Carcinogenicity of Chloroform in Drinking Water to Male Osborne-Mendel Rats and Female B6C3F1 Mice

Jorgenson, T.A.; Meierhenry, Earl F.; Rushbrook, C.J.; Bull, Richard J.; Robinson, Merrel

doi:10.1093/toxsci/5.4.760

Cited by 23 publications

(38 citation statements)

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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).…”

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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“…The U.S. EPA (2003) also concluded that those epidemiological data were insufficient to establish a causal relationship between exposure to chloroform and increased risk of cancer. However, chloroform-induced kidney tumors were reported by rodent bioassay carcinogenicity studies (Hard et al, 2000;Jorgenson et al, 1985;NCI, 1976;Reuber, 1979;Yamamoto et al, 2002). Chloroform was categorized as a possible human carcinogen (2B) by IARC (1999) and as being likely to be carcinogenic to humans by the U.S. EPA (2003).…”

Section: Enhancement Of Renal Carcinogenicity By Combined Inhalation mentioning

confidence: 99%

Enhancement of Renal Carcinogenicity by Combined Inhalation and Oral Exposures to Chloroform in Male Rats

Nagano¹,

Kano²,

Arito³

et al. 2006

Journal of Toxicology and Environmental Health, Part A

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Chloroform, ubiquitously present in indoor and outdoor air, drinking water, and some foodstuffs, enters the human body by inhalation, oral and dermal routes of exposure. In order to provide bioassay data for risk assessment of humans exposed to chloroform by multiple routes, effects of combined inhalation and oral exposures to chloroform on carcinogenicity and chronic toxicity in male F344 rats were examined. A group of 50 male rats was exposed by inhalation to 0 (clean air), 25, 50, or 100 ppm (v/v) of chloroform vapor-containing air for 6 h/d and 5 d/wk during a 104 w period, and each inhalation group was given chloroform-formulated drinking water (1000 ppm w/w) or vehicle water for 104 wk, ad libitum. Renal-cell adenomas and carcinomas and atypical renal-tubule hyperplasias were increased in the combined inhalation and oral exposure groups, but not in the oral- or inhalation-alone groups. Incidences of cytoplasmic basophilia and dilated tubular lumens in the kidney, as well as incidence of positive urinary glucose, were markedly increased by the combined exposures, compared with those after single-route exposures. It was concluded that combined inhalation and oral exposures markedly enhanced carcinogenicity and chronic toxicity in the proximal tubule of male rat kidneys, suggesting that carcinogenic and toxic effects of the combined exposures on the kidneys were greater than the ones that would be expected under an assumption that the two effects of single route exposures through inhalation and drinking were additive.

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“…More importantly, studies suggest that the carcinogenic response in male rat kidney (6,43,44), and possibly in rat liver (8), may not be mediated by a mechanism involving necrosis and regenerative cell proliferation.…”

Section: )mentioning

confidence: 99%

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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Carcinogenicity of Chloroform in Drinking Water to Male Osborne-Mendel Rats and Female B6C3F1 Mice

Cited by 23 publications

References 0 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

Enhancement of Renal Carcinogenicity by Combined Inhalation and Oral Exposures to Chloroform in Male Rats

Characterization of cancer risk associated with exposure to chloroform∗

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