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

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 (V(max⁡) = 3.8 mg/hour, K(m) = 0.35 mg/liter, and k(GST) = 4.7 /hour). The two binding site results were V(max⁡(1) ) = 3.7 mg/hour, K(m⁡(1) ) = 0.3 mg/hour, CL(2) = 0.047 liter/hour. In addition, we explore the sensitivity of different parameters for each model using our obtained optimized values.