REDUCING ANIMAL NUMBERS IN THE FIXED-DOSE PROCEDURE

The fixed-dose procedure (FDP) was proposed by the British Toxicology Society (1984)(1) as an alternative to assessment of acute oral toxici ty via estimation of the LD(50). The procedure is incorporated in OECD guidelines on acute oral toxicity testing.(2) Whitehead and Curnow (1 992)(3) used a mathematical model to describe the statistical properti es of the FDP. This paper uses a simplified model to investigate furth er the procedure. In particular the effects of altering the number of animals included at each stage in the procedure are evaluated. It is s hown that a reduction in the number of animals tested makes little dif ference to the toxic classification of a substance with a steep dose-r esponse curve, but has increasing effect as the dose-response curve be comes shallower. The simplified model. also shows that in the proposed procedure the most likely classification depends on the LD(7) of the substance tested. Changing the number of animals tested results in the most likely classification depending on other LD values.The effect of additional variation is also considered. Such variation might arise f rom within-laboratory differences, Although this increases the range o f substances for which misclassification is likely, the increase is no t much affected by the number of animals tested.