ASTM_E_1483_-_92_2004.pdf

Designation:E 1483 92(Reapproved 2004)Standard Test Method forAssessing Developmental Toxicity in Rats and Rabbits1This standard is issued under the fixed designation E 1483;the number immediately following the designation indicates the year oforiginal adoption or,in the case of revision,the year of last revision.A number in parentheses indicates the year of last reapproval.Asuperscript epsilon(e)indicates an editorial change since the last revision or reapproval.1.Scope1.1 This test method is designed to assess the potential of apesticide or chemical to present a hazard to the unborn arisingfrom exposure of the maternal animal during pregnancy.1.2 This test method assumes that the user is knowledgeablein animal toxicology and related pertinent areas,and it reliesheavily on the judgment of the evaluator.1.3 The values stated in SI units are to be regarded as thestandard.The values given in parentheses are for informationonly.1.4 This standard does not purport to address all of thesafety concerns,if any,associated with its use.It is theresponsibility of the user of this standard to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.For specific hazardstatements,see Section 6.2.Referenced Documents2.1 ASTM Standards:2E 609 Terminology Relating to PesticidesE 943 Terminology Relating to Biological Effects and En-vironmental Fate2.2Federal Standards:Title 40,Code of Federal Regulations(CFR),Environmen-tal Protection Agency,Subchapter E,Pesticide Programs:Part 160,Good Laboratory Practice Standards3Title 21,Code of Federal Regulations(CFR),Food andDrug Administration,Part 58,Good Laboratory Practicefor Nonclinical Studies3Title 40,Code of Federal Regulation(CFR),Toxic Sub-stance Control Act,Part 792,Good Laboratory PracticeStandards33.Terminology3.1 Definitions:3.1.1For definitions of terms used in this test method,seeTerminology E 609 and E 943.3.1.2 developmental toxicitythe property of a test sub-stance that causes in utero death,structural or functionalabnormalities(teratogenic),or growth retardation during theperiod of fetal development.To assess that property,the testsubstance is administered to the maternal animal during theperiod of major organogenesis.4.Summary of Test Method4.1 Rats and rabbits have been used extensively as animalmodels to determine whether a test substance is potentiallyhazardous to the developing fetus.The use of two species isdesirable because of differences in maternal and fetal metabo-lism,placental barriers,and chemical absorption.4.2 The test substance is administered in graded doses togroups of pregnant animals from the time of embryonicimplantation through the period during which major organsystems are formed.At least 20 pregnant rats and 12 pregnantrabbits are required for each of the three test groups and thecontrol group.4.3 A pilot study is conducted to establish the three doselevels for the full study.4.4 On Day 20 of gestation for rats and Day 29 for rabbits,the pregnant females are sacrificed,the uteri are removed,andthe contents are examined for embryonic or fetal deaths andlive fetuses.Collected fetuses are weighed,measured,tagged,and sacrificed in preparation for complete examination.4.5 If a limit test at an exposure of least 1000 mg/kg bodyweight produces no observable toxicity,a full study using threedose levels might not be necessary.5.Significance and Use5.1 In the assessment and evaluation of the toxic character-istics of a chemical,determination of the potential develop-mental toxicity is significant.1This test method is under the jurisdiction of ASTM Committee E35 onPesticides and Alternative Control Agents and is the direct responsibility ofSubcommittee E35.26 on Safety to Man.Current edition approved Oct.1,2004.Published October 2004.Originallyapproved in 1992.Last previous edition approved in 2000 as E 1483 92(2000).2For referenced ASTM standards,visit the ASTM website,www.astm.org,orcontact ASTM Customer Service at serviceastm.org.For Annual Book of ASTMStandards volume information,refer to the standards Document Summary page onthe ASTM website.3Available from U.S.Government Printing Office,Superintendent of Docu-ments,Washington,DC 20402.1Copyright ASTM International,100 Barr Harbor Drive,PO Box C700,West Conshohocken,PA 19428-2959,United States.5.2 This test method is intended to permit the determinationof a no-observed-effect level and the potential hazard to theunborn that may arise from exposure of the pregnant organismduring gestation.6.Hazards6.1 Contact with all test substances and solutions should beminimized with appropriate protective clothing,gloves,eyeprotection,etc.The use of fume hoods and increased ventila-tion in test rooms is necessary when handling volatile sub-stances.Information on acute mammalian toxicity and specialhandling procedures for all chemicals and products to be usedshould be known before this test method is employed.6.2 The disposal of excess test subs