Perspectives On The Application Of Mechanistic Information In Chemical Hazard And Dose-Response Assessments
This overview summarizes several EPA Assessment publications reviewing approaches for applying mechanistic information in human health risk assessment and exploring opportunities for progress in this area.
EPA initiated a multidisciplinary project to examine methods for applying mechanistic information in human health risk assessment, to identify challenges, and to suggest and explore opportunities for improvement. Motivations included the significant ability of mechanistic data to inform chemical hazard and dose-response assessments. This project examined approaches for interpreting observed effects in laboratory animals and their human relevance based on hypothesized modes of action. In addition, a critical aspect of the work was to explore issues pertinent to toxicity-pathway based risk assessment. This report summarizes published project results.
EPA initiated a multidisciplinary project to examine methods for applying mechanistic information in human health risk assessment, to identify challenges, and to suggest and explore opportunities for improvement. Motivations included the significant ability of mechanistic data to inform chemical hazard and dose-response assessments. This project examined approaches for interpreting observed effects in laboratory animals and their human relevance based on hypothesized modes of action. In addition, a critical aspect of the work was to explore issues pertinent to toxicity-pathway based risk assessment. This report summarizes published project results.
Impact/Purpose
This report summarizes published project results that examined approaches for interpreting observed effects in laboratory animals and their human relevance based on hypothesized modes of action.
Citation
U.S. EPA. Perspectives On The Application Of Mechanistic Information In Chemical Hazard And Dose-Response Assessments. U.S. Environmental Protection Agency, Washington, DC, 2010.
History/Chronology
| Date | Description |
|---|---|
| 2008 - 2009 | Project results are published in peer-reviewed journals. |
| Sep 2010 | EPA releases this summary report. |
This document has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.
- Perspectives on the Application of Mechanistic Information in Chemical Hazard (Summary Report) (PDF) (4 pp, 44 KB, about PDF)
- Chen C; Guyton K (2008). Do 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline data support the conclusion of threshold carcinogenic effects? Stoch Environ Res Risk Assess, 22: 487–494.
- Guyton K; Barone S; Brown R; Euling S; Jinot J; Makris S (2008). Mode of action frameworks: a critical analysis. J Toxicol Environ Health B Crit Rev, 11: 16-31.
- Guyton K; et al (2009). A reexamination of the PPAR-alpha activation mode of action as a basis for assessing human cancer risks of environmental contaminants. Environ Health Perspect, 117: 1664-1672.
- Guyton K; et al (2009). Improving prediction of chemical carcinogenicity by considering multiple mechanisms and applying toxicogenomic approaches. Mutat Res Rev Mutat Res, 681: 230-240.
- White R; et al (2008). State-of-the-Science Workshop Report: Issues and Approaches in Low Dose-Response Extrapolation for Environmental Health Risk Assessment . Environ Health Perspect.
- Woodruff T; et al (2008). Meeting report: moving upstream-evaluating adverse upstream end points for improved risk assessment and decision-making. Environ Health Perspect, 116: 1568-1575.