The Induction of Phagocytic Activation by Mixtures of the Water Chlorination By‐Products, Dichloroacetate‐ and Trichloroacetate, in Mice after Subchronic Exposure

Hassoun, Ezdihar A.; Cearfoss, Jacquelyn; Musser, Brian; Krispinsky, Sarah; Al-Hassan, Noor; Liu, Ming‐Cheh

doi:10.1002/jbt.21476

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“…Previously Hassoun et al (2010b) indicated a protective role of phagocytic activation against chronic DCA- and TCA-induced hepatotoxicity and that mixtures of compositions similar to Mix I and II produced additive effects on this mechanism. However, a mixture of similar composition to Mix III resulted in less than additive effects [Hassoun et al, 2013]. It is possible the less than additive effects of Mix.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Mixtures of Dichloroacetate and Trichloroacetate on Induction of Oxidative Stress in Livers of Mice After Subchronic Exposure

Hassoun

Cearfoss

Mamada

et al. 2014

Journal of Toxicology and Environmental Health, Part A

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Dichloroacetate (DCA) and trichloroacetate (TCA) are drinking water chlorination byproducts previously found to induce oxidative stress (OS) in hepatic tissues of B6C3F1 male mice. To assess the effects of mixtures of the compounds on OS, groups of male B6C3F1 mice were treated daily by gavage with DCA at doses of 7.5, 15, or 30 mg/kg/day, TCA at doses of 12.5, 25, or 50 mg/kg/day and three mixtures of DCA and TCA (Mix I, Mix II and Mix III), for 13 weeks. The concentrations of the compounds in Mix I, II and III corresponded to those producing approximately 15, 25 and 35%, respectively, of maximal induction of OS by individual compounds. Livers were assayed for production of superoxide anion (SA), lipid peroxidation (LP) and DNA single strand breaks (SSB). DCA, TCA and the mixtures produced dose-dependent increases in the three tested biomarkers. Mix. I and II effects on the three biomarkers, and Mix. III effect on SA production were found to be additive, while Mix. III effects on LP and DNA-SSB were shown to be greater than additive. Induction of OS in livers of B6C3F1 mice after sub-chronic exposure to DCA and TCA was previously suggested as an important mechanism in chronic hepatotoxicity/hepatocarcinogenicity induced by these compounds. Hence, there may be rise in exposure risk to these compounds as these agents co-exist in drinking water.

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Section: Discussionmentioning

confidence: 99%