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AR226-2785 """""i^sss FOR DU FONT USE ONLY Copies to: Haskell E. I. d" Pore de Nemours and Co., Inc. Laboratory for Toxicology and Industrial Elkton Road, P. 0. Box 50, Newark, Delaware 19711 Medicine HASKELL LABORATORY REPORT NO. 788-82 Material Tested* Uctanoic acid, pentadecafluoro-, amfflonium salt Haskell No. 12,037 Study Initiated/Completed 2/3/82-1U/15/82 ^ Material Submitted by CR&D Department ' Haskell Laboratory ACUTE OttAL TOXIC ITY Of[ A FUNCTION OF AGE ms Summary: Ammonium perfluorooctanoate single oral doses to the was slightly toxic when administered in Bales, LD50 -- 573 mg/k^ following groups and females, LD50 of rats: 580 weanlings (21 days old): a-lLf weeks rat-s: )ld): males, LD50 LD50 = 470 mg/kg = and nig/kg; young females, LD50 = adults (approx. 453 ing/kg; older males, days old): males, in regards Lo the = 336 mg/kg and females, LD50 LD5'J = 243 mg kg and females, sex ot th^ = 343 mg/kg ; newborn 2 LD50 = 258 mg/kg. Toxicity ynoeuwnbgornad(u.<lt 2 radatsys. old) and older rasthsowhedad nolowseigr nLiDfi5c0anvat ludeisffetrheanncew.eanHlionwgesveorr, f 'cedure; The b,.' intragastric test ."late-rial, intubation in as suspensions in corn oil, was administered groups were (1) Male - single Newborn 2 doses to groups of Ctl'.CVl rats. The old); (3) Male - Weanlings days old); (2) Female (21 days old); (4) Female Newborn 2 days old); rats; ^5) and Female - Young (7) Female adults (approx. 8-10 weeks - Weanlings (21 days old); (6) Male - Older - Older rats. A Range Finding Study was conducted to draettesr*m*.ine Ththe e suinrvitiviainlg droasets lewveerel wfoerighCeude aLnDd50obtessertveodn dNuewribnogrn a 14-2dadyays old) trheecomveoryrtapleitryioddataand usthinegn tshaecrmifeitcheodd . of ThDe. JLD. 5F0 invanleuye.s***were calculated from 1 - TSCACBl Sanrt.zed.0oes"ot contain Coinp1^ Results; Dose (mg/kg) Average Weight Male - Newborn Body (g)_ 2 days Suspension W__ old) Average Dose (nL) 370 6.2 330 6.1 280 6.4 240 6.2 200 6.9 13u 7.6 1.0 0.23 1.0 0.20 1.0 0.18 1.0 0.15 1.0 0.14 1.0 0.10 Deaths occurred up to 6 days after dosing. Mortality Ratio 10/10 10/10 10/10 4/10 0/10 0/10 LD50 **** 2*3 ag/kg Female Newborn 2 days old) 320 5.8 1.0 2HU 5.7 24U 1.0 220 b7..12 11..00 210600 8.0 1.0 130 76..70 11..00 Deaths occurred up to 4 days after 0.19 0.16 0.15 0.15 0.16 0.10 0.10 dosing. 10/10 6/10 5/10 0/10 0/10 0/10 0/10 258 ing/kg Male - Weanlings (21 days old) 710 6a 67o 82 525 69 450 87 -*00 84 350 87 3.0 1.62 2.5 2.21 3.0 1.20 2.5 1.56 2.5 1.34 2.5 1.21 CDelianthics aol ccSuigrrnesd: upSta';ione3d daaynsd awfetterpedroinseinagl . area, 8/10 7/10 3/;.0 2/10 2/10 0/10 weakness and 573 nig/kg weight loss. Female Weanlings (21 days old) b7u 80 450 87 2.5 400 80 2.5 350 82 2.5 2.5 Clinical Signs: Stained and wet weight loss. Deaths occurred up 2.14 1.55 1.28 1.15 6/10 3/10 3/10 1/10 perineal to 3 days area, after stained dosing. face, 580 ing/kg weakness and ^TSCACSi SanUns'J, 0^^r"'-.'lcon"-'" Comply Male - Young Adults (approx. 8-10 weeks 470 og/kg Female - Young Adults (approx. 8-10 weeks old) 670 185 500 185 425 182 350 180 5.0 2.48 10/10 5.0 1.85 8/10 5.0 1.54 2/10 5.0 1.26 1/10 Clinical Signs: Stained discharge, diarrhea and face, stained and wet perineal area, dosing. weight loss. Deaths occurred up to 4 453 mg/kg nasal days after Male - Older Rats 72U 500 4UU 350 3UO 24LI 20U Clinical tremors, occurred 563 10 4.06 558 10 2.79 543 10 2.18 564 10 1.98 501 3 4.95 644985 33 3.96 4.32 Signs: Stained face, stained and wet lethargy, chromodacryorrhea, diarrhea up to 9 days after dosing. 10/10 10/10 10/10 9/10 0/10 0/10 0/10 336 mg/kg perineal area, weakness, and weight loss. Deaths female - Older Rats f)7u 450 40U 350 225 Clinical tremors, cosing. 335550 1100 21..3640 190//1100 343 mg/kg 365 10 1.46 6/10 358 10 1.26 5/10 346 3 2.55 1/10 Signs: Stained face, lethargy and weight stained and wet perineal area, weakness, loss. Deaths occurred up to 5 days after - 3 - noloo^,nTSCAC3l Sanit^d-Does Cow?^ ** tonge-flnding Study Results, Newborn Bats; Dose "g/te Mortality Male 130 0/4 210 0/7 300 2/5 375 4/5 425 3/3 500 1/1 575 7/7 *** Finney, Press. D. J., Probit Analysis, 3rd Ed., 1971, Cambridge University **** 952 Confidence Limits: Male - Newborn 2 days old) female - Newborn 2 days old) lower (mg/kg) Undefined 244 Male - Weanlings (21 days old) 514 Female - Weanlings (21 days old) 470 Male - Young Adults 40J (approx. 8-10 weeks old) Female - Young Adulcs (approx. 8-10 weeks old) 413 Male - Older Rats Undefined Fem&ni - Older Rats 285 Upper (mg/kg) 276 55.7 19.9 664 8.0 2,258 4.7 536 8.6 503 15.0 390 8.0 --*- . ts"&!?^j^fg - i "iPE'i-;'-} .- 4 - Ciwipany Sanit^od. Does not conlain ^s^s-^SeSas'isS, Report by: an Hind Technician Reviewed by: 0. Louis Dashlell Study Director Approved by: ^gL.^-. ^ ^^..^ . Gerald L. Kennedy1 J^ Section Supervisor' Acute Investigations LH:Cac:Wp:n.a F--^aiBaa^----^--983^"^ t^skellLab^!epor'o^B^^B*l -5- .ooesnotcona,nTSCACBl C^^^^2^0