A computational investigation of the ventilation structure and maximum rate of metabolism for a physiologically based pharmacokinetic (PBPK) model of inhaled xylene
DOI:
https://doi.org/10.11145/j.biomath.2019.01.067Keywords:
PBPK modeling, xyleneAbstract
Physiologically based pharmacokinetic (PBPK) models are systems of ordinary differential equations that estimate internal doses following exposure to toxicants. Most PBPK models use standard equations to describe inhalation and concentrations in blood. This study extends previous work investigating the effect of the structure of air and blood concentration equations on PBPK predictions. The current study uses an existing PBPK model of xylene to investigate if different values for the maximum rate of toxicant metabolismВ can result in similar compartmental predictions when used with different equations describing inhalation. Simulations are performed using values based on existing literature. Simulated data is also used to determine specific values that result in similar predictions from different ventilation structures. Differences in ventilation equation structure may affect parameter estimates found through inverse problems, although further investigation is needed with more complicated models.References
Abbas, R, Fisher, JW (1997) A Physiologically Based Pharmacokinetic
Model for Trichloroethylene and Its Metabolites, Chloral Hydrate, Trichloroacetate, Dichloroacetate, Trichloroethanol, and Trichloroethanol Glucuronide in B6C3F1 Mice, Toxicol Appl Pharm, 147:15-30.
Allen, BC, Fisher, JW (1993) Pharmacokinetic Modeling of Trichloroethylene and Trichloroacetic Acid in Humans, Risk Anal, 13(1):71-86.
Blancato, JN, Evans, MV, Power, FW, Caldwell, JC (2007)
Development and Use of PBPK Modeling and the Impact of Metabolism on Variability in Dose Metrics for the Risk Assessment of Methyl Tertiary Butyl Ether (MTBE), Journal of Environmental Protection Science, 1:29-51.
Brautbar, N, Williams, J (2002) Industrial liver toxicity: Risk assessment, risk factors and mechanisms, Int J Hyg Envir Heal 205(6):479-491.
Brown, RP, Delp, MD, Lindstedt, SL, Rhomberg, LR, Beliles, RP (1997) Physiological Parameter Values for Physiologically Based Pharmacokinetic Models. Toxicol Ind Health 13(4):407-484.
Caldwell, JC, Evans, MV, Krishnan, K (2012) Cutting Edge PBPK Models and Analyses: Providing the Basis for Future Modeling Efforts and Bridges to Emerging Toxicology Paradigms, Journal of Toxicology 2012: 852384
(doi:10.1155/2012/852384).
Cheng, S, Bois, FY (2011) A mechanistic modeling framework for predicting metabolic interactions in complex mixtures. Environ Health Persp 119(12):1712-1718.
Clewell, HJ, Gentry, PR, Covington, TR, Gearhart, JM (2000) Development of a Physiologically Based Pharmacokinetic Model of Trichloroethylene and Its Metabolites for Use in Risk Assessment, Environ Health Persp 108(Suppl 2):283-305.
Cole, CE, Tran, HT, Schlosser, PM (2001) Physiologically Based Pharmacokinetic Modeling of Benzene Metabolism in Mice Through Extrapolation from In Vitro to In Vivo, J Toxicol Env Heal A 62(6):439-465.
Csanady, GA, Kessler, W, Hoffmann, HD, Filser, JG (2003) A toxicokinetic model for styrene and its metabolite styrene-7,8-oxide in mouse, rat and human with special emphasis on the lung, Toxicol Lett 138(1-2):75-102.
Cuello, WS, James, TAT, Jessee, JM, Venecek, MA, Sawyer, ME, Eklund, CR, Evans, MV (2012) Physiologically Based Pharmacokinetic (PBPK) Modeling of Metabolic Pathways of Bromochloromethane in Rats, Journal of Toxicology 2012:629781 (doi: 10.1155/2012/629781).
Dobrev, ID, Andersen, ME, Yang, RSH (2002) In silico toxicology:
simulating interaction thresholds for human exposure to mixtures of trichloroethylene, tetrachloroethylene, and 1, 1, 1-trichloroethane. Environ Health Persp 110(10):1031-1039.
El-Masri, HA, Portier, C (1198) Physiologically Based Pharmacokinetics
Model of Primidone and Its Metabolites Phenobarbital and Phenylethylmalonamide in Humans, Rats, and Mice, Drug Metab Dispos 26(6):585-594.
Evans, MV, Crank, WD, Yang, H, Simmons, JE (1994) Applications
of a sensitivity analysis to a physiologically based pharmacokinetic model for carbon tetrachloride in rats. Toxicol Appl Pharm 128:36-44.
Fisher, JW, Mahle, D, Abbas, R (1998) A Human Physiologically Based Pharmacokinetic Model for Trichloroethylene and Its Metabolites, Trichloroacetic Acid and Free Trichloroethanol, Toxicol Appl Pharm 152:339-359.
Gagnaire, F, Langlais, C, Grossman, S, Wild, P (2007) Ototoxicity in rats exposed to ethylbenzene and to two technical xylene vapours for 13 weeks, Arch Toxicol 81(2):127-143.
Greenberg, MS, Burton, GA, Jr., Fisher, JW (1999) Physiologically Based Pharmacokinetic Modeling of Inhaled Trichloroethylene and Its Oxidative Metabolites in B6C3F1 Mice, Toxicol Appl Pharm, 154:264-278.
Haddad, S, Beliveau, M, Tardif, R, Krishnan, K (2001) A PBPK Modeling-Based Approach to Account for Interactions in the Health Risk Assessment of Chemical Mixtures, Toxicol Sci 63(1):125-131.
Haddad, S, Krishnan, K (1998) Physiological modeling of toxicokinetic
interactions: implications for mixture risk assessment. Environ Health Persp 106(Suppl 6):1377-1384.
Haddad, S, Tardif, Charest-Tardif, G, Krishnan, K (1999) Physiological modeling of the toxicokinetic interactions in a quaternary mixture of aromatic hydrocarbons. Toxicol Appl Pharm 161(3):249-257.
Krishnan, K, Clewell, HJ 3rd, Andersen, ME (1994) Physiologically based pharmacokinetic analyses of simple mixtures. Environ Health Persp 102(Suppl 9):151-155.
Krishnan, K, Haddad, S, BВґeliveau, M, Tardif, R. (2002) Physiological
modeling and extrapolation of pharmacokinetic interactions from binary to more complex chemical mixtures. Environ Health Persp 110(Suppl 6):989-994.
Loizou, GD (2001) The application of physiologically based pharmacokinetic modelling in the analysis of occupational exposure to perchloroethylene. Toxicol Lett 124:59-69.
Loizou, GD, McNally, K, Jones, K, Cocker, J (2015) The application of global sensitivity analysis in the development of a physiologically based pharmacokinetic model for m-xylene and ethanol co-exposure in humans. Frontiers in Pharmacology 6(135):1-19.
Manning, CC, Schlosser, PM, Tran, HT (2010) A Multicompartment
Liver-based Pharmacokinetic Model for Benzene and its Metabolites in Mice, B Math Biol, 72(3):507-540.
Marchand, A, Aranda-Rodriguez, R, Tardif, R, Nong, A, Haddad, S (2015) Human Inhalation Exposures to Toluene, Ethylbenzene, and M-Xylene and Physiologically Based Pharmacokinetic Modeling of Exposure Biomarkers in Exhaled Air, Blood, and Urine. Toxicol Sci 144(2):414-424.
Matlab, http://www.mathworks.com/
fminsearch.m, Matlab Central File Exchange, http://www.mathworks.com/matlabcentral/fileexchange/8277-
fminsearchbnd–fminsearchcon/
McNally, K, Cotton, R, Cocker, J, Jones, K, Bartels, M, Rick, D, Price, P, Loizou, G (2012) Reconstruction of exposure to m- Xylene from human biomonitoring data using PBPK modelling, Bayesian inference, and Markov chain Monte Carlo simulation. Journal of Toxicology 2012 (doi:10.1155/2012/760281).
McNally, K, Cotton, R, Loizou, GD (2011) A workflow for global sensitivity analysis of PBPK models. Frontiers in pharmacology 2(31):1-22.
Mendoza-Cantu, A, Castorena-Torres, F, Bermudez de Leon, M, Cisneros, B, Lopez-Carrillo, L, Rojas-GarcД±a, AE, Aguilar-Salinas, A, Manno, M, Albores, A (2006) Occupational toluene exposure induces cytochrome P450 2E1 mRNA expression in peripheral lymphocytes. Environ Health Persp 114(4):494-499.
Peyret, T, Krishnan, K (2012) Quantitative property-property relationship for screening-level prediction of intrinsic clearance of volatile organic chemicals in rats and its integration within PBPK Models to predict inhalation pharmacokinetics in humans. Journal of Toxicology 2012
(http://dx.doi.org/10.1155/2012/286079).
Price, K, 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(1-2):107-128.
Ramsey, JC, Andersen, ME (1984) A physiologically based description of the inhalation pharmacokinetics of styrene in rats and humans, Toxicol Appl Pharm, 73(1):159-175.
Sarangapani, R, Teeguarden, JG, Cruzan, G, Clewell, HJ, Andersen,
ME (2002) Physiologically based pharmacokinetic modeling of styrene and styrene oxide respiratory-tract dosimetry in rodents and humans, Inhal Toxicol 14(8):789-834.
Sawyer, ME, Evans, MV, Wilson, CA, Beesley, LJ, Leon, LS, Eklund, CR, Croom, EL, Pegram, RA (2016) Development of a human physiologically based pharmacokinetic (PBPK) model for dermal permeability for lindane, Toxicol Lett 245: 106-109.
Simmons, JE, Boyes, WK, Bushnel, PJl, Raymer, JH, Limsakun, T, McDonald, A, Sey, YM, Evans, MV (2002) A Physiologically Based Pharmacokinetic Model for Trichloroethylene in the Male Long-Evans Rat, Toxicol Sci 69:3-15.
Tardif, R, Charest-Tardif, G, Brodeur, J, Krishnan, K (1997) Physiologically based pharmacokinetic modeling of a ternary mixture of alkyl benzenes in rats and humans. Toxicol Appl Pharm 144(1):120-134.
Tardif, R, LaparВґe, S, Charest-Tardif, G, Brodeur, J, Krishnan, K (1995) Physiologically-based pharmacokinetic modeling of a mixture of toluene and xylene in humans. Risk Anal 15(3):335-342.
Tardif, R, LaparВґe, S, Krishnan, K, Brodeur, J (1993) Physiologically
based modeling of the toxicokinetic interaction between toluene and m-xylene in the rat. Toxicol Appl Pharm 120(2):266-73.
Tassaneeyakul, W, Birkett, DJ, Edwards, JW, Veronese, ME, Tassaneeyakul, W, Tukey, RH, Miners, JO (1996) Human cytochrome P450 isoform specificity in the regioselective metabolism of toluene and o-, m-and p-xylene. J PharmacolExp Ther 276(1):101-108.
Thrall, KD, Gies, RA, Muniz, J, Woodstock, AD, Higgins, G (2002) Route-of-entry and brain tissue partition coefficients for common superfund contaminants. J Toxicol Env Heal A 65:2075-2086.
Valcke, M, Haddad, S (2015) Assessing human variability in kinetics for exposures to multiple environmental chemicals:a physiologically based pharmacokinetic modeling case study with dichloromethane, benzene, toluene, ethylbenzene, and mxylene, J Toxicol Env Heal A 78: 409-431.
Yang, RS (1998) Some critical issues and concerns related to research advances on toxicology of chemical mixtures. Environ Health Persp 106(Suppl 4):1059-1063.
Yang, RS, Thomas, RS, Gustafson, DL, Campain, J, Benjamin, SA, Verharr, HJ, M.M. Mumtaz, MM (1998) Approaches to developing alternative and predictive toxicology based on PBPK/PD and QSAR modeling. Environ Health Persp 106(Suppl 6):1385-1393.
Yokley, KA (2013) Investigations on Ventilation Equation Structure in Physiologically Based Pharmacokinetic (PBPK) Modeling of Inhaled Toxicants. International Journal of Pure and Applied Mathematics 82(1):95-123.
Yokley, KA, Evans, MV (2008) Physiological changes associated
with aging result in lower internal doses of toluene and perchloroethylene in simulations using pharmacokinetic modeling. Toxicol Environ Chem 90(3):75-492.
Yokley, KA, Evans, MV (2007) An Example of Model Structure Differences Using Sensitivity Analyses in Physiologically Based Pharmacokinetic Models of Trichloroethylene in Humans, B Math Biol 69(8):2591-2625.
Downloads
Published
Issue
Section
License
The journal Biomath is an open access journal. All published articles are immeditely available online and the respective DOI link activated. All articles can be access for free and no reader registration of any sort is required. No fees are charged to authors for article submission or processing. Online publications are funded through volunteer work, donations and grants.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License 4.0 that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
