Statistical evaluation of the fixed concentration procedure for acute inhalation toxicity assessment

Hum Exp Toxicol. 2003 Nov;22(11):575-85. doi: 10.1191/0960327103ht395oa.

Abstract

The conventional method for the assessment of acute inhalation toxicity (OECD Test Guideline 403, 1981) uses death of animals as an endpoint to identify the median lethal concentration (LC50). A new OECD Testing Guideline called the Fixed Concentration Procedure (FCP) is being prepared to provide an alternative to Test Guideline 403. Unlike Test Guideline 403, the FCP does not provide a point estimate of the LC50 but aims to identify an airborne exposure level that causes clear signs of nonlethal toxicity. This is then used to assign classification according to the new Globally Harmonized System of Classification and Labelling scheme (GHS). The FCP has been validated using statistical simulation rather than by in vivo testing. The statistical simulation approach predicts the GHS classification outcome and the numbers of deaths and animals used in the test for imaginary substances with a range of LC50 values and dose-response curve slopes. This paper describes the FCP and reports the results from the statistical simulation study assessing its properties. It is shown that the procedure will be completed with considerably less death and suffering than Test Guideline 403, and will classify substances either in the same or a more stringent GHS class than that assigned on the basis of the LC50 value.

MeSH terms

  • Animal Welfare*
  • Animals
  • Animals, Laboratory
  • Endpoint Determination
  • Guidelines as Topic*
  • Inhalation Exposure*
  • Lethal Dose 50
  • Models, Statistical*
  • Reference Values