Project Rationale
Historically, knowledge regarding dose-effect relationships and thresholds for effects has been central to the process of health risk assessment, and also central to establishing safe and effective doses for pharmaceuticals and nutrients. Recent scientific and technical advances, however, prompt us to ask whether current knowledge is being fully utilized to inform risk assessment and public health standard setting. For example, are we fully utilizing current understanding of molecular and cellular processes to refine predictions of human response? Are we adequately incorporating advances in toxicokinetics to improve estimates of relevant dose? Given technological advances in analytical methods, which detect increasingly low levels of substances in the environment, can our current risk assessment paradigm adequately guide attention to substances deserving concern? A fresh examination of such questions is warranted. Moreover, a “global” approach is needed to generate harmonized and consistent approaches - both across countries/regulatory authorities and across the range of biological agents and stressors.
Project Goal and Objectives
The project goal is to identify opportunities to more fully incorporate current knowledge and data regarding dose-effect relationships and biological thresholds into processes used to assess risk and set public health standards. To accomplish this, the project will examine and compare the biological processes underlying human health effects from exposure to four broad categories of agents: chemicals, microbial pathogens, allergens, and nutrients.
For each category of agent, the project will address such questions as:
• What types of data, models, and assumptions are currently used to characterize low dose dose-response relationships and biological thresholds? Are these models and assumptions supported by current knowledge? Are there newer data, technologies, or approaches that could be used to refine characterization of low dose dose-response relationships and biological thresholds?
• Can multiple biological thresholds be observed along the cascade of events between initial exposure and biological effect? If so, which threshold(s) appear to be most relevant to/predictive of an adverse or beneficial response, as opposed to a homeostatic response?
• What is the current relationship between biological thresholds and “regulatory” thresholds – i.e., standards intended to apply to a population? How can the relationship be strengthened?
Looking across the range of agents, the project will address such questions as:
• What are the similarities and differences across the four categories of agents with regard to:
o Fundamental biological processes underlying response to an agent?
o Approaches to characterizing biological thresholds for adverse or beneficial effects?
o Use of the “threshold concept” when setting public health standards?
• Do any central themes emerge that apply fundamentally to all categories? Where approaches differ, what are the strengths and limitations of each?
• Are there new insights/implications that could improve methods for risk assessment or standard setting?
• What should constitute reasonable evidence of a threshold for an adverse or beneficial effect?
Project Approach
A Working Group of recognized experts from the fields of chemical, allergen, microbial and nutrient risk assessment will systematically address the questions noted above, and seek to integrate findings and insights across disciplines. The Working Group will include scientists from academia, government and industry, and will be international in nature. The group will be charged with preparing a comprehensive and authoritative white paper, to be submitted for publication in the peer-reviewed scientific literature. This effort began in 2006 and is expected to be completed in 2008.
Steering Committee
Dr. Robert Buchanan – US FDA Center for Food Safety and Applied Nutrition
Dr. George Daston – Procter & Gamble Company
Dr. Arie Havelaar– National Institute of Public Health and the Environment (RIVM), the Netherlands
Dr. Sanford Miller – University of Maryland Center for Food, Nutrition, and Agriculture Policy
Dr. Ian Munro – CANTOX Health Sciences International, Canada
Dr. R. Julian Preston – USEPA National Health and Environmental Effects Research Laboratory
Dr. Peter van Bladeren – Nestlé Research Center, Switzerland
Dr. Stephen Olin – ILSI Research Foundation
Dr. Beth Julien – ILSI Research Foundation
Sponsors
The project is funded by both private and public sources, and additional sponsorship is being sought. Current funders include: the ILSI Research Foundation, Health Canada, Flavor and Extract Manufacturers Association, and members of the ILSI Strategic Issues Group, which represents several multinational corporations that are members of multiple branches of ILSI globally.
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