Accounting for missing data in noncancer risk assessment

Noncancer risk assessments are generally forced to rely on animal bioassay data to estimate a Tolerable Daily Intake or Reference Dose, as a proxy for the threshold of human response. In cases where animal bioassays are missing from a complete data base, the critical NOAEL (no-observed-adverse-effect level) needs to be adjusted to account for the impact of the missing bioassay(s). This paper presents two approaches for making such adjustments. One is based on regression analysis and seeks to provide a point estimate of the adjustment needed. The other relies on non-parametric analysis and is intended to provide a distributional estimate of the needed adjustment. The adjustment needed is dependent on the definition of a complete data base, the number of bioassays missing, the specific bioassays which are missing, and the method used for interspecies scaling. The results from either approach can be used in conjunction with current practices for computing the TDI or RfD, or as an element of distributional approaches for estimating the human population threshold.