ASTM E1674-99(2003)

Standard Test Method for Cardiac Sensitization Study on Dogs (Withdrawn 2010)

SIGNIFICANCE AND USE
This test method is designed to provide information as to any dose level of test material that gives rise to clear signs of compound-induced cardiac sensitization.
Cardiac sensitization has occurred in humans during periods of stress while being exposed to high concentrations of some unsubstituted and halogenated hydrocarbons.3  
The dog is employed for this study because the conclusions from this test method can be applied to man with much more certainty than those from other animals.4
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.
WITHDRAWN RATIONALE
This test method covers an inhalation procedure to investigate the cardiac sensitization of volatile chlorinated hydrocarbons and other volatile solvents.
Formerly under the jurisdiction of Committee E35 on Pesticides and Alternative Control Agents, this test method was withdrawn in October 2010 due to inactivity and a lack of interest.

General Information

• Status: Withdrawn
• Publication Date: 30-Sep-2003
• Withdrawal Date: 30-Sep-2010
• Technical Committee: E35 - Pesticides, Antimicrobials, and Alternative Control Agents

Relations

• Replaces: ASTM E1674-99 - Standard Test Method for Cardiac Sensitization Study on Dogs
• Effective Date: 01-Oct-2003

Standards Content (Sample)

NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
Contact ASTM International (www.astm.org) for the latest information
Designation:E1674–99 (Reapproved 2003)
Standard Test Method for
Cardiac Sensitization Study on Dogs
This standard is issued under the fixed designation E1674; 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 (´) indicates an editorial change since the last revision or reapproval.
1. Scope 4. Summary of Test Method
1.1 This test method covers an inhalation procedure to 4.1 Six healthy male dogs are employed for each test
investigate the cardiac sensitization of volatile chlorinated material. After the initial acclimation period, the dogs are
hydrocarbons and other volatile solvents. trained to maintain a standing position while supported in a
1.2 This test method is primarily a screening tool. The cloth sling and wearing an inhalation mask over their nose and
procedure does permit a rank order of the sensitization poten- mouth.
tial of the compounds tested, but is not recommended for 4.2 Since dogs can vary markedly in their cardiac response
establishing significant effect levels. to intravenous injection of adrenaline (epinephrine), each dog
1.3 Thistestmethodassumesthattheuserisknowledgeable is evaluated to select an appropriate dose. The selected dose is
in mammalian toxicology, electrocardiography with animals used in all subsequent work.
and other pertinent areas, and relies heavily on the judgment of 4.3 All six dogs are tested on the same day, one at a time.
the investigator. Each animal is placed in the sling, fitted with the inhalation
1.4 This standard does not purport to address all of the mask and standard electrocardiogram (ECG) leads connected
safety concerns, if any, associated with its use. It is the to an electrocardiograph.
responsibility of the user of this standard to establish appro- 4.4 The test proceeds as follows:
priate safety and health practices and determine the applica- 4.4.1 At zero time start the ECG recording.
bility of regulatory limitations prior to use. 4.4.2 At 2 min, administer the selected dose of adrenaline
into the cephalic vein.
2. Referenced Documents
4.4.3 At 7 min, start the inhalation of vapor of the test
2.1 ASTM Standards: material. Monitor the concentration of test material adminis-
E609 Terminology Relating to Pesticides
tered.
E943 Terminology Relating to Biological Effects and Envi-
4.4.4 At 12 min, administer a challenge injection of adrena-
ronmental Fate line.
4.4.5 At 17 min, stop the vapor inhalation and the ECG
3. Terminology
recording.
3.1 Definitions—for terms used in this test method, see
4.4.6 Returnthedogstotheirkennels.Theyshouldbetested
Terminology E609 and E943.
on a Monday, Wednesday, and Friday regimen.
3.2 Definitions of Terms Specific to This Standard:
4.5 The dogs are exposed to a 2.5 % concentration of the
3.2.1 cardiac sensitization, n—the reaction of the heart to
test material the first time; then exposed to 5 % on the next test
adrenaline (epinephrine) resulting in the production of ven-
day. If necessary, the dogs are exposed successively to 10 %,
tricular arrhythmias.
15 %, and 20 % as needed. As soon as ventricular tachycardia
is evidenced, the testing is stopped. If no appearance of
ventricular arrhythmia occurs in the ECG recording at the
This test method is under the jurisdiction of ASTM Committee E35 on
highest concentration and there are no other deleterious events,
Pesticides and Alternative Control Agents and is the direct responsibility of
Subcommittee E35.26 on Safety to Man. then no cardiac sensitization has occurred.
Current edition approved October 1, 2003. Published October 2003. Originally
approved in 1995. Last previous edition approved in 1999 as E1674 - 99. DOI:
10.1520/E1674-99R03.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM Reinhardt, C. F., Azar, A., Maxfield, M. E., Smith, P. E. Jr., and Mullin, L. S.,
Standards volume information, refer to the standard’s Document Summary page on “Cardiac Arrhythmias and Aerosol Sniffing,” Archives of Environmental Health,
the ASTM website. Vol. 22, No. 2, February 1971, pp. 265–279.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.
E1674–99 (2003)
5. Significance and Use 8.2.1 Place the animal in the sling and fit it with standard
ECG leads connected to an electrocardiograph. Hold the
5.1 This test method is designed to provide information as
electrodes in place on the dog by a rubber strap extending
to any dose level of test material that gives rise to clear signs
around the body and position over shaved areas as follows:
of compound-induced cardiac sensitization.
8.2.1.1 Two active electrodes, one on each side of the chest
5.2 Cardiac sensitization has occurred in humans during
just behind the foreleg.
periods of stress while being exposed to high concentrations of
8.2.1.2 One indifferent electrode, over the sternum.
some unsubstituted and halogenated hydrocarbons.
8.2.1.3 Run the ECG at a speed (at least 10 mm/s) sufficient
5.3 The dog is employed for this study because the conclu-
to allow identification of ectopic beats following adrenaline
sions from this test method can be applied to man with much
challenge.
more certainty than those from other animals.
8.2.2 Administertheinitialdoseofadrenalineintravenously
6. Facility into the cephalic vein on the foreleg. Make the injection by an
automatic infusion pump set to deliver the total dosage of
6.1 No precise physical requirements concerning facilities
0.008 mg adrenaline/kg of body weight in a volume of 0.1 ml
are set forth. However, the animal facility shall meet the
of normal saline per kg body weight; deliver at the rate of 0.1
established standard(s) that may be required by law or regula-
mL/sec.
tions. It is desirable that the animal facilities meet the guide-
8.2.2.1 Iftheresponsetothefirstadrenalinechallengeistoo
lines suggested by the Institute of Laboratory Resources or
small (as defined by no ectopic beats) or too large (as defined
facilities that have been approved by such organizations as the
by an excessive number of ectopic beats; more than approxi-
American Association for Accreditation of Laboratory Animal
mately 10), end the experimental session and allow the 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 m
...