Chloroform in Drinking Water Prevents Hepatic Cell Proliferation Induced by Chloroform Administered by Gavage in Corn Oil to Mice

Pereira, Michael A.; Grothaus, Matthew C

doi:10.1093/toxsci/37.1.82

Cited by 2 publications

(1 citation statement)

References 17 publications

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“…Further, the toxic and carcinogenic effects of chlorinated aliphatic hydrocarbons vary, depending on the routes of administration (Pereira et al, 1985;Klaunig et al, 1986;Coffin et al, 2000). For example, CHF was carcinogenic in mice when administered by gavage, but it was not carcinogenic and did not promote liver cancer when administered in the drinking water (Larson et al, 1994b;Pereira, 1994;Pereira and Grothaus, 1997). Similarly, F344/N rats administrated 1,2-dichloroethane in drinking water exhibited less liver and kidney toxicity than those administered similar doses by gavage (Morgan, 1991).…”

Section: Introductionmentioning

confidence: 99%

Immunotoxicological profile of chloroform in female B6C3F1 mice when administered in drinking water

Auttachoat

Germolec

Collins

et al. 2009

Drug and Chemical Toxicology

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Chloroform can be formed as a disinfection by-product during water chlorination, one of the primary modalities for purifying municipal water supplies for human consumption. The aim of this study was to characterize the immunotoxic effects of chloroform in female B6C3F1 mice when exposure occurred via the drinking water. Consistent with human exposure, female B6C3F1 mice were exposed to chloroform-containing drinking water at 2.5, 10, 25, 100, and 250 ppm for 28 days. The examined endpoints included the effects of chloroform on body and organ weights, water consumption, hematology, innate immunity, humoral immunity, and cell-mediated immunity. The functions of natural killer, B-, and T-cells were not altered by chloroform in drinking water at the concentrations tested, except that an increase in splenocyte basal proliferation was observed at chloroform levels of 100 and 250 ppm. Following chloroform administration, there was a decreased number of circulating neutrophils in the blood in all treatment groups, but neutrophil function in lung homogenates, as evaluated using an assay for myeloperoxidase activity following lipopolysaccharide and N-Formyl-Met-Leu-Phe stimulation, was not compromised. Further, the results of host resistance to Listeria monocytogenes infection also suggested that neutrophil function was normal. At the highest treatment level of chloroform (250 ppm), erythrocyte number and hemoglobin levels were significantly decreased. Some significant changes were also observed for body weights, water consumption, and organ weights; however, most of these effects were only observed at the highest treatment level of chloroform (250 ppm). Taken together, the results demonstrate that while chloroform administered via the drinking water affects body weight and selected hematological parameters at high dose levels, overall immune responses, as measured in several tests for immune function, are not compromised.

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Section: Introductionmentioning

confidence: 99%

Immunotoxicological profile of chloroform in female B6C3F1 mice when administered in drinking water

Auttachoat

Germolec

Collins

et al. 2009

Drug and Chemical Toxicology

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Effect of Trihalomethanes on Cell Proliferation and DNA Methylation in Female B6C3F1 Mouse Liver

Coffin

2000

Toxicological Sciences

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Trihalomethanes (chloroform, bromodichloromethane, chlorodibromomethane, and bromoform) are regulated organic contaminants in chlorinated drinking water. In female B6C3F1 mouse liver, the 4 trihalomethanes have demonstrated carcinogenic activity when administered by oral gavage; however, chloroform was not carcinogenic when administered in drinking water. Female B6C3F1 mice were administered the trihalomethanes for 11 days by gavage at 2 dose levels or in the drinking water at approximately 75% saturation. When administered by gavage, the trihalomethanes were toxic to the liver, increased the liver:body weight (bw) ratio, and increased the proliferating cell nuclear antigen-labeling index (PCNA-LI). Chloroform and bromodichloromethane were the most toxic, and they increased the liver:bw ratio the most, while bromoform and chloroform increased the PCNA-LI the most. When administered in drinking water, the toxicity of the trihalomethanes was similar to their low gavage-dose. Furthermore, only chloroform significantly increased the liver:bw ratio and bromoform and chloroform increased the PCNA-LI. Chloroform and bromodichloromethane decreased the level of 5-methylcytosine in hepatic DNA. Methylation in the promoter region of the c-myc gene was reduced by the trihalomethanes. Chloroform administered by gavage was more efficacious than given in drinking water; the efficacy of the other trihalomethanes did not differ for the 2 routes. Thus, in mouse liver, the trihalomethanes administered by gavage enhanced cell proliferation and decreased the methylation of the c-myc gene, consistent with their carcinogenic activity. Furthermore, the more modest toxicity, enhancement of cell proliferation, and decreased methylation induced by chloroform administered in drinking water correlated with its lack of carcinogenic activity. Hence, the activity of the trihalomethanes was dependent on the rate of delivery, i.e. rapid by oral gavage and more slowly in drinking water.

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Chloroform in Drinking Water Prevents Hepatic Cell Proliferation Induced by Chloroform Administered by Gavage in Corn Oil to Mice

Cited by 2 publications

References 17 publications

Immunotoxicological profile of chloroform in female B6C3F1 mice when administered in drinking water

Immunotoxicological profile of chloroform in female B6C3F1 mice when administered in drinking water

Effect of Trihalomethanes on Cell Proliferation and DNA Methylation in Female B6C3F1 Mouse Liver

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