Ms. Bogdanffy et al., INHALATION ONCOGENICITY BIOASSAY IN RATS AND MICE WITH VINYL FLUORIDE, Fundamental and applied toxicology, 26(2), 1995, pp. 223-238
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.