title: Statistical evaluation of an acute dermal toxicity test using the dermal fixed dose procedure.
abstract: The conventional method for the assessment of acute dermal toxicity (OECD Test Guideline 402, 1987) uses death of animals as an endpoint to identify the median lethal dose (LD50). A new OECD Testing Guideline called the dermal fixed dose procedure (dermal FDP) is being prepared to provide an alternative to Test Guideline 402. In contrast to Test Guideline 402, the dermal FDP does not provide a point estimate of the LD50, but aims to identify that dose of the substance under investigation that causes clear signs of nonlethal toxicity. This is then used to assign classification according to the new Globally Harmonised System of Classification and Labelling scheme (GHS). The dermal FDP has been validated using statistical modelling rather than by in vivo testing. The statistical modelling approach enables calculation of the probability of each GHS classification and the expected numbers of deaths and animals used in the test for imaginary substances with a range of LD50 values and dose-response curve slopes. This paper describes the dermal FDP and reports the results from the statistical evaluation. It is shown that the procedure will be completed with considerably less death and suffering than guideline 402, and will classify substances either in the same or a more stringent GHS class than that assigned on the basis of the LD50 value.
authors.affiliation: Medical and Pharmaceutical Statistics Research Unit, The University of Reading, Reading, UK. n.stallard@reading.ac.uk
authors.forename: Nigel
authors.initials: N
authors.lastname: Stallard
authors.forename: Anne
authors.initials: A
authors.lastname: Whitehead
authors.forename: Ian
authors.initials: I
authors.lastname: Indans
mesh_terms: D000279:Administration, Cutaneous; D000827:Animal Welfare; D000818:Animals; D000830:Animals, Laboratory; D023381:Endpoint Determination; D017408:Guidelines as Topic; D007928:Lethal Dose 50; D015233:Models, Statistical