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SOURCES OF VARIATION IN TOXICOLOGICAL STUDIES AND THEIR EFFECTS ON PRECISION OF RESULTS: INDIVIDUAL DIFFERENCES.
Citation:
MACPHAIL, R. C. SOURCES OF VARIATION IN TOXICOLOGICAL STUDIES AND THEIR EFFECTS ON PRECISION OF RESULTS: INDIVIDUAL DIFFERENCES. Presented at Society of Risk Analysis, Orlando, FL, December 07 - 10, 2005.
Description:
The ultimate goal of risk assessment is to estimate the adverse effects of exposures to environmental contaminants in the population. However, populations of humans and other species vary widely in many key factors such as age, genetic makeup, gender, and health status. Any or all of these factors may influence risk. Such diversity in the population underscores the crucial importance of efforts to estimate quantitatively individual differences in susceptibility to toxicant exposures. Traditional laboratory experimental designs, where each subject is assigned to a single dose group, are limited for this purpose. Our approach involves repeatedly testing individual subjects and, over time, establishing in each individual a complete dose-effect function for acute exposures to the toxicant of interest. The function is then mathematically described, from which a dose is estimated to produce a fixed (benchmark) effect (e.g., a 10% change from baseline). With replication of the design in a sufficient number of subjects distributions of ED10s can be created, and differences between individuals in ED10s can then be quantified. The approach has been applied to studies on the behavioral effects of a variety of solvents and pesticides in adult healthy male laboratory mice and rats. The results indicate that the range of individual differences in chemical-induced susceptibility can span orders of magnitude. Moreover, since these studies used relatively homogenous samples of subjects they can only be considered lower-bound estimates on variability in susceptibility in the human population. Individual differences in chemical-induced susceptibility in the human population may be much greater than traditionally assumed in risk assessment. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.