Document jBDw1Lrbp2R8GJ7n2xayEO7dR

.. 17amy Ty Acute oral Toxici. ty Screen NNeo oR LsoDa T of with T-20650oC in Albino Rats apes int: No. Conducted At: bates Conducted; Conducted By: ose1aR01es } RSaifkeetryLBabvoarlautsotriioens,LabIonrc.atory Se. Paul, Mimesota april 2, 1981 to April 16, 1981 i' vLxaon5.cteodtvaTeloex,i)c,olo55gistsh51 iData Study Director Reviewed By: acimX.. I7.. cEabsbeens WF.b.C. Mcreicfoeriiecnk HFs KL. fobens, Bs = Supervisor, Acute Toxicology 01202 . sumenry 2 acute oral toxicity screen with T-30650oC was conducted fron April 2, 1961 to april 16, 1981 using male and female albino rats zanging in body weight from 209-293 grams. The test material was adainistered by gastric intubation at a dosage level of 5,000 pg/kg body weight with mortalities of 3/10 noted fron day1 to day post dose adainistration. Dissehea, lethargy and hypoactivity wero the untoward reactions which vere noted from 120 minutes to day fou and body welsh gains vere noted in all animals which iT survived the 14 day observation period. Necropsy of the sninals performed upon termination of the study revealed no visible lesions while hemorrhage of the gastrointestinal tract and lungs vere noted in the animals which "ated acutely. The LDSO of T-3065CoC appears to be greater than 5,000 mg/kg in fasted male and female rats. 4 Introsuction he objective of this study was to approxinate the acute oral LDSO of T-3065CoC in fasted albino sats. This study is not regulated by the Food and Drug Mainistration's Good Laboratory Practice Megulation of 1978, although the standard operating procedures of this laboratory adiers to the general principals of this regulation. The Taw data generated by the Study Director and the Final report are stored in the conducting laboratory's axchives. 01203 2 Method and Resuits "oung atin rats? vere used in this test. ALL animals were held under quarantine for several days prior to testing with only animals which appeared to be in good health and suitable as test animals at the initiation of the study used. he rats vere housed in suspended, wire-nesh cages in temperature and humidity controlled rooms and permitted a standard laboratory diet plus vatera Libitun except during the 16 - 20 hour period immediately prior to gastric intubation vhen food vas withheld. Five male and five female rats vere adainistered the test material at a preselected dosage level. ALL doses were administered at a constant volume of 10 al/kg dixectly into the stomachs of the rats using a hypodermic syringe equipped with a ball-tipped intubating needleS. acter gastric administration of the test article, the ats vere retumed | to their cages and observed for the following 14 days. Initial and final body weights, mortalities (rable 1) and adverse reactions (Table 2) vers recorded. A necropsy vas conducted on all animals that ied during the study uc well as those euthanatized at the end of the 14 day observation period (rable 11. he protocol, principal personnel involved in the study, composition characteristics, and guality Assurance statesent are contained in Appendices FE 2Dhare ies River brreeedkinagrLyaboCrhaotwo.riSeasl,stIonnc.T,urWiinlam,inSgvt.onT,ouAts, Missouri) popper and Sons, Inc., New Hyde Park, New York 01204 . auc 1 ACUTE ORAL TOXICITY SCREEN - ALBINO RATS with T-3085C0c Mortality, Necropsy and Body Weight Data -(bgo/skeg)& sex _annoimmbaolr S.000 M meeoosr 1m2e6l0o9 wen IndivTiedsutalDayBodMyuaWbee1ri:g4hts (g) 229m3 3&77oays) 22079 a@npay) 267 @ Days) SNomubmebrerTDeestaedd srs 5.000 mmsess 223as mse: 2a 22671 275 oss mmsseess 220m9 227551 a Perbecaednt 0 _-- 2 he test article vas administered as a suspension in cottonseed oil. Talhbeinaopprraotxsi.mate oral LDSO appears to be greater than 5,000 mg/kg in fasted male and fema NNneeecccrrrooopppsasyiyesofpetrhfeoramneidmaulpsonwhitcehrmdiineatdioancuotfelythezesvteuallyedrheevmeoarlsehdagnloevigsaisbtlreolnletseisotnisn,ilhorwaecveesr, and hemorrhagic lugs (one incidence). 01205 | --[ _---- [ET us -- [SEaomt-- maatioyns pr EE ey 8 wx fnrienty wo sa ey w-- -C om sveasrs sCoL-IoTo ILILILT aWweaaloI TmTeII n IL II IL oe titioinon 0) . &zg mme Se ea a FoERy o RfESE i e Li SART 5 Riker:ExperimentNumber {iit ea e PROTm GOOEn T CA C EE RR " ARAN Rap TE PIRIWAABtABtIkERiE CTSPEOOSNNTDS;UOCRT:ED An3M BY: "S_SCaEofmeYhtoyvovina]GleuiraCtheimoincaLlasborator: y, i Riker LaborViaFT tories; T~ohci,T iSEb.iPtaiuln,DMm iivnio eesioornavsdt PCTREOOSNPTTORSAOERLDTAIRCSTLTIEAC:RLT_EISNTG~./E3O0N6yP5LsCECF--ION--BR--IE OF FEST: zm yi ESA irs TEST SYsSeTxEsMHA,M1D SOURCE: jist, Liweles, River wwonding ELaboratories, Tho:; WAllmigten, WA. Weight Range: 200-400" pi: SRT S RS ee OBJECTIVE: The objectiovfe this test will betocharaEnaclastutseGrLiEsReNE i{7tSoaLexgicsiA eetnresyrtoEaefln a`fStovhrae ltcEleeaspbtrioEflaruitcviR lyculiesot.lsa itiiyn'ofalnbrisenE eopi.ainrsnasti,sMnTMseisiosi r:diooletlnntwsieI ,wR asraen;asteiR ln[M9atseediB atnsp e oaCtl: MEFTEEHDODt: eiFmpTheperiaenoidrmaal}asfawtenittdleiblhnaibmtsihaaontuaesoyueaadtnaristHseo{n:leses sesnteaellL`asEusS : Es"nerq mesh cageisniil i tent BunyicolorE1c1ocaoirnrge,"spacocnodrdGionga:cesartdnaafeilnaebodrcatoortyheaTeStanidaredofeShie'opedcrataingvve)er x Sete an: ddooassdaadgigetei.olonefavlelLanJdiom)easlsi.nowBti./llakdgebqewuiaaltdlemlibyneiCsahtaedrraemcdtietrhnieziettesshsteatcatehroatxrinicicelieatd;yathoofsvutephpveleetrmeeisnittsaaltrhtdioisgcailgieei)i. Plreovteolcso:l.`AnTyheaddtietsitonaarltidcolseagvei`lllevbeelas dwimlli'nbeidsotc'uetmoretnehtdeed'aannidmaflisilendtwihtehflothmi.s'ivy hIaaenvgiieaeiarylaesldVrfierlaoLcmtbtiehoenrsespt6ou7nntshoeerEdo.Aftofhltelelofrwicanadggme1is4nsdinasdytsorbsaaitsIitnoovifentditahlfeoartensdatn'ayfr.tiulnoanlleytbiotohdeyrwr aeitg1hat1i syief1r: hJeialrlt,b"elurnegcso,rdeldi.verx,gkriodsnseyn s ae nd gcenwr ehriaco lh gwipalslstinry cloui. den,tbuetisntotiwbnieall1libiaeit'tcerodnta=otc,it ducted on all animals danuirmianlgstsheurcvoinvdiuncgtthoef which die during test period. Any the conduct ofthe test as gross abnormalities which well'as the ti! areobserve:d the necropsy will be recorded vith specific mention to i" 2Gt%ehsetthoearrgetanincdlaeonfdw/tiohlrelsobibetseecraovlbacstueilrvaoetndep.de,rTihioefd.paocsuAstieLbLlmeer,daiva.udnsaitnlagetaahnapdlrotdbhoiestefai(nnDaaSllO)yr.seoipfosrt'thmweeitlihiloi!d!, : CFboeResEltosreRS dbinl,thea Riker LlaboaratodErRieas ARrecS hives, dh te. PSaulS a , Mie ma a ea b Pioatdionpstiddsuerbbioonrgwaaictr1hy6i-Ce2hl0odw,h,Towalpneorinoddrmiaodni,Ea8tE5elfyopurliosrMtaoS gdoeseingG wi heni li hs E EL: iEL aSSal Lisa g Sek ya Aa Re E S L JEa S TSa SG l S eE Sponsor et LO mnie RI Cn a ee i EERCoggaa ds Te a he BOWER Lh her resi Sr ERlenn eel Ty A DRE MRE eba Pee . 5 APPENDIXIT Principal Participating Personnel Involved in the stuty ------ MNeammee GE. Hare X. 0. O'Malley, Bs K. L. Ebbens, Bs G. c. Pecore rFuumncctiioonn LAcaubtoeraTtooxriycToelcohgnyician AstduvdaynceDdirTeocxtiocrologist AScuupteervTiosxoircology iSunpaerlviLsaobroratory ) CO1208 . . ApENDIX TTT 7. CompositionCharacteristics 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. \ . 01209 APPENDIX IV Quaiity Assurance statement This study is not regulated by the Good Laboratory Practice Regulation of 1578 and therefore a statement signed and prepared by the Quality Assurance Szoup is not applicable. This study was, however, audited by the Quality Aesszanse grou. In addition to the data audit, different significant phases for studies underway in the Toxicology Laboratory are inspected weekly on a recurring cycle, and the facilities are exanined by Laboratory Quality Assurance on a three month schedule. ) . CoL210