A framework for fit-for-purpose dose response assessment

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• 作者：M.E. Bette Meek^a ; ^{bmeek@uottawa.ca} ; Michael Bolger^b ; ¹ ; ^{mbolger33@gmail.com} ; James S. Bus^c ; ² ; ^{jbus@exponent.com} ; John Christopher^d ; ^{dr.tox@comcast.net} ; Rory B. Conolly^e ; ^{conolly.rory@epa.gov} ; R. Jeffrey Lewis^f ; ^{r.jeffrey.lewis@exxonmobil.com} ; Gregory M. Paolini^g ; ^{gpaoli@risksciences.com} ; Rita Schoeny^h ; ^{Schoeny.Rita@epamail.gov} ; Lynne T. Haberⁱ ; ^{haber@tera.org} ; Amy B. Rosenstein^j ; ^{EnvRiskExpABR@aol.com} ; Michael L. Doursonⁱ ; ^{dourson@tera.org}
• 关键词：ARA ; alliance for risk assessment ; CPF ; chlorpyrifos ; MOA ; mode of action ; NAS ; National Academy of Sciences ; NGO ; non-governmental organization ; NRC ; National Research Council ; PBPK/PD ; physiologically-based pharmacokinetic/pharmacodynamic ; RfD ; referenc
• 刊名：Regulatory Toxicology and Pharmacology
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：66
• 期：2
• 页码：234-240
• 全文大小：362 K

文摘

The NRC report Science and Decisions: Advancing Risk Assessment made several recommendations to improve chemical risk assessment, with a focus on in-depth chronic dose-response assessments conducted by the U.S. Environmental Protection Agency. The recommendations addressed two broad elements: improving technical analysis and utility for decision making. To advance the discussions in the NRC report, in three multi-stakeholder workshops organized by the Alliance for Risk Assessment, available and evolving risk assessment methodologies were considered through the development and application of case studies. A key product was a framework () to guide risk assessors and managers to various dose-response assessment methods relevant to a range of decision contexts ranging from priority setting to full assessment, as illustrated by case studies. It is designed to facilitate selection of appropriate methodology for a variety of problem formulations and includes a variety of methods with supporting case studies, for areas flagged specifically by the NRC committee for consideration - e.g., susceptible sub-populations, population variability and background. The framewok contributes to organization and communication about methodologies for incorporating increasingly biologically informed and chemical specific knowledge into dose-response analysis, which is considered critical in evolving fit-for-purpose assessment to address relevant problem formulations.