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INTEGRATION OF PATHOLOGY AND TOXICOLOGY IN RISK ASSESSMENT
Citation:
WOLF, D. C. INTEGRATION OF PATHOLOGY AND TOXICOLOGY IN RISK ASSESSMENT. Presented at Latin American Society of Toxicologic Pathology Annual Meeting, Sao Paulo, BRAZIL, March 28 - 29, 2008.
Impact/Purpose:
This presentation will provide an overview of how the human relevance framework and mode-of-action analysis is applied in the interpretation of pathology results derived from carcinogenicity bioassays and its application in the submission of study data to regulatory agencies.
Description:
In order to develop a scientifically defensible assessment of the risk for the development of cancer after long-term exposure to xenobiotics, regulatory agencies have adopted a uniform approach which includes the characterization of a carcinogenic mode of action and its biological plausibility in exposed humans. The Human Relevance Framework (HRF) and Mode-of-Action (MoA) analysis is used to assess the relevance of an increased frequency of neoplastic lesions in rodents identified in carcinogenicity studies. This approach provides a framework for assessing possible cancer risks from exposures to pollutants or other agents in the environment. The goal is to make greater use of the scientific understanding of the process of carcinogenesis. The process includes analysis of all available information, identifying the key events in the cancer processes from exposure to adverse health consequence, mode(s) of action, a description of the biological plausibility for the MoA to occur in humans. considering differential susceptibility to subpopulations, and finally characterizing the risk to humans based on the weight of scientific evidence. The MoA is considered biologically plausible in humans unless these is mechanistic evidence to refute this conclusion. Within this framework, default approaches to risk assessment are to be used only when there are insufficient data to support a mode of action analysis and human relevancy approach. This presentation will provide an overview of how the human relevance framework and mode-of-action analysis is applied in the interpretation of pathology results derived from carcinogenicity bioassays and its application in the submission of study data to regulatory agencies. [This abstract has been reviewed and approved for publication but does not necessarily represent the policies or opinions of the U. S. Environmental Protection Agency.]