ASTM_E_1372_-_95_2003.pdf

Designation:E 1372 95(Reapproved 2003)Standard Test Method forConducting a 90-Day Oral Toxicity Study in Rats1This standard is issued under the fixed designation E 1372;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 has been designed to examine thesubchronic oral toxicity of a test substance during a 90-dayperiod of continuous oral exposure to rats(Rattus norvegicus)following initial acute toxicity tests.1.2 The values stated in SI units are to be regarded as thestandard.The values given in parentheses are for informationonly.1.3 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.2.Referenced Documents2.1 ASTM Standards:E 609 Definitions of Terms Relating to Pesticides2E 1163 Test Method for Estimating Acute Oral Toxicity inRats22.2Federal Standards:Title 40,Code of Federal Regulations(CFR),Environmen-tal Protection Agency,Part 798,Health Effects TestingGuidelines,Subpart C,Subchronic Exposure,Oral Toxic-ity3Title 40,Code of Federal Regulations(CFR),Environmen-tal Protection Agency,Part 798,Health Effects TestingGuidelines,Subpart B,General Toxicity Testing,AcuteOral Toxicity3Title 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 Laboratory Studies3Title 40,Code of Federal Regulations(CFR),Toxic Sub-stance Control Act,Part 792,Good Laboratory PracticeStandards33.Terminology(see Definitions E 609)3.1 Definitions:3.1.1 concentrationThe weight of the test substance perunit weight of the diet(expressed as mg/kg of diet).The weightof the test substance per volume of H2O(expressed as mg/mlof H2O),or at a constant rate in the diet(expressed as ppm).3.1.2 dose,dosageThe quantity of a substance applied perunit treated or applied to or entered into organism.This isexpressed as the weight of the test substance per unit weight oftest animal(mg/kg).3.1.3 feed effciencyThis value is a measure of the effi-ciency with which the animals convert food to body weight.The calculation is the total body weight gain per total foodconsumed.3.1.4 gavageforced feeding,as by tube that is passeddown the throat to the stomach.3.1.5 LD50The statistically derived estimate of the dose ofa test substance that would be expected to cause 50%mortalityto the test population under the specified test conditions.3.1.6 no observed effect dose(NOED)The highest testeddose of a substance at which the measured biological variablesof a specific group under test conditions show no statisticallysignificant dose-related adverse difference from the controltreatment group.3.1.7 nulliparousHaving never borne an offspring.3.1.8 subchronic oral toxicityThe adverse effects occur-ring as a result of the daily exposure of experimental rats to atest substance by diet,water,capsule or gavage for a 90-dayperiod.3.1.9 test substancePesticide or other material(element,chemical compound,formulation,known mixture)adminis-tered orally for the purpose of determining subchronic oraltoxicity.4.Summary of Test Method4.1 Equal numbers of rats(minimum of 80),40 of each sex,of the same source,age,and strain are randomly divided intoat least four test groups(control,low,medium,and high dosage1This 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.1,2003.Published October 2003.Originallyapproved in 1990.Last previous edition approved in 1999 as E 1372 95(1999).2Annual Book of ASTM Standards,Vol 11.05.3Available 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.groups).If it is determined that an interim sacrifice is neces-sary,the number of animals per test group shall be increased(atleast 5 male and 5 female per dosage group),before theinitiation of the study.The highest dosage level shall result intoxicological effects,but not cause more than 20%fatalities.The lowest dosage level should be one that does not induce anyevidence of toxicity.This level should be(if possible)higherthan that expected for human exposure.The intermediatedosage should produce a minimal observable effect.If morethan one intermediate dose is used,the dose levels should bespaced to produce a gradation of toxic