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Larry R. Zobel, MD, MPH Staff Vice President a and Medical Director ^ 3M Medical Department 3M Center, Building 220-2E-02 . PO Box 33220 St. Paul, MN 55133-3220 651 733 5181 Office 651 733 5152 Fax Contain NO GBl ge# _\noo - 373 December 4, 2000 rCS> CcOn O O p ti -Ora i CO "O o ( "ft oTc 0 3 rr'i Document Processing Center (7407) (Attn: Section 8(e) Coordinator) Office of Toxic Substances USEPA 401 M Street, SW Washington, DC 20460 CERTIFIED MAIL 03 TSCA 8(E) SUBSTANTIAL RISK SUPPLEMENTAL NOTICE ON: N-Ethyl perfluorooctylsulfonamido ethanol, see Docket 8EHQ 1288-0373 Dear 8(e) Coordinator: 3M has received a draft statistical report from Covance Laboratory on a 2-year rat feeding study o f N-EtFOSE {N-Ethyl Perfluorooctanesulfonamido Ethanol (CAS 1691-99-2)}. The results o f this study are corroborative o f results submitted in 1988 to EPA in docket 8EHQ 1288-0373. This study was conducted using N-EtFOSE at a purity o f approximately 98%, in contrast to the earlier study which was believed to be 84-88%. Groups o f male and female rats received the compound in their feed. There were seven groups o f rats - two control groups, a low dose o f 1 ppm in diet, a low intermediate dose o f 3 ppm in diet, a high intermediate dose o f 30 ppm in diet, a high dose o f 100 ppm in diet and a high dose recovery group. The high dose recovery animals received the compound for the first year o f the study at 100 ppm in diet and no compound during the second year o f the study. Statistical analyses of the tumor data from this study revealed that the high dose female group showed a statistically significant increase in benign liver tumors. The liver tumor data are presented below. MALES Hepatocellular Adenoma Carcinoma Control 1 Control 2 lppm 3ppm 30ppm lOOppm 100 ppm rec 2/55 5/60 4/60 4/50 2/50 5/60 0/40 0/55 0/60 0/60 0/50 0/50 0/60 0/40 EPA-OTS 000811811K OOGliailK I C3 rn c~y CO 050 "O ra -o o --ir n --if kD 03 vJD o rn oO US EPA Office o f Toxic Substances December 4, 2000 Page 2 FEMALES Hepatocellular Adenoma Control 1 Control 2 lppm 3ppm 30ppm lOOppm 100 ppm rec 0/55 2/60 1/60 1/50 3/50 6/60* 3/40* Carcinoma 0/55 0/60 0/60 0/50 0/50 1/60 0/40 * significant p< 0.05, paired and trend, based on Control 1 Control 2 and the 1 ppm dose group were added after a 300 ppm dose group was discontinued. This was done two months into the study, when it became apparent that the 300 ppm dose group would not tolerate this level as a lifetime dose. The liver is the target organ o f toxicity for N-EtFOSE. Liver toxicity was present in the high dose (100 ppm) males and females. The liver toxicity was manifested histologically as hepatocellular vacuolation and hepatocellular centrilobular hypertrophy. These histologic liver changes were not manifested in the high dose (100 ppm) recovery animals indicating that the liver toxicity was a reversible effect. The compound is not genotoxic, having been negative in multiple in vitro and in vivo genotoxicity assays. The final report will be submitted to EPA upon receipt. Please contact me, 651-733-5181, for further information. Regards, Larry R. Zobel, MD MPH Staff Vice President & Medical Director