Inhalation Oncogenicity Bioassay in Rats and Mice with Vinyl Fluoride

The purpose of this study was to assess the oncogenic potentialof vinyl fluoride in rats and mice when administered by inhalation.Male and female rats and mice were exposed to 0, 25, 250, or2500 ppm vinyl fluoride 6 hr per day, 5 days per week, for 2years (rats) or 18 months (mice). Slight body weight gain decrementswere noted in groups of vinyl fluoride-exposed rats and mice.No significant clinical signs of toxicity were noted other thanan increase in the incidence of palpable masses in the regionof the mammary gland in female mice exposed to vinyl fluoride.Survival was decreased in male rats and mice of the 250 and2500 ppm groups and female rats and mice of all vinyl fluoride-exposedgroups compared to controls. Urinary fluoride excretion, anindicator of vinyl fluoride metabolism, increased with concentrationand time although the dose relationship appeared to plateauat concentrations 250 ppm. Gross observations made at necropsyof rats supported histological observations of hepatic hemangiosarcoma,hepatocellular adenoma and carcinoma, hepatic foci of clearcell and basophilic alteration, hepatic sinusoidal dilatation,metastatic lung tumors, and Zymbal's gland tumors. Hepatic hemangiosarcomawas the sentinel lesion in rats. Gross observations made atnecropsy of mice supported histological observations of bronchioloalveolaradenoma and hyperplasia, hepatic hemangiosarcoma and hepatocellularhyperplasia with angiectasis and peliosis, and mammary glandadenocarcinoma and hyperplasia. Bronchioloalveolar adenoma appearedto be the sentinel lesion in mice. The spectrum of vinyl fluoride-inducedtumors is similar to that induced by other monohaloethylenesin rats and mice. Under the conditions of this study, vinylfluoride was carcinogenic in male and female rats and mice atconcentrations greater than or equal to 25 ppm.