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Exposure Research

EPA Researchers Combine Science and Visualizations to Predict Chemical Exposures and Manage Risk

In short, this animation employs PAVA to compare models describing two exposure route scenarios, in 7 different organs, on a female anatomy. Oral exposure is red; intravenous, or IV, exposure is blue. Here, PAVA is used to visualize the differences between two ethanol PBPK model outputs. A PAVA comparison of the two routes suggest: (1) the oral exposure route peaks in the liver before the other organs (indicated in a bright red liver). (2) Within 45 minutes, regardless of exposure route, the pharmacokinetic profile to the other tissues would remain similar for about 15 minutes (white peripheral tissues, with a red liver also), and (3) would switch by about 60 minutes to remain higher in all tissues via oral exposure (all tissues change to red). (4) Within about 180 minutes, the levels in both scenarios, tailing to zero, become similar as tissues all fade to white.

Posted: June 1, 2010

Researchers at the U.S. Environmental Protection Agency (EPA) create and use computer models to predict what happens inside the human body when it is exposed to chemicals. The results developed by the models help EPA understand and manage risks posed to public health from chemicals in the environment.

Part of EPA's chemical risk-assessment process relies on physiologically-based pharmacokinetic (PBPK) modeling to understand human exposures to chemicals. PBPK modeling is a peer-reviewed scientific approach for predicting the absorption, distribution, metabolism, and excretion of a chemical in the human body. The models use mathematical calculations to produce results in the form of tables, pie charts, and graphs.

To improve on these models, EPA researcher Dr. Michael (Rocky) Goldsmith, and colleagues, developed an innovative tool that displays PBPK modeling results in a contemporary venue to help scientists visualize — in a new way — how the human body responds to various chemicals. The results of this research were published in the May 22, 2010 issue of the Journal of Pharmacokinetics and Pharmacodynamics in an article titled "Physiological and Anatomical Visual Analytics for Mapping Tissue-specific Concentration and Time-course Data."

Called Physiological and Anatomical Visual Analytics, or PAVA, this new approach improves scientists' ability to illustrate complex, quantitative research and communicate it to the broader research community. The tool is a Web-based framework that allows users to import and combine results from multiple PBPK models, and transform them into one or more animated visualizations that help scientists see how a human's anatomy responds to chemicals. Scientists are able to use PAVA to hone in and examine specific factors, including chemicals, organs, exposure durations, and the way gender may influence the metabolism of a chemical.

"Results from PAVA are rendered in a way that lets scientists see changes in chemical concentrations in tissues over time, from chemical to chemical, scenario to scenario, and model to model", said Goldsmith, who specializes in researching relationships between chemical dose and exposure.

The new PAVA tool supports EPA's priority for assuring the safety of chemicals. The tool will help EPA researchers analyze critical exposure information needed to make chemical risk predictions, and will strengthen EPA's ability to manage chemicals in the environment.

Because PAVA results almost come to life in their multi-dimensional, color-coded representations of human anatomy, a new maxim may emerge — if one picture is worth a thousand words, one PAVA rendering may be worth a thousand tables, charts, and graphs.

Citation: PAVA: Physiological and Anatomical Visual Analytics for Mapping Tissue-specific Concentration and Time-course Data. Michael-Rock Goldsmith, Thomas R. Transue, Daniel T. Chang, Rogelio-Tornero Velez, Michael S. Breen, Curtis C. Dary, Journal of Pharmacokinetics and Pharmacodynamics, 2010

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