Approaches to Representation of Dose-Response Relationships for Chemicals Causing Non-Cancer Effects & Policy Implications
Waterfront Plaza Hotel, 10 Washington Street
Jack London Square, Oakland, California
January 27-28, 2005
Rationale
Current approaches to assessing chronic, non-cancer health effects are designed to develop an estimate of dose that is without appreciable risk, use this to define regulatory targets, and do not otherwise quantify the overall dose-response relationship. This raises two important questions. One is whether there are ways to quantify the full dose-response relationship that would be informative in policy contexts. The other is whether there are ways that to represent the dose-response relationship below the observed range of the data that are equally appropriate from a scientific point of view to those used at present. This workshop is intended to discuss these issues.
Objectives
Develop and review case studies of relatively well studied chemicals that are associated with different types of adverse, non-cancer heath effects and that present results from human and/or animal studies relating doses to adverse effects; studies of biology and mechanisms of action relevant to the identified adverse effects; and modeling of data produced by the human and/or animal studies.
Consider the following key questions as they apply to these case studies:
What does the presented evidence suggest about the nature of the relationship between dose and effects, in the observed range and below the observed range?
Do existing data from human or animal studies provide a reasonable basis to select between models of the relationships between dose and response? If data are not sufficient to select between options, do they suggest that one type of model is more likely to be correct than others? Can other conclusions be drawn about an appropriate way or ways to represent the dose-response relationship through the full range?
Does existing information about the biology or mechanism of action provide a reasonable basis to select between models of the relationships between dose and response? If the existing information is not sufficient to select between options, does it suggest that one is more likely than others? Can other conclusions be drawn about an appropriate way or ways to represent the dose-response relationship through the full range?
How does the variability of the population in terms of differences in background rates of disease, susceptibility, absorption, metabolism or other traits affect your thinking about the dose-response relationship when considered in light of the population as a whole?
How does the existing background exposure level for agents in question and related compounds affect your conclusions about the dose-response relationship when considered in light of the population as a whole?
Given the information presented from human or animal studies, biology and mechanisms of action, population variability, and background exposure levels, what are your observations or conclusions about appropriate ways to represent the dose-response relationship through the full range?
What are the implications of the conclusions reached on these questions for risk assessment and benefits assessment? Will the conclusions address information needs that arise from the policy contexts discussed?
Consider whether the conclusions reached in the individual case studies could be generalized beyond the case studies presented in this workshop.
Workshop Sponsors
Superfund Basic Research Program, School of Public Health, University of California Berkeley
National Center for Environmental Economics, U.S. Environmental Protection Agency
Office of Environmental Health Hazard Assessment, California Environmental Protection Agency
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