INHALATION ONCOGENICITY BIOASSAY IN RATS AND MICE WITH VINYL FLUORIDE

The purpose of this study was to assess the oncogenic potential of vin yl 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 fl uoride 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 vin yl fluoride-exposed rats and mice. No significant clinical signs of to xicity were noted other than an increase in the incidence of palpable masses in the region of the mammary gland in female mice exposed to vi nyl 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-exp osed groups compared to controls. Urinary fluoride excretion, an indic ator of vinyl fluoride metabolism, increased with concentration and ti me although the dose relationship appeared to plateau at concentration s greater than or equal to 250 ppm. Gross observations made at necrops y of rats supported histological observations of hepatic hemangiosarco ma, hepatocellular adenoma and carcinoma, hepatic foci of clear cell a nd basophilic alteration, hepatic sinusoidal dilatation, metastatic lu ng tumors, and Zymbal's gland tumors. Hepatic hemangiosarcoma was the sentinel lesion in rats. Gross observations made at necropsy of mice s upported histological observations of bronchioloalveolar adenoma and h yperplasia, hepatic hemangiosarcoma and hepatocellular hyperplasia wit h angiectasis and peliosis, and mammary gland adenocarcinoma and hyper plasia. Bronchioloalveolar adenoma appeared to be the sentinel lesion in mice. The spectrum of vinyl fluoride-induced tumors is similar to t hat induced by other monohaloethylenes in rats and mice. Under the con ditions of this study, vinyl fluoride was carcinogenic in male and fem ale rats and mice at concentrations greater than or equal to 25 ppm. ( C) 1995 Society of Toxicology.