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IS THE DOSE-RESPONSE LINEAR OR NONLINEAR FOR GENOTOXIC EFFECTS?
Citation:
Preston, R J. IS THE DOSE-RESPONSE LINEAR OR NONLINEAR FOR GENOTOXIC EFFECTS? Presented at Environmental Mutagen Society, Miami Beach, Florida, 5/9-15/03.
Description:
IS THE DOSE-RESPONSE LINEAR OR NONLINEAR FOR GENOTOXIC EFFECTS?
Preston, RJ. Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
For considerations of cancer risk assessment from exposure to environmental chemicals, the default position is generally that the dose-response curve for genotoxicity is linear. However, this position is based to a great extent on a data base that has been developed for individual endpoints, for acute exposures, and for specific cell types (largely in vitro). For studies of a mechanism of mutagenesis this might sometimes be appropriate, as too might it be when a qualitative assessment of genotoxicity is all that is required. When genotoxicity data are to be utilized in a quantitative cancer risk assessment, then single endpoint data are generally inadequate. For example, the most informative genotoxicity dose-response is for composite effects (e.g., mutations/DNA repair/DNA replication delay); for chronic exposures; and for target cell types or cancer-related genes, wherever possible. In situations, where some of these confounders of dose-response shape have been taken into consideration, nonlinear dose-response curves are observed or can be predicted. The need is to consider the outcome as regards doseresponse curve shape on a case-by-case basis, taking into account the potential and/or known confounders.
(This abstract does not necessarily reflect U.S. EPA policy).