Document wv235Dbkz0wvw01ZxK0e1ooV

AR 236- 0657 | N-Et FOSE alcohol Acute Toxicity - | uo ! International Research and Development Corporation spoNsoR: TEST ATERIAL: sussCT: 3 Company ez dSetuucdey OirnalRacTso.xtedey (10) WDiilrseoctno7r. oDfeaAsc,tcBe.AT.oxicology a(nSdtacSypedciiraelctSourc)ies 7 , A57ssoSctLasId TDiJreescsutroyF:a R0esearsa Collsborators: GarGyrouTphomTpescohnn,ica3l.5.Supervisor GeeUsnieRomTiegc,hni5c.5a.l Supervisor DavUinide PoSwueplelr,vis3o.r4,. aRceustoret anPdrepSapreactiiaoln,Scudtes Deparcaent 137-084 000259 International Research and Development Corporation TABLE oF coNTENTS To SymoRsfs oi eee.Page IL Test Materfal Li... ..i........... 2 IIL Method tei a eee. I. Results Lo. ii ieee. & A. Morcanad LlD)iVatluyes +. oo... Lo... 4 B. PharmacotoxicSigns . . .. ............4. C. Body Welghts o.oo.. .... .. 910 D. Necropsy Findings +. +... i... .....10 Table Yo. 1. Number of Rats Showing Pharmacotoxic Signs and Time [Hour) (Day) Observed (Ma ..l.e . .s .. ). 5-6 2. Number of Racs Showing Pharmacotoxic Signs and Time [Hour] (Day) Observed (Females) . . . . ... 7-8 137-084 0002950 International Research and Development Corporation Page 1 I. smopsis Based upon the daca obtained, the acuce oral LD, values and 95% confidence lints were calculated to be as follovs: Male Rats: 1615 (818 - 3188) mg/ks, Female Rats: 1333 (715 - 2487) mg/kg, Combined Yale and Female Rats: 1467 (923 - 2332) mg/kg. 137-084 000291 International Research and Development Corporation Page 2 0. TEST MATERIAL The test material vas received from the I Company, St. Paul, Minnesota on October 28, 1977. Ic was identified as "FM-3422, 41-27003422-0, Lot 784/Net-35, RR-1" and was received as an off-white to tan vaxy substance. 137-084 000292 International Research and Development Corporation Page 3 mr. Emon Tuenty-five male and 25 female rats of the Charles River CD strain (btained from Charles River Breeding Laboratories, Iac., Portage, Michigan), weighing from 171 to 259 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 recomendations contained in H.E.W. Publication No. 74-23 (N.I.H.) entitled "Guide for the Care and Use of Laboratory Animals". Water and Purina Laboratory Chow were available ad libitun, except for an overnight period immediately preceding oral administration during uhich food, but not water, was wiehheld. The test material was administered orally by gavage as an emulsion in 40% acetone/60% corm oil at the following dosage levels to male and female race: 464, 1000, 2150, 4640 and 10000 mg/kg. Five rats of each sex were used at each dosage level. Volumes of 10 al/kg of body weight were administered at all dosage levels wich the exception of the 10000 ag/kg dosage level which was administered at a volume of 20 ml/kg. ALL rats were observed for morcalits and phammacotsxic signs during the first four hours after dosing, at 24 hours and daily thereafter for a total of 14 days. Body weights vere recorded imediately prior to dosing (control weight) and at 7 and 14 days. All rats which died on study were subjected to gross necropsy examinations as were all survivors at the end of the 14 day study period. 137-086 000293 International Research and Development Corporation wv A marssmn, vu Sa soccer pas Dosage Hrs[ Days | Level bdTX7273--5% 7-14 Total Mortalities Sis PN TRTWTRPR rRTTfm] hwead 1000 aime Si dotsost 0, aiseent35 eEbnRtoCiymEnIEtintgl ouT) i we 10000 i 11 11 21 12 22/5 2 25/5 "fs 6/10| 5/5 | 10/10] tale Rats: 1615 (318 - 3188) mg/kg, Cnvine Hal Female Rats: and Fests acre 1333 (715 - 2487) 148 325 mg/kg, rieenerapc:s 0.8o0t,o, ravine wei m0 Psat acs: 0.8. 2352 see. Neil, C. 5. 1952. Tables for Conventent Calculation of "Thompson, . R. and Weil, C. S. 1952. On the Construction > 3eny, R. Tmheefolnlowein hvaroacatos sigs vse shared dios ch 16 1957. Statistical Tables for Dose Evaluation, Re- dy rere reso 2 reo 000294 oe 1. | como- viz: Sn10aaorTI84N7E(8nSoOvWeI)NG P(oAaw)UCoOnsTeOeXvIeGn nurs | ansenvation Wwe| wen | moe |dew To ormat pen. sein in, saz | p-- opeorats____ eine iat {| 2) [20] La 10-0) omen 4 reecction | 20) | N w irroctivicy ecrrenmama rne p F 1E05STE,T r STs,i yS Sstns a fSs atas,nSe ata 5i0nm, | 13, 300. Bn] 3 si6s6 a sansa-- s[i i heSa sro Ireanrin ani peh lJ 1053l,a 2e0.1g 5S0Oa [A[5s,0a0hn 0S4GF00lTs) O.seNwseaffeEaitearr: O0IS0| Sirs 20.5005, |30S)h2ad0S.i1a0no 0.10% [[aaaah anh. [30h S80 aeerssrt croet ntve strtamoo.two icer ii f] rame mere10,s2r02e10r, e] 66 [3I s00ahSstE5 Gl, 2065 3 veacry |_| -- ban. 1m. 100 |. 10-0 300. 16-0 Bor vo ams @ i | ee roa-- dbed nm - moi 2.2, osm | ne | wane | ween | awn | mere Death uss 1,1) 166), 107) 205), 16), 1D, |20, 105), 200) | f wI g " Gy tW0n07 113 Jy reunyes ss [omni For | ners one Fow am |r | wan a raters | Station [ee | my area TTT EC -- | CE -- h oo o 0TT Tae ov a2 "2, TT 28) ear | ---- a [iypoactivity mee Tn [SS FTL ASTTS O s [ aoTneh r HES m | eXS s rss |3T035.37, S03, |3TiT, STagaT, |31250, Sr SIT. 4T85, 47,508) s Saar e sn 311, 35,41, 50-0), MBsRE L[eRRuen et wh Maxis TaEnaTsn| , hByYsma, Sf t vr i: Soy wsron 3 oe ae (Cont) a tiorsmrrion | | --si wwe|vom esis eae | aso mine emmaa ] |p| e--n] "640 wiskg 10000 mg/g .= for| International Research and Development Corporation Page 9 C. BODYWEIGHTS: The following body weights were obtained during che 16 day observation period: DLoesvaegle Individual WCeoingthrol W7eiDgahyt W1e6dgphaty Balke sh Rat No. 17218 Sex rae grams: 220 grams' Died grams; Died 7777222109 vYaallee 2m2w8 215875 229386 72722221 vvaallee 22336 225693 230844 72722234 FFeezmaallee 212362 221006 77225 Female 230 237 2280 22 7777222216 FFeemmaallee 2224 22210 225308 1000 7777006610 svaallee 22585 220290 226880 7777006632 vaallee 22519 DDiieedd DDiieedd 77064 vale 25 29 310 7777006665 FeFemmaallee 220092 1D5ie6d DDiieedd 7777006687 FFeemmaallee 202103 Di18e6d 2D3i1ed 77069 Female 201 150 Died 2150 7766885598 rMaatlee 119936 Di16e0 d 2Di8ed 7766886610 savallee 191852 Di14e0d D1i%ed 76862 vale 183 160 218 7766887703 FFeemmaallee 11985 116700 a20s2 7766887756 FFeemmaallee 18im3 11320 D1i7e6d 76877 Female 200 150 Died 4660 7766886643 aallee 118822 DDiieedd DDiieedd 7676886665 Haallee 18521 D1i5e4d DDiieedd 76867 ale 195 Died Died 137-084 000299 International Research and Development Corporation Page 10 LDeovsealge Individual (os/ks) at No. Sex 4640 7766887789 FFeemmaallee 7766888801 FFeemmaallee 76882 Female 10000 7766886689 Maallee 7766887701 aallee 76872 rale 7766888843 FFeemmaallee 7766888865 FFeemmaallee 76887 Female D. NECROPSY FINDINGS: Gross necropsy observations were WCeoingthrtol (grams) 11786 117768 185 19711 1192% 178 11997 17762 13 W7eiDgahyt (sams) 12L0o DDiieedd 18 DDiieedd DDiieedd Died D1i0e5d D1i3e8d Died noted as indicated on Table W1e6igDhaty (roms) D1i3e0d DDDiiieeeddd DDiieedd DDiieedd Died DDiieedd DDiieedd Died 2. 137-084 000360 w-- meee BESTCOPY AVAILABLE ae Sp Gey EE g Hew 2 Cie 2 . y J --_ CE #