Interspecies comparison of kinetic data of chlorinated chemicals of potential relevance to risk assessment

Abstract

Most noncancer risk assessments focus on the NOAEL (the no observed adverse effect level), an external dose. However, the internal dose considers the ongoing kinetics between chemical intake and target site and will provide a better dose-response relationship. The purpose of this study was to conduct a literature search for kinetic parameters in animals and humans administered chlorinated chemicals by the oral or inhalation routes. Frequendy used industrial solvents as well as pesticides were evaluated. Animal to human kinetic ratios were calculated and compared to the proposed kinetic default subfactors of Renwick for oral chemicals and of the USEPA for inhaled compounds. Kinetic default subfactors were then replaced by data-derived values and the interspecies factors were recalculated. Seventy percent of data-derived kinetic ratios were lower than proposed default values. Thus, incorporation of internal dose can reduce uncertainty in animal-human extrapolation. Furthermore, metabolites should be examined because for some compounds, species differences in toxicity may be due to metabolites.