Document DvdyRdz7OOjoMbzY04D6wnzmo

Acute Orel Toxicity Screen with T--30670OC in Albino Bats j:xfim I<nr'iti: N o . CoiM luctt:Ll A L: U Lu l C o n d u c t e d : Conducted by: R eview ] By: de: M. T. Case K. L. Ebbene P . D . Griffith N. C. MeC o m i c i 0981AR0147 Safety Evaluation Laboratory RiAer Laboratories, Inc. St. Paul, Minnesota April B, 1981 to April 22, 19B1 A. D. O'Malley, BS Advanced Toxicologist Study Director Oste K. L. Ebbens, BS Date Supervisor, Acuta Toxicology 1. Summarv to acute oral toxicity screen with T-3067COC was condcutad iron April 8 1981 to April 22, 1981 using male and female alb ino rats ranging in body weight from 225-299 grams. The test material was administered by gastric intubation at a dosage level of 5,000 mg/Xg body weight. No mortalities, untoward behavioral reactions or body weight losses occurred during the 14 day observation period. Necropsy of the animals performed upon termination of the study revealed no visible lesions. The approximate oral LD50 of T-3067COC is greater than 5,000 mg/Xg in fasted male and female albino rats. Introduction The objective of this study was to approximate the acute oral LD50 of T-3067COC in fasted albino rate. This study is not regulated by the Food and Drug Administration1b Good laboratory Practice Regulation of 1978, although the standard operating procedures of this laboratory adhere to the general principals of this regulation. The rew data generatad by the Study Director and the final report ere stored in the conducting laboratory's archives. 2. Method and Results young albino rate*- re 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. The rats were housed in suspended, wire-mesh cages in temperature and humidity controlled rooms and permitted a standard laboratory diet- plus water ad libitum except during the 16 - 20 hour period immediately prior to gastric intubation when food was withheld. Five male amd five female rats were administered the test mataril at a preselected dosage level. All doses were administered at a constant volume of 10 ml/kg directly into the stomachs of the rats using a hypodermic syringe equipped with a ball--tipped intubating needle . After gastric administration of the test article, the rats were returned to their cages and observed for the following 14 days. Initial and final body weights, mortalities (Table 1) and adverse reactions (Table 1 ) were re corded. A necropsy was conducted on all animals 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, composition characteristics, and Quality Assurance statement are contained in Appendices I - IV. TTCharles River Breeding Laboratories, Inc., Wilmington, MA -- Ralston Purina Laboratory Chow, Ralston Purina, St. Lours, Missouri -- Popper end Sons, Inc., New Hyde Park, New York TAHU': 1 ACUTE ORAL TOXICITY SCREEN - ALBINO RATS with T-3067COC Mortality, Necropsy, Body Weight Data and Behavioral Reactions 3. 1 n o s e " (nu |/ K M ) .'i< 5,000 M A n im al NlJIftix.T 1R27O0 1R2701 1R2702 1R2703 1R2704 individual Body Woights (g) Test Day Number: a 14 Number Dead Number Tested 297 419 0/5 299 421 270 382 283 401 274 380 Percent Pond 0 5,000 i 1R2717 240 294 0/5 1R2718 225 285 1R2719 245 301 1R2720 241 288 1R2721 238 258 0 -- The test article was administered as an aqueous suspension. The approximate oral LD50 is greater than 5,000 mg/Xg in fasted mala and female albino rats. Necropsy Necropsies performed upon termination of the study revealed no visible lesions. Behavioral Reactions No untoward behavioral reactions were noted during the 14 day evaluation period. Riker Experiment Number: PROTOCOL TEST: Orel Toxicity------ ---------------------------------------------------- SPONSOR: 4 3H ' Chemicals______________________________________________ Division CONDUC^Ei) Safety Evaluation Laboratory, Riker Laboratories, Inc., St. Paul, Minnesota TEST ARTICLE | t-.lfl67CoC_______ _____________________________________ _______________________ CONTROL' ARTICLE: / S Q M ' _________________________ PROPOSED STARTING/COMPLETION DATE OF TEST: */Q1 " 7>IH1 ___ TEST SYSTEM AND SOURCE: Sat# Chari* Xlva r Breeding laboratories l#c. Wilinungton, t\a Sex: M,F 'Number: 5,5. .... Weight Range: 300-300 gu. - ,> * .. ' - _______ , . OBJECTIvS':-* The* objective of this test will be to characterize the acute oral________ toxicity of the test article in albino rata____ . Rata were selected as a test system for reproducibility of response, historical use, ease in handling -and general availability. METHOD: , -' . The animals will be housed in stainless steel suspended wire mesh cages in temperature and humidity controlled rooms during^both the quarantine and test periods, with food-- and water offered ad libitum-- . Each animal will be identified by color coding, according to the laboratory's standard operating procedure, which will correspond to a card affixed to the outside of the cage. A single dosage of t .000 m g A g will be administered each animal, however, if this dosage level does not adequately characterize the toxicity of the test article, additional animals 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. sf -- Purina Laboratory Chow, Ralston Purina, St. Louis, Missouri b Except during a 16-2C hour period immediately prior to doaing whan food will ba withheld. 1 fyU-s (J, Sponsor 5/? #4 ' Date Sttudy Director Date 4* Form 1917116PWO APPENDIX II Principal Participating Personnel Involved in the Study _________ Nang_____ G- E . Hart K. D. O'Malley, BS K . L . Ebbens, BS G. C. Pecore Function laboratory Technician Acute Toxicology Advanced Toxicologist Study Director Supervisor Acute Toxicology Supervisor Aniaal Laboratory appehdix_!H Composition Characteristics This study is not regulated by the Good Labor.tory Practice Rsgul.tion of 1978 and therefore information pertaining to composition characteristics is not applicable for inclusion in this study. APPENDIX XV Quality Assurance Statement This study is not regulated by the Good Laboratory Practice Regulation oi 1978 and therefore a statement signed and prepared by the Quality Assurance group is not applicable. This study was, however, audited by the Quality Assurance group. i n 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 examined by Laboratory Quality Assurance on a three month schedule.