title: A new sighting study for the fixed concentration procedure to allow for gender differences.
abstract: The fixed concentration procedure (FCP) has been proposed as an alternative to the median lethal concentration (LC(50)) 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 LC(50) 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.
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK. n.stallard@warwick.ac.uk
authors.forename: Nigel
authors.initials: N
authors.lastname: Stallard
authors.forename: Charlotte
authors.initials: C
authors.lastname: Price
authors.forename: Stuart
authors.initials: S
authors.lastname: Creton
authors.forename: Ian
authors.initials: I
authors.lastname: Indans
authors.forename: Robert
authors.initials: R
authors.lastname: Guest
authors.forename: David
authors.initials: D
authors.lastname: Griffiths
authors.forename: Philippa
authors.initials: P
authors.lastname: Edwards
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004391:Dust; D005260:Female; D008297:Male; D012727:Sex Characteristics; D023382:Toxicity Tests, Acute / Q000379:methods*
chemical_list: D000336:Aerosols; D004391:Dust