Document 7OJ9vkQmnmzanzyzakJJb2NJa

SRPT 15*375 Study No. T-7098.2; ST54 Oral Toxicity Rangefinder for Perfluorooctane 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 Director: Andrew M. Seacat, PLD., Sr. Research Toxicologist 3M Medical 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 Medical Dept / Corporate Toxicology 3M Center, Building 220-2E-02 Saint Paul, MN 55144 Ph: 651-737-1374 FAX: 651-733-1773 Sponsored fay 3M Specialty Materials M arkets Group 3M Center Bldg 236 St. Paul, MN 55144 Page 1 o f7 T-7098.2;ST54 POSF Oral Toxicity Rangefinder Study Objective The research objective o f this study was to provide preliminary data to characterize the toxicity 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 protocol (1) and classified as a "Class B Study" as explained in TOX SOP 0950, Strategic ToxicologyLab 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 sofids was performed with 5 strokes o f the tissue grinder pestle before the sample was drawn-up in dbe syringe for dosing. A vehicle control animal 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 comparison 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-7576-1, 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 offthe 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. Results and Discussion All POSF dosed animals survived to the end o f the two-week study period and gained an average 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 animaik Transient weight loss was observed in the animals dosed with 300 mg/kg POSF on day-one p a st dose. Treatment group results are shown in Table 1. All propylene glycol treated vehicle control animals survived to the end o f the two-week study period, and gained an average o f 50 0.16 grams, or 16 percent o f their average initial body weight. The results o f the control group are shown in Table 2. The dose levels o f POSF were chosen in order to compare the relative oral toxicity o f POSF dhe 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 oral 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 POSF dosed was present in the liver, and on day 4 post-dose, approximately 11% o f the dose was fnamd as PFOS in the liver. Very 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 1 or 4 respectively. Assuming that only ten percent o f the dose o f POSF is available to the liver as PFOS, that 25% o f the dose is available following a similar 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 approximately 2.5 times higher than that o f PFOS. Based on these assumptions, the 600 mg/kg dose o f POSF used in this study was 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. C on clu sion s 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 List o f Tables Table 1: Treatment Group Results - POSF Oral Toxicity Rangefinder Table 2: Control Group Results - POSF Oral Toxicity Rangefinder Page4of 7 T-7098.2; ST54 POSF Oral Toxicity Rangefinder fable 1: Treatment Group Results - POSF Oral Toxicity Rangefinder Body Weight toQ__________ Body Welg ht Gain (a )_________________ Dose (mg/kg) / Animal # Sex date day 1 Day 4 Day 7 Day 14 Day 0-1 Day 1-3 day 0 PD , s PD PD PD PD Day 7- Day 0? r 7 14 PD 14 PD 1R00165 M 100/1-22-01 287 287 297 303 319 342 C 1C G 16 23 55 1R00166 M 300 /1-22-01 285 277 287 295 313 343 -8 1C 8 18 30 58 1R00167 M 300 /1-22-01 282 285 291 293 306 328 : 3 6 2 13 22 46 Table 2: Control Group Results - POSF Oral Toxicity Rangefinder Body Weight (g) Body Weight Gain (g) date of Animal# Sex dosing ,T[day 2 dayO PD Day 14 Day 0- Day 2- Day 7- bay 0-14 D 2 PD 7 PD 14 PD PD 1R00184* M 1R00185*JM 1R00186*W 01/29/2001 01/29/2001 01/29/2001 31C 293 3181 324 337 303 316 327 335 362 343 365 14 10 9 13 13 8 25 27 30 52 50 47 * Control animals also used In studies STS5 & ST65; dosed with 5ml/kg propylene glycol Page 5 o f7 Signatures: Prepared By: T-7098.2; ST54 POSF Oral Toxicity Rangefinder Deanna Luebker, MS Advanced Research Toxicologist Study Director Andrew Seacat, PhD . Toxicology Specialist Study Toxicologist Reviewed By: Paul Lieder, PhD . Senior Toxicology Specialist &ouAeJlcd{J2QA~- Dan Hakes Sponsor Representative `- i f H e l d l __________________ D ate *7/ / / / Z Date S'/oj/ol . Date s /n /o t_____ ^D ate/ Page6of7 References T-7098.2; ST54 POSF Oral Toxicity Rangefinder 1) 3M M edical Department, Corporate Toxicology Protocol for Study No. T-7098.2; ST54 Oral Toxicity Rangefinder for Perfluorooctane Sulfonyl Fluoride (POSF) in Rats, January 2001. 2) 3M M edical Department, Corporate Toxicology Strategic Toxicology Laboratory Standard Operating Procedure (TOX SOP) No. 0950 --GLP Program Procedure, 1999. 3) Dean, W .P., Jessup. D.C- Thompson, G., Romig, G. and Powell, D. 1978. Fluorad Fluorochemical Surfactant FC-95 acute oral toxicity (LD50) study in rats. Report No. 137-083. International Research and Development Corporation, M attawan. MI. Page7of 7