Document x1O1w2anayrVM2RKnQyBaYQ8m

Coy 8EHQ - 0200-373 AT 2 International Research and Development Corporation ond # v sors: TEST MATERIAL: susszCT: womey R226 -0955 Fluorad Fluorochemical Surfactant FC-95 ASctuutdey OirnalRatTso.xleity (LD;)) 3 Ss g os . & EPA-OTS - NIGHT 0 AsYYPoRs Collaborators: Gary Thompson, B.S. GreGgrouRpomiTge,chnB.iSc.al Supervisor DavUindit PoTweeclhln,icaBl.A.Superyisor URneiptortSupPerrevpiasroart,ion, ADceuptaertmaenndtSpecial Studies 137-083 WDiilrseocntoPr.oDfeaAnc,utBe.AT.oxicology and Special Studies (study Director) 7 DTIEETofd Jessup 7h. associacd Directoy/d: Research g2 T crm Ls = 55 J~E Date:_ Mav 31, 1978 o1772 International Research and Development Corporation TABLE OF CONTENTS Page To SYOPSIS + see.. 1 IL TestMaterial Lo. ..a.i..i.............. 2 II Method + teehee... 3 TV. Results ove nnn. 4 A. Mortanad LlDgiVatluyes +. . +... ......... 4 B. Phatmacotoxic SIGNS + +. +L... .......... C. Body Weights + + tue i ia... 5 D. Necropsy FARINGS + + + si... ii... 6 TableNo. 1. Pharmacotoxic SIENS + +... ............. 7-8 2. Sumaryof Gross Necropsy Obser..v.a.t..i.o..n.s. 9 137-083 001773 International Research and Development Corporation Page 1 I. smopsts Based upon the data obtained, the acute oral LD; values and 95% confidence limits were calculated to be as follows: Male Rats: 233 (160 - 339) mg/kg, Female Rats: 271 (200 - 369) mg/kg, Combined Male and Female Rats: 251 (199 - 318) mg/kg. 137-083 001774 International Research and Development Corporation Page 2 IL TEST MATERIAL The test material was received from the 3M Company, St. Paul, Minnesota on October 24, 1977. It was identified as "Fluorad Fluorochenical Surfactant FC-95, 34 Stock No. 98-0207-0103-7, Lot 640, Net wt. 5 bs. 2.2 kg." and was received as a white powder. 137-083 . 0177S International Research and Development Corporation Page 3 I. METHOD Tuenty male and 20 female rats of the Charles River CD strain (ob- tained fron The Charles River Breeding Laboratories, Inc., Portage, Michigan), weighing from 172 to 212 grams, vere used for this study. The rats were housed by sex in groups of 5 rats per cage, in hanging wire-nesh cages in temperature and humidity controlled quarters. They were maintained in accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.I.H.) entitled "Guide for the Care and Use of Laboratory Annals". Water and Purina Laboratory Chow were available ad libitum, except for an overnight period immediately preceding oral aduinistration during which food, but not vater, was withheld. The test material was suspended in a 20% acetone/80% corn oil mixture and administered orally by gavage at the following dosage levels to male and female rats: 100, 215, 466 and 1000 mg/kg. Five rats of each sex were used at cach dosage level. Volumes of 10 ml/kg of body weight were administered at all dosage levels. ALL rats vere observed for mortality and pharmacotoxic signs during the first four hours after dosing, at 24 hours and daily thereafter for a total of 14 days. Body weights were recorded {mediately prior to dosing (control weight) and at 7 and 14 days. ALL rats which died on study were subjected to gross necropsy examination as vers all survivors at the end of the 14 day study period. 157-083 01776 [International Research and Development Corporation Page 4 IW. RESULTS A. MORTALITYAND L_, VALUES: Dose = Mortality Data 1 Number of Deaths. Dleovsealge [H[r0-s4| [T 7 "h3 ay4s 5% om| sgfig | F|W FH FHF NF HF HF OH r| 211050 2 a 1a0s0h0 112 11111 21 12 13]1| MortTaoltailties Vale |Female]Tol oass || oowsss || aomnoo s5//55| s5i/s5 | 110001100 The Acute Oral LD, Values and 95% Confidence Limits: Male Rats: 233 (160 - 339) mg/kg, Female Rats: 271 (200 - 369) mg/kg, Combined Male and Female Rats: Slope: Male Rats: 1.00, Female Rats: 1.00, 251 (199 - 318) mg/kg. Coabined Male and Female Rats: 1.00. Statistical References: EffectiveWeDiols,e Ca.ndS.Ins19t5r2u.ctiToanbliensThfeoirrCoUsnev.endeBnitomeCtarliccusl,ati8:on o2f49-M2e6d3i.an Tables fo"rThMomopvsionng,AvH.eraR.geanIdntWeeriplo,latC.ionS.. 19B5i2o.metrOincst,he8:Cons5t1r-5u4c.tion of No. 5711.3ebyM,ilRe.s-A1n95e7s. ReSsteaatricshtiLcaabloraTtaobrlye,s EflokrhaDrots,e EIvnadliuaanat.ion, Report B. PHARMACOTOXIC SIGNS: The following pharmacotoxic signs were observed during the 14 day observation period: (see Table 1): 137-083 coL77? International Research and Development Corporation Page 5 C. BODY WEIGHTS: The following body weights were observations DoLesvaegle (sg/kg) 100 21s 464 1000 periods: Individual Rat Number 7766883398 776688610 7682 7766881198 76820 7766882212 76863 7766884454 7676884676 7766882243 76825 7766882276 76848 7766885609 7766885521 7766882289 7678638130 76832 76853 76854 7676885556 76857 Sex vMaallee MMaallee Male FFeemmaallee Female FFeemmaallee Maallee MMaallee Male FFeemmaallee Female FFeemmaallee Male MMaallee MMaallee FFeemmaallee FFeemmaallee Female Male vale MMaallee vale obtained WCeoingthrtol (grams) 211722 127090 188 117891 191 118840 11872 118988 201 118889 177 117998 117953 118873 78 128099 118833 178 78 180 1193530 107 during the W7eiDgahyt (grams) 226 22580 223050 119s5 150 127180 D1i7e0d 119600 Died 1u5s2 118500 132 DDiieedd 1D6i0ed Died DDiieedd Di13e0d Died DDiieedd DDiieedd Died 14 day W1e4igdhaty (grams) 272 228921 227760 220108 21 222030 D2i3e0d 22148 Died 22040 D20i0ed 152 DDiieedd DDiieedd Died DDiieedd DDiieedd Died DDiieedd DDiieedd Died 137-083 . 001778 International Research and Development Corporation Page 6 DLoesvaegle Individual VCeoingthrtol (ag/kg) Rat Number Sex (grams) 1000 7676883343 FFeemmaallee 118953 7766883356 FFeemmaallee 119813 76837 Female 195 W7eiDgahyt (grams) DDiieedd DDiieedd Died W16eiDghaty (grams) DDiieedd DDiieedd Died D. NECROPSY FINDINGS: Gross necropsy observations vere noted as indicated in Table 2. 13>7-083 001779 EagSoETTp COMPOUND ~ Fluorad Fluorochenical Surfactant FC-95; onsmarion 100 mg/g 5 walks mls Somata l30e6ma),n e50o2216) e200),mc301e-16e) .| _-- 1000jes A -TT T-- T ye r pt Te=eoT iiwrosoeiS mor AfJoRrE TTI DecreaseLdiwh SILT, 50-0), | " [SLAY 500-0) 21, TT, 30) ATI, I BL, B5,a1, nipot on 3,, 10fa [2 sa 0. |<r prsT. SAD), [31,2041 40); 111], 525,41, 10-2) 3 [Ty GAT, | TT --Ny Death - OL T@, 2), (1, 2), 1@, | I < s3z zZ: NUMBER 7ry OF RATS SHOWING snr: PHARMACOTOXIC : COMPOUND ~ Fluorad Fluorochetcal Surfactant FC-95: onswrvation Normal 100 mefke pO,G5) , 306) 25 maike =, Sem, us Wh mali ey 00 mis| TT orPilosrection ka i nt Ataxia 155) fur osworss p12,41, 21), 32) Te 16 TTT fis' G4), 36-0), 10[26%4), 365), 16) [isiATEsa va oiy[t AToT | [212%], 314], 2(2) 24,4), 20), 32)| S14, STA, 104) iT "iagthhccoorrrivegis og|e| [ER EE 8S23ty wo. ingen Hi208t), 2010), -- _ RAI [te I E-- f{5 SFulrofvaecatdantFlFoEu-oc3h5esteal ne 2. seLeesion ber necropsied Ho gross lesions Extyeerlnlaolw skated wrogential xegton bprreaodrkeesnnctalltyettcaarnofnurinobdnatlsloieusgtehd Shite seat around south Sosmteanton mSuiccoossaa,, thhyipcekreenaeids lFaluniddulfoarilemudcosa, bypeceata lBlaanndduulloorc mmoccoossaa,, etrhoircikoenned EBllaanndduullaarr mmuuccoossaa,, udloccekraretdionfsoct LanCgoengestion By Intlceousntttdianteafssittterdansparent red scold-like material Acute Oral Toxtciey (Dy) Study fn Rats. Summary of Gross Necropey Observations. Deaths swoels dSbhmEsii 1A0E 00 mks : 1s sss 1 2 ai 2 2 1 1a a 3 3a o 1a 3 43FU s 2 1 12 1 1 11 or 42 a a1 2 1 o wom R3B o28S Terston) Sacrifice 1W00omeis 1w5 mwalin 5s sa 5s 1 2 12i 1 2 1 7 :