Exposure biology for a systems approach in studying environmental health risks
P.G. Georgopoulos1, S.S. Isukapalli1, W. Tong2, P.J. Lioy1, W.J. Welsh1
1Environmental & Occupational Health Sciences Institute, Piscataway, NJ; 2USFDA National Center for Toxicological Research, Jefferson, AR
Exposure biology as a "systems approach" provides an integrative framework for human health risk analyses, as human health state reflects multiscale body "system dynamics" spanning multiple levels of bionetworks (genome, transcriptome, proteome, metabolome, cytome, physiome), each potentially affected by various types of environmental factors. Assessment of environmental health risks requires understanding the sequence of events and processes in the sequence from "source" (e.g. the release of a "stressor", such as a chemical, radiological, or biological agent in an environmental medium) to "outcome" (e.g. development of an environmentally caused disease). Exposure biology allows significant improvements over the traditional approach of studying risks on a "stressor by stressor basis" for a given environmental medium (e.g. atmosphere, groundwater, etc.) typically associated with a single exposure route (e.g. inhalation, ingestion, dermal absorption, etc.) Recent developments include integrated "person-oriented" or anthropocentric approaches and models, that account for total ("cumulative" and "aggregate") exposures of individuals and populations, to cooccurring stressors (e.g. contaminants in air, water, soil, food, etc.) These approaches focus on real or "virtual" individuals with well defined physiological, socioeconomic, etc., attributes, and take into account effects of behavior/activities on exposure "microenvironments" and on physiological processes determining biologically relevant dose, as well as genomic and extragenomic factors (e.g. development and aging) that determine susceptibility to environmental stressors. The Modeling ENvironment for TOtal Risk studies (MENTOR) provides a library for "source-to-dose" analysis, while the DOse Response Information ANalysis system (DORIAN), that is currently being developed, provides tools for "dose-to-outcome" analysis. Together, they provide integrated, "systems-based" tools that can enhance our understanding towards "personalized" risk assessments.
This work is funded in part by the USEPA through STAR Grant GAD R 832721-010 and Cooperative Agreement CR-83162501. Viewpoints expressed here are the responsibility of the authors and do not necessarily reflect views of the USEPA or its contractors.