, and hum ans and relevance to hum an exposure via drinking water. Toxicol Sci 2008, 104(1):40-53. 6 8 . H offm an K, W ebster TF, Bartell SM, W eisskopf M G, Fletcher T, V ieira VM: Private drinking w ater wells as a source o f exposure to perfluorooctanoic acid (PFOA) in comm unities surrounding a fluoropolym er production facility. Environ Health Perspect 2011, 119(1):92-97. 69. Lindh CH, Rylander L, Toft G, Axm on A, Rignell-Hydbom A, Giwercman A, Pedersen HS, G oalczyk K, Ludw icki JK, Z vyezday V et al: B lood serum concentrations o f perfluorinated compounds in m en from Greenlandic Inuit and European populations. Chemosphere 2012, 88(11):1269-1275. 70. W eihe P, K ato K, Calafat AM, N ielsen F, W anigatunga AA, N eedham LL, Grandjean P: Serum concentrations of polyfluoroalkyl compounds in Faroese w hale m eat consumers. Environ Sci Technol 2008, 42(16):6291-6295. 71. Lindstrom AB, Strynar M J, Libelo EL: Polyfluorinated compounds: past, present, and future. E nviron Sci Technol 2011, 45(19):7954-7961. 72. Gilliland FD, M andel JS: M ortality am ong em ployees o f a perfluorooctanoic acid production plant. J O ccup M e d 1993, 35(9):950-954.734 73. Leonard RC, K reckm ann KH, Sakr CJ, Symons JM: Retrospective cohort m ortality study of workers in a polym er production plant including a reference population of regional workers. A nn Epidem iol 2008, 18(1):15-22. 74. Sakr CJ, Symons JM, Kreckm ann KH, Leonard RC: Ischaemic heart disease m ortality study among w orkers w ith occupational exposure to amm onium perfluorooctanoate. Occup Environ M ed 2009, 66(10):699-703. 127 CONFIDENTIAL - SUBJECT TO A PROTECTIVE ORDER ENTERED IN HENNEPIN COUNTY DISTRICT COURT, NO. 27-CV-10-28862