A new approach to minimizing the number of animals used in acute toxicity testing and optimizing the information of test results

Abstract

170 acute toxicity determinations, carried out in rats, mice, and guinea pigs after oral and parenteral administration during the past 5 years, using 5 ♂/5 ♀ animals per dose, were evaluated with respect to the possibility of a reduction of animals necessary for obtaining LD₅₀ values with limits of confidence. Calculations were performed on existing data; no additional animal experiments were initiated for the purpose of this paper.

For the majority of substances 3 ♂/3 ♀ animals per dose would have sufficed for the determination of a LD₅₀ value with limits of confidence. Even when using 2 ♂/2 ♀ animals per dose, in most cases sufficently acceptable LD₅₀ values can be determined, if the period of observation — conventionally 4 weeks — would be doubled. Using this procedure, 75% of the animals could be saved. The reduced number of animals and the labor saved thereby would allow for a more individualized observation of single animals thus optimizing the evaluation of acute toxicity testing.