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A new sighting study for the fixed concentration procedure to allow for gender differences

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Stallard, Nigel, Price, Charlotte L, Creton, Stuart, Indans, Ian, Guest, Robert, Griffiths, David and Edwards, Philippa. (2011) A new sighting study for the fixed concentration procedure to allow for gender differences. Human & Experimental Toxicology, Vol.30 (No.3). pp. 239-249. ISSN 0960-3271

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Official URL: http://dx.doi.org/10.1177/0960327110370983

Abstract

The fixed concentration procedure (FCP) has been proposed as an alternative to the median lethal concentration (LC50) test (organisation for economic co-operation and development (OECD) test guideline [TG] 403) for the assessment of acute inhalation toxicity. The FCP tests animals of a single gender (usually females) at a number of fixed concentration levels in a sequential fashion. It begins with a sighting study that precedes the main FCP study and is used to determine the main study starting concentration. In this paper, we propose a modification to the sighting study and suggest that it should be conducted using both male and female animals, rather than just animals of a single gender. Statistical analysis demonstrates that, when females are more sensitive, the new procedure is likely to give the same classification as the original FCP, whereas, if males are more sensitive, the new procedure is much less likely to lead to incorrect classification into a less toxic category. If there is no difference in the LC50 for females and males, the new procedure is slightly more likely to classify into a more stringent class than the original FCP. Overall, these results show that the revised sighting study ensures gender differences in sensitivity do not significantly impact on the performance of the FCP, supporting its use as an alternative test method for assessing acute inhalation toxicity.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of 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
Date:	March 2011
Volume:	Vol.30
Number:	No.3
Page Range:	pp. 239-249
Identification Number:	10.1177/0960327110370983
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	National Centre for the Replacement, Refinement, and Reduction of Animals in Research (Great Britain) (NC3R)
References:	1. OECD.Guidelines for the testing of chemical substances. No. 403. Acute inhalation toxicity. Paris, 1981. 2. OECD. Guidelines for the testing of chemical substances. No. 436. Acute inhalation toxicity – acute toxic class method. Paris, 2009. 3. OECD. Guidelines for testing of chemical substances. Draft No. 433. Acute inhalation toxicity – fixed concentration procedure. Paris, 2004. 4. Stallard N, Whitehead A, Indans I. Statistical evaluation of the fixed concentration procedure for acute inhalation toxicity assessment. Hum Exp Toxicol 2003; 22: 575–585. 5. Price C, Stallard N, Creton S, et al. A statistical evaluation of the effects of gender differences in assessment of acute inhalation toxicity. HumExp Toxicol 2010. DOI 10.1177/0960327110370982. 6. OECD. Harmonized integrated hazard classification system for human health and environmental effects of chemical substances. Paris, 1998. 7. Greiner M. ‘Report on biostatistical performance assessment of draft TG 436 acute toxic class method for acute inhalation toxicity,’ 2008, http://www. oecd.org/ LongAbstract/0,3425,en_33873108_33844437_41762050_ 1_1_1_1,00.html (2008). Accessed 23 April 2010.
URI:	http://wrap.warwick.ac.uk/id/eprint/4501