Application of quantitative information on the uncertainty in the RfD to noncarcinogenic risk assessments

Recent efforts to improve risk assessment methodologies have sought to prov ide a fuller representation of the variability and uncertainty in risk esti mates in order to provide risk managers with a more complete description of risks. Recently, we and others (Swartout et al., 1998; Price et at, 1997; Slob and Pieters, 1997; Baird et al., 1996) have proposed approaches to cha racterize the uncertainty in the reference dose, (RfD) a key component of t he non-carcinogenic risk estimation process. The operational definition of the RfD as the "lower-bound" estimate of the NOAEL in a sensitive human sub population (NOAEL(HS)) is used along with information on the inter-chemical variation in ratios associated with the uncertainty factors used in settin g the RfD to characterize the uncertainty in the NOAEL(HS) (Swartout et al. , 1998). This paper presents a description of how information on the uncert ainty in the NOAEL(HS) can be used to characterize the uncertainty and vari ability in estimates of noncarcinogenic risks for individuals and populatio ns. The paper also explores the impact of using alternative estimates of th e inter-chemical variation in the ratios. The analysis suggests the followi ng findings. First, the current method of estimating risks from mixtures of chemicals may overestimate the risks when two or more compounds contribute significantly to the estimate of the hazard index. Second, the uncertainty in the NOAEL(HS) of a mixture is affected by the number and size of the un certainty factors used in setting the RfDs of the mixture's components. Thi rd,jointly assessing both the uncertainty and variability in exposure and t he uncertainty in the estimate of the NOAEL(HS) can have a significant impa ct on the characterization of noncarcinogenic risks for individuals and pop ulations. Finally, these findings are independent of the choice of distribu tions for interchemical variation in ratios.