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Application of Key Events and Analysis to Chemical Carcinogens and Noncarcinogens
Citation:
Boobis, A., G. Daston, J. PRESTON, AND S. Olin. Application of Key Events and Analysis to Chemical Carcinogens and Noncarcinogens. Critical Reviews in Food Science and Nutrition. Taylor & Francis Group, London, Uk, 49(8):690-707, (2009).
Impact/Purpose:
Understanding inter-indvidual variability in the events in toxicological effects may enable a true population threshold(s) to be identified
Description:
The existence of thresholds for toxicants is a matter of debate in chemical rsk assessment and regulation. Current risk assessment methods are based on the assumption that, in the basense of sufficient data, carcinogenesis does not have a threshold, while non-carcinogenic endpoints are assumed to be thresholded. The first section illustrates how a fundamental understanding of mode of action for the hepatic toxicity and the hepatocarcinogenicity of chloroform in rodents can replace the assumption of low-dose linearity. The second section describes how advances in our understanding of the molecular aspects of carcinogenesis allow us to consider the critical steps in genotoxic carcinogenesis in a key events framework. The third section deals with the case of endocrine disrupters, where the most signficant question regarding thresholds is the possible additivity to an endogenous background of hormonal activity.