Trichloroethylene hepatotoxicity

Okino T, Nakajima T, Nakano M. 1991. Morphological and biochemical analyses of trichloroethylene hepatotoxicity Differences in ethanol- and phenobarbital-pretreated rats. Toxicol Appl Pharmacol 108 379-389. 

Acute oral LDjgS have been determined for mice (2,402 mg/kg) (Tucker et al. 1982) and rats (7,208 mg/kg) (Smyth et al. 1969). In a study in which pregnant rats were treated by gavage with trichloroethylene in com oil on gestation days 6-15, 2 of 13 died at 1,125 mg/kg/day, while all survived at 844 mg/kg/day (Narotsky etal. 1995). The lethality of trichloroethylene may be related to the delivery vehicle. Administration of trichloroethylene in an aqueous Emulphor vehicle proved to be more lethal but less hepatotoxic than similar administration of trichloroethylene in com oil during a 4-week exposure period (Merrick et al. 1989). Further... 

By enhancing the metabolism of trichloroethylene to its cytotoxic metabolites, compounds that induce the hepatic mixed-function oxidase system can potentiate the hepatotoxicity of trichloroethylene. 

Trichloroethylene may occur in drinking water along with other chlorinated hydrocarbons, so effects of these chemicals in combination are of interest to public health. Hepatotoxicity, as measured by plasma enzyme activity, was increased synergistically in rats by oral administration of carbon tetrachloride combined with trichloroethylene (Borzelleca et al. 1990). In addition, synergistic effects were implicated in a 3-day study in... 

Buben JA, O Flaherty EJ. 1985. Delineation of the role of metabolism in the hepatotoxicity of trichloroethylene and perchloroethylene A dose-effect study. Toxicol Appl Pharmacol 78 105-122. 

Carlson GP. 1974. Enhancement of the hepatotoxicity of trichloroethylene by inducers of drug metabolism. Res Commun Chem Pathol Pharmacol 7 637-640. 

Merrick BA, Robinson M, Condie LW. 1989. Differing hepatotoxicity and lethality after subacute trichloroethylene exposure in aqueous or com oil gavage vehicles in B6C3Fj mice. J Appl Toxicol 9 15-21. 

Moslen MT, Reynolds ES, Szabo S. 1977. Enhancement of the metabolism and hepatotoxicity of trichloroethylene and perchloroethylene. Biochem Pharmacol 26 369-375. 

Pessayre D, Cobert B, Decatoire V, et al. 1982. Hepatotoxicity of trichloroethylene-carbon tetrachloride mixtures in rats. Gastroenterology 83 761-772. 

Steup DR, Wiersma D, McMillan DA, et al. 1991. Pretreatment with drinking water solutions containing trichloroethylene or chloroform enhances the hepatotoxicity of carbon tetrachloride in Fischer 344 rats. Fund Appl Toxicol 16 798-809. 

Kylin B, Reichard H, Sumegi I, et al. 1963. Hepatotoxicity of inhaled trichloroethylene, tetrachloroethylene and chloroform. Single exposure. Acta Pharmacol Toxicol 20 16-26. 

In animal studies acetone has been found to potentiate the toxicity of other solvents by altering their metabolism through induction of microsomal enzymes, particularly cytochrome P-450. Reported effects include enhancement of the ethanol-induced loss of righting reflex in mice by reduction of the elimination rate of ethanol increased hepatotoxicity of compounds such as carbon tetrachloride and trichloroethylene in the rat potentiation of acrylonitrile toxicity by altering the rate at which it is metabolized to cyanide and potentiation of the neurotoxicity of -hexane by altering the toxicokinetics of its 2,4-hexane-dione metabolite.Because occupationally exposed workers are most often exposed to a mixmre of solvents, use of the rule of additivity may underestimate the effect of combined exposures. ... 

Haloalkanes. Certain haloalkanes and haloalkane-containing mixtures have been demonstrated to potentiate carbon tetrachloride hepatotoxicity. Pretreatment of rats with trichloroethylene (TCE) enhanced carbon tetrachloride-induced hepatotoxicity, and a mixture of nontoxic doses of TCE and carbon tetrachloride elicited moderate to severe liver injury (Pessayre et al. 1982). The researchers believed that the interaction was mediated by TCE itself rather than its metabolites. TCE can also potentiate hepatic damage produced by low (10 ppm) concentrations of carbon tetrachloride in ethanol pretreated rats (Ikatsu and Nakajima 1992). Acetone was a more potent potentiator of carbon tetrachloride hepatotoxicity than was TCE, and acetone pretreatment also enhanced the hepatotoxic response of rats to a TCE-carbon tetrachloride mixture (Charbonneau et al. 1986). The potentiating action of acetone may involve not only increased metabolic activation of TCE and/or carbon tetrachloride, but also possible alteration of the integrity of organelle membranes. Carbon tetrachloride-induced liver necrosis and lipid peroxidation in the rat has been reported to be potentiated by 1,2- dichloroethane in an interaction that does not involve depletion of reduced liver glutathione, and that is prevented by vitamin E (Aragno et al. 1992). 

Interactive hepatotoxicity was demonstrated by the concurrent administration of mixtures of any two or all three of the chlorinated hydrocarbons trichloroethylene, tetrachloroethylene, and 1,1,1-trichloroethane. All binary mixtures as well as the ternary mixture significantly increased hepatotoxicity in vitro on rat hepatocytes as well as in vivo on laboratory ratsJ20 ... 

Kylin B, Sumegi I, Yllner S. 1965. Hepatotoxicity of inhaled trichloroethylene and tetrachloroethylene— long-term exposure. Acta Pharmacol Toxicol 22 379-385. 

Liver halogenated hydrocarbons (e.g., caib[Pg.1319]

While the halogenated hydrocarbons discussed here include carbon tetrachloride, chloroform, 1,1,1-trichloroefliene, trichloroethylene are significantly hepatotoxic, the literature on the toxicity of the non-halogenated hydrocarbons is a combination of positive and negative studies. Several studies looking into the hepatotoxicity of both aliphatic solvents such as kerosene, hexane and aromatics such as xylene, toluene and styrene have reported mixed results. Xylene is an aromatic hydrocarbon which is used heavily in the industry, as well as medical technology as a solvent. 

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