Exposure science and the U.S. EPA National Center for Computational Toxicology

Abstract

The emerging field of computational toxicology applies mathematical and computer models and molecular biological and chemical approaches to explore both qualitative and quantitative relationships between sources of environmental pollutant exposure and adverse health outcomes. The integration of modern computing with molecular biology and chemistry will allow scientists to better prioritize data, inform decision makers on chemical risk assessments and understand a chemical's progression from the environment to the target tissue within an organism and ultimately to the key steps that trigger an adverse health effect. In this paper, several of the major research activities being sponsored by Environmental Protection Agency's National Center for Computational Toxicology are highlighted. Potential links between research in computational toxicology and human exposure science are identified. As with the traditional approaches for toxicity testing and hazard assessment, exposure science is required to inform design and interpretation of high-throughput assays. In addition, common themes inherent throughout National Center for Computational Toxicology research activities are highlighted for emphasis as exposure science advances into the 21st century.

Consideration of dosimetry in evaluation of ToxCast™ data

“…Because the vision for twenty‐first century toxicity testing eventually encompasses a near‐total reliance on assessments that do not require in vivo testing, the development of methods for the identification of chemical characteristics and screening criteria to provide insight into these exposure‐related factors should be given priority similar to that now focused on development of screening methods for toxicologic responses. The ExpoCast effort by EPA signals recognition of these issues (http://epa.gov/ncct/expocast/; Cohen Hubal et al , ). A number of in vitro assays and in silico modeling approaches currently exist for estimating pharmacokinetic properties of chemicals (reviewed in Lipscomb and Poet, ; Blaauboer, ); efforts to expand and validate the toolbox of such methods, and integrate the results with the in vitro toxicity data, are warranted.…”

Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework

“…Completing the source to outcome continuum by joining the AEP and AOP networks sets the stage for more efficient integration of toxicity testing information and exposure information, creating opportunities for development and deployment of novel computational tools that enable more comprehensive, more rapid exposure-based, hazard-based, and risk-based decision making 38 .…”

Air Pollutant Hazards

“…THE RISKS OF AIR POLLUTION 7.1 HAZARDS at multiple levels of biological organization (see Figure 7.1). 4 The food chain or web is, therefore, a means by which an ecological hazard becomes a human health hazard. It is also the means by which a hazard can change physicochemical forms to become more hazardous, such as the methylation of mercury (Figure 7.2).…”