Carcinogenicity and chronic toxicity in mice and rats administered vinyl acetate monomer in drinking water.
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.
Umeda
Yumi
Y
Japan Bioassay Research Center, Japan Industrial Safety and Health Association, Hadano, Kanagawa, Japan. yumeda@jisha.or.jp
Matsumoto
Michiharu
M
Yamazaki
Kazunori
K
Ohnishi
Makoto
M
Arito
Heihachiro
H
Nagano
Kasuke
K
Yamamoto
Seigo
S
Matsushima
Taijiro
T
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000473:pathology; D004067:Digestive System Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000139:chemically induced* / Q000473:pathology; D015994:Incidence; D007822:Laryngeal Neoplasms / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D013997:Time Factors; D018675:Toxicity Tests; D014753:Vinyl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014881:Water Supply
D002273:Carcinogens; D014753:Vinyl Compounds; D014874:Water Pollutants, Chemical; C011566:vinyl acetate