Introduction. Median lethal dose (MLD) has been a controversial subject among biologists and animal ethicists since its inception in 1927 by Trevan. Toxicologists use MLD (LD 50 ) as the first step to assess the toxicity of a substance. Animal ethicists criticize LD 50 tests because animals suffer pain, and LD 50 is irreproducible. The disadvantage of classifying chemicals based on LD 50 , the importance of the 'characteristics' proposed by Trevan, and the ideal mortality range for determining the best estimate of LD 50 are also discussed. Objective. The aim of this review was to understand Trevan's concept of LD 50 and the method of Litchfield and Wilcoxon (L and W), and Finney's probit analysis for LD 50 determination. Materials and method. A literature survey was conducted using Google search and Pubmed. Simulated data set was used for identifying the ideal mortality range for calculating the 'best estimate' of LD 50 . Brief description of the state of knowledge. After Trevan, the extensively used classical methods for LD 50 determination are Finney's probit analysis and the L and W method. Animal ethicists questioned LD 50 , because of its irreproducibility. Presently used methods for LD 50 tests do not provide information on the dose-response, hence assessing the complete spectrum of toxicity is not possible. However, LD 50 is used to classify chemicals. Conclusions. 'The 'characteristic' is more specific than the slope or LD 50 of a dose-response curve. LD 50 does not manifest the exact nature of the toxicity of a substance; hence, classifying chemicals based on LD 50 s may have little relevance.

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Statistical significance is one of important criteria on judgment of regulatory toxicological testing. The decision tree for analysing quantitative data obtained from repeated dose administration studies in rodents has been in use in Japan around 1981. Since then, several authors proposed improved versions of the decision tree incorporating all possible situations of statistical analysis normally encountered in such studies. Recently, a decision tree, which traces a simple route, unlike the previously proposed ones which trace complex routes has been proposed by a few researchers in Japan. While tracing to the most appropriate statistical tool using a decision tree, we propose to consider following points which also play a significant role in selecting the most appropriate statistical tool: (1) statistical tools that fails to detect a significant difference in the low dose group, (2) use of the one-sided test with high power to detect a significant difference compared with two-sided, (3) as far as possible avoid carrying out statistical analysis on the transformed data, since the analytical result of such data is difficult to interpret, (4) it is important to mention what statistical tools of the decision tree are used for the analysis, (5) examine the data for both normality and homogeneity and (6) for testing homogeneity, use Levene's test. Selection of widely accepted statistical tools is usually preferred to less popular and complex statistical analysis. It has been observed that in recent years the preferred statistical tools for analyzing quantitative data obtained from toxicity studied are of simple in nature but with high power to detect a significant difference.

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