title: A lifestage-specific approach to hazard and dose-response characterization for children's health risk assessment.
abstract: In 2006, the U.S. EPA published a report entitled A Framework for Assessing Health Risks of Environmental Exposures to Children (hereafter referred to as the "Framework") describing a lifestage approach to risk assessment that includes the evaluation of existing data from a temporal perspective (i.e., the timing of both the exposure and the outcome). This article summarizes the lifestage-specific issues discussed in the Framework related to the qualitative and the quantitative hazard and dose-response characterization. Lifestage-specific hazard characterization includes an evaluation of relevant human and experimental animal studies, focusing on the identification of critical windows of development (i.e., exposure intervals of maximum susceptibility) for observed outcomes, evaluation of differential exposure at individual lifestages, the relevance and impact of lifestage-specific toxicokinetic and toxicodynamic data, mode of action information, variability and latency of effects from early lifestage exposure, and describing uncertainties. The interpretation of the hazard data to determine the strength of association between early life exposures and the timing and type of outcomes depends upon the overall weight of evidence. Lifestage-specific dose-response characterization relies on the identification of susceptible lifestages in order to quantify health risk, information on the point of departure, key default assumptions, and descriptions of uncertainty, sensitivity, and variability. Discussion of the strength and limitations of the hazard and dose-response data provides a basis for confidence in risk determinations. Applying a lifestage approach to hazard and dose-response characterization is likely to improve children's health risk assessment by identifying data gaps and providing a better understanding of sources of uncertainty.
authors.affiliation: National Center for Environmental Assessment (NCEA), Office of Research and Development (ORD), U.S. Environmental Protection Agency (USEPA), 1200 Pennsylvania Avenue, NW, Washington, DC 20460, USA. makris.susan@epa.gov
authors.forename: Susan L
authors.initials: SL
authors.lastname: Makris
authors.forename: Chad M
authors.initials: CM
authors.lastname: Thompson
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Euling
authors.forename: Sherry G
authors.initials: SG
authors.lastname: Selevan
authors.forename: Babasaheb
authors.initials: B
authors.lastname: Sonawane
mesh_terms: D002648:Child; D002657:Child Development; D002669:Child Welfare; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000009:adverse effects*; D006801:Humans; D018570:Risk Assessment / Q000379:methods*; D014481:United States; D014484:United States Environmental Protection Agency
chemical_list: D004785:Environmental Pollutants