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Aging and the Environment: Importance of Variability Issues in Understanding Risk
Citation:
MACPHAIL, R. C. Aging and the Environment: Importance of Variability Issues in Understanding Risk. Presented at American Aging Association, Raleigh, NC, June 06, 2011.
Impact/Purpose:
A number of studies have shown increased variability in baseline function with advancing age, which may indeed be prodromal of neurodegenerative disease. Considerably fewer investigations have focused on age-related variability in response to toxicant exposures
Description:
Of the many features of aging that could enhance susceptibility to environmental stressors, including toxic chemicals, the role of variability is arguably the least understood. This conclusion is surprising, since increased variability is a widely accepted feature of old age. Increased variability could complicate the demonstration of enhanced susceptibility, by reducing statistical power, as well as the estimation of toxic risk due to old age. A number of studies have shown increased variability in baseline function with advancing age, which may indeed be prodromal of neurodegenerative disease. Considerably fewer investigations have focused on age-related variability in response to toxicant exposures. Results will be described of studies on the effects of the volatile organic solvent toluene on the behavior of adolescent, young-adult, middle-age and senescent male Brown Norway rats. Under baseline conditions, behavior (motor activity) generally decreased with age, while variability increased both between-and within subjects. Toluene (1000 mg/kg) increased motor activity in direct proportion with age; variability in toluene's effect also increased with age. Creating distributions of response for each age group, based on z-scores, allowed quantitative estimation of the increase in susceptibility to toluene in senescent rats. The results suggest that increased variability in toxic response due to old age can greatly amplify risk estimates. (This is an abstract of a proposed presentation and does not reflect USEPA policy.)