Pathophysiological Progression and Relationships for Selected Endpoints

A compendium containing the categorization of endpoints along a pathophysiological continuum (from no effect to adverse effect) would serve to do the following: (1) Weigh the relative importance of effects induced by a chemical or across chemicals, (2) Provide information valuable in the determination of species sensitivity and relevance of animal effects to humans, (3) Provide interpretative, descriptive and graphical information that can aid in the standardization and uniformity of chemical health assessments, and (4) Serve as a reference source for chemical-mode of action (MOA) characterization.

Abstract

The Environmental Protection Agency (EPA), Office of Research and Development (ORD), National Center for Environmental Assessment (NCEA) is currently developing methodologies and information sources to use as guidelines for acute exposure to various compounds, including air toxics. The goal of this project is to identify/categorize toxicological endpoints along a pathophysiological continuum. This will serve as preliminary work for the development of a pathophysiological progression model to characterize toxicity endpoints used in human health assessments. An endpoint is defined in this document as an objective or subjective (e.g. self reported symptoms in a study using human research subjects) measure that serves as an indicator of a response (normal and/or pathological) to chemical/toxicant exposure.