Journal
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
Volume 49, Issue 8, Pages 682-689Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/10408390903110692
Keywords
low dose dose-response; uncertainty; variability; default extrapolation
Categories
Funding
- ILSI Research Foundation
- Health Canada
- Ajinomoto
- Coca-Cola Company
- Groupe Danone
- Kellogg Company
- Kraft Foods, Inc.
- Mars, Inc.
- Mead Johnson Nutritionals
- Monsanto Company
- Nestle
- PepsiCo, Inc.
- Procter Gamble Company
- Syngenta Ltd.
- Flavor Extract Manufacturers Association
- Grocery Manufacturers Association
- NATIONAL CANCER INSTITUTE [R01CA090214] Funding Source: NIH RePORTER
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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 agentsfood allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical frameworkthe 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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