Acute inhalation toxicity of chemicals has conventionally been assessed by the median lethal concentration\ud (LC50) test (organisation for economic co-operation and development (OECD) TG 403). Two new methods,\ud the recently adopted acute toxic class method (ATC; OECD TG 436) and a proposed fixed concentration procedure\ud (FCP), have recently been considered, but statistical evaluations of these methods did not investigate\ud the influence of differential sensitivity between male and female rats on the outcomes. This paper presents an\ud analysis of data from the assessment of acute inhalation toxicity for 56 substances. Statistically significant differences\ud between the LC50 for males and females were found for 16 substances, with greater than 10-fold differences\ud in the LC50 for two substances. The paper also reports a statistical evaluation of the three test\ud methods in the presence of unanticipated gender differences. With TG 403, a gender difference leads to a\ud slightly greater chance of under-classification. This is also the case for the ATC method, but more pronounced\ud than for TG 403, with misclassification of nearly all substances from Globally Harmonised System (GHS) class 3\ud into class 4. As the FCP uses females only, if females are more sensitive, the classification is unchanged. If males\ud are more sensitive, the procedure may lead to under-classification. Additional research on modification of the\ud FCP is thus proposed
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