1、Designation:E 1674 99(Reapproved 2003)Standard Test Method forCardiac Sensitization Study on Dogs1This standard is issued under the fixed designation E 1674;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 an inhalation procedure toinvestigate the cardiac sensitization of volatile chlorinatedhydrocarbons and other vola
3、tile solvents.1.2 This test method is primarily a screening tool.Theprocedure does permit a rank order of the sensitization poten-tial of the compounds tested,but is not recommended forestablishing significant effect levels.1.3 This test method assumes that the user is knowledgeablein mammalian toxi
4、cology,electrocardiography with animalsand other pertinent areas,and relies heavily on the judgment ofthe investigator.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
5、 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 943 Terminology Relating to Biological Effects and En-vironmental Fate23.Terminology3.1 Definitionsfor ter
6、ms used in this test method,seeDefinitions E 609 and Terminology E 943.3.2 Definitions of Terms Specific to This Standard:3.2.1 cardiac sensitizationthe reaction of the heart toadrenaline(epinephrine)resulting in the production of ven-tricular arrhythmias.4.Summary of Test Method34.1 Six healthy mal
7、e dogs are employed for each testmaterial.After the initial acclimation period,the dogs aretrained to maintain a standing position while supported in acloth sling and wearing an inhalation mask over their nose andmouth.4.2 Since dogs can vary markedly in their cardiac responseto intravenous injectio
8、n of adrenaline(epinephrine),each dogis evaluated to select an appropriate dose.The selected dose isused in all subsequent work.4.3 All six dogs are tested on the same day,one at a time.Each animal is placed in the sling,fitted with the inhalationmask and standard electrocardiogram(ECG)leads connect
9、edto an electrocardiograph.4.4 The test proceeds as follows:4.4.1 At zero time start the ECG recording.4.4.2 At 2 min,administer the selected dose of adrenalineinto the cephalic vein.4.4.3 At 7 min,start the inhalation of vapor of the testmaterial.Monitor the concentration of test material adminis-t
10、ered.4.4.4 At 12 min,administer a challenge injection of adrena-line.4.4.5 At 17 min,stop the vapor inhalation and the ECGrecording.4.4.6 Return the dogs to their kennels.They should be testedon a Monday,Wednesday,and Friday regimen.4.5 The dogs are exposed to a 2.5%concentration of thetest material
11、 the first time;then exposed to 5%on the next testday.If necessary,the dogs are exposed successively to 10%,15%,and 20%as needed.As soon as ventricular tachycardiais evidenced,the testing is stopped.If no appearance ofventricular arrhythmia occurs in the ECG recording at thehighest concentration and
12、 there are no other deleterious events,then no cardiac sensitization has occurred.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.1,2003.
13、Published October 2003.Originallyapproved in 1995.Last previous edition approved in 1999 as E 1674-99.2Annual Book of ASTM Standards,Vol 11.05.3Reinhardt,C.F.,Azar,A.,Maxfield,M.E.,Smith,P.E.Jr.,and Mullin,L.S.,“Cardiac Arrhythmias and Aerosol Sniffing,”Archives of Environmental Health,Vol.22,No.2,F
14、ebruary 1971,pp.265279.1Copyright ASTM International,100 Barr Harbor Drive,PO Box C700,West Conshohocken,PA 19428-2959,United States.5.Significance and Use5.1 This test method is designed to provide information asto any dose level of test material that gives rise to clear signsof compound-induced ca
15、rdiac sensitization.5.2 Cardiac sensitization has occurred in humans duringperiods of stress while being exposed to high concentrations ofsome unsubstituted and halogenated hydrocarbons.35.3 The dog is employed for this study because the conclu-sions from this test method can be applied to man with
16、muchmore certainty than those from other animals.46.Facility6.1 No precise physical requirements concerning facilitiesare set forth.However,the animal facility shall meet theestablished standard(s)that may be required by law or regula-tions.It is desirable that the animal facilities meet the guide-lines suggested by the Institute of Laboratory Resources orfacilities that have been approved by such organizations as theAmerican Association for Accreditation of Laboratory AnimalCare(AAALAC).6.2 Env
