Biologically Based Dose Response Models for Developmental Toxicity RiskAssessment

摘要

Present risk assessment procedures for non-cancer endpoints generally rely on thedetermination of No Observed Adverse Effects levels (NOAELS) in animal models followed by the application of various Uncertainty Factors (UFs) to account for unknowns in extrapolating high dose toxicology studies to potentially sensitive human subpopulations. The Reference Dose (RfD) or Concentration (RfC) which results from the process is an estimate, with an uncertainty spanning an order of magnitude, of the exposure level to the human population that is likely to be without appreciable risk of deleterious effects during a lifetime. The US Environmental Protection Agency, through its Research to Improve Health Risk Assessment Program (RIHRA), has embarked on a concerted effort to introduce more pharmacokinetic and mechanistic information into the risk assessment process for non-cancer endpoints and to do this in a quantitative and predictive fashion. Such approaches are collectively termed biologically based dose-response (BBDR) models, and the presentation will focus on examples of such research in the area of developmental toxicity currently being conducted or supported by the EPA.