Species differences in the metabolism of trichloroethylene to the carcinogenic metabolites trichloroacetate and dichloroacetate☆,☆☆
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Cited by (91)
Systematic evaluation of mechanistic data in assessing in utero exposures to trichloroethylene and development of congenital heart defects
2020, ToxicologyCitation Excerpt :Such an exercise demonstrates that the oral TCE doses required to achieve the internal TCA levels associated with the TCA-CHD effect levels would approximate or exceed the LD50 of TCE in rats (i.e., acutely lethal; data not shown). For DCA, the limited empirical data indicate that oral administration of TCE in rats leads to internal DCA levels ∼1000-fold lower than TCA (Delinsky et al., 2005; Larson and Bull, 1992b), which would result in substantially greater TCE equivalent doses for the DCA oral studies than those of the TCA oral studies in rats. Further, because multiple, high dose in utero studies are available for TCE in mammalian models, the potential impact of a TCE metabolite on cardiac development is already accounted for in the TCE studies.
Effect of dose and exposure protocol on the toxicokinetics and first-pass elimination of trichloroethylene and 1,1,1-trichloroethane
2018, Toxicology and Applied PharmacologyCitation Excerpt :In contrast, male mice gavaged daily for 6 weeks were reported to exhibit linear metabolism of TCE up to 1600 mg/kg (Buben and O'Flaherty, 1985). Male B6C3F1 mice have a substantially greater capacity to oxidize TCE than do male S-D rats (Larson and Bull, 1992). The higher rate of TCE metabolism is attributable to higher liver microsomal CYP2E1 levels in the mice (Nakajima et al., 1993).
Comparative analysis of metabolism of trichloroethylene and tetrachloroethylene among mouse tissues and strains
2018, ToxicologyCitation Excerpt :A larger portion of the parent compound undergoes metabolism in TCE-treated mice (15.7%–38.3%) as compared to PCE-treated mice (6.6%–9.7%), a finding that provides empirical data in strong support of the estimates from PBPK models (Chiu et al., 2014; Chiu and Ginsberg, 2011). The more efficient oxidative metabolism of TCE as compared to PCE is also concordant with previous animal studies (Cichocki et al., 2017a; Green and Prout, 1985; Larson and Bull, 1992) and PBPK modeling estimates (Chiu et al., 2014; Chiu and Ginsberg, 2011; Chiu et al., 2009). Among the most notable findings of this study is the observation of high levels of conjugates of metabolites of PCE in the kidney.
Trichloroethylene biotransformation and its role in mutagenicity, carcinogenicity and target organ toxicity
2014, Mutation Research - Reviews in Mutation ResearchCitation Excerpt :In addition, kinetic analysis of blood levels of DCA and TCA following oral administration of TCE in the mouse also shows that TCA is not the only source of DCA in vivo [34,35]. DCA has an extremely rapid disposition [36,37] to glyoxylic, oxalic, and monochloroacetic acids. The major pathway for DCA biotransformation is complete dechlorination to glyoxylate in a reaction catalyzed by glutathione transferase ζ (GSTz) [38].
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This work was supported by U.S. Air Force Grant AFOSR-86-0284 and by EPA Cooperative Agreement CR-815216-01.
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Presented in part at the 29th Annual Meeting of the Society of Toxicology, February 1990, Miami, FL.