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A statistical evaluation of the effects of gender differences in assessment of acute inhalation toxicity
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Price, Charlotte L, Stallard, Nigel, Creton, Stuart, Indans, Ian, Guest, Robert, Griffiths, David and Edwards, Philippa (2011) A statistical evaluation of the effects of gender differences in assessment of acute inhalation toxicity. Human & Experimental Toxicology, Vol.30 (No.3). pp. 217-238. doi:10.1177/0960327110370982 ISSN 0960-3271.
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Official URL: http://dx.doi.org/10.1177/0960327110370982
Abstract
Acute inhalation toxicity of chemicals has conventionally been assessed by the median lethal concentration
(LC50) test (organisation for economic co-operation and development (OECD) TG 403). Two new methods,
the recently adopted acute toxic class method (ATC; OECD TG 436) and a proposed fixed concentration procedure
(FCP), have recently been considered, but statistical evaluations of these methods did not investigate
the influence of differential sensitivity between male and female rats on the outcomes. This paper presents an
analysis of data from the assessment of acute inhalation toxicity for 56 substances. Statistically significant differences
between the LC50 for males and females were found for 16 substances, with greater than 10-fold differences
in the LC50 for two substances. The paper also reports a statistical evaluation of the three test
methods in the presence of unanticipated gender differences. With TG 403, a gender difference leads to a
slightly greater chance of under-classification. This is also the case for the ATC method, but more pronounced
than for TG 403, with misclassification of nearly all substances from Globally Harmonised System (GHS) class 3
into class 4. As the FCP uses females only, if females are more sensitive, the classification is unchanged. If males
are more sensitive, the procedure may lead to under-classification. Additional research on modification of the
FCP is thus proposed.
Item Type: | Journal Article | ||||
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Subjects: | R Medicine > RC Internal medicine | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
Library of Congress Subject Headings (LCSH): | Pulmonary toxicology -- Sex differences, Toxicity testing | ||||
Journal or Publication Title: | Human & Experimental Toxicology | ||||
Publisher: | Sage Publications Ltd. | ||||
ISSN: | 0960-3271 | ||||
Official Date: | March 2011 | ||||
Dates: |
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Volume: | Vol.30 | ||||
Number: | No.3 | ||||
Page Range: | pp. 217-238 | ||||
DOI: | 10.1177/0960327110370982 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Funder: | National Centre for the Replacement, Refinement, and Reduction of Animals in Research (Great Britain) (NC3R) | ||||
Grant number: | NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research) |
Data sourced from Thomson Reuters' Web of Knowledge
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