A framework for fit-for-purpose dose response assessment

作者：Meek M E Bette^*; Bolger Michael; Bus James S; Christopher John; Conolly Rory B; Lewis R Jeffrey; Paolini Gregory M; Schoeny Rita; Haber Lynne T; Rosenstein Amy B; Dourson Michael L

来源：Regulatory Toxicology and Pharmacology, 2013, 66(2): 234-240.

DOI：10.1016/j.yrtph.2013.03.012

• Mode of action
• Fit-for-purpose
• Problem formulation
• Framework
• Tier
• Endogenous
• Methods compendium

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 (http://www.allianceforrisk.org/Workshop/Framework/ProblemFormulation.html) 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.

• 出版日期2013-7