ASTM E1163-10

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:E1163–98 (Reapproved 2002) Designation:E1163–10
Standard Test Method for
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Estimating Acute Oral Toxicity in Rats
This standard is issued under the fixed designation E1163; 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 determines the lethality (LD50 value) value, slope and 95% confidence interval (CI)) and signs of acute
toxicity from a material using a limited number of rats. The technique used in this test method is referred to as the “Up-and-Down
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Procedure.”“Stagewise, Adaptive Dose Method.” This test method is an alternative to the classical LD50 test and is applicable
to both liquids and solids.
1.2 This test method is not recommended for test materials which typically produce deaths beyond 2 days postdosing.
1.3 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.
2. Referenced Documents
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2.1 ASTM Standards:
E 609 Terminology Relating to Pesticides
IEEE/ASTM SI 10 Standard for Use of the International System of Units (SI) (the Modernized Metric System)
3. Terminology
3.1 Definitions:
3.1.1 delayed death—an animal which does not die or appear moribund within 24 h but dies later during the observation period.
3.1.2 gavage—forced feeding,oral dosing, as by a tube that is passed down the throat to the stomach.
3.1.3 LD50—the statistically derived estimate of the dose of a test substance that would be expected to cause 50 % mortality
to the test population under the specified test conditions.
3.1.4 moribund—at the point of death or extinction.
3.1.5 suspension—a mixture in which very small particles remain suspended without dissolving. pharmacotoxic—gross
physiological signs in response to a toxic material.
3.1.6 toxicity—poisonous quality.
3.1.7signs of toxicity—objective, observable evidence of toxicity.
3.1.7 suspension—a mixture in which very small particles remain suspended without dissolving.
3.1.8 pharmacotoxic—gross physiological signs in response to a toxic material. toxicity—poisonous quality.
4. Summary of Test Method
4.1Female rats are dosed one at a time starting the first animal at the best estimate of the LD50. If this animal survives, then
the next animal receives a higher dose; but if the first animal dies, the next animal receives a lower dose. If possible, subsequent
doses are adjusted by a constant multiplicative factor, for example 1.3.The dose for each animal is adjusted up or down depending
upon the outcome for the previous animal.
4.2The dosing is repeated as above until four animals have been dosed after reversal of the initial outcome.
4.3The LD50 is calculated using the maximum likelihood method.
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ThistestmethodisunderthejurisdictionofASTMCommitteeE47onBiologicalEffectsandEnvironmentalFateandisthedirectresponsibilityofSubcommitteeE47.02
on Terrestrial Assessment and Toxicology.
Current edition approved Oct. 10, 2002. Published March 2003 . Originally approved in 1987. Last previous edition approved in 1998 as E1163–98. DOI:
10.1520/E1163-98R02.
Current edition approved Nov. 1, 2010. Published June 2011. Originally approved in 1987. Last previous edition approved in 2002 as E1163 – 98(2002). DOI:
10.1520/E1163-10.
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Bruce, R. D., “An Up-and-Down Procedure for Acute Toxicity Testing,” Fundamental and Applied Toxicology, Vol 5, 1985, pp. 151–157.
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Feder, P.I., Statistical Design Considerations for Stagewise, stagewise, adaptive dose allocation in dose responsive studies. In: Peace, Karl E., ed. Biopharmaceutical
sequential statistical applications. New York: Marcel Dekker 1992.
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For referencedASTM standards, visit theASTM website, www.astm.org, or contactASTM Customer Service at service@astm.org. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
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E1163–10
4.1 Three to five different doses of the target compound are selected such that the doses span the entire dose response curve,
with separat
...