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Dichloroacetate (DCA) is a rodent carcinogen commonly found in municipal drinking water supplies. Toxicokinetic studies have established that elimination of DCA is controlled by liver metabolism, which occurs by the cytosolic enzyme glutathione-S-transferase-zeta (GST-zeta). DCA is also a mechanism based inhibitor of GST-zeta, and a loss in GST-zeta enzyme(More)
Conflicting data have been published related to the formation of dichloroacetate (DCA) from trichloroethylene (TRI), chloral hydrate (CH), or trichloroacetic acid (TCA) in B6C3F1 mice. TCA is usually indicated as the primary metabolic precursor to DCA. Model simulations based on the known pharmacokinetics of TCA and DCA predicted blood concentrations of DCA(More)
A commonly used endpoint in bioassays testing the estrogenicity of chemicals is the induction of the egg yolk precursor vitellogenin (VTG) in male fish. However, relatively little is known about the kinetics of induction and elimination of VTG in fish exposed to xenoestrogens. In this study, we administered graded intra-arterial doses (0.001, 0.1, 1.0 and(More)
Chloro, bromo, and mixed bromochloro haloacetates (HAs) are by-products of drinking water disinfection and are hepatocarcinogenic in rodents. We compared the toxicokinetics of a series of di-HAs, dichloro (DCA), bromochloro (BCA), dibromo (DBA) and tri-HAs: trichloro (TCA), bromodichloro (BDCA), chlorodibromo (CDBA), and tribromo (TBA) after iv and oral(More)
A key question in the risk assessment of trichloroethylene (TRI) is the extent to which its carcinogenic effects might depend on the formation of dichloroacetate (DCA) as a metabolite. One of the metabolic pathways proposed for the formation of DCA from TRI is by the reductive dehalogenation of trichloroacetate (TCA), via a free radical intermediate.(More)
Chloral hydrate (CH) is a short-lived intermediate in the metabolism of trichloroethylene (TRI). TRI, CH, and two common metabolites, trichloroacetic acid (TCA) and dichloroacetic acid (DCA) have been shown to be hepatocarcinogenic in mice. To better understand the pharmacokinetics of these metabolites of TRI in humans, eight male volunteers, aged 24-39,(More)
Trichloroacetic acid (TCA) is a major metabolite of trichloroethylene (TRI) thought to contribute to its hepatocarcinogenic effects in mice. Recent studies have shown that peak blood concentrations of TCA in rats do not occur until approximately 12 hours following an oral dose of TRI. However, blood concentrations of TRI reach a maximum within an hour and(More)
Chloral hydrate (CH) is a commonly found disinfection by-product in water purification, a metabolite of trichloroethylene, and a sedative/hypnotic drug. CH and two of its reported metabolites, trichloroacetic acid (TCA) and dichloroacetic acid (DCA), are hepatocarcinogenic in mice. Another metabolite of CH, trichloroethanol (TCE), is also metabolized into(More)
The equipment, methods, logistics, and results of doping-control analyses for the 1984 Los Angeles Olympic Games are discussed in this article. Within 15 days, 1510 different urine specimens underwent 9440 screening analyses by a combination of gas chromatography, gas chromatography-mass spectrometry, "high-performance" liquid chromatography, and(More)
Nine male and five female human liver microsomal sample were examined for laurate 11- and 12-hydroxylase activities. The mean specific activities for the 11- and 12-hydroxylation reactions were 0.78 +/- 0.33 and 1.07 +/- 0.12 nmol/min/mg protein, respectively. Antibody inhibition experiments, using a polyclonal antibody to a cytochrome P450 (P450) isolated(More)