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Advancing Exposure Characterization for Chemical Evaluation and Risk Assessment
COHEN-HUBAL, E. A., A. M. RICHARD, L. AYLWARD, S. W. EDWARDS, J. GALLAGHER, M. GOLDSMITH, S. ISUKAPALLI, R. TORNERO-VELEZ, E. J. WEBER, AND R. J. KAVLOCK. Advancing Exposure Characterization for Chemical Evaluation and Risk Assessment. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART B: CRITICAL REVIEWS. Taylor & Francis, Inc., Philadelphia, PA, 13(2):299-313, (2010).
A new generation of scientific tools has emerged to rapidly measure signals from cells, tissues, and organisms following exposure to chemicals. High-visibility efforts to apply these tools for efficient toxicity testing raise important research questions in exposure science. As vast quantities of data from high-throughput screening (HTS) in vitro toxicity assays become available, this new toxicity information must be translated to assess potential risks to human health from environmental exposures. Exposure information is required to link information on potential toxicity of environmental contaminants to real-world health outcomes. In the immediate term, tools are required to characterize and classify thousands of environmental chemicals in a rapid and efficient manner to prioritize testing and assess potential for risk to human health. Rapid risk assessment requires prioritization based on both hazard and exposure dimensions of the problem. To address these immediate needs within the context of longer term objectives for chemical evaluation and risk management, a translation framework is presented for incorporating toxicity and exposure information to inform public health decisions at both the individual and population levels. Examples of required exposure science contributions are presented with a focus on early advances in tools for modeling important links across the source-to-outcome paradigm. ExpoCast, a new U.S. Environmental Protection Agency (EPA) program aimed at developing novel approaches and metrics to screen and evaluate chemicals based on the potential for biologically relevant human exposures is introduced. The goal of ExpoCast is to advance characterization of exposure required to translate findings in computational toxicology to information that can be directly used to support exposure and risk assessment for decision making and improved public health.
Exposure modeling is evolving from assessing health risks for single-chemical, single-pathway exposures to individuals toward assessing health risks to populations from exposures to multiple chemicals and other stressors through various routes and pathways. Since exposures and resulting health risks are governed by multiscale processes both in space and time, mechanistic models are needed that can coherently address processes occurring at different scales. These models can be applied in a predictive mode to estimate route-specific exposure and dose levels for general populations as well as for vulnerable groups (based on life stage or behavior). Applications of these models can thus inform interpretation of HTS results toward development of environmentally relevant hazard information.
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Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL CENTER FOR COMPUTATIONAL TOXICOLOGY