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A TOXICOLOGICAL VIEW OF ISSUES AND APPROACHES
Citation:
BIRNBAUM, L. S. A TOXICOLOGICAL VIEW OF ISSUES AND APPROACHES. Presented at Society for Risk Analysis Annual Meeting, San Antonio, TX, December 09 - 12, 2007.
Impact/Purpose:
Mode of action (MOA) is a powerful approach which can be used to improve extrapolations and understanding of relevance from studies of animals to humans, to inform differential susceptible states, and from high to low doses.
Description:
Mode of action (MOA) is a powerful approach which can be used to improve extrapolations and understanding of relevance from studies of animals to humans, to inform differential susceptible states, and from high to low doses. In using mode of action, a key event is identified which is pre-requisite to the phenotypic outcome in question. Key events are empirically observable precursor steps that are necessary elements of the mode-of-action, or are markers for such an element. Examples include metabolism, receptor-ligand changes, DNA or chromosome effects, “omics” data and pattern recognition, increased cell growth and organ weight, hormone or other physiological perturbations, hyperplasia, cell proliferation, or metaplasia. However, a given chemical can have multiple MOAs which may depend upon species, dose, or susceptibility. What occurs at a high dose may be irrelevant to what occurs at a low dose, and what occurs during development may say nothing about an MOA which may occur in the adult. However, elucidation of a MOA in a given species and dose and susceptibility state can be used as a hypothesis to test whether a similar MOA is occurring in the species, dose, and state of concern. (This abstract does not reflect Agency policy.)