Document ym4E22YM71Jq9828jy4YDGYXV

Acute oral Toxicity Screen with T-30670*C in Albino PAts ColicitIL:Lt.A'LL:l IJ;jLu- CGIIUUCL(-Id: Conducted by: 0961AR014'7 SafGtY EV&Iuat4on LiLboratoxy Pik@ LiLboratorigs, Inc. St. Paul, KinneactiL April 8, 1981 to April 22, 1981 ICDBM&@ x. D. 00AL1* , ss Adv--d Toxicologist study Director Date R(-Iviflwc@B(yi. dc: M. T. Case Y- L. M3bans P-'-.D.Cciffith W. C. mcco=mick Ebbwm, SS Date Supervisor, Acute Toxicology summarv An acute OX&I tcyac'ty screen ,th T-3067ooC was cmdcuted from April 8, 1981 to April 22, 1981 using male and fenmae albino rats ranging in body weight from 225-299 grams. The text material was administered by gastric intubation at a dosage level of 5,000 mg/kg body weight. No mortalities, untoward behavioral reactions or body weight losses occurred during the 14 day observation period. Necropsy of the --'-*ls partemed upon termination of the study revealed no visible losims. The approximate oral LDSO of ,I,-:3u67coi(s: greater than 5,000 mg/kg in fasted male and foalle &Ibino rats. Introduction The objective of this study was to approximate the &cuts oral LDSO of T-3067COC in fasted albino rats. This study is not regulated by the Food and Drug Administration's Good IAboratory practice jwgul&tion of 1978, although the standard operating procedures of this 1&borat=T adhere to the general Principals of this regulation. The raw data ganeratad by the study Director and the final report &re stared in the conducting 1-bara archives. t4-.dt.hRoedsults young albino ratt were used in this test. Ali -,i-jr, were held under quarantine for several days prior to testing with only animals which appeared to be Ln good health and suitable as test animals at the initiation of the study used. The rats were housed in suspended, wire-ibash r-ages in temperature b and humidity controlled ro@c and permitted a standard 1&1--yatory diet plus water ad libitum except during the 16 - 20 hour period innediately prior to gastric intubation when food was withheld. Fivo-male amd five female rats were aa-inistaxed the text material at a preselected dosage level. All doses were ma-inistered at a constant volume of 10 ml/kg directly into the stcoacbm of the z-ate using a hypodermic c syringe equipped with a ball-tipped Lntubating nee e@-. After gastric -A-inistration of the test article, the rats ware returned to their cages and observed for the following 14 days. initial and final body weights, mortalities (Table 1) and adverse reactions (Table1 ) were recorded. A nor-ropsywas conducted on all arti-ls that died during the study as well as those euthanatized at the end of the 14 day observation period (Table 1) . The protocol, principal personnel involved in the study, c@po ition characteristics, and Quality Assurance st&tA=Ont &re contained in Appendices I - IV. 1;Charles River Breading Laboratories, Inc , Wilmington, KA Ralston llt=ina Laboratory Chow, Ralston *;,@@i.,-S,t. L.., Popper and Sons, Inc., Now Hyde PaLrk, Now York Missouri I'AISLJ': ACLRZE:ORAL '.ROXXCM SCREEN - ALBINO RATS with T-3D67CoC Mortality, Necropsy, Body Weight Data and Behavioral Reactions :LjtdividualLiody Weights (9) I)osc /Lnimal (11111/it:i;l,)!;:Ntilaix!r Test Day Number. 0 -14 Number DeadNumber Tested 5,ooo m lR2700 297 419 0/5 lP2701 299 421 lR2702 270 382 lR2703 283 401 lR2704 274 380 Percent Dead 0 5,000 1.- ln2717 240 294 0/5 0 IR2718 225 285 IR2719 245 301 IR2720 241 288 lR2721 238 258 The test Article was administered as an Aqueous suspension. The approximate oral LD50 is greater than 5,000 mg/kg in fastad male and fmale albino rats. Necropsy Necropsies per:forned upon termination of the study revealed no visible lesi=*. Behavioral Reactions No untoward behavioral reactions were noted during the 14 day evaluation period. Riker Experiment Number: PRC)TIDCOL TF-ST: SPONSOPI- - a Oral Toxlalty IM,-M fid Chmical CONr);;;i@1,3@,-.r.SafeVEvaluation s Laboratory, Riker Laboratories, TESI ARTI='J"* 'T*.Smi6c CONTROL ARTICLE: Jim& PROPOSED STARTING/COMPL,ETION TEST SYSTEM AND SOURCE: ant, DATE Cho OF TEST: 71581 las nive r Breedirag Laboratories, Sex: M, F ..Number: S,S, Range: 2W-300 Sm. Division Inc., St. Paul, Minnesota Inc.# Wiiinijigton, 77- o&=r@@-'- I The'-o@jectivLi of this test will toxicity of the test article in test system for reproducibility alnd general availability. be to characterize the acute Oral albino rats Rats were selected as a of response, historical use, ease in handling METHOD: The animals will be housed in stainless steel suspended wire mesh cages in temperature and humidity controlled rooms duringbboth the quarantine and test periods, with fc>o4 and water offered ad libiturrr--.Each animal will be identified by color coding, according to the laboratory's standard operating procedure, which will correspond to a card affixe*d to the outside of the cage. A single dosage of 2;.Con g/kg will be administered each animal, however, if this dosage level does not adequately characterize the toxicity of the test article, additional aniraals will be administered the test article at supplemental dosage levels. Any additional dosage levels will be documented and filed with this protocol. The test article will be administered to the animals in the form. received from the sponsor. After administration of the test article, the animals will be returned to their cages and observed for any untoward be- havioral reactions for the following 14 days. Initial and final body weights will be recorded. A gross necropsy which will include, but not be limited to, heart, lungs, liver, kidneys and general gastrointestinal tract will be con- ducted on all animals which die during the conduct of the test as well as the animals surviving the test period. Any gross abnormalities which are observed during the conduct of the necropsy will be recorded with specific mention to the organ and/or site observed. The acute median lethal dose (LD50) of the test article will be calculated, if possible, using a probit analysis method at the end of the observation period. All raw data and the final report will be stored in the Riker Laboratories Archives, St. Paul, Minnesota. Purina Laboratory Chow, Ralston Purina, St. Louis, Missouri b xxceyt during a 16-2C hour Period immxu&toly food will be withholcl. yriot to doaing wi-isn sponsor Dafe Study Director CS Date Fafm 19171.16.PWO .APPENDIX Il Principal Participating Personnel involved.in the Study Name C- E. Hart K. D. O'Malley, Es K. L. Ebt>ens, BS G. C. Pecore Function Laboratory Technician Acute Toxicology Advanced Tax.Leologist Study Director Supervisor Acute Toxicoloqy Supervisor Anima Laboratory APP -MIX 117 Composition CharaCtPristics This study is not regulated by the Good laboratery Practice Regulation of 1978 and therefore information pertaining to composition characteristics is not applicable for inclusion in this study. 7. APPENDIX r-V O"Jity Assurance Statement This study is not regulated by the Good Laboratory Practice Rogul;,tion of 1978 and therefore a statement signed and prepalred by the 9"3.ity Assurance group is not applicable. This study was, however, audited by the Quality Assurance group. in addition to the data audit, different significant phases for studies undcrway in the Toxicology Laboratory are inspected we@)Lly on a recurring cycle, and the facilities are examined by Laboratory Q""ty Assurance on a three month schedule.