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The Key Events Dose-Response Framework: A Cross-Disciplinary Mode-of-Action Based Approach to Examining Dose-Response and Thresholds

Authors
  • JULIEN, ELIZABETH1
  • BOOBIS, ALAN R.2
  • OLIN, STEPHEN S.1
  • 1 ILSI Research Foundation, Washington, DC, USA
  • 2 Department of Experimental Medicine and Toxicology, Imperial College London, London W12 0NN, UK
Type
Published Article
Journal
Critical Reviews in Food Science and Nutrition
Publisher
Informa UK (Taylor & Francis)
Publication Date
Sep 11, 2009
Volume
49
Issue
8
Pages
682–689
Identifiers
DOI: 10.1080/10408390903110692
PMID: 19690994
PMCID: PMC2840877
Source
PubMed Central
Keywords
License
Green

Abstract

The ILSI Research Foundation convened a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categories of bioactive agents—food allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical framework—the Key Events Dose-Response Framework (KEDRF)—for systematically examining key events that occur between the initial dose of a bioactive agent and the effect of concern. Individual key events are considered with regard to factors that influence the dose-response relationship and factors that underlie variability in that relationship. This approach illuminates the connection between the processes occurring at the level of fundamental biology and the outcomes observed at the individual and population levels. Thus, it promotes an evidence-based approach for using mechanistic data to reduce reliance on default assumptions, to quantify variability, and to better characterize biological thresholds. This paper provides an overview of the KEDRF and introduces a series of four companion papers that illustrate initial application of the approach to a range of bioactive agents.

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