ABSTRACT
Mechanistic toxicology is the study of molecular, biochemical, cellular and tissue-level interactions, pathways and changes leading to the toxicological effects of xenobiotics. It is a discipline that provides insight into how chemicals and other substances exert their toxic effects in biological systems and aims to determine the principal cascade of events occurring between exposure and the manifestation of toxicity. It is an indispensable tool for the evaluation of health risks and safety in pharmacological and environmental toxicology. Mechanistic toxicology is applied in safety evaluations of medicines; household, environmental and industrial chemicals; pollutants; novel foods and food additives; and many other products produced from either natural or synthetic sources. Research in this field has led to the discovery of biomarkers that enable monitoring of the potential progression of toxicity following exposures to these substances. Specific areas of investigation often include biotransformation, metabolism and toxicokinetics, signaling pathways, nuclear receptor-mediated events, gene activation and regulation, oxidative stress, covalent binding, cell death and proliferation, and off-target effects. Current regulations, approaches to species selection in testing and the investigation of human relevance within the scope of well-designed safety studies are discussed to give readers an overview of the scope and pertinence of this research area.
