Two‐year Study of Carcinogenicity and Chronic Toxicity of Biphenyl in Rats

Umeda, Yumi; Arito, Heihachiro; Kano, Hirokazu; Ohnishi, Makoto; Matsumoto, Michiharu; Nagano, Kasuke; Yamamoto, Seigo; Matsushima, Taijiro

doi:10.1539/joh.44.176

Cited by 16 publications

(38 citation statements)

References 8 publications

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“…A recent publication reported that 2-year oral administration of a diet containing biphenyl induced bladder papillomas and carcinomas in male rats. 21 We failed to find a relationship between this product and deaths from bladder cancer in Besançon, but it should be noted that mortality might not reflect the importance of bladder cancer, which is a cancer with long survival duration.…”

Section: Discussionmentioning

confidence: 73%

Cancer mortality in a synthetic spinning plant in Besançon, France

Hours¹,

Févotte

Lafont

et al. 2007

Occup Environ Med

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Objectives: To assess the mortality of a cohort of workers in a synthetic textile spinning plant and to evaluate the relationship between mortality from lung, liver and bladder cancer and the processes or the products used. Methods: The study population consisted of male workers present for at least 6 months in the plant from 1968 to 1984. The cohort was followed until 1999. Vital status and the causes of death were determined by consulting national registries. The population of the Franche-Comté region was used for comparison. In total, 17 groups of exposure were assessed by the industrial hygienist, based on the consensus of an expert group that determined the exposure levels of each job to selected occupational hazards. Each worker was assigned to one or several groups, according to his occupational history. Confounding factors could not be assessed. Standardised mortality ratios (SMR) and 95% bilateral confidence intervals were calculated based on an assumed Poisson distribution of the number of cases to compare the plant mortality and the population mortality. Internal analyses were performed with Cox models in order to assess the risks of death related to the various exposures.

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Section: Discussionmentioning

confidence: 73%

Cancer mortality in a synthetic spinning plant in Besançon, France

Hours¹,

Févotte

Lafont

et al. 2007

Occup Environ Med

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“…Therefore, it is inferred on the basis of the above literature that the genotoxic mode of action operates in the biphenyl-induced hepatocarcinogenicity, mediating through the possible DNA damage by active biphenyl metabolites. We previously reported that the 2-year oral administration of a biphenyl-containing diet at 4,500 ppm induced bladder transitional cell papillomas and carcinomas in male F344 rats, in close association with formation of bladder calculi [30]. In addition, any histopathological changes in the liver were not observed in the male and female rats fed 4,500 ppm diet for 2 years [30].…”

Section: Discussionmentioning

confidence: 92%

“…Imai et al [10] reported that any tumor was not induced by either oral administration of biphenyl or combined administration of biphenyl and thiabendazole in feed to female ddY mice for 2 years. However, we previously reported that 2-year oral administration of biphenylcontaining diets induced both benign and malignant bladder tumors in male F344 rats, in close association with formation of bladder calculi [30].…”

mentioning

confidence: 94%

“…Data of cancer epidemiology and animal carcinogenicity are important determinants for the classification and evaluation of carcinogenic potential of biphenyl. There are few animal carcinogenicity data available for the evaluation of carcinogenic potential of biphenyl by bioassay studies with rodents exposed to biphenyl for long term [10,11,30]. Innes et al [11] reported as a preliminary note that any tumor was not induced by oral administration of biphenyl to B6AKF 1 and B6C3F 1 mice of both sexes for 18 months.…”

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confidence: 99%

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Carcinogenicity of Biphenyl in Mice by Two Years Feeding

Umeda

Aiso

Yamazaki

et al. 2005

The Journal of Veterinary Medical Science

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ABSTRACT. Carcinogenicity and chronic toxicity of biphenyl was examined in the male and female BDF 1 mice fed a diet containing biphenyl at 667, 2,000 or 6,000 ppm for 2 years. There was no difference in survival rate between any biphenyl-containing diet-fed group of either sex and the respective control. Body weights of the males and females fed 6,000 ppm diet were significantly lower than the respective control. Incidences of hepatocellular carcinomas and hepatocellular adenomas in the females fed diets containing biphenyl were significantly increased in a dose-related manner, and exceeded a range of the historical control data in the Japan Bioassay Research Center. Incidences of basophilic cell foci in the liver were increased in the females fed 2,000 and 6,000 ppm diets. There was no increase in tumor or tumor-related lesion in the males fed diets containing biphenyl. Chronic toxicity of biphenyl was characterized by increased incidences of urothelial desquamation in the renal pelvis in males and females and mineralization in the inner stripe of renal outer medulla in females, as well as changes in serum levels of BUN, ALP and some electrolytes in males and females. In conclusion, the 2-year oral administration of biphenyl-containing diets induced pre-neoplastic and neoplastic lesions in the liver of females and non-neoplastic lesions in the kidney of males and females. Causative factors for the biphenyl-induced hepatocarcinogenicity were discussed in light of our published finding of peroxisome proliferation.

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“…Relevance for extrapolation of the rat urinary bladder tumors to humans has also been argued 32) , since close association between chemically induced rodent urinary bladder carcinogenicity and calculus formation has been established [33][34][35][36] , and since the formation of calculus by biphenyl is considered to be species-and sex-specific 37,38) . In addition to the reported findings of positive mutagenicity of ACP [9][10][11] , the present 13-wk and 2-yr studies confirmed that neither the crystalline or amorphous precipitate in the urinary bladder nor the hematuria, possibly resulting from the mechanical damage of transitional epithelium by the precipitate, occurred in any ACP-fed rat of either sex.…”

Section: Extrapolation To Human Cancer Riskmentioning

confidence: 99%

Oral Carcinogenicity and Toxicity of 2‐Amino‐4‐chlorophenol in Rats

Yamazaki

Suzuki

Kano

et al. 2009

Journal of Occupational Health

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Oral Carcinogenicity and Toxicity of 2-Amino-4-chlorophenol in Rats: Kazunori YAMAZAKI, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health AssociationObjectives: This study was carried out to clarify the subchronic and chronic toxicity, and carcinogenicity of 2 -a m i n o -4 -c h l o r o p h e n o l ( A C P ) . M e t h o d s : Carcinogenicity, and chronic and subchronic toxicity of ACP were examined by feeding 10 rats of both sexes ACP-containing diet at a dose level of 0 (control), 512, 1,280, 3,200, 8,000 or 20,000 ppm (w/w) for 13 wk and 50 rats of both sexes at a dose level of 0, 1,280, 3,200 or 8,000 ppm for 2 yr. Results: The 13-wk oral subchronic toxicity of ACP was characterized by proliferative lesions leading to development of tumors in the forestomach and urinary bladder and by erythrocyte toxicity as evidenced by decreases in red blood cell counts, hemoglobin and hematocrit and concurrent increases in methemoglobin levels and reticulocyte counts. Both simple and papillary and/or nodular types of transitional cell hyperplasias were observed in the urinary bladder of ACP-fed male rats. The proliferative lesions appeared at higher doses of ACP after the 13-wk administration than clear erythrocyte toxicity did. The 2-yr oral administration of ACP significantly increased incidences of squamous cell papillomas and carcinomas in the forestomach of male and female rats and transitional cell carcinomas in the urinary bladder of male rats. These tumor incidences increased dose-dependently. Notably, clear signs of erythrocyte toxicity were not evident after the 2-yr administration of ACP. Conclusion: Clear evidence of carcinogenic activity of ACP was shown in male and female rats. These data might be useful for the health risk assessment of workers exposed to ACP. (J Occup Health 2009; 51: 249-260)

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Two‐year Study of Carcinogenicity and Chronic Toxicity of Biphenyl in Rats

Cited by 16 publications

References 8 publications

Cancer mortality in a synthetic spinning plant in Besançon, France

Cancer mortality in a synthetic spinning plant in Besançon, France

Carcinogenicity of Biphenyl in Mice by Two Years Feeding

Oral Carcinogenicity and Toxicity of 2‐Amino‐4‐chlorophenol in Rats

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