Chronic Toxicity and Oncogenicity Study with Vinyl Acetate in the Rat: In Utero Exposure in Drinking Water

Bogdanffy, Matthew S.; Tyler, T. R.; Vinegar, Marlee; Rickard, Robert W.; Carpanini, F.M.B.; CASCIERI, T. C.

doi:10.1006/faat.1994.1099

Cited by 24 publications

(11 citation statements)

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“…The present finding of VA-induced squamous cell carcinomas and papilloma in the upper digestive tract of mice and rats is in apparent contrast to the results from the VA-formulated drinking water studies by Bogdanffy et al 7) and Lijinsky and Reuber 5) , but consistent with the results by Maltoni et al 8) The difference and similarity in the VA-induced carcinogenicity between the results so far reported and the present findings appear to exist in a difference in the amount of daily VA intake. Indeed, a BMDL 10 value resulted in 477 mg/kg/d for the oral cavity squamous cell tumors as shown in Figure 6.…”

Section: Discussioncontrasting

confidence: 99%

“…VA has been reported to cause an irritation effect on the respiratory system of workers 3) and an excess risk for cancer of the respiratory system in a synthetic chemicals plant 4) . Rodent bioassay studies available for cancer risk assessment of workers exposed to VA have been limited [5][6][7][8][9] . Lijinsky and Reuber 5) reported induction of both thyroid and uterine tumors in the Fischer rat given VA-formulated drinking water for two years.…”

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confidence: 99%

“…Lijinsky and Reuber 5) reported induction of both thyroid and uterine tumors in the Fischer rat given VA-formulated drinking water for two years. Bogdanffy et al 6) reported a significantly increased incidence of nasal tumors in Sprague-Dawley (SD) rats exposed to VA by 2-yr inhalation but not in ICR mice, but they 7) showed no treatment-related increase in tumor incidence of the SD rats administered VA in drinking water for in utero and subsequent lifetime. Maltoni et al 8) and Minardi et al 9) reported induction of carcinomas at multiple sites in Swiss mice and SD rats administered VA-formulated drinking water for two years, respectively.…”

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Carcinogenicity and Chronic Toxicity in Mice and Rats Administered Vinyl Acetate Monomer in Drinking Water

Umeda

Matsumoto

Yamazaki

et al. 2004

Journal of Occupational Health

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Carcinogenicity and Chronic Toxicity in Mice and Rats Administered Vinyl Acetate Monomer in Drinking Water: Yumi Umeda, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health Association—Carcinogenicity and chronic toxicity of vinyl acetate monomer (VA) were examined in male and female Crj:BDF1 mice and F344/DuCrj Rats. Groups of 50 mice and 50 rats of each sex were orally administered VA in drinking water containing 0, 400, 2,000 or 10,000 ppm (g/g) VA for 104 wk. Squamous cell tumors were clearly evident in the upper digestive tract of treated mice and rats, and in the larynx of treated mice of both sexes. In mice, squamous cell carcinomas and papillomas were observed in the oral cavity, esophagus, forestomach and larynx of the 10,000 ppm group, together with basal cell hyperplasia, squamous cell hyperplasia and epithelial dysplasia. In rats, incidences of squamous cell carcinomas and papillomas were increased in the oral cavity of the 10,000 ppm group of both sexes, and an esophagus squamous cell carcinoma was observed in a 10,000 ppm female. Pre‐neoplastic hyperplasias were also noted. Mapping of the neoplastic and pre‐neoplastic lesions in the oral cavity of the 10,000 ppm group revealed that both the lesions occurred predominantly at Level V in mice and at Level VI in rats. A lower confidence limit of a benchmark dose (BMDL10) of 477 mg/kg/d was obtained from a dose‐response relationship between combined incidence of squamous cell carcinomas and papillomas in the oral cavity of mice and rats and the estimated daily VA intakes per body weight, and compared with literature values.

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Section: Discussioncontrasting

confidence: 99%

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Carcinogenicity and Chronic Toxicity in Mice and Rats Administered Vinyl Acetate Monomer in Drinking Water

Umeda

Matsumoto

Yamazaki

et al. 2004

Journal of Occupational Health

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“…The authors contend the study supports an evaluation of vinyl acetate monomer (VA) as a possible human carcinogen in contrast with previous studies (e.g., Bogdanffy et al 1) ), that failed to find treatment related increases in tumor incidence. Based on our review, the results from the present study are of questionable significance to human health as they only substantiate a carcinogenic response at the highest dose (10,000 ppm)-a dose that may have exceeded the maximum tolerated dose (MTD).…”

Section: Dear Editormentioning

confidence: 50%

Response to Umeda et al.

Bogdanffy

Valentine

Goodman

et al. 2004

Journal of Occupational Health

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“…It is interesting to note that the incidence of oral cavity tumors induced by oral administration of 5,000 ppm VA to mice (Maltoni et al 4) ) and two cases of oral cavity squamous cell carcinomas in the male rats given 5,000 ppm VA (Bodganffy et al 5) ) follow the internal dose-tumor response curve (Fig. 6 …”

Section: Response To Dr Bogdanffy Et Al's Comments On Our Papermentioning

confidence: 96%