Comparison of five methods for the determination of lethal dose in acute toxicity studies

The aim of the present study was to compare the reliability of LD50 determination using the traditional Litchfield and Wilcoxon method with that obtained by four alternative tests requiring smaller numbers of animals, for the purpose of classifying chemicals according to their acute toxicity. Acute lethal dose determinations were carried out in mice for oral and intraperitoneal administration of hexachlorophene, lidocaine, methanol, phenobarbital and physostigmine. The Molinengo method proved not to be as reliable as suggested by its author. Determination of LD50 using the Thompson and Weil method or, alternatively, the maximal non-lethal dose and the approximate lethal dose permitted the classification of the chemicals in essentially the same order. The approximate lethal dose method, in particular, seems to be a very suitable alternative method to the classical LD50 test since it requires only about 6 animals, provides enough information to order chemicals according to their toxicities, and provides useful information for planning subsequent repeated-dose studies.