ASTM E1619-11

Standard Test Method for Chronic Oral Toxicity Study in Rats

SIGNIFICANCE AND USE
This test method should generate data to identify the majority of chronic effects and shall serve to define long-term dose response relationships. In addition the test should allow for the detection of general toxic effects including neurological, physiological, biochemical, and hematological effects and exposure-related morphological (pathology) effects.
This test method should provide information on target organs, the possibilities of accumulation, and may be used for establishing safety criteria for human exposure. It provides information on potential health hazards likely to arise from repeated exposure over a long period of time.
SCOPE
1.1 This test method covers a long-term study to determine the effects of a substance in a mammalian species such as the rat following prolonged and repeated oral exposure. Under the conditions of the chronic toxicity test, effects that require a long latency period or that are cumulative should become manifest.
1.2 This test method assumes that the user is knowledgeable in mammalian toxicology and related pertinent areas, and relies heavily on the judgment of the evaluator.
1.3 The values stated in SI units are to be regarded as the standard. The inch-pound units given in parentheses are for information only.
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. For specific hazard statements, see Section 6.

General Information

• Status: Historical
• Publication Date: 30-Sep-2011
• Technical Committee: E50 - Environmental Assessment, Risk Management and Corrective Action
• Drafting Committee: E50.47 - Biological Effects and Environmental Fate

Relations

• Replaced By: ASTM E1619-11(2016) - Standard Test Method for Chronic Oral Toxicity Study in Rats
• Effective Date: 01-Feb-2016

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NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.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: E1619 − 11
StandardTest Method for
1
Chronic Oral Toxicity Study in Rats
This standard is issued under the fixed designation E1619; 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 Administration, Part 58, Good Laboratory Practice for
Nonclinical Studies
1.1 This test method covers a long-term study to determine
Title 40, CFR, Toxic Substance ControlAct, Part 792, Good
the effects of a substance in a mammalian species such as the
Laboratory Practice Standards
rat following prolonged and repeated oral exposure. Under the
Title 40, CFR, Environmental Protection Agency, Part 798,
conditions of the chronic toxicity test, effects that require a
Health Effects Testing Guidelines, Subpart D, Chronic
long latency period or that are cumulative should become
Exposure, Chronic Toxicity
manifest.
1.2 This test method assumes that the user is knowledgeable
3. Terminology
inmammaliantoxicologyandrelatedpertinentareas,andrelies
3.1 Definitions—See Terminology E609 and Terminology
heavily on the judgment of the evaluator.
E943.
1.3 The values stated in SI units are to be regarded as the
3.2 Definitions of Terms Specific to This Standard:
standard. The inch-pound units given in parentheses are for
3.2.1 chronic toxicity, n—the adverse effects occurring as a
information only.
result of the daily exposure of mammalian species to a test
1.4 This standard does not purport to address all of the
substance by diet, water, capsule, or gavage for a one-year
safety concerns, if any, associated with its use. It is the
period.
responsibility of the user of this standard to establish appro-
3.2.2 concentration, n—the weight of test substance per unit
priate safety and health practices and determine the applica-
weight of the diet (expressed as milligrams per kilogram of
bility of regulatory limitations prior to use. For specific hazard
diet). The weight of test substance per volume of H O
2
statements, see Section 6.
(expressed as milligrams per millilitre of water), or at a
constant rate in the diet (expressed as parts per million).
2. Referenced Documents
2 3.2.3 feed effıciency, n—this value is a measure of the
2.1 ASTM Standards:
efficiency with which the animals convert food to body weight.
E609 Terminology Relating to Pesticides
The calculation is the total body weight gain per total food
E943 Terminology Relating to Biological Effects and Envi-
consumed.
ronmental Fate
3 3.2.4 gavage, n—forced feeding, as by tube that is passed
2.2 Federal Standards:
down the throat to the stomach.
Title 40, Code of Federal Regulations (CFR), Environmental
3.2.5 test substance, n—pesticide or other material
Protection Agency, Subchapter E, Pesticide Programs:
Part 160, Good Laboratory Practice Standards (element, chemical compound, formulation, known mixture)
administered orally for the purpose of determining chronic
Title21, CodeofFederalRegulations(CFR).FoodandDrug
toxicity.
4
1
4. Summary of Test Method
This test method is under the jurisdiction of ASTM Committee E50 on
Environmental Assessment, Risk Management and Corrective Action and is the
4.1 One mammalian species, a rodent, is required; the rat is
direct responsibility of Subcommittee E50.47 on Biological Effects and Environ-
the preferred rodent. Forty rats (twenty females and twenty
mental Fate.
Current edition approved Oct. 1, 2011. Published November 2011. Originally
males) are used at each of the five dose levels (control-, low-,
approved in 1994. Last previous edition approved in 2003 as E1619 – 95 (2003).
two intermediate levels-, and high-dosage groups). If it is
DOI: 10.1520/E1619-11.
determined that an interim sacrifice is necessary, the number
2
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM
Standards volume information, refer to the standard’s Document Summary page on
the ASTM website.
3 4
Available from Superintendent of Documents, U.S. Government Printing Benitz, K. F., “Measurement of Chronic Toxicity,” Methods of Toxicology, ed.
Office, Washington DC 20402. G. E. Paget, Blackwell Scientific Publications, Oxford, England, 1970, pp. 32-131.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
1

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E1619 − 11
should be increased by the number of animals scheduled to be lines suggested by the Institute of Laboratory Resources or
sacrificed during the course of the study (see CFR, Title 40, facilities that have been approved by such organiza
...

This document is not anASTM standard and is intended only to provide the user of anASTM standard an indication of what changes have been made to the previous version. Because
it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version
of the standard as published by ASTM is to be considered the official document.
Designation:E1619–95(Reapproved 2003) Designation: E1619 – 11
Standard Test Method for
1
Chronic Oral Toxicity Study in Rats
This standard is issued under the fixed designation E1619; 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
1.1 This test method covers a long-term study to determine the effects of a substance in a mammalian species such as the rat
followingprolongedandrepeatedoralexposure.Undertheconditionsofthechronictoxicitytest,effectsthatrequirealonglatency
period or that are cumulative should become manifest.
1.2 This test method assumes that the user is knowledgeable in mammalian toxicology and related pertinent areas, and relies
heavily on the judgment of the evaluator.
1.3 The values stated in SI units are to be regarded as the standard. The inch-pound units given in parentheses are for
information only.
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. For specific hazard statements, see Section 6.
2. Referenced Documents
2
2.1 ASTM Standards:
E609 Terminology Relating to Pesticides
E943 Terminology Relating to Biological Effects and Environmental Fate
3
2.2 Federal Standards:
Title 40, Code of Federal Regulations (CFR), Environmental Protection Agency, Subchapter E, Pesticide Programs: Part 160,
Good Laboratory Practice Standards
Title21, CodeofFederalRegulations(CFR).FoodandDrugAdministration,Part58,GoodLaboratoryPracticeforNonclinical
Studies
Title 40, CFR, Toxic Substance Control Act, Part 792, Good Laboratory Practice Standards
Title 40, CFR, Environmental Protection Agency, Part 798, Health Effects Testing Guidelines, Subpart D, Chronic Exposure,
Chronic Toxicity
3. Terminology
3.1 Definitions—See Terminology E609 and Terminology E943.
3.2 Definitions of Terms Specific to This Standard:
3.2.1 chronic toxicity, n—theadverseeffectsoccurringasaresultofthedailyexposureofmammalianspeciestoatestsubstance
by diet, water, capsule, or gavage for a one-year period.
3.2.2 concentration, n—the weight of test substance per unit weight of the diet (expressed as milligrams per kilogram of diet).
The weight of test substance per volume of H O (expressed as milligrams per millilitre of water), or at a constant rate in the diet
2
(expressed as parts per million).
3.2.3 feed effıciency, n—this value is a measure of the efficiency with which the animals convert food to body weight. The
calculation is the total body weight gain per total food consumed.
3.2.4 gavage, n—forced feeding, as by tube that is passed down the throat to the stomach.
3.2.5 test substance, n—pesticide or other material (element, chemical compound, formulation, known mixture) administered
orally for the purpose of determining chronic toxicity.
1
ThistestmethodisunderthejurisdictionofASTMCommitteeE47onBiologicalEffectsandEnvironmentalFateandisthedirectresponsibilityofSubcommitteeE47.02
on Terrestrial Assessment and Toxicology.
Current edition approved Oct. 1, 2003.2011. Published October 2003.November 2011. Originally approved in 1994. Last previous edition approved in 19992003 as
E1619 – 95 (1999).(2003). DOI: 10.1520/E1619-95R03.10.1520/E1619-11.
2
For referencedASTM standards, visit theASTM website, www.astm.org, or contactASTM Customer Service at [e-mail]. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
3
Available from Superintendent of Documents, U.S. Government Printing Office, Washington DC 20402.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.
1

---------------------- Page: 1 ----------------------
E1619 – 11
4
4. Summary of Test Method
4.1 One mammalian species, a rodent, is required; the rat is the preferred rodent. Forty rats (twenty females and twenty males)
are used at each of the fourfive dose levels (control-, low-, medium-two intermediate levels-, and high-dosage groups). If it is
determined that an interim sacrifice is necessary, the number should be increased by the number of animals scheduled to be
sacrificed during the course of the study (see CFR, T
...