1、Designation:E 1811 96(Reapproved 2001)Standard Test Method forOncogenicity Study in Rats and Mice1This standard is issued under the fixed designation E 1811;the number immediately following the designation indicates the year oforiginal adoption or,in the case of revision,the year of last revision.A
2、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 covers a long-term study to determinethe oncogenicity potential of a substance in mammalian speciessuch as the rat and mo
3、use.The objective is to observe the testanimals for a major portion of their life span for neoplasticlesions during exposure to various doses of a test substance byoral administration.1.2 This test may also provide some information on long-term general toxicity.1.3 This test method assumes that the
4、user is knowledgeablein mammalian toxicology and related pertinent areas,and itrelies heavily on the judgment of the evaluator.1.4 The values stated in SI units are to be regarded as thestandard.The values given in parentheses are for informationonly.1.5 This standard does not purport to address all
5、 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.Specific hazardsstatements are given in Section 6.2.Referenced Docu
6、ments2.1 ASTM Standards:E 609 Definitions of Terms Relating to Pesticides2E 943 Terminology Relating to Biological Effects and En-vironmental Fate22.2Federal Standards:3Title 21 CFR,Part 58,Good Laboratory Practice for Non-clinical Studies,Food and Drug AdministrationTitle 40 CFR,Part 798,Health Eff
7、ects Testing Guidelines,Subpart D,Chronic Exposure,Chronic Toxicity and On-cogenicity,Environmental Protection AgencyTitle 40 CFR,Subchapter E,Pesticide Program:Part 160,Good Laboratory Practice Standards,Environmental Pro-tection AgencyTitle 40 CFR,Part 792,Good Laboratory Practice Stan-dards,Toxic
8、 Substance Control Act3.Terminology3.1 DefinitionsSee Definitions E 609 and TerminologyE 943.3.2 Definitions of Terms Specific to This Standard:3.2.1 chronic toxicitythe adverse effects occurring as aresult of the daily exposure of mammalian species to a testsubstance by diet,water,capsule,or gavage
9、 for an extendedperiod of time.3.2.2 gavageadministration of the test substance byplacement into the stomach through an orogastric tube.3.2.3 neoplasticcapable of producing abnormal tissuegrowth.3.2.4 nulliparoushaving never borne an offspring.3.2.5 oncogenicitythe condition of producing tumors.4.Su
10、mmary of Test Method(Title 40 CFR,Part 798)4.1 Two mammalian species are required.Rats and mice arethe species of choice because of their relatively short life spans,the limited cost of their maintenance,their widespread use inpharmacological and toxicological studies,and the availabilityof inbred s
11、trains.4.2 One hundred twenty-four rats(62 females and 62 males)and 112 mice(56 females and 56 males)are used for each ofthe four dose levels(control-,low-,intermediate-,and high-dosage groups).4.3 The test substance is administered either in the diet orwater or by gavage at levels based on results
12、from prior feedingstudies.The administration of test substance is for two yearsfor rats;it is 18 months for mice.4.4 An interim sacrifice is made at the end of one year forboth rats and mice;after 18 months the interim sacrifice is forrats only.4.5 Daily observations of all individual animals for si
13、gns oftoxicity and mortality are recorded.4.6 Hematology blood samples are collected for analysisprior to interim sacrifices and termination of the test.4.7 Data collected from treatment and control groups arecompared statistically for changes and to note the formation oftumors.Histopathological exa
14、minations are performed on se-lected tissues.5.Significance and Use5.1 This test method should generate data to determine thepresence,incidence,and severity of abnormalities(including1This test method is under the jurisdiction of ASTM Committee E35 onPesticides and is the direct responsibility of Su
15、bcommittee E35.26 on Safety to Man.Current edition approved May 10,1996.Published July 1996.2Annual Book of ASTM Standards,Vol 11.05.3Available from U.S.Government Printing Office,Superintendent of Docu-ments,Washington,DC 20402.1Copyright ASTM,100 Barr Harbor Drive,West Conshohocken,PA 19428-2959,U
16、nited States.behavioral and clinical abnormalities)and whether significanttumor production has occurred.In addition,the test shouldallow for the detection of general toxic effects.5.2 This test method provides information on potentialhealth hazards likely to arise from repeated exposure over along period of time.6.Hazards6.1 Minimize contact with all test substances and solutionswith appropriate protective clothing,gloves,eye protection,and so forth.The use of fume hoods and increased ventilatio
