ASTM E1674-99
(Test Method)Standard Test Method for Cardiac Sensitization Study on Dogs
Standard Test Method for Cardiac Sensitization Study on Dogs
SCOPE
1.1 This test method covers an inhalation procedure to investigate the cardiac sensitization of volatile chlorinated hydrocarbons and other volatile solvents.
1.2 This test method is primarily a screening tool. The procedure does permit a rank order of the sensitization potential of the compounds tested, but is not recommended for establishing significant effect levels.
1.3 This test method assumes that the user is knowledgeable in mammalian toxicology, electrocardiography with animals and other pertinent areas, and relies heavily on the judgment of the investigator.
1.4 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.
General Information
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Standards Content (Sample)
NOTICE: This standard has either been superceded and replaced by a new version or discontinued.
Contact ASTM International (www.astm.org) for the latest information.
Designation: E 1674 – 99
Standard Test Method for
Cardiac Sensitization Study on Dogs
This standard is issued under the fixed designation E 1674; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (e) indicates an editorial change since the last revision or reapproval.
1. Scope cloth sling and wearing an inhalation mask over their nose and
mouth.
1.1 This test method covers an inhalation procedure to
4.2 Since dogs can vary markedly in their cardiac response
investigate the cardiac sensitization of volatile chlorinated
to intravenous injection of adrenaline (epinephrine), each dog
hydrocarbons and other volatile solvents.
is evaluated to select an appropriate dose. The selected dose is
1.2 This test method is primarily a screening tool. The
used in all subsequent work.
procedure does permit a rank order of the sensitization poten-
4.3 All six dogs are tested on the same day, one at a time.
tial of the compounds tested, but is not recommended for
Each animal is placed in the sling, fitted with the inhalation
establishing significant effect levels.
mask and standard electrocardiogram (ECG) leads connected
1.3 This test method assumes that the user is knowledgeable
to an electrocardiograph.
in mammalian toxicology, electrocardiography with animals
4.4 The test proceeds as follows:
and other pertinent areas, and relies heavily on the judgment of
4.4.1 At zero time start the ECG recording.
the investigator.
4.4.2 At 2 min, administer the selected dose of adrenaline
1.4 This standard does not purport to address all of the
into the cephalic vein.
safety concerns, if any, associated with its use. It is the
4.4.3 At 7 min, start the inhalation of vapor of the test
responsibility of the user of this standard to establish appro-
material. Monitor the concentration of test material adminis-
priate safety and health practices and determine the applica-
tered.
bility of regulatory limitations prior to use.
4.4.4 At 12 min, administer a challenge injection of adrena-
2. Referenced Documents
line.
4.4.5 At 17 min, stop the vapor inhalation and the ECG
2.1 ASTM Standards:
recording.
E 609 Definitions of Terms Relating to Pesticides
4.4.6 Return the dogs to their kennels. They should be tested
E 943 Terminology Relating to Biological Effects and En-
on a Monday, Wednesday, and Friday regimen.
vironmental Fate
4.5 The dogs are exposed to a 2.5 % concentration of the
3. Terminology
test material the first time; then exposed to 5 % on the next test
day. If necessary, the dogs are exposed successively to 10 %,
3.1 Definitions—for terms used in this test method, see
15 %, and 20 % as needed. As soon as ventricular tachycardia
Definitions E 609 and Terminology E 943.
is evidenced, the testing is stopped. If no appearance of
3.2 Definitions of Terms Specific to This Standard:
ventricular arrhythmia occurs in the ECG recording at the
3.2.1 cardiac sensitization—the reaction of the heart to
highest concentration and there are no other deleterious events,
adrenaline (epinephrine) resulting in the production of ven-
then no cardiac sensitization has occurred.
tricular arrhythmias.
5. Significance and Use
4. Summary of Test Method
5.1 This test method is designed to provide information as
4.1 Six healthy male dogs are employed for each test
to any dose level of test material that gives rise to clear signs
material. After the initial acclimation period, the dogs are
of compound-induced cardiac sensitization.
trained to maintain a standing position while supported in a
5.2 Cardiac sensitization has occurred in humans during
periods of stress while being exposed to high concentrations of
some unsubstituted and halogenated hydrocarbons.
This test method is under the jurisdiction of ASTM Committee E-35 on
5.3 The dog is employed for this study because the conclu-
Pesticides and is the direct responsibility of Subcommittee E35.26 on Safety to Man.
Current edition approved October 10, 1999. Published November 1999. Origi- sions from this test method can be applied to man with much
nally published as E 1674 - 95. Last previous edition E 1674 - 95.
Annual Book of ASTM Standards, Vol 11.05.
Reinhardt, 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, February 1971, pp. 265–279.
Copyright © ASTM, 100 Barr Harbor Drive, West Conshohocken, PA 19428-2959, United States.
NOTICE: This standard has either been superceded and replaced by a new version or discontinued.
Contact ASTM International (www.astm.org) for the latest information.
E 1674
more certainty than those from other animals. 8.2.2 Administer the initial dose of adrenaline intravenously
into the cephalic vein on the foreleg. Make the injection by an
6. Facility
automatic infusion pump set to deliver the total dosage of
0.008 mg adrenaline/kg of body weight in a volume of 0.1 ml
6.1 No precise physical requirements concerning facilities
of normal saline per kg body weight; deliver at the rate of 0.1
are set forth. However, the animal facility shall meet the
mL/sec.
established standard(s) that may be required by law or regula-
tions. It is desirable that the animal facilities meet the guide- 8.2.2.1 If the response to the first adrenaline challenge is too
small (as defined by no ectopic beats) or too large (as defined
lines suggested by the Institute of Laboratory Resources or
facilities that have been approved by such organizations as the by an excessive number of ectopic beats; more than approxi-
mately 10), end the experimental session and allow the animal
American Association for Accreditation of Laboratory Animal
Care (AAALAC). to rest at least 20 min.
6.2 Environment—House animals in kennels to hold labo-
8.2.2.2 Repeat the procedure with an adrenaline dose either
ratory animals. Maintain all animals in a temperature-, of 0.004 mg adrenaline/kg body weight or 0.012 mg
humidity-, and light-controlled room. The conditions should be
adrenaline/kg body weight, based upon the prior response.
18° to 26°C (64.4° to 78.8°F) for temperature, 40 % to 70 %
8.2.3 When a suitable dose of adrenaline that produces one
for humidity and a 12-h light, 12-h dark lighting cycle.
to five ectopic beats per min has been selected for each dog,
that dose will be used for all subsequent work.
7. Test Animal
8.3 Test all six dogs individually on the same day; test on a
7.1 Use six healthy, male beagle dogs, 13 to 26 months old, Monday, Wednesday, and Friday regimen. Place the dog in the
weighing 7 to 14 kg (15.4 to 30.9 lb) for each test material to sling and attach the inhalation mask through which either vapor
be evaluated. Keep the dogs in a laboratory kennel for 14 days of the test material or fresh air can be passed. Attach the
to acclimate them. standard ECG leads to the dog and to the electrocardiograph.
7.2 Feed the dogs daily with a standard dog chow and Run the
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