Document nN3peokamn4YB8p2x0xv3VZNR

woo ge CR ] . ARAR6-0as New Data Completion of two generation reproductive studies for perfluorooctane sulfonate and EtFOSE, and cross-fostering follow up to perfluorooctane sulfonate study Pharmacokinetics during pregnancy studies Second species (rabbit) teratology study + Completion of 180 day repeat dose study in primates with one year recovery 3MMedical Department March, 2000 1 ' | Pending + Two-year feeding studies EtFOSE - In-life done 4/2000 Perfluorooctane sulfonate - In-life done 4/2000 + 6 month and one year recovery after 180 day feeding study in primates + ADME study in primates 3MMedical Deparment March, 2000 o& Pending Human sera studies Health claims study Update mortality study Mechanistic and metabolic studies 3M Medical Department Mar7,c20h00 3 | Results - Reproduction/Cross- Fostering Studies 0.4 mg/kg/d of perfluorooctane sulfonate is NOEL for reproductive endpoints Perinatal mortality is predominantly a pup effect rather than a maternal effect Effect on cholesterol metabolism is hypothesized mechanism - studies planned to test hypothesis 3M Medical Deparment March 7,200 3 Results - Primate Repeat Dose Study 0.15 mg/kg/d well tolerated for 6 months (apparent NOEL) Cholesterol level decreased at perfluorooctane sulfonate serum concentrations greater than 100 ppm (in the high dose group) 2 deaths in males at 0.75 mg/kg/d that were apparently compound related At the high dose (0.75 mg/kg/d) body weight liver weight and liver morphology were 3aMfMfeteiccatleDedparment March 7,2000 Ss | Results - Sera Concentrations Perfluorooctane sulfonate serum concentrations increase linearly with dose in low and mid dose groups (16-20 ppm and 83-107 ppm) Perfluorooctane sulfonate serum concentrations followed a biphasic curve in the high dose groups, with maximum values at 250-300 ppm 3M Medical Department March?,2000 | Background | "Qrganic fluorine" reported in human sera in | 1968 3M medical surveillance from 1976 to present Analyses for specific fluoroorganic compounds dose after 1992 - detection limit less than 50 ppb in 1997 + Multiple analysis from historic and contemporary sera samples (non- occupationally exposed) find perfluorooctane sulfonate at less than 50 ppb 3M Medica Department March, 2000 7 | Background Various studies, including medical surveillance, done over the last 25 years In the last two years have used outside experts to identify needs and help define studies Have created Scientific Advisory Panel for additional review 3M Medical Deparment March, 200 2 Review - Data in Health Effects Paper | + ADME Metabolic precursors to perfluorooctane | sulfonate Repeat dose feeding studies - rat and primate Genotoxicity Teratology 3M Medical Deparment March ,2000 q Review - Data in Health Effects Paper (Continued) Cross-sectional study of exposed employees + Mortality study at production plant site | Interim data from 2-generation reproductive study + Interim data from new repeat dose primate study 3MMidial Department Mar7,c20h00 0 | Results The additional data does not suggest a health risk associated with the levels of perfluorooctane sulfonate found in the sera of occupationally or non-occupationally exposed employees, blood bank samples or commercially available serum. 3M Medica Deparment March 1,200 i