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Application of Mode of Action Analysis and Human Relevance Framework
Citation:
Wolf, D. Application of Mode of Action Analysis and Human Relevance Framework. Presented at 1st INTERNATIONAL COURSE-SEMINAR OF ENVIRONMENTAL TOXICOLOGICAL PATHOLOGY, August 23 - 24, 2012.
Impact/Purpose:
This presentation will provide an overview of how the mode of action analysis and human relevance framework is applied in both a regulatory setting and for designing research studies
Description:
Animal bioassays have been used for more than a half century to determine whether pesticides, pharmaceuticals, industrial chemicals, and other products might cause health problems in humans. As such, animal bioassays have become the standard for detecting the potential for adverse effects in humans of products where human use or exposure is anticipated. For most compounds extrapolations (dose and species) are typically necessary for animal data to predict and estimate human risk because few agents have sufficient human data upon which to base assessments. Inherent in these animal based assessments are the assumptions that observation in animals is relevant for human health risk, and that responses observed at high doses in animals are meaningful to doses of regulatory relevance for humans. Data from molecular and cellular studies have resulted in a fuller biological understanding of how chemicals induce adverse effects in animal studies. Such mechanistic work has also raised concern regarding the appropriateness of extrapolating positive responses in rodents to human risk. Significant progress has been made in the last twenty years in our understanding of the biological processes, mode of action, of how adverse health effects occur in both animals and humans. Risk assessments have improved through the organized scientific use of data on the pharmacokinetics and pharmacodynamics of agents that characterize the biological basis underlying the development or enhancement of disease after chemical exposure. The adoption of the mode of action framework is widespread and it is now commonly used by many regulatory agencies and international organizations. To refine and improve the process of hazard identification, and to avoid misidentification of harmless substances as possible human hazards, it has become imperative that mode of action analysis be the standard analytic approach for regulatory purposes and that data to support such analysis be collected in a thoro