OECD Guide lines for testing of chemicals acute oral toxicity-up-and-down procedure

OECD guidelines for the Testing of Chemicals are periodically reviewed in the light of scientific progress or changing assessment practices. The concept of the up-and-down testing approach was first described by Dixon and Mood (1)(2)(3)(4). In 1985, Bruce proposed to use an up-and-down procedure (UDP) for the determination of acute toxicity of chemicals (5). There exist several variations of the up and-down experimental design for estimating an LD50. This guideline is based on the procedure of Bruce as adopted by ASTM in 1987 (6) and revised in 1990. A study comparing the results obtained with the UDP, the conventional LD50 test and the Fixed Dose Procedure (FOP, Guideline 420) was published in 1995 (7). Since the early papers of Dixon and Mood, papers have continued to appear in the biometrical and applied literature, examining the best conditions for use of the approach (8)(9)(10)(11) . Based on the recommendations of several expert meetings in 1999, an additional revision was considered timely because: i) international agreement had been reached on harmonised LD50 cut- off values for the classification of chemical substances, ii) testing in one sex (usually females) is generally considered suffi cient, and iii) in order for a point estimate to be meaningful, there is a need to estimate confidence intervals (CI)