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Application of PBPK modeling in support of the derivation of toxicity reference values for 1,1,1-trichloroethane.
Regul Toxicol Pharmacol. 2008 Mar; 50(2):249-60.RT

Abstract

PBPK modeling has been increasingly applied in chemical risk assessment for dose, route, and species extrapolation. The use of PBPK modeling was explored in deriving toxicity reference values for 1,1,1-trichloroethane (1,1,1-TCE). This effort involved a 5-step process: (i) reconstruction of several published PBPK models for 1,1,1-TCE in the rat and human; (ii) selection of appropriate pharmacokinetic datasets for model comparison; (iii) determination of the most suitable PBPK model for supporting reference value derivation; (iv) PBPK model simulation of two critical studies to estimate internal dose metrics; and (v) calculation of internal dose metrics for human exposure scenarios for reference value derivation. The published model by Reitz et al. [Reitz, R.H., McDougal, J.N., Himmelstein, M.W., Nolan, R.J., Schumann, A.M., 1988. Physiologically based pharmacokinetic modeling with methylchloroform: implications for interspecies, high dose/low dose, and dose route extrapolations. Toxicol. Appl. Pharmacol. 95, 185-199] was judged the most suitable. This model has liver, fat, and rapidly and slowly perfused compartments, contains a saturable process for 1,1,1-TCE hepatic metabolism, and accommodates multiple exposure pathways in three species. Data from a human volunteer study involving acute inhalation exposure [Mackay, C.J., Campbell, L., Samuel, A.M., Alderman, K.J., Idzikowski, C., Wilson, H.K., Gompertz, D., 1987. Behavioral changes during exposure to 1,1,1-trichloroethane: time-course and relationship to blood solvent levels. Am. J. Ind. Med. 11, 223-239] and a chronic rat inhalation study [Quast, J.F., Calhoun, L.L., Frauson, L.E., 1988. 1,1,1-Trichloroethane formulation: a chronic inhalation toxicity and oncogenicity study in Fischer 344 rats and B6C3F1 mice. Fundam. Appl. Toxicol. 11, 611-625] were selected to simulate appropriate internal dosimetry data from which to derive reference value points of departure. Duration, route, and species extrapolations were performed based on internal dose metrics.

Authors+Show Affiliations

Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523-1681, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

18226845

Citation

Lu, Yasong, et al. "Application of PBPK Modeling in Support of the Derivation of Toxicity Reference Values for 1,1,1-trichloroethane." Regulatory Toxicology and Pharmacology : RTP, vol. 50, no. 2, 2008, pp. 249-60.
Lu Y, Rieth S, Lohitnavy M, et al. Application of PBPK modeling in support of the derivation of toxicity reference values for 1,1,1-trichloroethane. Regul Toxicol Pharmacol. 2008;50(2):249-60.
Lu, Y., Rieth, S., Lohitnavy, M., Dennison, J., El-Masri, H., Barton, H. A., Bruckner, J., & Yang, R. S. (2008). Application of PBPK modeling in support of the derivation of toxicity reference values for 1,1,1-trichloroethane. Regulatory Toxicology and Pharmacology : RTP, 50(2), 249-60. https://doi.org/10.1016/j.yrtph.2007.12.001
Lu Y, et al. Application of PBPK Modeling in Support of the Derivation of Toxicity Reference Values for 1,1,1-trichloroethane. Regul Toxicol Pharmacol. 2008;50(2):249-60. PubMed PMID: 18226845.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Application of PBPK modeling in support of the derivation of toxicity reference values for 1,1,1-trichloroethane. AU - Lu,Yasong, AU - Rieth,Susan, AU - Lohitnavy,Manupat, AU - Dennison,James, AU - El-Masri,Hisham, AU - Barton,Hugh A, AU - Bruckner,James, AU - Yang,Raymond S H, Y1 - 2007/12/14/ PY - 2007/09/24/received PY - 2007/11/20/revised PY - 2007/12/03/accepted PY - 2008/1/30/pubmed PY - 2008/4/24/medline PY - 2008/1/30/entrez SP - 249 EP - 60 JF - Regulatory toxicology and pharmacology : RTP JO - Regul Toxicol Pharmacol VL - 50 IS - 2 N2 - PBPK modeling has been increasingly applied in chemical risk assessment for dose, route, and species extrapolation. The use of PBPK modeling was explored in deriving toxicity reference values for 1,1,1-trichloroethane (1,1,1-TCE). This effort involved a 5-step process: (i) reconstruction of several published PBPK models for 1,1,1-TCE in the rat and human; (ii) selection of appropriate pharmacokinetic datasets for model comparison; (iii) determination of the most suitable PBPK model for supporting reference value derivation; (iv) PBPK model simulation of two critical studies to estimate internal dose metrics; and (v) calculation of internal dose metrics for human exposure scenarios for reference value derivation. The published model by Reitz et al. [Reitz, R.H., McDougal, J.N., Himmelstein, M.W., Nolan, R.J., Schumann, A.M., 1988. Physiologically based pharmacokinetic modeling with methylchloroform: implications for interspecies, high dose/low dose, and dose route extrapolations. Toxicol. Appl. Pharmacol. 95, 185-199] was judged the most suitable. This model has liver, fat, and rapidly and slowly perfused compartments, contains a saturable process for 1,1,1-TCE hepatic metabolism, and accommodates multiple exposure pathways in three species. Data from a human volunteer study involving acute inhalation exposure [Mackay, C.J., Campbell, L., Samuel, A.M., Alderman, K.J., Idzikowski, C., Wilson, H.K., Gompertz, D., 1987. Behavioral changes during exposure to 1,1,1-trichloroethane: time-course and relationship to blood solvent levels. Am. J. Ind. Med. 11, 223-239] and a chronic rat inhalation study [Quast, J.F., Calhoun, L.L., Frauson, L.E., 1988. 1,1,1-Trichloroethane formulation: a chronic inhalation toxicity and oncogenicity study in Fischer 344 rats and B6C3F1 mice. Fundam. Appl. Toxicol. 11, 611-625] were selected to simulate appropriate internal dosimetry data from which to derive reference value points of departure. Duration, route, and species extrapolations were performed based on internal dose metrics. SN - 0273-2300 UR - https://www.unboundmedicine.com/medline/citation/18226845/Application_of_PBPK_modeling_in_support_of_the_derivation_of_toxicity_reference_values_for_111_trichloroethane_ DB - PRIME DP - Unbound Medicine ER -