Toxicity and cell proliferation in the liver, kidneys and nasal passages of female F-344 rats, induced by chloroform administered by gavage

Larson, Jeffrey; Wolf, Douglas C.; Mèry, Stephane; Morgan, Kevin T.; Butterworth, Byron E.

doi:10.1016/0278-6915(95)00013-r

Cited by 43 publications

(15 citation statements)

References 28 publications

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“…Chlorinated organic compounds have been demonstrated to be carcinogenic in rodents (NCI, 1976;Jorgenson et al, 1985). Chloroform exposure by gavage at doses ranging from 180 to 400 mg/kg in rodents produced toxicities in several organ systems, including nasal and olfactory mucosal degradation, as well as liver and kidney toxicity (Larson et al, 1994a(Larson et al, , 1995a(Larson et al, , 1995bTemplin et al, 1996;Dorman et al, 1997;Miyagawa et al, 1998). In addition, CHF administration for 14 or 90 days by gavage at doses of 50-250 mg/kg in CD-1 mice reduced the number of antibody-forming cells to the T-dependent antigen sheep erythrocytes up to 30%, demonstrating that CHF was immunotoxic when administered as a bolus dose (Munson et al, 1982).…”

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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“…Chloroform (CHCl 3 ) ( Figure 7) has been used as a solvent and is generated as a trace contaminant in the chlorination of drinking water with a maximum allowable concentration as total trihalomethanes of 80 ppb. Oral administration to female F344 rats of 34 mg/kg/day or greater produced degeneration of the OE and superficial BGs (Larson et al, 1995), which was not associated with detectable olfaction deficit (Dorman et al, 1997). The OE, RE, and BGs have substantial chloroform biotransformation capabilities (Lofberg and FIGURE 5.-Benzophenone.…”

Section: Introductionmentioning

confidence: 99%

Nasal Cytotoxic and Carcinogenic Activities of Systemically Distributed Organic Chemicals

2006

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Toxicity and carcinogenicity in the mucosa of the nasal passages in rodents has been produced by a variety of organic chemicals which are systemically distributed. In this review, 14 such chemicals or classes were identified that produced rodent nasal cytotoxicity, but not carcinogenicity, and 11 were identified that produced nasal carcinogenicity. Most chemicals that affect the nasal mucosa were either concentrated in that tissue or readily activated there, or both. All chemicals with effects in the nasal mucosa that were DNA-reactive, were also carcinogenic, if adequately tested. None of the rodent nasal cytotoxins has been identified as a human systemic nasal toxin. This may reflect the lesser biotransformation activity of human nasal mucosa compared to rodent and the much lower levels of human exposures. None of the rodent carcinogens lacking DNA reactivity has been identified as a nasal carcinogen or other cancer hazard to humans. Some DNA-reactive rodent carcinogens that affect the nasal mucosa, as well as other tissues, have been associated with cancer at various sites in humans, but not the nasal cavity. Thus, findings in only the rodent nasal mucosa do not necessarily predict either a toxic or carcinogenic hazard to that tissue in humans.

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“…A number of studies have recently been performed to define the route-, time-and dose-response pattern for chloroform-induced cytotoxicity and regenerative cell proliferation in liver and kidney of F-344 rats and B6C3F1 mice (45)(46)(47)(48)(49)(50)(51). All these studies by Larson et al are short-term studies with exposure duration of 4 to 21 days.…”

Section: Correlation Of Cancer With Cell Proliferation (Labeling Imentioning

confidence: 96%

“…Patterns of chloroform-induced cell proliferation in the livers of male B6C3F1 mice and female F-344 rats exposed to chloroform by com oil gavage are generally similar (47,50). No BRDU labeling index experiments were performed on male B6C3F1 mice or female F-344 rats exposed to chloroform in drinking water.…”

Section: Ivermentioning

confidence: 98%

Characterization of cancer risk associated with exposure to chloroform∗

Chiu

Orme‐Zavaleta

Chiu

et al. 1996

Journal of Environmental Science and Health, Part C

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Toxicity and cell proliferation in the liver, kidneys and nasal passages of female F-344 rats, induced by chloroform administered by gavage

Cited by 43 publications

References 28 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

Nasal Cytotoxic and Carcinogenic Activities of Systemically Distributed Organic Chemicals

Characterization of cancer risk associated with exposure to chloroform∗

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