A statistical evaluation of the effects of gender differences in assessment of acute inhalation toxicity

Charlotte Price, Nigel Stallard, Stuart Creton, Ian Indans, Robert Guest, David Griffiths, Philippa Edwards

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
29 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)217-238
Number of pages22
JournalHuman and Experimental Toxicology
Issue number3
Early online date20 May 2010
Publication statusPublished - 1 Mar 2011
Externally publishedYes

Bibliographical note

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (http://www.uk.sagepub.com/aboutus/openaccess.htm).


  • acute inhalation toxicity
  • fixed concentration procedure
  • gender differences
  • OECD test guidelines

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis


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