Document 3JJLQ8bVrD5GegRj644EDqrZ6

Study No. T-7098.2; ST54 Oral Toxicity Rangefinder for perfluorooctane Snlfon 1 Fluoride OSF in Rats Study Location: 3M SUategic Toxicology Laboratory CorporateToiicology 3M Medical Department 3M Center, Building 270-SB-314 St. Paul, MN 55144 Study Director:. Andrew M. Seacat,Ph.D., Sr. Reseaw.h Toxicologist 3M MedicalDept. / Corporate Toxicology 3M Center, Building 220-2E-02 Saint Paul, MN 55144 Ph.: 651-575-3161 FAX: 651-733-1773"" Study Toxioleglst: Deanna J. Luebker,M.S., Advanced Research Toxicologist 3M Medical Dept. / CorporateToxicology 3M Center, Building 220-2E-02 Saint Paul, MN 55144 Ph: 651-737-1374 FAX: 651-733-1773 Sponsored by 3M Specialty Materials Markets Group 3M Center Bldg 236 St. Paul, MN $$144 PIqpI d7 T-7098.2_51"54 POSFOralToxicityRangefmder Study. Objective The research objective of this study was to provide preliminary data to characterize the toxi_ of per_uorooctanesulfonyl fluoride (POSF) following a single oral exposm'e in rats. Method Summary This study was performed in the 3M Strategic Toxicology Laboratory under a defined protocD1 (I) 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 of 100, 300 and 600 mg/kg body weight (N=I per close level) using a dosage volume of 5 ral suspension / kg body weight. A uniform suspension was prepared in 2% Tween 80 immediately prior to dosing. Re-suspension of soFds was performed with 5 strokes oftbe tissue grinder pestle before the sample was drawn-up indm syringe for dosing. A vehicle control animal received 2% Tween 80 at a dose volume of 5 ml/kg. This animal, however, was humanely sacrificed on day one post-dose in order to obtafin liver tissues for histological comparison in another study. A second group of age-matched control animals (N=3) were treated with propylene glycol at a dose volume of 5ml/kg body weight and were used for weight gain comparison purposes. This second group of control animals was shared between this study and T-7585.1, T-7576.1, T-7574.1, T-7575. I, T-7576._1, and T-7577.1. Historical toxicity data on these two vehicle control substances indicate that substitution ofpropylene glycol for 2% Tween 80 would not significantly effect the results of the 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 of the two-week study period and gained an aveuzge of 53 0. l 8 grams of body weight. From day 2-post dose through the end of the 14-day stay period, the rate of weight gain was comparable to the propylene glycol vehicle control animak Transient weight loss was observed in the _ dosed with 300 mg/kg POSF on day-one lmSt dose. Treatment group results are shown in Table 1. All propylene glycol treated vehicle cornel animals survived to the end of the two-week study period, and gained an average of 50 -*-0.16 grams, or 16 percent of their average initial body weight. The results of the control group are shown in Table 2. The dose levels of POSF were chosen in order to compare the relative oral toxicity ofPOSF Ibe known oral LD50 ofperflnorooctanesulfonate (PFOS), which is 251 mg/kg in male rats (3). The hypothesis has been put forth that toxicity resultingfrom POSF exposurecan be attn_ to the PFOS exposure resulting fi'om absorption and hydrolysis of POSF toPFOS following omll dosing. In a previous study on the toxickokinetics of POSF in rats (T-7098.1), rms were dosed by oral garage with 5 mg/kg of POSF. On day one post-dose, approximately 5% of the POSF dosed was present in the fiver, and on day 4 post-dose, approximately 11% of the dose was Fnmnd as PFOS in the liver. Very little PFOS was found in the serum, only about 0.1% of the POSF Page2of7 %7098.2;ST54 POSFOralToxicityRangefinder dosed on days 1 or4 respectively. Assuming that only ten percent of the dose of POSF is available to the liver as PFOS, that25% oft.he dose is available following a similar oral dose of PFOS, and that toxicity resulting fi-omPOSF exposure can be attributedto the resulting PFOS exposure, the predicted oral LD50 of POSF would be approximately 2.5 times higt_ than that of PFOS. Based on these assumptions, the 600 mg/kg dose of POSF used in this study was not high enough to determine whether the toxicity resulting _om POSF exposure can be attn'butedto the resulting PFOS exposure. In order to investigate tb.ishypothe$_ a dose of at least 628 mg/kg POSF would be needed. Conclusions results of 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. Page3of 7 %7095.2;ST54 POSF OralToxicity Rangefindcr Li0t of Tables Table 1: Treatment Group Results - POSF OralToxicity Rangefinder Table 2: Control GroupR.esults- POSF OralToxicity Rangefinder Page4of 7 itl a i lr: = |e <[<fd i EBlelLasfE| F|| EHLPEPIEHR|| SLL | ELLREEN | LLL LalHEL | i i: EY sisi id i LRhRP| E fre jheafle]t LEEPTR ELT | WLL is LF] z : i .- D Signatures: Prepared By: Advanced Research Toxicologist Study Director Andrew Scacat,Ph.D. ToxicologySpecialist StudyToxicologist Reviewed By: Paul Lieder, Ph.D. Senior Toxicology Specialist Dan Hikes Sponsor _ve T-709S.2S; T54 POSFOralToxicityl_mgefinder Date Date ( Date_ Plge6of7 t References T-709g.2; ST54 POSFOralToxicityRangefinder 1) 3M Medical Department, Corporate Toxicology Protocol for Study No. T-7098.2; ST54 Oral Toxicity Rangeflnder for Perfluorooctane Sulfonyl Fluoride ('POSF) in Rats, January 2001. 2) 3M Medical Department, Corporate Toxicology Strategic Toxicology Laboratory Standard Operating Procedxn'e (TOX SOP) No. 0950 - GLP Program Procedure, 1999. 3) Dean, W.P., Jessup. D.C- Thompson, G., Romig, G. and PoweU, D. 1978. Fluorad Fluorochemical Surfactant FC-95 acute oral toxicity (LD50) study in rats. Report No. 137-083. International Research and Development Corporation, Mattawan. MI. P'aOe7 d 7 ..