Accounting for susceptibility in risk assessment: current practice and new directions

Abstract

Differences in susceptibility between individuals can lead to variability in response to chemical exposures which in turn modify the risk of illness. As a means of exploring the basis for such differences in susceptibility, a project was undertaken to determine what data were available on the range of response variability for several health effects: neurotoxicity, reproductive/developmental toxicity, pulmonary toxicity, and cancer. In addition, modeling approaches for characterizing response variability were examined and evaluated. The main goal of this effort was to determine whether human response variability was adequately accounted for in the current risk assessment procedures for human health effects. The conclusions of the project were that few data are available, both because variability has rarely been the primary focus of study, and because data are not usually reported in such a way that response variability can be determined. Several recommendations were made to facilitate better characterization of interindividual variability, including the study of variability in available human data (e.g. the NHANES database) and allowing greater access to raw data from epidemiologic studies. In addition, the identification of relevant biomarkers, improved understanding of sources of variability, interaction of chemical effects with other exposures or pre-existing disease, and retrospective evaluations of risk assessments were recommended. It is hoped that these recommendations will stimulate research on susceptibility and response variability and encourage the reporting of data in a way that facilitates analysis of interindividual variability in response.