Evaluation of the influence of chloroacetic acids on the pharmacokinetics of trihalomethanes in the rat.
Chloroacetic acids (monochloroacetic acid [MCA], dichloroacetic acid [DCA], and trichloroacetic acid [TCA]) and trihalomethanes (THMs: chloroform [CHCl(3)], bromodichloromethane [BDCM], dibromochloromethane [DBCM], and bromoform [TBM]) are common by-products of the chlorination of drinking water. The purpose of this study was to evaluate the influence of chloroacetic acids on the pharmacokinetics of trihalomethanes in the male Sprague-Dawley rat. In the first series of studies, groups of 5 animals were given, by intravenous injections, a single dose of 0.125 mmol/kg of one of the four THMs. Additional groups received a binary mixture containing 0.125 mmol/kg of a THM plus 0.125 mmol/kg of a chloroacetic acid. The venous blood concentrations of unchanged THMs were measured by headspace gas chromatography from 5 min to 6 h postadministration. The areas under the blood concentration versus time curves (AUCs) of CHCl(3), BDCM, and DBCM were increased by a factor of 3.5, 1.6, and 2, respectively, by coadministration of TCA. DCA coadministration resulted in an increase in the AUC of DBCM (x2.5) and TBM (x1.3), whereas MCA modified the Cmax (x1.5) and AUC (x1.8) of BDCM and the AUC of DBCM (x2.5). In the second series of experiments, animals received either a single dose of 0.03125 mmol/kg of one of the four THMs, a mixture containing 0.03125 mmol/kg of each of the four THMs (total dose = 0.125 mmol/kg), or a mixture containing 0.03125 mmol/kg of each of the four THMs plus 0.125 mmol/kg of either TCA or DCA. Results indicated that the AUCs of CHCl(3), BDCM, DBCM, and TBM were increased during coadministration compared to single administrations (+2.5-fold). Combined administration of the four THMs with TCA, and not DCA, resulted in an increase of the AUCs of THMs (CHCl(3): x11.7; BDCM, DBCM, and TBM: x3.9) and an increase in the Cmax of CHCl(3) (x1.9). Overall, these results indicate that, at the dose levels tested in this study, TCA alters the blood concentration profiles of THMs.
St-Pierre
Annie
A
TOXHUM (Human Toxicology Research Group), Department of Occupational and Environmental Health, University of Montreal, Montreal, Quebec, Canada.
Krishnan
Kannan
K
Tardif
Robert
R
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004203:Disinfection; D004347:Drug Interactions; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014238:Trichloroacetic Acid / Q000494:pharmacology*; D022882:Trihalomethanes / Q000493:pharmacokinetics*; D018508:Water Purification
D000085:Acetates; D022882:Trihalomethanes; C006972:chloroacetic acid; D014238:Trichloroacetic Acid; D003999:Dichloroacetic Acid