A two-year drinking-water study of dichloromethane in rodents. I. Rats

Serota, David G.; Thakur, Ajit Kumar; Ulland, Borge M.; Kirschman, John C.; Brown, Nicole M.; Coots, Robert H.; Morgareidge, Kenneth

doi:10.1016/0278-6915(86)90323-6

Cited by 44 publications

(8 citation statements)

References 8 publications

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“…[46], the statistical results are presented in the full report of the study (Hazleton Laboratories, [45]): the trend p-value was 0.058; p-values for the pair-wise comparisons with the combined control group were p = 0.071, 0.023, 0.019, and 0.036 for the 50, 125, 185, and 250 mg/kg per day dose groups, respectively. None of the chronic exposure studies in rats have shown a relation between dichloromethane exposure and liver or lung tumors [3,45,47–49]. …”

Section: Discussionmentioning

confidence: 99%

Insights from Epidemiology into Dichloromethane and Cancer Risk

Cooper

Scott

Bale

2011

IJERPH

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Dichloromethane (methylene chloride) is a widely used chlorinated solvent. We review the available epidemiology studies (five cohort studies, 13 case-control studies, including seven of hematopoietic cancers), focusing on specific cancer sites. There was little indication of an increased risk of lung cancer in the cohort studies (standardized mortality ratios ranging from 0.46 to 1.21). These cohorts are relatively small, and variable effects (e.g., point estimates ranging from 0.5 to 2.0) were seen for the rarer forms of cancers such as brain cancer and specific hematopoietic cancers. Three large population-based case-control studies of incident non-Hodgkin lymphoma in Europe and the United States observed odds ratios between 1.5 and 2.2 with dichloromethane exposure (ever exposed or highest category of exposure), with higher risk seen in specific subsets of disease. More limited indications of associations with brain cancer, breast cancer, and liver and biliary cancer were also seen in this collection of studies. Existing cohort studies, given their size and uneven exposure information, are unlikely to resolve questions of cancer risks and dichloromethane exposure. More promising approaches are population-based case-control studies of incident disease, and the combination of data from such studies, with robust exposure assessments that include detailed occupational information and exposure assignment based on industry-wide surveys or direct exposure measurements.

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Section: Discussionmentioning

confidence: 99%

Insights from Epidemiology into Dichloromethane and Cancer Risk

Cooper

Scott

Bale

2011

IJERPH

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“…Hepatocellular carcinomas, but not cancers of the biliary passages or gallbladder, have been induced in mice exposed to methylene chloride via inhalation (NTP 1986). In similar studies, no liver or biliary tract cancers were observed in rats or hamsters (NTP 1986;Serota et al 1986;Burek et al 1984).…”

Section: Liver and Biliary Tract Cancermentioning

confidence: 65%

Critical review of the epidemiology literature on the potential cancer risks of methylene chloride

Dell

Mundt

McDonald

et al. 1999

International Archives of Occupational and Environmental Health

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Continued follow-up of the established cohorts may elucidate the few and inconsistent relationships reported to date; however, it appears likely that risks associated with methylene chloride exposure, if any, are small and limited to rare cancers. The usefulness of additional cohort studies for the evaluation of cancer risks associated with methylene chloride exposure will depend largely on whether the relevant exposure period has passed and whether exposure characterization (e.g., peak or intermittent exposure or intensity) can be improved.

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“…Dichloromethane (DCM) is another haloalkane associated with the occupational cholangiocarcinoma cases and was therefore classified as probably carcinogenic to human (Group 2A) (Benbrahim-Tallaa et al, 2014;Sobue et al, 2015). In terms of cholangiocarcinogenicity in experimental rodents, similarly to 1,2-DCP, DCM did not induce cholangiocarcinogenesis in inhalation or drinking water carcinogenicity studies in mice, rats, or hamsters (Burek et al, 1984;Serota et al, 1986aSerota et al, , 1986b, while it induced hepatocellular tumors and lung tumors in inhalation carcinogenicity studies in mice (NTP, 1986b). Given the fact that so far there is no experimental evidence for 1,2-DCP or DCM cholangiocarcinogenicity when administered alone and the possibility that the occurrence of occupational cholangiocarcinomas in Japan might be attributed to exposure to multiple chemicals (Benbrahim-Tallaa et al, 2014;Sobue et al, 2015), studies are needed to determine the carcinogenic effects of concurrent exposure to 1,2-DCP and DCM or other organic solvents contained in the stripers to which the workers with cholangiocarcinoma were exposed.…”

Section: Discussionmentioning

confidence: 99%

Modifying effects of 1,2-dichloropropane on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in male Syrian hamsters

Fujioka

Yamano

et al. 2015

J. Toxicol. Sci.

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-Based on the findings of epidemiological studies in Japan that occupational exposure to 1,2-dichloropropane (1,2-DCP) was associated with increased cholangiocarcinomas, 1,2-DCP has recently been classified as being carcinogenic to humans (Group 1). However, the cholangiocarcinogenicity of 1,2-DCP has not been demonstrated experimentally, and it was negative for cholangiocarcinogenicity in rats and mice. The present study determined the effects of 1,2-DCP on N-nitrosobis(2-oxopropyl)amine (BOP)-induced cholangiocarcinogenesis in male hamsters. We found that 1,2-DCP did not enhance the development of BOP-induced atypical biliary hyperplasia and did not induce any lesions in liver bile duct when administered alone. Notably, 1,2-DCP had no effect on the proliferative activity of bile duct epithelial cells regardless of BOP-initiation. These results demonstrate that 1,2-DCP lacks promoting effects on BOP-induced cholangiocarcinogenesis and suggest the possibility that 1,2-DCP is not cholangiocarcinogenic to the hamster in the present model. In addition, 1,2-DCP also lacks promoting effects on pancreatic, lung, and renal carcinogenesis. As the occurrence of occupational cholangiocarcinomas in Japan might be attributed to exposure to multiple chemicals, the results of the present study indicate that it will be necessary to determine the cholangiocarcinogenic effects of concurrent exposure of 1,2-DCP and the other halogen solvents to which workers with cholangiocarcinomas were exposed.

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A two-year drinking-water study of dichloromethane in rodents. I. Rats

Cited by 44 publications

References 8 publications

Insights from Epidemiology into Dichloromethane and Cancer Risk

Insights from Epidemiology into Dichloromethane and Cancer Risk

Critical review of the epidemiology literature on the potential cancer risks of methylene chloride

Modifying effects of 1,2-dichloropropane on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in male Syrian hamsters

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