Cutting Edge PBPK Models and Analyses Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms.pdfVIP

Hindawi Publishing Corporation Journal of Toxicology Volume 2012, Article ID 852384, 10 pages doi:10.1155/2012/852384 Review Article Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms Jane C. Caldwell,1 Marina V. Evans,2 and Kannan Krishnan3 1 National Center for Environmental Assessment Offi ce of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, Washington, DC 20460, USA 2 National Health and Environmental Eff ects Research Laboratory, Offi ce of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA 3 Department of Occupational and Environmental Health, Universite de Montreal, Montreal, QC, Canada H3C 3J7 ´ ´ Correspondence should be addressed to Jane C. Caldwell, caldwell.jane@ Received 9 April 2012; Accepted 21 June 2012 Academic Editor: Jack Ng Copyright © 2012 Jane C. Caldwell et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Physiologically based Pharmacokinetic (PBPK) models are used for predictions of internal or target dose from environmental and pharmacologic chemical exposures. Their use in human risk assessment is dependent on the nature of databases (animal or human) used to develop and test them, and includes extrapolations across species, experimental paradigms, and determination of variability of response within human populations. Integration of state-of-the science PBPK modeling with emerging