Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms
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 ex...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2012/852384 |
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| author | Jane C. Caldwell Marina V. Evans Kannan Krishnan |
| author_facet | Jane C. Caldwell Marina V. Evans Kannan Krishnan |
| author_sort | Jane C. Caldwell |
| collection | DOAJ |
| description | 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 computational toxicology models is critical for extrapolation between in vitro exposures, in vivo physiologic exposure, whole organism responses, and long-term health outcomes. This special issue contains papers that can provide the basis for future modeling efforts and provide bridges to emerging toxicology paradigms. In this overview paper, we present an overview of the field and introduction for these papers that includes discussions of model development, best practices, risk-assessment applications of PBPK models, and limitations and bridges of modeling approaches for future applications. Specifically, issues addressed include: (a) increased understanding of human variability of pharmacokinetics and pharmacodynamics in the population, (b) exploration of mode of action hypotheses (MOA), (c) application of biological modeling in the risk assessment of individual chemicals and chemical mixtures, and (d) identification and discussion of uncertainties in the modeling process. |
| format | Article |
| id | doaj-art-3c94288dd7304183a50952cabbf8455e |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-3c94288dd7304183a50952cabbf8455e2025-02-03T01:12:37ZengWileyJournal of Toxicology1687-81911687-82052012-01-01201210.1155/2012/852384852384Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology ParadigmsJane C. Caldwell0Marina V. Evans1Kannan Krishnan2National Center for Environmental Assessment Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, Washington, DC 20460, USANational Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USADepartment of Occupational and Environmental Health, Université de Montréal, Montreal, QC, H3C 3J7, CanadaPhysiologically 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 computational toxicology models is critical for extrapolation between in vitro exposures, in vivo physiologic exposure, whole organism responses, and long-term health outcomes. This special issue contains papers that can provide the basis for future modeling efforts and provide bridges to emerging toxicology paradigms. In this overview paper, we present an overview of the field and introduction for these papers that includes discussions of model development, best practices, risk-assessment applications of PBPK models, and limitations and bridges of modeling approaches for future applications. Specifically, issues addressed include: (a) increased understanding of human variability of pharmacokinetics and pharmacodynamics in the population, (b) exploration of mode of action hypotheses (MOA), (c) application of biological modeling in the risk assessment of individual chemicals and chemical mixtures, and (d) identification and discussion of uncertainties in the modeling process.http://dx.doi.org/10.1155/2012/852384 |
| spellingShingle | Jane C. Caldwell Marina V. Evans Kannan Krishnan Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms Journal of Toxicology |
| title | Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms |
| title_full | Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms |
| title_fullStr | Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms |
| title_full_unstemmed | Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms |
| title_short | Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms |
| title_sort | cutting edge pbpk models and analyses providing the basis for future modeling efforts and bridges to emerging toxicology paradigms |
| url | http://dx.doi.org/10.1155/2012/852384 |
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