Iain Gardner

TL;DR: The history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods.

TL;DR: This presentation is intended to provide an introductory overview of the life cycle of a drug in the animal body and indicates the significance of such information for a full understanding of mechanisms of action and toxicity.

TL;DR: An in vitro/in silico method was established that predicts the risk of human DILI in relation to oral doses and blood concentrations of test compounds to the probability of hepatotoxicity and application to the rat hepatotoxicant pulegone resulted in an ADI similar to values previously established based on animal experiments.

TL;DR: The rate of 1'-hydroxylation of methyleugenol in vitro in 13 human liver samples varied markedly (by 37-fold), with the highest activities being similar to the activity evident in control rat liver microsomes, which suggests that the risk posed by dietary ingestion of methylesugenol could vary markedly in the human population.

TL;DR: The results suggest that the balance between metabolic bioactivation by CYP2E1 and detoxication of reactive metabolites by cellular nucleophiles could be an important metabolic risk factor in halothane hepatitis.