Toxicity of chloroform

The renal toxicity of chloroform in rats after intraperitoneal dosing has also been reported (Kroll et al. 1994a, 1994b). 

Dermal Effects. No reports are available on the toxicity of chloroform to skin after inhalation and oral exposures in humans. Stratum comeum damage was reported after a topical exposure of chloroform of 15 minutes duration for 6 consecutive days (Malten et al. 1968). Chloroform was used as a vehicle for the topical application of aspirin for the treatment of painful herpes zoster lesions in male and female humans. The only reported side-effect was an occasional burning sensation to the skin as the chloroform evaporated after application (King 1993). 

Despite a relatively fast clearance of chloroform from the body, toxic effects may develop in exposed individuals. No method is commonly practiced to enhance the elimination of the absorbed dose of chloroform. Although there is evidence that ethanol pretreatment of rats can increase the in vitro metabolism of chloroform (Sato et al. 1981), such treatment would not be recommended (Kutob and Plaa 1962) because it would increase the toxicity of chloroform and it is a very poor practice generally. 

Chu I, Villeneuve DC, Secours VE, et al. 1982b. Toxicity of trihalomethanes I. The acute and subacute toxicity of chloroform, bromodichloromethane, chlorodibromomethane and bromoform in rats. J Environ Sci Health B 17 205-224. 

Hill RN. 1977. Differential toxicity of chloroform in the mouse. Ann NY Acad Sci 298 170-176. 

McLean AEM. 1970. The effect of protein deficiency and microsomal enzyme induction by DDT and phenobarbitone on the acute toxicity of chloroform and a pyrrolizidine alkaloid, retrorsine. Br J Exp Pathol 51 317-321. 

Mery S, Larson JL, Butterworth BE, et al. 1994. Nasal toxicity of chloroform in male F-344 rats and female B6C3Fj mice following a 1-week inhalation exposure. Toxicol Appl Pharmacol 125(2) 214-227. 

Shubik P, Ritchie AC. 1953. Sensitivity of male dba mice to the toxicity of chloroform as a laboratory hazard. Science 117 285. 

Torkelson TR, Oyen F, Rowe VK. 1976. The toxicity of chloroform as determined by single and repeated exposure of laboratory animals. Am Ind Hyg Assoc J 37 697-705. 

Tumasonis CF, McMartin DN, Bush B. 1985. Lifetime toxicity of chloroform and bromodichloromethane when administered over a lifetime in rats. Ecotoxicol Environ Safety 9 233-240. 

Wang P-Y, Kaneko T, Sato A, et al. 1995. Dose and route dependent alteration of metabolism and toxicity of chloroform in fed and fasting rats. Toxicol Appl Pharm 135(1) 119-126. 

Several substances alter the toxicity of chloroform in animals— most probably by modifying the metabolism to a reactive intermediate. Factors that potentiate chloroform s toxic effects include ethanol, polybrominated biphenyls, steroids, and ketones. Disulfiram, its metabolites, and a high-carbohydrate diet... 

Probably the best example of a sex difference in toxicity is that of the renal toxicity of chloroform in mice. The males are markedly more sensitive than the females, and this difference can be removed by castration of the male animals and subsequently restored by administration of androgens. 

A sex difference in the toxicity of chloroform has been reported. In which species does this occur and which is the more sensitive sex and why ... 

Metabolic activation. Although the kidney does not contain as much cytochromes P-450 as the liver, there is sufficient activity to be responsible for metabolic activation, and other oxidative enzymes such as those of the prostaglandin synthetase system are also present. Such metabolic activation may underlie the renal toxicity of chloroform and paracetamol (see chap. 7). Other enzymes such as C-S lyase and GSH transferase may also be involved in the activation of compounds such as hexachlorobutadiene (see chap. 7). In some cases, hepatic metabolism may be involved followed by transport to the kidney and subsequent toxicity. 

A sex difference in the toxicity of chloroform to the kidney occurs in mice. Male animals are more sensitive than females. The reason is that chloroform is metabolized more rapidly in male mice than females and this is affected by male hormones (androgens). 

The hepatic and renal toxicities of chloroform are selectively modified by induction of the drug-metabolizing enzyme systems in those organs (ref. 39) and the production of phosgene is strongly indicated (ref. 40). 

Kluwe, W.M., K.M. McCormack and J.B. Hook, "Selective Modification of Renal and Hepatic Toxicities of Chloroform by Induction of Drug-Metabolizing Enzyme Systems in Kidney... 

It has been clearly established that phosgene, as the major metabolite of chloroform, is responsible for the acute toxicity of chloroform (54). As part of a study towards the mechanism of the potential carcinogenicity of chlorform, Fabrizi et alS55-showed that phosgene was able to form adducts with the N-terminus of human histone H2B, through lysine residues. 

Amphibians appear to be quite sensitive to the effects of chloroform. Very little information is available on terrestrial microorganisms and vertebrates. No information was identified on the toxicity of chloroform to birds or wild animals. 

Lilly PD, Ross Tm, Pegram RA. Trihalomethane comparative toxicity Acute renal and hepatic toxicity of chloroform and bromodichloromethane following aqueous gavage. FundAppl Toxicol 1997 40(1) 101—10. 

As discussed earlier, chloroform and dichloroacetic acid are formed as byproducts when drinking water is chlorinated (Section 8.9). In a study on laboratory rats, the co-administration of dichloroacetic acid and chloroform was found to greatly increase the liver toxicity of chloroform J23 ... 

Chloroform, dichloroacetic acid, and trichloroacetic acid are disinfection byproducts of water chlorination. In a study of laboratory rats it was shown that both dichloroacetic acid and trichloroacetic acid increase the renal toxicity of chloroform in test animals J10l... 

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