Metabolism of inhaled brominated hydrocarbons: Validation of gas uptake results by determination of a stable metabolite

Abstract

Gas uptake studies infer metabolism from the disappearance of chemical from a recirculated atmosphere. To insure the validity of this technique, we studied the metabolism of several brominated hydrocarbons in rats both by gas uptake and by direct measurement of liberated inorganic bromide. Chemicals used were: vinyl bromide (VB), halothane (HAL), bromochloromethane (BCM), and methyl bromide (MB). Gas uptake was determined by previously published methods, and plasma bromide levels were measured by an ion-specific electrode. Based on bromide release, VB metabolism had two distinct saturable components, HAL metabolism had one saturable process, BCM metabolism was of mixed form having both first-order and saturable components, and MB metabolism was first order. Gas uptake results were similar, except only one saturable process was observed for VB, and HAL had contributions from both saturable and first-order component. First-order rate constants for MB and BCM from bromide release studies were, respectively, 0.32 and 0.085/kg/hr; from gas uptake they were 0.55 and 0.106/kg/hr. The first-order rate constant for HAL by gas uptake was 0.058/kg/hr. For VB, HAL, and BCM, bromide release studies gave estimates for K m of 33, 73, and 79 ppm, respectively. Estimates of V max were 2.3, 9.7, and 10.0 mg of parent compound metabolized/kg/hr. From gas uptake, K m were 18, 81, and 91 ppm, while the estimates of V max were 2.4, 10.0, and 10.5 mg/kg/hr. With these four chemicals, gas uptake studies provided reliable estimates of the kinetic constants of metabolism.