John William Trevan’s concept of Median Lethal Dose (LD50/LC50) – more misused than used

Abstract

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.