About this Journal Submit a Manuscript Table of Contents
Journal of Toxicology
Volume 2012 (2012), Article ID 904603, 11 pages
http://dx.doi.org/10.1155/2012/904603
Review Article

Application of Physiologically Based Pharmacokinetic Models in Chemical Risk Assessment

1Computational Toxicology and Methods Development Laboratory, Division of Toxicology and Environmental Medicine (DTEM), Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA 30333, USA
2National Center for Toxicological Research, USFDA, Jefferson, AR 72079, USA
3Division of Laboratory Studies, National Center for Environmental Health, Centers for Disease Control and Prevention (CDC), Atlanta, GA 30341, USA

Received 20 October 2011; Accepted 21 December 2011

Academic Editor: Kannan Krishnan

Copyright © 2012 Moiz Mumtaz 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.

Linked References

  1. Y.-M. Tan, H. Clewell, J. Campbell, and M. Andersen, “Evaluating pharmacokinetic and pharmacodynamic interactions with computational models in supporting cumulative risk assessment,” International Journal of Environmental Research and Public Health, vol. 8, no. 5, pp. 1613–1630, 2011. View at Publisher · View at Google Scholar · View at PubMed
  2. K. S. Pang and M. R. Durk, “Physiologically-based pharmacokinetic modeling for absorption, transport, metabolism and excretion,” Journal of Pharmacokinetics and Pharmacodynamics, vol. 37, no. 6, pp. 591–615, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. R. S. DeWoskin, “PBPK models in risk assessment-A focus on chloroprene,” Chemico-Biological Interactions, vol. 166, no. 1–3, pp. 352–359, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. M. Reddy, R. S. H. Yang, H. J. Clewell, and M. E. Andersen, Eds., Physiologically Based Pharmacokinetic Modeling, John Wiley & Sons, Hoboken, NJ, USA, 2005.
  5. R. Dixit, J. Riviere, K. Krishnan, and M. E. Andersen, “Toxicokinetics and physiologically based toxicokinetics in toxicology and risk assessment,” Journal of Toxicology and Environmental Health—Part B, vol. 6, no. 1, pp. 1–40, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. R. S. DeWoskin, S. Barone, H. J. Clewell, and R. W. Setzer, “Improving the development and use of biologically based dose response models (BBDR) in risk assessment,” Human and Ecological Risk Assessment, vol. 7, no. 5, pp. 1091–1120, 2001. View at Scopus
  7. U.S. Environmental Protection Agency, Approaches for the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment, EPA/600/R-05/043F, U.S. Environmental Protection Agency, Washington, DC, USA, 2006.
  8. L. H. Clark, R. W. Setzer, and H. A. Barton, “Framework for evaluation of physiologically-based pharmacokinetic models for use in safety or risk assessment,” Risk Analysis, vol. 24, no. 6, pp. 1697–1717, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. M. E. Andersen, “Development of physiologically based pharmacokinetic and physiologically based pharmacodynamic models for applications in toxicology and risk assessment,” Toxicology Letters, vol. 79, no. 1–3, pp. 35–44, 1995. View at Publisher · View at Google Scholar · View at Scopus
  10. H. A. El-Masri, M. M. Mumtaz, G. Choudhary, W. Cibulas, and C. T. De Rosa, “Applications of computational toxicology methods at the Agency for Toxic Substances and Disease Registry,” International Journal of Hygiene and Environmental Health, vol. 205, no. 1-2, pp. 63–69, 2002. View at Scopus
  11. M. M. Mumtaz, L. A. Knauf, D. J. Reisman et al., “Assessment of effect levels of chemicals from quantitative structure- activity relationship (QSAR) models. I. Chronic lowest-observed-adverse- effect level (LOAEL),” Toxicology Letters, vol. 79, no. 1–3, pp. 131–143, 1995. View at Publisher · View at Google Scholar · View at Scopus
  12. P. Ruiz, B. A. Fowler, J. D. Osterloh, J. Fisher, and M. Mumtaz, “Physiologically based pharmacokinetic (PBPK) tool kit for environmental pollutants—metals,” SAR and QSAR in Environmental Research, vol. 21, no. 7, pp. 603–618, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. P. Ruiz, M. Mumtaz, J. Osterloh, J. Fisher, and B. A. Fowler, “Interpreting NHANES biomonitoring data, cadmium,” Toxicology Letters, vol. 198, no. 1, pp. 44–48, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. P. Ruiz, M. Mumtaz, and V. Gombar, “Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models,” Toxicology and Applied Pharmacology, vol. 254, no. 2, pp. 198–205, 2011. View at Publisher · View at Google Scholar · View at PubMed
  15. E. Demchuk, P. Ruiz, J. D. Wilson et al., “Computational toxicology methods in public health practice,” Toxicology Mechanisms and Methods, vol. 18, no. 2-3, pp. 119–135, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. H. J. Clewell, P. R. Gentry, and J. M. Gearhart, “Investigation of the potential impact of benchmark dose and pharmacokinetic modeling in noncancer risk assessment,” Journal of Toxicology and Environmental Health—Part A, vol. 52, no. 6, pp. 475–515, 1997. View at Scopus
  17. Agency for Toxic Substances and Disease Registry (ATSDR), “Minimal risk levels for priority substances and guidance for derivation,” Federal Register, vol. 61, no. 125, pp. 33511–33520, 1996.
  18. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Mercury Compounds, Update, ATSDR, Atlanta, Ga, USA, 1997.
  19. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Mercury Compounds, Update, ATSDR, Atlanta, Ga, USA, 1995.
  20. J. L. Campbell, K. Krishnan, H. J. Clewell, and M.E. Andersen, “Kinetic interactions of chemical mixtures,” in Principles and Practice of Mixtures Toxicology, M. Mumtaz, Ed., Wiley, Weinheim, Germany, 2010.
  21. K. Kannan, A. Sasso, and P. Georgopoulos, “Phramocokinetic mechanisms of interactions in chemical mixtures,” in Principles and Practice of Mixtures Toxicology, M. Mumtaz, Ed., Wiley, Weinheim, Germany, 2010.
  22. M. M. Mumtaz and P. R. Durkin, “A weight-of-evidence approach for assessing interactions in chemical mixtures,” Toxicology and Industrial Health, vol. 8, no. 6, pp. 377–406, 1992. View at Scopus
  23. M. M. Mumtaz, C. T. De Rosa, J. Groten, V. J. Feron, H. Hansen, and P. R. Durkin, “Estimation of toxicity of chemical mixtures through modeling of chemical interactions,” Environmental Health Perspectives, vol. 106, no. 6, pp. 1353–1360, 1998. View at Scopus
  24. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile of Chlorpyrifos, U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry, Atlanta, GA, USA, 1997.
  25. H. A. El-Masri, M. M. Mumtaz, and M. L. Yushak, “Application of physiologically-based pharmacokinetic modeling to investigate the toxicological interaction between chlorpyrifos and parathion in the rat,” Environmental Toxicology and Pharmacology, vol. 16, no. 1-2, pp. 57–71, 2004. View at Publisher · View at Google Scholar
  26. J. E. Dennison, M. E. Andersen, I. D. Dobrev, M. M. Mumtaz, and R. S.H. Yang, “PBPK modeling of complex hydrocarbon mixtures: gasoline,” Environmental Toxicology and Pharmacology, vol. 16, no. 1-2, pp. 107–119, 2004. View at Publisher · View at Google Scholar · View at PubMed
  27. E. D. McLanahan, M. E. Andersen, M. Mumtaz, and J. W. Fisher, “BBPK model of the hypothalamic-pituitary-thyroid axis in the adult rat,” The Toxicologist, vol. 96, no. 1, article 394, 2007.
  28. E. D. Mclanahan, M. E. Andersen, and J. W. Fisher, “A biologically based dose-response model for dietary iodide and the hypothalamic-pituitary-thyroid axis in the adult Rat: evaluation of iodide deficiency,” Toxicological Sciences, vol. 102, no. 2, pp. 241–253, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. J. E. Dennison, P. L. Bigelow, M. M. Mumtaz, M. E. Andersen, I. D. Dobrev, and R. S. H. Yang, “Evaluation of potential toxicity from co-exposure to three CNS depressants (toluene, ethylbenzene, and xylene) under resting and working conditions using PBPK modeling,” Journal of Occupational and Environmental Hygiene, vol. 2, no. 3, pp. 127–135, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. Occupational Safety and Health Administration (OSHA), “Air Contaminants,” Code of Federal Regulations, Title 29, Part 1910.1000, 2004.
  31. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile of Polychlorinated Biphenyls, U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry, Atlanta, Ga, USA, 2000.
  32. R. J. Lutz, R. L. Dedrick, and H. B. Matthews, “A preliminary pharmacokinetic model for several chlorinated biphenyls in the rat,” Drug Metabolism and Disposition, vol. 5, no. 4, pp. 386–396, 1977.
  33. F. M. Parham, M. C. Kohn, H. B. Matthews, C. DeRosa, and C. J. Portier, “Using structural information to create physiologically based pharmacokinetic models for all polychlorinated biphenyls I. Tissue:Blood partition coefficients,” Toxicology and Applied Pharmacology, vol. 144, no. 2, pp. 340–347, 1997. View at Publisher · View at Google Scholar · View at Scopus
  34. F. M. Parham and C. J. Portier, “Using structural information to create physiologically based pharmacokinetic models for all polychlorinated biphenyls. II: rates of metabolism,” Toxicology and Applied Pharmacology, vol. 151, no. 1, pp. 110–116, 1998. View at Publisher · View at Google Scholar · View at Scopus
  35. A. N. Edginton and G. Joshi, “Have physiologically-based pharmacokinetic models delivered?” Expert Opinion on Drug Metabolism and Toxicology, vol. 7, no. 8, pp. 929–934, 2011. View at Publisher · View at Google Scholar · View at PubMed
  36. R. I. Macey and G. F. Oster, Berkeley Madonna. Version 8.3.9, Berkeley Madonna, 1996–2006.
  37. M. M. Mumtaz, M. Ray, S. R. Crowell, D. Keys, J. Fisher, and P. Ruiz, “Translational research to develop a human pbpk models tool kit-volatile organic compounds (VOCS),” Journal of Toxicology and Environmental Health—Part A, vol. 75, no. 1, pp. 6–24, 2012. View at Publisher · View at Google Scholar · View at PubMed
  38. K. Yokley, H. T. Tran, K. Pekari et al., “Physiologically-based pharmacokinetic modeling of benzene in humans: a Bayesian approach,” Risk Analysis, vol. 26, no. 4, pp. 925–943, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. K. D. Thrall, M. E. Vucelick, R. A. Gies et al., “Comparative metabolism of carbon tetrachloride in rats, mice, and hamsters using gas uptake and PBPK modeling,” Journal of Toxicology and Environmental Health—Part A, vol. 60, no. 8, pp. 531–548, 2000. View at Scopus
  40. R. M. David, H. J. Clewell, P. R. Gentry, T. R. Covington, D. A. Morgott, and D. J. Marino, “Revised assessment of cancer risk to dichloromethane II. Application of probabilistic methods to cancer risk determinations,” Regulatory Toxicology and Pharmacology, vol. 45, no. 1, pp. 55–65, 2006. View at Publisher · View at Google Scholar · View at PubMed
  41. T. R. Covington, P. Robinan Gentry, C. B. Van Landingham, M. E. Andersen, J. E. Kester, and H. J. Clewell, “The use of Markov chain Monte Carlo uncertainty analysis to support a Public Health Goal for perchloroethylene,” Regulatory Toxicology and Pharmacology, vol. 47, no. 1, pp. 1–18, 2007. View at Publisher · View at Google Scholar · View at PubMed
  42. J. W. Fisher, D. Mahle, and R. Abbas, “A human physiologically based pharmacokinetic model for trichloroethylene and its metabolites, trichloroacetic acid and free trichloroethanol,” Toxicology and Applied Pharmacology, vol. 152, no. 2, pp. 339–359, 1998. View at Publisher · View at Google Scholar · View at PubMed
  43. H. J. Clewell, P. R. Gentry, J. M. Gearhart, B. C. Allen, and M. E. Andersen, “Comparison of cancer risk estimates for vinyl chloride using animal and human data with a PBPK model,” Science of the Total Environment, vol. 274, no. 1–3, pp. 37–66, 2001. View at Publisher · View at Google Scholar · View at Scopus
  44. H. J. Clewell, P. R. Gentry, T. R. Covington, and J. M. Gearhart, “Development of a physiologically based pharmacokinetic model of trichloroethylene and its metabolites for use in risk assessment,” Environmental Health Perspectives, vol. 108, no. 2, pp. 283–305, 2000. View at Scopus
  45. H. J. Clewell, P. R. Gentry, J. E. Kester, and M. E. Andersen, “Evaluation of physiologically based pharmacokinetic models in risk assessment: an example with perchloroethylene,” Critical Reviews in Toxicology, vol. 35, no. 5, pp. 413–433, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. R. P. Brown, M. D. Delp, S. L. Lindstedt, L. R. Rhomberg, and R. P. Beliles, “Physiological parameter values for physiologically based pharmacokinetic models,” Toxicology and Industrial Health, vol. 13, no. 4, pp. 407–484, 1997. View at Scopus
  47. A. L. Cowles, H. H. Borgstedt, and A. J. Gillies, “Tissue weights and rates of blood flow in man for the prediction of anesthetic uptake and distribution,” Anesthesiology, vol. 35, no. 5, pp. 523–526, 1971. View at Scopus
  48. R. A. Corley, S. M. Gordon, and L. A. Wallace, “Physiologically based pharmacokinetic modeling of the temperature- dependent dermal absorption of chloroform by humans following bath water exposures,” Toxicological Sciences, vol. 53, no. 1, pp. 13–23, 2000. View at Scopus
  49. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Perchloroethylene, U.S. Department of Health and Human Services, Public Health Service, Atlanta, Ga, USA, 1997.
  50. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Trichloroethylene, U.S. Department of Health and Human Services, Public Health Service, Atlanta, Ga, USA, 1997.
  51. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Dichloromethane, U.S. Department of Health and Human Services, Public Health Service, Atlanta, Ga, USA, 2000.
  52. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Carbon Tetrachloride, U.S. Department of Health and Human Services, Public Health Service, Atlanta, Ga, USA, 2005.
  53. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Vinyl Chloride, U.S. Department of Health and Human Services, Public Health Service, Atlanta, Ga, USA, 2006.
  54. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Benzene, U.S. Department of Health and Human Services, Public Health Service, Atlanta, Ga, USA, 2007.
  55. Centers for Disease Control and Prevention (CDC), Fourth National Report on Human Exposure to Environmental Chemicals, Division of Laboratory Sciences, National Center for Environmental Health, Atlanta, Ga, USA, 2009.
  56. H. A. El-Masri and E. M. Kenyon, “Development of a human physiologically based pharmacokinetic (PBPK) model for inorganic arsenic and its mono- and di-methylated metabolites,” Journal of Pharmacokinetics and Pharmacodynamics, vol. 35, no. 1, pp. 31–68, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. G. Carrier, R. C. Brunet, M. Caza, and M. Bouchard, “A toxicokinetic model for predicting the tissue distribution and elimination of organic and inorganic mercury following exposure to methyl mercury in animals and humans. I. Development and validation of the model using experimental data in rats,” Toxicology and Applied Pharmacology, vol. 171, no. 1, pp. 38–49, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. G. Carrier, M. Bouchard, R. C. Brunet, and M. Caza, “A toxicokinetic model for predicting the tissue distribution and elimination of organic and inorganic mercury following exposure to methyl mercury in animals and humans. II. Application and validation of the model in humans,” Toxicology and Applied Pharmacology, vol. 171, no. 1, pp. 50–60, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. H. Choudhury, T. Harvey, W. C. Thayer et al., “Urinary cadmium elimination as a biomarker of exposure for evaluating a cadmium dietary exposure—biokinetics model,” Journal of Toxicology and Environmental Health—Part A, vol. 63, no. 5, pp. 321–350, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. G. L. Diamond, W. C. Thayer, and H. Choudhury, “Pharmacokinetics/pharmacodynamics (PK/PD) modeling of risks of kidney toxicity from exposure to cadmium: estimates of dietary risks in the U.S. population,” Journal of Toxicology and Environmental Health—Part A, vol. 66, no. 22, pp. 2141–2164, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. T. Kjellström and G. F. Nordberg, “A kinetic model of cadmium metabolism in the human being,” Environmental Research, vol. 16, no. 1–3, pp. 248–269, 1978. View at Scopus
  62. Y.-M. Tan, K. H. Liao, and H. J. Clewell, “Reverse dosimetry: interpreting trihalomethanes biomonitoring data using physiologically based pharmacokinetic modeling,” Journal of Exposure Science and Environmental Epidemiology, vol. 17, no. 7, pp. 591–603, 2007. View at Publisher · View at Google Scholar · View at PubMed
  63. S. M. Hays, R. A. Becker, H. W. Leung, L. L. Aylward, and D. W. Pyatt, “Biomonitoring equivalents: a screening approach for interpreting biomonitoring results from a public health risk perspective,” Regulatory Toxicology and Pharmacology, vol. 47, no. 1, pp. 96–109, 2007. View at Publisher · View at Google Scholar · View at PubMed
  64. Y. M. Tan, K. Liao, R. Conolly, B. Blount, A. Mason, and H. Clewell, “Use of a physiologically based pharmacokinetic model to identify exposures consistent with human biomonitoring data for chloroform,” Journal of Toxicology and Environmental Health—Part A, vol. 69, no. 18, pp. 1727–1756, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. K. H. Liao, Y. M. Tan, and H. J. Clewell, “Development of a screening approach to interpret human biomonitoring data on volatile organic compounds: reverse dosimetry on biomonitoring data for trichloroethylene,” Risk Analysis, vol. 27, no. 5, pp. 1223–1236, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. H. J. Clewell, Y. M. Tan, J. L. Campbell, and M. E. Andersen, “Quantitative interpretation of human biomonitoring data,” Toxicology and Applied Pharmacology, vol. 231, no. 1, pp. 122–133, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  67. M. A. Lyons, R. S. H. Yang, A. N. Mayeno, and B. Reisfeld, “Computational toxicology of chloroform: reverse dosimetry using Bayesian inference, Markov chain Monte Carlo simulation, and human biomonitoring data,” Environmental Health Perspectives, vol. 116, no. 8, pp. 1040–1046, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. P. G. Georgopoulos, A. Roy, and M. A. Gallo, “Reconstruction of short-term multi-route exposure to volatile organic compounds using physiologically based pharmacokinetic models,” Journal of Exposure Analysis and Environmental Epidemiology, vol. 4, no. 3, pp. 309–328, 1994. View at Scopus
  69. C. P. Weisel, H. Kim, P. Haltmeier, and J. B. Klotz, “Exposure estimates to disinfection by-products of chlorinated drinking water,” Environmental Health Perspectives, vol. 107, no. 2, pp. 103–110, 1999. View at Scopus
  70. C. R. Kirman, L. L. Aylward, B. C. Blount, D. W. Pyatt, and S. M. Hays, “Evaluation of NHANES biomonitoring data for volatile organic chemicals in blood: application of chemical-specific screening criteria,” Journal of Exposure Science and Environmental Epidemiology, vol. 22, no. 1, pp. 24–34, 2012. View at Publisher · View at Google Scholar · View at PubMed
  71. L. L. Aylward, C. R. Kirman, B. C. Blount, and S. M. Hays, “Chemical-specific screening criteria for interpretation of biomonitoring data for volatile organic compounds (VOCs)—application of steady-state PBPK model solutions,” Regulatory Toxicology and Pharmacology, vol. 58, no. 1, pp. 33–44, 2010. View at Publisher · View at Google Scholar · View at PubMed
  72. S. M. Hays, L. L. Aylward, J. S. LaKind et al., “Guidelines for the derivation of biomonitoring equivalents: report from the biomonitoring equivalents expert workshop,” Regulatory Toxicology and Pharmacology, vol. 51, no. 3, supplement, pp. S4–S15, 2008. View at Publisher · View at Google Scholar · View at PubMed
  73. A. Forsby and B. Blaauboer, “Integration of in vitro neurotoxicity data with biokinetic modelling for the estimation of in vivo neurotoxicity,” Human and Experimental Toxicology, vol. 26, no. 4, pp. 333–338, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  74. B. J. Blaauboer, “The integration of data on physico-chemical properties, in vitro-derived toxicity data and physiologically based kinetic and dynamic as modelling a tool in hazard and risk assessment. A commentary,” Toxicology Letters, vol. 138, no. 1-2, pp. 161–171, 2003. View at Publisher · View at Google Scholar · View at Scopus
  75. S. S. De Buck and C. E. Mackie, “Physiologically based approaches towards the prediction of pharmacokinetics: in vitro-in vivo extrapolation,” Expert Opinion on Drug Metabolism and Toxicology, vol. 3, no. 6, pp. 865–878, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  76. B. J. Blaauboer, “Biokinetic modeling and in vitro-in vivo extrapolations,” Journal of Toxicology and Environmental Health—Part B, vol. 13, no. 2–4, pp. 242–252, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  77. J. Louisse, E. de Jong, J. J. M. van de Sandt et al., “The use of in vitro toxicity data and physiologically based kinetic modeling to predict dose-response curves for in vivo developmental toxicity of glycol ethers in rat and man,” Toxicological Sciences, vol. 118, no. 2, pp. 470–484, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  78. M. D. Sohn, T. E. McKone, and J. N. Blancato, “Reconstructing population exposures from dose biomarkers: inhalation of trichloroethylene (TCE) as a case study,” Journal of Exposure Analysis and Environmental Epidemiology, vol. 14, no. 3, pp. 204–213, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. T. E. McKone, “Linking a PBPK model for chloroform with measured breath concentrations in showers: implications for dermal exposure models,” Journal of Exposure Analysis and Environmental Epidemiology, vol. 3, no. 3, pp. 339–365, 1993. View at Scopus
  80. K. T. Bogen and T. E. McKone, “Linking indoor air and pharmacokinetic models to assess tetrachloroethylene risk,” Risk Analysis, vol. 8, no. 4, pp. 509–520, 1988. View at Publisher · View at Google Scholar · View at Scopus
  81. D. M. Rotroff, B. A. Wetmore, D. J. Dix et al., “Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening,” Toxicological Sciences, vol. 117, no. 2, pp. 348–358, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  82. B. A. Wetmore, J. F. Wambaugh, S. S. Ferguson et al., “Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment,” Toxicological Sciences, vol. 125, no. 1, pp. 157–174, 2012. View at Publisher · View at Google Scholar · View at PubMed