Assessing Human Variability in Kinetics for Exposures to Multiple Environmental Chemicals: A Physiologically Based Pharmacokinetic Modeling Case Study with Dichloromethane, Benzene, Toluene, Ethylbenzene, and m-Xylene

REFERENCES

• Abraham, K., Mielke, H., Huisinga, W., and Gundert-Remy, U. 2005a. Elevated internal exposure of children in simulated acute inhalation of volatile organic compounds: effects of concentration and duration. Arch. Toxicol. 79: 63–73.
   PubMed Web of Science ®Google Scholar
• Abraham, K., Mielke, H., Huisinga, W., and Gundert-Remy, U. 2005b. Internal exposure of children by simulated acute inhalation of volatile organic compounds: The influence of chemical properties on the child/adult concentration ratio. Basic Clin. Pharmacol. Toxicol. 96: 242–243.
   PubMed Web of Science ®Google Scholar
• Agency for Toxic Substances and Disease Registry. 2007. Toxicological profile for benzene. Atlanta, GA: U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry.
   Google Scholar
• Agency for Toxic Substances and Disease Registry. 2000. Toxicological profile for dichloromethane. Atlanta, GA: U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry.
   Google Scholar
• Alcorn, J., and McNamara, P. J. 2002. Ontogeny of hepatic and renal systemic clearance pathways in infants: Part I. Clin. Pharmacokinet. 41: 959–998.
   PubMed Web of Science ®Google Scholar
• Ali, N., and Tardif, R. 1999. Toxicokinetic modeling of the combined exposure to toluene and n-hexane in rats and humans. J. Occup. Health 41: 95–103.
   Web of Science ®Google Scholar
• Baynes, R. E., Brooks, J. D., Mumtaz, M., and Riviere, J. E. 2002. Effect of chemical interactions in pentachlorophenol mixtures on skin and membrane transport. Toxicol. Sci. 69: 295–305.
   PubMed Web of Science ®Google Scholar
• Benignus, V. A., Bushnell, P. J., Boyes, W. K., Eklund, C., and Kenyon, E. M. 2009. Neurobehavioral effects of acute exposure to four solvents: Meta-analyses. Toxicol. Sci. 109: 296–305.
   PubMed Web of Science ®Google Scholar
• Blackburn, A. C., Tzeng, H. F., Anders, M. W., and Board, P. G. 2000. Discovery of a functional polymorphism in human glutathione transferase zeta by expressed sequence tag database analysis. Pharmacogenetics 10: 49–57.
   PubMedGoogle Scholar
• Boobis, A., Budinsky, R., Collie, S., Crofton, K., Embry, M., Felter, S., et al. 2011. Critical analysis of literature on low-dose synergy for use in screening chemical mixtures for risk assessment. Crit. Rev. Toxicol. 41: 369–383.
   PubMed Web of Science ®Google Scholar
• Clewell, H. J., Gentry, P. R., Covington, T. R., Sarangapani, R., and Teeguarden, J. G. 2004. Evaluation of the potential impact of age- and gender-specific pharmacokinetic differences on tissue dosimetry. Toxicol. Sci. 79: 381–393.
   PubMed Web of Science ®Google Scholar
• Dobrev, I. D., Andersen, M. E., and Yang, R. S. 2001. Assessing interaction thresholds for trichloroethylene in combination with tetrachloroethylene and 1,1,1-trichloroethane using gas uptake studies and PBPK modeling. ,Arch. Toxicol. 75: 134–144.
   Web of Science ®Google Scholar
• Dobrev I. D., Andersen, M. E., and Yang, R. S. 2002. In silico toxicology: Simulating interaction thresholds for human exposure to mixtures of trichloroethylene, tetrachloroethylene, and 1,1,1-trichloroethane. Environ. Health Perspect. 110: 1031–1039.
   PubMed Web of Science ®Google Scholar
• Dorne, J. L. 2007. Human variability in hepatic and renal elimination: implications for risk assessment. J. Appl. Toxicol. 27: 411–420.
   PubMed Web of Science ®Google Scholar
• El-Masri, H. A., Bell, D. A., and Portier, C. J. 1999. Effects of glutathione transferase theta polymorphism on the risk estimates of dichloromethane to humans. Toxicol. Appl. Pharmacol. 158: 221–230.
   PubMed Web of Science ®Google Scholar
• Ginsberg, G., Hattis, D., Sonawane, B., Russ, A., Banati, P., Kozlak, M., et al. 2002. Evaluation of child/adult pharmacokinetic differences from a database derived from the therapeutic drug literature. Toxicol. Sci. 66: 185–200.
   PubMed Web of Science ®Google Scholar
• Ginsberg, G. L., Foos, B. P., and Firestone, M. P. 2005. Review and analysis of inhalation dosimetry methods for application to children’s risk assessment. J. Toxicol. Environ. Health A 68: 573–615.
   PubMed Web of Science ®Google Scholar
• Haber, L. T., Maier, A., Gentry, P. R., Clewell, H. J., and Dourson, M. L. 2002. Genetic polymorphisms in assessing interindividual variability in delivered dose. Regul. Toxicol. Pharmacol. 35: 177–197.
   PubMed Web of Science ®Google Scholar
• Haddad, S., Tardif, R., Boyd, J., and Krishnan, K. 2010. Physiologically based modeling of the pharmacokinetic interactions in chemical mixtures. In Quantitative modeling in toxicology, ed. K. Krishnan and M. E. Andersen, 83–105. Chichester, UK: John Wiley & Sons Ltd.
   Google Scholar
• Haddad, S., Tardif, R., Charest-Tardif, G., and Krishnan, K. 1999. Physiological modeling of the toxicokinetic interactions in a quaternary mixture of aromatic hydrocarbons. Toxicol. Appl. Pharmacol. 161: 249–257.
   PubMed Web of Science ®Google Scholar
• Haddad, S., Charest-Tardif, G., and Krishnan, K. 2000. Physiologically based modeling of the maximal effect of metabolic interactions on the kinetics of components of complex chemical mixtures. J. Toxicol. Environ. Health A 61: 209–223.
   PubMed Web of Science ®Google Scholar
• Haddad, S., Charest-Tardif, G., Tardif, R., and Krishnan, K. 2000. Validation of a physiological modeling framework for simulating the toxicokinetics of chemicals in mixtures. Toxicol. Appl. Pharmacol. 167: 199–209.
   PubMed Web of Science ®Google Scholar
• Haddad, S., Beliveau, M., Tardif, R., and Krishnan, K. 2001. A PBPK modeling-based approach to account for interactions in the health risk assessment of chemical mixtures. Toxicol. Sci. 63: 125–131.
   PubMed Web of Science ®Google Scholar
• Haddad, S., Tardif, G. C., and Tardif, R. 2006. Development of physiologically based toxicokinetic models for improving the human indoor exposure assessment to water contaminants: trichloroethylene and trihalomethanes. J. Toxicol. Environ. Health A 69: 2095–2136.
   PubMed Web of Science ®Google Scholar
• Health Canada. 2009. Guidelines for Canadian drinking water quality: Guideline technical document—Benzene. Ottawa, ON, Canada: Federal-Provincial-Territorial Committee on Drinking Water of the Federal-Provincial-Territorial Committee on Health and the Environment, Health Canada.
   Google Scholar
• Health Canada. 2011. Guidelines for Canadian drinking water quality: Guideline technical document—Dichloromethane. Ottawa, ON, Canada: Federal-Provincial-Territorial Committee on Drinking Water of the Federal-Provincial-Territorial Committee on Health and the Environment, Health Canada.
   Google Scholar
• Health Canada. 2014. Guidelines for Canadian drinking water quality: Guideline technical document—Toluene, ethylbenzene and xylene. Ottawa, ON, Canada: Federal-Provincial-Territorial Committee on Drinking Water of the Federal-Provincial-Territorial Committee on Health and the Environment, Health Canada.
   Google Scholar
• Hendriksen, P. J., Freidig, A. P., Jonker, D., Thissen, U., Bogaards, J. J., Mumtaz, M. M., et al. 2007. Transcriptomics analysis of interactive effects of benzene, trichloroethylene and methyl mercury within binary and ternary mixtures on the liver and kidney following subchronic exposure in the rat. Toxicol. Appl. Pharmacol. 225: 171–188.
   PubMed Web of Science ®Google Scholar
• Johnsrud, E. K., Koukouritaki, S. B., Divakaran, K., Brunengraber, L. L., Hines, R. N., and McCarver, D.G. 2003. Human hepatic CYP2E1 expression during development. J. Pharmacol. Exp. Ther. 307: 402–407.
   PubMed Web of Science ®Google Scholar
• Jonsson, F., and Johanson, G. 2001. A Bayesian analysis of the influence of GSTT1 polymorphism on the cancer risk estimate for dichloromethane. Toxicol. Appl. Pharmacol. 174: 99–112.
   PubMed Web of Science ®Google Scholar
• Lampa, E., Lind, L., Lind, P. M., and Bornefalk-Hermansson, A. 2014. The identification of complex interactions in epidemiology and toxicology: A simulation study of boosted regression trees. Environ. Health 13: 57.
   PubMed Web of Science ®Google Scholar
• Li, W., Gu, Y., James, M. O., Hines, R. N., Simpson, P., Langaee, T., and Stacpoole, P. W. 2012. Prenatal and postnatal expression of glutathione transferase ζ 1 in human liver and the roles of haplotype and subject age in determining activity with dichloroacetate. Drug Metab. Dispos. 2: 232–239.
   Web of Science ®Google Scholar
• Lipscomb, J. C., and Poet, T. S. 2008. In vitro measurements of metabolism for application in pharmacokinetic modeling. Pharmacol. Ther. 118: 82–103.
   PubMed Web of Science ®Google Scholar
• Lipscomb, J. C., Teuschler, L. K., Swartout, J., Swan, G. E., and Snawder, J. E. 2003. Variance of microsomal protein and cytochrome P450 2E1 and 3A forms in adult human liver. Toxicol. Mech. Methods 13: 45–51.
   PubMed Web of Science ®Google Scholar
• Meek, M. E., Boobis, A. R., Crofton, K. M., Heinemeyer, G., Raaij, M. V., and Vickers, C. 2011. Risk assessment of combined exposure to multiple chemicals: A WHO/IPCS framework. Regul. Toxicol. Pharmacol. 60: S1–S14.
   PubMed Web of Science ®Google Scholar
• Meek, M. E., Renwick, A., Ohanian, E., Dourson, M., Lake, B., Naumann, B. D., et al. 2002. Guidelines for application of chemical-specific adjustment factors in dose/concentration-response assessment. Toxicology 181–182:115–120.
   PubMed Web of Science ®Google Scholar
• Mumtaz, M. M., Tully, D. B., El-Masri, H. A., and De Rosa, C. T. 2002. Gene induction studies and toxicity of chemical mixtures. Environ. Health Perspect. 110(suppl. 6): 947–956.
   PubMed Web of Science ®Google Scholar
• Mumtaz, M. M., Rosa, C. T., Cibulas, W., and Falk, H. 2004. Seeking solutions to chemical mixtures challenges in public health. Environ. Toxicol. Pharmacol. 18: 55–63.
   PubMed Web of Science ®Google Scholar
• Mumtaz, M. M., Ruiz, P., and De Rosa, C. T. 2007. Toxicity assessment of unintentional exposure to multiple chemicals. Toxicol. Appl. Pharmacol. 223: 104–113.
   PubMed Web of Science ®Google Scholar
• Neafsey, P., Ginsberg, G., Hattis, D., Johns, D. O., Guyton, K. Z., and Sonawane, B. 2009. Genetic polymorphism in CYP2E1: Population distribution of CYP2E1 activity. J. Toxicol. Environ. Health B 12: 362–388.
   PubMed Web of Science ®Google Scholar
• Nong, A., McCarver, D. G., Hines, R. N., and Krishnan, K. 2006. Modeling interchild differences in pharmacokinetics on the basis of subject-specific data on physiology and hepatic CYP2E1 levels: A case study with toluene. Toxicol. Appl. Pharmacol. 214: 78–87.
   PubMed Web of Science ®Google Scholar
• Pelekis, M., Gephart, L. A., and Lerman, S. E. 2001. Physiological-model-based derivation of the adult and child pharmacokinetic intraspecies uncertainty factors for volatile organic compounds. Regul. Toxicol. Pharmacol. 33:12–20.
   PubMed Web of Science ®Google Scholar
• Pelekis, M., Nicolich, M. J., and Gauthier, J. S. 2003. Probabilistic framework for the estimation of the adult and child toxicokinetic intraspecies uncertainty factors. Risk Anal. 23: 1239–1255.
   PubMed Web of Science ®Google Scholar
• Pounds, J. G., Haider, J., Chen, D. G., and Mumtaz, M. 2004. Interactive toxicity of simple chemical mixtures of cadmium, mercury, methylmercury and trimethyltin: model-dependent responses. Environ. Toxicol. Pharmacol. 18: 101–113.
   PubMed Web of Science ®Google Scholar
• Price, K., Haddad, S., and Krishnan, K. 2003. Physiological modeling of age-specific changes in the pharmacokinetics of organic chemicals in children. J. Toxicol. Environ. Health A 66: 417–433.
   PubMed Web of Science ®Google Scholar
• Price, K., and Krishnan, K. 2011. An integrated QSAR-PBPK modelling approach for predicting the inhalation toxicokinetics of mixtures of volatile organic chemicals in the rat. SAR QSAR Environ. Res. 22: 107–128.
   PubMed Web of Science ®Google Scholar
• Purcell, K. J., Cason, G. H., Gargas, M. L., Andersen, M. E., and Travis, C. C. 1990. In vivo metabolic interactions of benzene and toluene. Toxicol. Lett. 52: 141–152.
   PubMed Web of Science ®Google Scholar
• Renwick, A. G., and Lazarus, N. R. 1998. Human variability and non-cancer risk assessment—An analysis of the default uncertainty factor. Regul. Toxicol. Pharmacol. 27: 3–20.
   PubMed Web of Science ®Google Scholar
• Ronis, M. J. J., Lindros, K. O., and Ingelman-Sundberg, M. 1996. The CYP2E family. In Cytochrome P450 metabolic and toxicological aspects, ed. C. Ioannides, 211–240. Boca Raton, FL: CRC Press.
   Google Scholar
• Soni, M. G., Ramaiah, S. K., Mumtaz, M. M., Clewell, H., and Mehendale, H. M. 1999. Toxicant-inflicted injury and stimulated tissue repair are opposing toxicodynamic forces in predictive toxicology. Regul. Toxicol. Pharmacol. 29:165–174.
   PubMed Web of Science ®Google Scholar
• Starr, J. M., Scollon, E. J., Hughes, M. F., Ross, D. G., Graham, S. E., Crofton, K. M., et al. 2012. Environmentally relevant mixtures in cumulative assessments: an acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids. Toxicol. Sci. 130: 309–318.
   PubMed Web of Science ®Google Scholar
• Sarangapani, R., Gentry, P. R., Covington, T. R., Teeguarden, J. G., and Clewell, H. J. III. 2003. Evaluation of the potential impact of age- and gender-specific lung morphology and ventilation rate on the dosimetry of vapors. Inhal. Toxicol. 15: 987–1016.
   PubMed Web of Science ®Google Scholar
• Tang, Y., Donnelly, K. C., Tiffany-Castiglioni, E., and Mumtaz, M. M. 2003. Neurotoxicity of polycyclic aromatic hydrocarbons and simple chemical mixtures. J. Toxicol. Environ. Health A 66: 919–940.
   PubMed Web of Science ®Google Scholar
• Tardif, R., Lapare, S., Krishnan, K., and Brodeur, J. 1993. Physiologically based modeling of the toxicokinetic interaction between toluene and m-xylene in the rat. Toxicol. Appl. Pharmacol. 120: 266–273.
   PubMed Web of Science ®Google Scholar
• Tardif, R., Lapare, S., Charest-Tardif, G., Brodeur, J., and Krishnan, K. 1995. Physiologically-based pharmacokinetic modeling of a mixture of toluene and xylene in humans. Risk Anal. 15: 335–342.
   PubMed Web of Science ®Google Scholar
• Tully, D. B., Collins, B. J., Overstreet, J. D., Smith, C. S., Dinse, G. E., Mumtaz, M. M., et al. 2000. Effects of arsenic, cadmium, chromium, and lead on gene expression regulated by a battery of 13 different promoters in recombinant HepG2 cells. Toxicol. Appl. Pharmacol. 168: 79–90.
   PubMed Web of Science ®Google Scholar
• Tully, D. B., Cox, V. T., Mumtaz, M. M., Davis, V. L., and Chapin, R. E. 2000. Six high-priority organochlorine pesticides, either singly or in combination, are nonestrogenic in transfected HeLa cells. Reprod. Toxicol 14: 95–102.
   PubMed Web of Science ®Google Scholar
• U.S.Environmental Protection Agency. 2003. A review of the reference dose and reference concentration process, ed. Risk Assessment Forum. Washington, DC: U.S. Environmental Protection Agency.
   Google Scholar
• Valcke, M., and Krishnan, K. 2013. Assessing the impact of child/adult differences in hepatic first-pass effect on the human kinetic adjustment factor for ingested toxicants. Regul. Toxicol. Pharmacol. 65: 126–134.
   PubMed Web of Science ®Google Scholar
• Valcke, M., Nong, A., and Krishnan, K. 2012. Modeling the human kinetic adjustment factor for inhaled volatile organic chemicals: Whole population approach vs distinct subpopulation approach. J. Toxicol. open access. Article ID 404329. doi:10.1155/2012/404329
   Google Scholar
• Valcke, M., and Krishnan, K. 2010. An assessment of the interindividual variability of internal dosimetry during multi-route exposure to drinking water contaminants. Int. J. Environ. Res. Public Health 7: 4002–4022.
   PubMed Web of Science ®Google Scholar
• Valcke, M., and Krishnan, K. 2011a. Evaluation of the impact of the exposure route on the human kinetic adjustment factor. Regul. Toxicol. Pharmacol. 59: 258–269.
   PubMed Web of Science ®Google Scholar
• Valcke, M., and Krishnan, K. 2011b. An assessment of the impact of physico-chemical and biochemical characteristics on the human kinetic adjustment factor for systemic toxicants. Toxicology 246: 36–47.
   Web of Science ®Google Scholar
• Valcke, M., and Krishnan, K. 2011c. Assessing the impact of the duration and intensity of inhalation exposure on the magnitude of the variability of internal dose metrics in children and adults. Inhal. Toxicol. 23: 863–877.
   PubMed Web of Science ®Google Scholar
• World Health Organization/International Programme on Chemical Safety. 2005. Chemical-specific adjustment factors (CSAFs) for interspecies differences and human variability: Guidance document for the use of data in dose/concentration-response assessment. Report WHO/IPCS/01.4. http://www.inchem.org/documents/harmproj/harmproj/harmproj2.pdf
   Google Scholar
• Yu, X., Johanson, G., Ichiara, G., Shibata, E., Kamijima, M., Ono, Y., and Takeuchi, Y. 1998. Physiologically based pharmacokinetic modeling of metabolic interactions between n-hexane and toluene in humans. J. Occup. Health 40: 293–301.
   Web of Science ®Google Scholar
• Zeise, L., Bois, F. Y., Chiu, W. A., Hattis, D., Rusyn, I., and Guyton, K. Z. 2013. Addressing human variability in next-generation human health risk assessments of environmental chemicals. Environ. Health Perspect. 121: 23–31.
   PubMed Web of Science ®Google Scholar