Characterization of the Metabolic Interaction between Trihalomethanes and Chloroacetic Acids using Rat Liver Microsomes

Abstract

The aim of this study was to investigate the in vitro metabolism of trihalomethanes (THMs) in the presence of trichloroacetic acid (TCA), dichloracetic acid (DCA), monochloroacetic acid (MCA), and 4-methylpyrazole (4-MP) using liver microsomes from male Sprague-Dawley rats. Using the vial equilibration technique, initial experiments were carried out with starting concentrations of approximately 40 ppm THMs and 12-22 mM chloroacetic acids. The results indicated a mutual metabolic inhibition between THMs present as binary or quaternary mixtures. Although DCA and MCA had no influence on THMs, TCA produced a marked inhibition of the metabolism of all THMs: chloroform (CHCl3) (55%), bromodichloromethane (BDCM) (34%), dibromochloromethane (DBCM) (30%), and bromoform (TBM) (23%). The presence of 4-MP also reduced THM metabolism, the importance of which decreased in the following order: CHCl3 > BDCM > DBCM = TBM. In further vial equilibration experiments, using 9-140 ppm as starting concentrations of THMs, enzyme kinetic parameters (i.e., Michaelis constant, K(m), and maximum velocity, V(max)) were determined both in the absence and in the presence of TCA (12.2 mM). Results are consistent with a competitive inhibition between TCA and CHCl3, whereas the metabolic inhibition of BDCM and TMB by TCA was non-competitive. As for DBCM, results suggest a more complex pattern of inhibition. These results suggest that CYP2E1 is involved in the metabolism of THMs as well as in the metabolic interaction between THMs and TCA.

Predictors of Third Trimester Blood Trihalomethanes and Urinary Trichloroacetic Acid Concentrations among Pregnant Women

“…Trihalomethanes (THMs) and haloacetic acids (HAAs) are the two most prevalent classes of DBPs found in chlorinated drinking water worldwide including in China. , Human exposure to DBPs occurs through water-use activities such as chlorinated water consumption, showering/bathing, and swimming . After exposure, DBPs such as brominated THMs and HAAs are metabolized into mutagenic intermediates through a conjugation with glutathione, resulting in potentially adverse health effects. Epidemiological studies have suggested that exposure to DBPs is associated with elevated risk of cancer , and adverse male reproductive effects. − Prenatal exposure to DBPs has also been reported to be associated with a variety of adverse birth outcomes such as preterm delivery, small for gestational age, low birth weight, and fetal growth restriction. − However, the findings remain inconclusive and inconsistent. , …”

“…1,2 Human exposure to DBPs occurs through water-use activities such as chlorinated water consumption, showering/bathing, and swimming. 3 After exposure, DBPs such as brominated THMs and HAAs are metabolized into mutagenic intermediates through a conjugation with glutathione, 4 resulting in potentially adverse health effects. Epidemiological studies have suggested that exposure to DBPs is associated with elevated risk of cancer 5,6 and adverse male reproductive effects.…”