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Journal of Toxicology
Volume 2012 (2012), Article ID 629781, 14 pages
http://dx.doi.org/10.1155/2012/629781
Research Article

Physiologically Based Pharmacokinetic (PBPK) Modeling of Metabolic Pathways of Bromochloromethane in Rats

1Research Experience for Undergraduate participant, Department of Mathematics, North Carolina State University, Raleigh, NC 27695, USA
2Department of Mathematics, North Carolina State University, Raleigh, NC 27695, USA
3National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Office of Research and Development, Research Triangle Park, NC 27709, USA

Received 18 January 2012; Revised 27 March 2012; Accepted 30 March 2012

Academic Editor: Kannan Krishnan

Copyright © 2012 W. S. Cuello 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.

Abstract

Bromochloromethane (BCM) is a volatile compound and a by-product of disinfection of water by chlorination. Physiologically based pharmacokinetic (PBPK) models are used in risk assessment applications. An updated PBPK model for BCM is generated and applied to hypotheses testing calibrated using vapor uptake data. The two different metabolic hypotheses examined are (1) a two-pathway model using both CYP2E1 and glutathione transferase enzymes and (2) a two-binding site model where metabolism can occur on one enzyme, CYP2E1. Our computer simulations show that both hypotheses describe the experimental data in a similar manner. The two pathway results were comparable to previously reported values (Vmax=3.8 mg/hour, Km=0.35 mg/liter, and kGST=4.7 /hour). The two binding site results were Vmax1=3.7 mg/hour, Km1=0.3 mg/hour, CL2 = 0.047 liter/hour. In addition, we explore the sensitivity of different parameters for each model using our obtained optimized values.