Document 9LQoB6Y0Ybap7mOm8GbML93d7

SRPT T-6295.8, T-6316.4, T-6868.2, T-7071.1, T-7132.1 DT15-B f t 3 3M MEDICAL DEPARTMENT, CORPORATE TOXICOLOGY Title: Comparative Molecular Biology of Perfluorooctanesulfonate (PFOS, T-6295), N-ethyl perfluorooctanesulfonamido ethanol (N-EtFOSE, T-6316), N-Ethyl perfluorooctanesulfonamide (N-EtFOSA, T-6868), Perfluorooctanesulfonamido acetate (FOSAA, T-7071), and/or Perfluorooctanesulfonamide (FOSA, T-7132) of in Rats and Guinea Pigs following Oral dosing. AMENDED Final Report Date: July, 16 2004 Study Numbers. T-6295.8, T-6316.4, T-6868.2, T-7071.1, T-7132.1 Strategic Toxicology Study Number: DT-15-B Sponsor; 3M Specialty Chemicals Division 3M Center, Building 236 Saint Paul MN 55133-3220 Study Location(s): 1. 3M Strategic Alternative Toxicology Laboratory 3M Center, Building 270-SB-181 Saint Paul, MN 55133-3220 2. University of Minnesota, Duluth Dept, of Biochemistry and Molecular Biology School of Medicine 10 University Drive Duluth, MN 55812-2496 Study Director: Andrew M. Seacat Ph.D., DABT Toxicology Specialist 3M Medical Dept. Corporate Toxicology and Regulatory Services Study Toxicologist: Deanna Luebker M.S Senior Toxicologist 3M Medical Dept. In-Life Start Date In-Life End Date In-Life Start Date In-Life End Date In-Life Start Date In-Life End Date Protocol: Protocol: Amendment #1 : Amendment #1 : Amendment #2 : Amendment #2: 11/16/1998 11/20/1998 03/01/1999 03/05/1999 02/19/2001 02/23/2001 tnvzoz SRPT T-6295.8, T-6316.4, T-6868.2, T-707U, T-7132.1 DT15-B The purpose for this amendment was to change the conclusion drawn in the summary that Lin Xu and Drag Anders wrote in Appendix 6E (page 59) which read: The original statement: ''These data showed that FOSA was consistently identified as a metabolite of PFOS, whether PFOS was administered directly or formed as a metabolite, but the source of the amino group is not readily apparent." Was changed to read: "These data showed that FOSA was consistently identified as a metabolite of PFOS, but that the source of the amino group is not readily apparent." The rational for these changes were that the original conclusion was not directly supported by the data presented in this study. That conclusion was not entirely correct because all of the administered compounds, besides PFOS, have a sulfonamido group within the parent compound. Therefore, the likely source of the amino group for sulfonamide moiety containing compounds would be the parent compound itself. There is quantitative evidence in these studies suggesting that the perfluorooctanesulfonamides were metabolized first to PFOS followed by metabolism of that PFOS back to a sulfonamide. The only evidence for a possible metabolism of PFOS to FOSA came from the PFOS dose groups, not the perfluorooctanesulfonamido derivative parent compound dose groups. Furthermore, in two out of three independent studies analyzed at Rochester, the control group liver samples had a high background of FOSA, suggesting possible contamination of the liver samples. Therefore, as stated, the conversion of PFOS to PFOSA would have to be verified by further studies. Dr Anders is in agreement with the amended conclusion stated above. CC9P.Q3 TRIG mg/dL By PFOS (ROC) (ug/g) ------Bivariate Normal Ellipse P=0.500 Dose Group (mg/Kg/da=CONT -- Bivariate Normal Ellipse P=0.500 Dose Group (mg/Kg/da=N-EtFOSA40mkd ------ Bivariate Normal Ellipse P=0.500 Dose Group (mg/Kg/da=N-EtFOSE40mkd ------Bivariate Normal Ellipse P=0.500 Dose Group (mg/Kg/da=PFOS40mkd Variable PFOS (ROC) (ug/g) TRIG mg/dL Bivariate Dose Group (mg/Kg/da=CONT Mean Std Dev Correlation 0.016667 0.040825 -0.50738 128.1667 42.64466 Bivariate Dose Group (mg/Kg/da=N-EtFOSA40mkd Variable Mean Std Dev Correlation PFOS (ROC) (ug/g) 100.4 22.36172 0.198189 TRIG mg/dL 138.5 45.38355 Bivariate Dose Group (mg/Kg/da=N-EtFOSE40mkd Variable Mean Std Dev Correlation PFOS (ROC) (ug/g) 66.55 60.59266 -0.19932 TRIG mg/dL 123.25 24.04683 Bivariate Dose Group (mg/Kg/da=PFOS40mkd Variable Mean Std Dev Correlation PFOS (ROC) (ug/g) 148.2 106.5116 0.595121 TRIG mg/dL 106 19.74842 Signif. Prob Number 0.3042 6 Signif. Prob Number 0.8018 4 Signif. Prob Number 0.8007 4 Signif. Prob Number 0.4049 4 SRPT T-6295.8, T-6316.4, T-6868.2, T-7071.1, T-7132.1 DT15-B Signatures: Final Report Amendment #1 prepared by, j u d A j-J Y L Andrew M. Seacat, PhD, DABT Study Director i/(b ( j Date CC 02.05