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% AR226-2789 FOR DU PONT USE ONLY Haskell E. I. du Pont de Nemours and Co., Inc. Laboratory for Toxicology and Industrial Elkton Road, P. 0. Box 50, Newark, Delaware 19711 Hedicine HASKELL LABORATORY REPORT NO. 79-84 Material Tested* 1) Octanoic acid. Pentadecafluoro-, ammonium salt 2) Ethanol Haskell No. 12,037 14,.547 Other Codes C-8 PubLrcker Chjeffl. Co. Study Initiated/Completed 5/24/82-6/22/82 ^Material Submitted by "Central Research & Development Haskell Laboratory ACUTE URAL EFFECTS OF C-8 AND ETHANOL IN THE RAT Sumnijry: Young adult male Cr1:CD rats were administered a single dose of etn'artol by intragast'ic intubation at 6,000 mg/kg or a 15% (v/v) solution in drinking water for ]4 consecutive days and/or a single dose of ammonium perfitorooctanoate jt dose levels of either 670,.480, or 200 n-ig/kg. Ail rats died within 8 day after dosing with ammonium perfluorooctonoate at 670 mg/kg. Liver weight/body weight ratios showed a sharp increase in all rats that received ammonium perfluorooctanoate when compared to the untreated controls and the animals that received only ethanol. There were no significant differences between the untreated controls arid thr.' animals that received only ethanol or between the ethanol pro-treated ammonium perfluorooctanoate and the rats that received only ammonium perfluorooctanoate. Purpose: To determine if pre-trpatment with ethanol modifies the toxicity of ammonium perfluorooctanoate. Procedure: Seventy-two young adult .male Crl:CD* rats were divided into 12 groups, 6 rats per group, and individually housed. Eleven-groups of rats were administered either a single dose of ethano] at 6,000 mg/kg by intragastn'c intubation as a 60% aqueous solution or a 15% aqueous solution (v/v) in drinking water for 14 consecutive days and/or a single dose of ammonium perfluorooctanoate as a 60% solution at dose levels of either 670, 480, or 200 nig/kg. An additional group of untreated rats served as controls. Clinical signs were recorded daily and body weights were recorded at 0, 1 2, 3, 6. 7, 8, 10 and 14 days. Liver weights were recorded at the 14-day sacrifice. Company Sanitized. Does not contain TSCA CIM Results; Ethanol Dose Level 0 6.000 mg/kg 15% (v/v) Average Body Weight Average Liver 0 Day14 DaysWeight (g) 351 416 339 399 346 393 19.61 18.43 17.52 Average Liver Weight/ Body Weight Ratio (mg/kg body weight) 4.72 4.59 4.44 Clinical Signs: Prostration on day of dosing at 6,000 mg/kg. loss for the first 2 days of ethanol in drinking water. Slight we'ght Fourteen days of ethanol in drinking water at 15% (v/v) followed on the 15th day by ammonium perfluorooctanoate Dose Level (mg/kg) Average Body Weight 0 Day 14 Days Average Liver Weight (g) Average Liver Weight/ Body Weight Ratio (mg/kg body weight) 670 330 - 480 329 - 200 335 390 - 24.18 - 6.23 Clinical Signs: Wet and stained perinea! area and weakness at 200 mg/kg. All animals died within 6 days after dosing at 670 and 480 mg/kg. Single dose of ethanol at 6,000 mg/kg followed 24 hours later with doses of ammonium perfluorooctanoate Dose Level (mg/kg) 670 480 200 Average Body Weight Average Liver 0 Day14 DaysWeight (g) 343 - 343 369 341 389 25.83 24.99 Average Liver Weight/ Body Weight Ratio (mg/kg body weight) 6.97 6.41 Clinical Signs: All rats at 670 mg/kg died within 8 days after dosing. One animal died at 480 mg/kg. Wet and/or stained perinea! area at all levels tested. Stained face and alopecia at 480 mg/kg. ^.^e^-"" , (i^^ACO^-- - Results: (cont'd) Ammonium Perfluorooctanoate Dose Level (nig/teg) Average Body Meight 0_&j^ 14 &ays Average Liver Weight (g) Average Liver Weight/ Body Weight Ratio (nig/kg body weight) 670 345 480 353 392 200 374 424 23.99 30.59 6.23 7.20 Clinical Signs: Met and stained perinea! area, weakness and lethargy at 670 and 430 Tig/kg. All animals were found dead at 670 ing/kg within 4 days after dosing and 1 died at 480 mg/kg. * H-l^.037 Purity: Contaminants: Synonyms: CAS Registry Number:n *. H-14.547 Purity: Synonym: CAS Registry Num&er: SC^ - 3 - ulte6-Ooest,-,ol co"iiat^ co^ny58"' Report by'': 'l^ if-c^t^1-l'^- ^ ^' .L<-Z.T^^^' (John Henry/ E. Supervisor, Toxicology" Approved by: JEH:sg1:1.35 .Date Issued: October 8, 198< Haskell Lab. Report No. 79-84 Number of pages in this report: 4 A Sera Id L. Kennedy,-Ji Section Supervisor! Acute Investigations ^^sc^ - 4 - san-ife^-00 COWP^-SS------