Document M4JOGjK95zOLVb2og990LLw77

' r e c e i v e d OPPT SRPT 20G1MV 12 ^ Cj: 10 Study No. T-7098.2; ST54 Oral Toxicity Rangefinder for Ferfluorooctane Sulfonvl Fluoride (POSF) In Rats Study Location: 3M Strategic Toxicology Laboratory Corporate Toxicology 3M Medical Department 3M Center, Building 270-SB-314 St. Paul, MN 55144 Study D irector: Andrew M. Seacat, Ph.D., Sr. Research Toxicologist 3M M edical Dept. / Corporate Toxicology 3M Center, Building 220-2E-02 Saint Paul. MN 55144 Ph.:651-575-3161 FAX: 651-733-1773'" Study Toxicologist: Deanna J. Luebker, M .S., Advanced Research Toxicologist 3M M edical D ept / Corporate Toxicology 3M Center, Building 220-2E-G2 Saint Paul, MN 55144 Ph: 651-737-1374 FAX: 651-733-1773 Sponsored by 3M Specialty Materials M arkets Group 3M Center Bldg 236 S t Paul, MN 55144 Pag 1 o f7 T-7098.2; ST54 POSF Oral Toxicity Rangefinder Study O bjective The research objective o f this study was to provide prelim inary data to characterize the toxkxity o f perfluorooctanesulfonyl fluoride (POSF) following a single oral exposure in rats. M ethod Sum m ary This study was performed in the 3M Strategic Toxicology Laboratory under a defined protocoil (1) and classified as a "Class B Study" as explained in TOX SOP 0950, Strategic Toxicology Lab GLP Program Procedure (2). POSF was administered to male rats at dose levels o f 100,300 and 600 mg/kg body weight (N = l per dose level) using a dosage volume o f 5 ml suspension / kg body weight. A uniform suspension was prepared in 2% Tween 80 immediately prior to dosing. Re-suspension o f so lis was performed with 5 strokes o f the tissue grinder pestle before the sample was drawn-up in tibe syringe for dosing. A vehicle control anim al received 2% Tween 80 at a dose volume o f 5 ml/kg. This animal, however, was humanely sacrificed on day one post-dose in order to obtain liver tissues for histological com parison in another study. A second group o f age-matched control animals (N=3) were treated with propylene glycol at a dose volume o f 5ml/kg body weight and were used for weight gain comparison purposes. This second group o f control animals was shared between this study and T-7585.1, T-7576.1, T-7574.1, T-7575.1, T-7576-3, and T-7577.1. Historical toxicity data on these two vehicle control substances indicate that substitution o f propylene glycol for 2% Tween 80 would not significantly effect the results offtbe endpoints monitored in this study. All animals were monitored for morbidity, mortality, and bodyweight changes for two weeks following dosing, and were then humanely euthanized. R esults and Discussion All POSF dosed animals survived to the end o f the two-week study period and gained an a v en g e o f 53 0.18 grams o f body weight. From day 2-post dose through the end o f the 14-day study period, the rate o f weight gain was comparable to the propylene glycol vehicle control liw fc Transient weight loss was observed in the animals dosed with 300 m g/kg POSF on day-one p o st dose. Treatment group results are shown in Table 1. All propylene glycol treated vehicle canflrol animals survived to the end o f the two-week study period, and gained an average o f 50 0 .1 6 grams, o r 16 percent o f their average initial body weight. The results o f the control group a re shown in Table 2. The dose levels o f PQSF were chosen in order to compare the relative oral toxicity o f POSF th e known oral LD50 o f perfluorooctanesulfonate (PFOS), which is 251 mg/kg in male rats (3). The hypothesis has been put forth that toxicity resulting from POSF exposure can be attributed to the PFOS exposure resulting from absorption and hydrolysis o f POSF to PFOS following o ra l dosing. In a previous study on the toxickokinetics o f POSF in rats (T-7098.1), rats were dosed by oral gavage with 5 mg/kg o f POSF. On day one post-dose, approximately 5% o f the PO SF dosed was present in the liver, and on day 4 post-dose, approximately 11% o f the dose w as fin a d as PFOS in the liver. V ery little PFOS was found in the serum, only about 0.1% o f the POSF Page 2 o f 7 T-7098.2; ST54 POSF Oral Toxicity Rangefinder dosed on days I or 4 respectively. Assuming that only ten perait o f the dose o f POSF is available to the liver as PFOS, that 25% o f the dose is available following a sim ilar oral dose o f PFOS, and that toxicity resulting from POSF exposure can be attributed to the resulting PFOS exposure, the predicted oral LD50 o f POSF would be approxim ately 2.5 tim es higher than that o f PFOS. Based on these assumptions, the 600 mg/kg dose o f POSF used in this study w as not high enough to determine whether the toxicity resulting from POSF exposure can be attributed to the resulting PFOS exposure. In order to investigate this hypothesis, a dose o f at least 628 mg/kg POSF would be needed. gnchW W The results o f this study indicate that the POSF is not acutely toxic to male rats at oral doses less than or equal to 600 mg/kg body weight (N =l/dose group), under the conditions used in this study. Page 3 of 7 T-7098.2; ST54 POSF Oral Toxicity Rangefinder Table 1: Treatment Group Results - POSF Oral Toxicity Rangefinder Table 2: Control Group Results - POSF Oral Toxicity Rangefinder Page4of7 T-7098.2; ST54 POSF Oral Toxicity Rangefinder Table 1: Treatment Qrotip Results - POSF Oral Toxicity Rangefinder Body Weight to) Body Weight Gain la) Doe# (mg/kg) / Animal# Sex date day1 dayO PD 1R00165 M 100/1-22-01 287 287 1R00166 M 300/1-22-01 285 277 1R00187 M 300/1-22-01 282 288 207 287 291 7 302 319 295 313 293 306 s 342 343 32 D j y M Day 4-7 Lay 7- Day 0- r 5T M PD I14PD 14 PD C 1C 8 18 23 55 -8 1C 8 18 3G 58 ; 3 8 2 13 22 46 table 2: Control Group ReeuHe - P O SF Oral Toxicity Rangefinder Body W eight (g) | Body W eight Gain (g) date of Anim al# Bex dosing dayO 1R00184* U! 01/29/2001 310 1R00185* M 01/29/2001 293 1R00186* M 01/29/2001 318 Day 14 Day 0- Day 2- Day7- M y 0-14 2 PD 7 P D 14 P D 324 337 362 14 13 303 318 343 1C 13 25 27 52 50 327 335 38S 9 i 3C 47 * Control animals also used in studies ST56 & ST85: dosed with 5ml/kg propylene glycol, Page 5 o f7 S ig n a tu re s: Prepared By: T-709S.2; ST54 POSF Oral Toxicity Raogefinder Deanna Luebker, MS Advanced Research Toxicologist Study D irector _________HilipfOll D ate /ft? . Andrew Seacat, Ph.D. Toxicology Specialist Study Toxicologist R eview ed B y: Paul Lieder, Ph.D. Senior Toxicology Specialist *7/ / C e j / D ate s^ / 0 9 / o i D ate P sg e 6 o f7 T-709S.2; ST54 POSF Oral Toxicity Rangefinder R eferen ces 1) 3M M edical Department, Corporate Toxicology Protocol for Study No. T-7098.2; ST54 .O ral Toxicity Rangefinder for Perfhiorooctane Sulfonyl Fluoride (POSF) in Rats, January 2001 2) 3M M edical Department, Corporate Toxicology Strategic Toxicology Laboratory Standard Operating Procedure (TOX SOP) No. 0950 - OLP Program Procedure, 1999. 3) Dean, W .P., Jessup. D.C- Thompson, G ., Romig, G. and Powell, D. 1978. Fhiorad Fluorochem ical Surfactant FC-95 acute oral toxicity (LD50) study in rats. Report No. 137-083. International R esearch and Development Corporation, M attawan. M I. Pao*7of 7