Trichloroethylene-induced formic aciduria: Effect of dose, sex and strain of rat

Yaqoob, Noreen; Evans, Andrew R.; Lock, Edward A.

doi:10.1016/j.tox.2012.11.014

Cited by 6 publications

(2 citation statements)

References 42 publications

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“…To date, there is no consensus on TCOH-induced kidney toxicity, but it may be resulting through perturbation of formate metabolism. The oxidative metabolites of TCE, TCA and TCOH, are known to mediate formic aciduria in rats (Yaqoob et al 2013) and mice (Lock et al 2017). It was also reported that TCE, but not TCOH, can induce elevated renal injury markers in rats after 12 weeks of exposure (Yaqoob et al 2014), even though both chemicals can cause formic aciduria in rats and mice.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of metabolism of trichloroethylene and tetrachloroethylene among mouse tissues and strains

et al. 2018

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Trichloroethylene (TCE) and tetrachloroethylene (PCE) are structurally similar chemicals that are metabolized through oxidation and glutathione conjugation pathways. Both chemicals have been shown to elicit liver and kidney toxicity in rodents and humans; however, TCE has been studied much more extensively in terms of both metabolism and toxicity. Despite their qualitative similarities, quantitative comparison of tissue- and strain-specific metabolism of TCE and PCE has not been performed. To fill this gap, we conducted a comparative toxicokinetic study where equimolar single oral doses of TCE (800 mg/kg) or PCE (1000 mg/kg) were administered to male mice of C57BL/6J, B6C3F1/J, and NZW/LacJ strains. Samples of liver, kidney, serum, brain, and lung were obtained for up to 36 h after dosing. For each tissue, concentrations of parent compounds, as well as their oxidative and glutathione conjugation metabolites were measured and concentration-time profiles constructed. A multi-compartment toxicokinetic model was developed to quantitatively compare TCE and PCE metabolism. As expected, the flux through oxidation metabolism pathway predominated over that through conjugation across all mouse strains examined, it is 1,200-3,800 fold higher for TCE and 26-34 fold higher for PCE. However, the flux through glutathione conjugation, albeit a minor metabolic pathway, was 21-fold higher for PCE as compared to TCE. The degree of inter-strain variability was greatest for oxidative metabolites in TCE-treated and for glutathione conjugation metabolites in PCE-treated mice. This study provides critical data for quantitative comparisons of TCE and PCE metabolism, and may explain the differences in organ-specific toxicity between these structurally similar chemicals.

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Section: Discussionmentioning

confidence: 99%

Comparative analysis of metabolism of trichloroethylene and tetrachloroethylene among mouse tissues and strains

et al. 2018

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“…Over the last decades, worldwide studies about the occupational epidemiology, prevention, and pathogenesis of THS have been published, but the mechanism remains unclear (Gilbert et al, 2016; Jiang et al, 2014; Yaqoob et al, 2013). Many scholars argued that skin lesions and organ injury caused by TCE belong to type IV hypersensitivity (Huang et al, 2015; Xu et al, 2011), and the injury is mainly mediated by T and B lymphocytes (Dai et al, 2006).…”

Section: Cellular Immunity Of Tcementioning

confidence: 99%

The immune response in trichloroethylene hypersensitivity syndrome: A review

Zhang

Wang

et al. 2017

Toxicol Ind Health

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Trichloroethylene (TCE) has been used for a variety of industrial and consumer cleaning purposes because of its ability to dissolve organic substances. The multisystem injuries include those of skin, liver, and kidney, which are defined as TCE hypersensitivity syndrome (THS). THS is a serious occupational health issue. However, the mechanism of immune dysfunction leading to organ injury is poorly understood. Many studies reveal that skin lesions and organ injury caused by TCE are consistent with type IV hypersensitivity, also called delayed hypersensitivity, mediated by T cells. However, many researchers found T cell-mediated type IV hypersensitivity could not account for the pathogenesis of THS fully. Humoral immunity, including immunoglobulins and complement activation, may also play a possible role in THS pathogenesis. This review will describe the history, current understanding, and future research directions of the mechanism of THS.

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