Toxicology: Open Access
Open Access

Abstract

During the past few years, there has been a paradigm shift in the field of toxicological risk assessment for chemicals, including an emerging consensus on the need for a flexible, innovative and interdisciplinary science-based approach for investigative toxicology. As a matter of necessity, the potential for a chemical agent to produce adverse health effects in humans is investigated in experimental animals, typically rodents and non-rodents. Toxicological effects observed in the experimental animals may be taken as evidence that humans might show similar responses to equivalent chemical exposures. The use of these surrogates is premised upon the high degree of unique physiological, biochemical and anatomical similarities or variations among mammalian species. This uniqueness is reflected by inter-species differences in protein binding, drug metabolism and drug transport in pharmacokinetic phase and changes in receptor expression, affinity and distribution in pharmacodynamic phase to result in interspecies variation in toxicity profile. Allometric scaling is an empirical approach which considers these species differences including body surface area in normalization of different parameters. Interspecies scaling is not without short comings and failures. Over the years, interspecies scaling has drawn enormous attention and new scaling methods have been developed in order to improve the performance of these predictions. During dose-response extrapolation and setting acceptable levels of human exposure, a quantitative relationship between the dose levels in humans and in animals is to be specified, that is expected to result in the same degree of adverse effect. The empirical data on comparative toxicological potencies support the general practice of scaling animal potencies to humans and theoretical support for scaling toxicity should be available from analysis of the allometric variation of key physiological parameters across mammalian species. Such an analysis has the benefit of providing an articulated rationale for the scaling methodology and of setting out the underlying assumptions explicitly.

Biography

Email: ravichandra.vedamurthy@bnsthamelabs.co.uk