Inhalation oncogenicity bioassay in rats and mice with vinyl fluoride

The purpose of this study was to assess the oncogenic potential of vinyl fluoride in rats and mice when administered by inhalation. Male and female rats and mice were exposed to 0, 25, 250, or 2500 ppm vinyl fluoride 6 hr per day, 5 days per week, for 2 years (rats) or 18 months (mice). Slight body weight gain decrements were noted in groups of vinyl fluoride-exposed rats and mice. No significant clinical signs of toxicity were noted other than an increase in the incidence of palpable masses in the region of the mammary gland in female mice exposed to vinyl fluoride. Survival was decreased in male rats and mice of the 250 and 2500 ppm groups and female rats and mice of all vinyl fluoride-exposed groups compared to controls. Urinary fluoride excretion, an indicator of vinyl fluoride metabolism, increased with concentration and time although the dose relationship appeared to plateau at concentrations > or = 250 ppm. Gross observations made at necropsy of rats supported histological observations of hepatic hemangiosarcoma, hepatocellular adenoma and carcinoma, hepatic foci of clear cell and basophilic alteration, hepatic sinusoidal dilatation, metastatic lung tumors, and Zymbal's gland tumors. Hepatic hemangiosarcoma was the sentinel lesion in rats. Gross observations made at necropsy of mice supported histological observations of bronchioloalveolar adenoma and hyperplasia, hepatic hemangiosarcoma and hepatocellular hyperplasia with angiectasis and peliosis, and mammary gland adenocarcinoma and hyperplasia. Bronchioloalveolar adenoma appeared to be the sentinel lesion in mice. The spectrum of vinyl fluoride-induced tumors is similar to that induced by other monohaloethylenes in rats and mice. Under the conditions of this study, vinyl fluoride was carcinogenic in male and female rats and mice at concentrations greater than or equal to 25 ppm.