Accounting for Inter-Individual Variation in the Current System of Safety Factors. P. S. Price, R. E. Keenan, and S. Su, ChemRisk - A Division of McLaren/Hart, 1685 Congress Street, Portland, ME 04102
The current system of evaluating noncarcinogenic hazards used by EPA and other regulatory agencies involves the use of a set of standardized uncertainty factors which are used to adjust findings (LOAELs and NOAELS) from toxicological studies to estimate a "reference dose". One source of uncertainty that this system addresses is inter-personal variation in responses to toxic chemicals. Several authors (Calabrese, 1985; Calabrese and Gilbert, 1993; Hattis and Silver, 1990) have suggested that the current system does not provide adequate protection for the range of variation that has been demonstrated to occur in toxicological and physiological endpoints in the general population. This analysis examines how the current system of setting RfDs accounts for inter-personal variability both in the use of a specific uncertainty factor and in the use of NOAELs and LOAELs as the initial starting point of the analysis. Based upon this review we concluded that the current system of setting RfDs will be protective even in cases where inter-individual variation in susceptibility varies by three orders of magnitude.