Document qk4QodKpGnzLoa1Z4RGY3RN7j

acute Oral Toxicity Screen vith 7-3066c0c in Albino Rats // ECE au5390,1557) Keon "4, Sh J \% y V4 - Experiment No: Conducted at: Dates Conducted: Conducted By: ose1amoLds SRStia.kfeerPtayuLlBa,bvoaMrliauntsomtreiisoenosr,aLabInocr.atory April 2, 1981 to May 14, 1981 0 Fame "fs ASK.tduvdaD.ynceOD'diMraTelcoltxeoiyr,e'olBoSgtat Date Reviewed By: ' PR X. 2. moans 7wico0.. GMercaotmimeinck CL Tae Z=s ar Supervisor, Acute Toxicology C0061 1. Summary The acute oral toxicity screen with T-3066CoC was conducted from April 2, 1981 to May 14, 1981 at Riker Laboratories, Inc., St. Paul, Minnesota using male and female albino rats ranging in body weight from 157-289 grams. The test article was administered by gastric intubation at dosage levels of 5,000 and 500 mg/kg body weight with mortalities of 7/10 and 0/10 respectively. Untoward behavioral reactions were noted only in the 5,000 mg/kg dose group animals and consisted of hypoactivity, lethargy, prostration and diarrhea. The onset of the reactions occurred from 120 minutes to 1 day post dose and all reactions subsided by day 4 or death precluded recovery. Body weight gains were noted in all animals which survived the 14 day study period. Necropsies performed at termination of the study revealed no visible lesions among the surviving animals while hemorrhage of the gastrointestinal track or lungs were noted in all animals which died acutely. The approximate LDSO Of T-3066CC is less than 5,000 mg/kg and greater than 500 mg/kg in fasted male and female albino rats. Introduction The objective of this study was to approximate the acute oral LDSO of T-3066CoC in fasted male and female albino rats. This study is not regulated by the Food and Drug Administration's Good Laboratory Practice Regulation of 1978, although the standard operating procedures of this laboratory adhere to the general principles of this regulation. The raw data generated by the Study Director and the final report are stored in the conducting laboratory's archives. 600362 . vathos ang resusee Young Guesantine albino rats were used for several days prior in fo ttahsitsintgestv.ithAolnllyanisnmiaslaslswewrheichhelsdppuensdceerd So be 40 3008 Bealeh nd suitable as test animals at the dniciaion of the stuey used. oe sats vere housed in suspended, vire-sesh cages in sempesatie ane hemsatey conteetied rooms and permitied a standard laboratory diet Pius water a8 Libteum except Qusing the 16 = 20 hous period immediately peter 0 gastric intubation when food vas vit. Groups of five sale and five female sats vere administered the sest article at preselected dosage Levels. The doses were administered a a constant volume of 10a1 /45 directly into the stomachs of the rats vaing a hypodermic syrinAgetoesquigpupsetrdiwciatahmiantbaatlela-ttiiopnpeodfitnhteubtaetsitonarnteiecdllee,S.the xase vere secumed to thetx cages and observed for the following 14 Gays. Initial and fined Body weights, mortalities (Table 1) and adverse reactions (Fable 2) vere Secorded. A necropsy vas conducted on a1) animals that dled during the study a0 VELL 5 those euthanatized st the end of the 14 day absesvation period (Rabie 1). he protocol, prizctpal personnel involved in the seuty, composition characteristics, and Quality Masuance statement are contained in `appendices I-71. CDmuorarpiieoorsranPnduirviSenoransa,TciebeIoanriceen,cgorWryoawshoProswsc,orFiKaeassth,i,toinoncw.P,urTiWonimal,sin5gionT,outae, wissourt 600363 . maze 2 . ACUTE ORAL TOXICITY SCREEN - ALBINO RATS vith 7-306800c b(oPsaeg) sox hamtmmard soo nw men 1R2613 me1Rae26es14 soo roaimammsssse iismes Mortality, Necropsy and Body Weight Data Em0Tesmt DayEmiRme)Eia e mJeuempremrepteneds T Pezbceesnat a a oe) srs 100 267 Q pay) 2ss8ee9 @a(4 Dmoaaanyp)s) aaamu 5@@2bpaayyss)) ws 3 o25e0 500 M alm1Rlae41ese13 2oaa3mn% s2232n0s0 0/5 na a 5 so ramlInnoooss: iieeesr inmen ors TTnaaoosss 119s7 21501 o ! / FE Note: 2 me eFsitguarretsicilnepvaraesntshcensiinsistinedriscdataes time of death. a suspension in cottonseed oil" aThieeatcnuatefeomraalle LsDiSOninigs rlaetses. than 5000 mg/kg and greater than 500 mg/kg in fasted SNLeeicnCrgoosppssYwyhiolfetnhoe vainsiisballse wlheisicohnsdiveedreacnuotetleyd urpeovneanleecdrohpesmyorosfhatshiec agnaismtarloefnwtheiscthinsaulrvtirvaecdk thea day heervation period. 600364 Table 2 ACUTE ORNLTOXICITYSCREBN -ALOTNO RATS teh 2066000 SumofaRearctiyons Reactions Ee ate e sBexe rey B10BeoO10 s000 po"uceivity = Prostmation' = - ~- blarbe = Cus s000 mp.osctivi= ty wProistrraytion o-C- 00 Wo3skgniticant reaction 500 Wovsigniticant reaction F"Tootsatlgndteeattchant reactions (-) bearetets bays ---- t1t2et 3 t 4 e 5s 6 L7 E8 I9 BoBun0BnM u S noona onnHJI ee swVisoeononasIoono.II-oooo IIoeDI .0 Io DI 0o0:0 e &gg > a . w: ore see res emeiay Riker Experiment Number: Zo |- : APPENDIX I = BESTCOPYAVAILABLE = E F e ----r -------------------- EST SYSTEM AND SOURCE: Rau, "herins "ive: Srecdins Lah-ratrriss, Jilmingsom, * Teer ou pee or an vere wis Pe ve ShevemeerEeY oe eee es Ee eeee eee TorTe te ii Saco: eTThoerpeaevrioanneiss weidflmobpetehioovnsaesdomsianressLhtLtaeeiscnelsersosBoamstHeseedbirseugsEpoernhBdeadenovimzeeerstasaohnTcagoeaesnisnbTeenstssties Ea e P AS aE e EEe oL eeeimeseteaooreoets esr omosmsaeioeFe eeeromeFocomeoarttecy ,ie1psr seiisoeoaessliee, me Er i eott Brest eF td r rom anee Spereere Bier Sb nEaimnitrreaa titoes SF s etrh atorree es rseemoeoreons EE ee It omar te btis Toran afoot Sod weights SOe ieIeanetvaivvniongsiah5e bese oSabneeespeeos:ttoB,neaTanocyueegperenTeesrshimeeesmnl1eitezhiaerhstdoeworrrhi eiTeh owbroepccheheneerTryiee ESoE:re eaTaeice vhietISemeexaA ttonoinvenpter1iode posAsiLbh neeheHrecnatas nmaL?Etoohtnefeir0ne2e0e)onfTtehe| 2 Purina Laboratory Chow, Ralston Purina, St. Louis, Missouri Db TLE Except durin- a 16-iC hour period imrediztely pricr to @osin: whexn wl Thue Connild fpf wn Buns Sponsor Date, study Director (1 Form 19171-18-4Wi sllDate fect wellR30 8!\ 6003S e APPENDIX Ie (ConcludedTEBERSTTACROEPYY RAiVl}AIITT ABLEE ---- PS -- . e Susy Do irectorn,bateS7a/st _ : -"'w oo ---_---- = EE --_--, } EE -- EE 2. : --_-- Te .. EE . 000367 AeeENDIX TI fe Principal Participating Personnel Involved in the Stud Name G. E. Hare X. D. O'Malley, BS K. L. Ebbens, BS G. C. Pecore Function ALcaubtoeraTtoorxyicToelcohgnyician ASdtvuadnyceDidreTcotxoirc.ologist AScuupteervTiosxoircology ASnuipmearlvisLoarboratory ' C0068 APPENDIX 111 = Composition Characteristics This study is not regulated by the Good Laboratory Practice Regulation of 1978 and therefore information pertaining to composition characteristics is not applicable for inclusion in this study. ' 600369 a. apEDIX TV This study is not regulated by the Good Laboratory Practice Regulation of 1576 and therefore a statement signed and prepared by the Quality Assurance group 1s not applicable. This study was, hovever, audited by the Quality Assurance group. In addition to the data audit, different significant phases for studies undervay in the Toxicology Laboratory are inspected weekly on a recurring cycle, and the facilities are examined by Laboratory Quality Assurance on a three month schedule. , 600370