An Animal Model for Assessing Individual Differences in Susceptibility to Environmental Pollutants. R. C. MacPhail, Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. EPA, RTP, NC 27711; and J. R. Glowa, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892
Current approaches to risk assessment for systemic (non-cancer) toxicity typically include an uncertainty factor of 10 to account for individual differences in susceptibility to toxicants. Variability in a heterogeneous human population could easily exceed a factor of 10 due to differences in gender, age and health status. A behavioral approach was developed to quantitatively assess individual differences in the sensitivity of laboratory animals to toxic substances that might reflect a lower-bound estimate of the range of sensitivity in the human population. A repeated-measures (baseline) design was used to establish complete acute dose-effect functions in individual male outbred mice and rats exposed to solvents and pesticides respectively. Dose-effect functions for each animal were quantitatively described, from which a dose producing a 10% decrement in behavioral function was calculated (ED10). Distributions of ED10s were then established, from which doses producing 10% decrements in successively smaller proportions of the population were estimated (i.e., a probabilistic dose-tolerance model). Ratios of the highest-to-lowest ED10s (X " 3SD) varied by 1 1/2-4 orders of magnitude. These data suggest an uncertainty factor of 10 may greatly underestimate intraspecies differences in susceptibility to environmental pollutants.