SUBSTANCE PROFILES

REPORT ON CARCINOGENS, ELEVENTH EDITION

Vinyl Fluoride 

CAS No. 75-02-5

Reasonably anticipated to be a human carcinogen

First Listed in the Tenth Report on Carcinogens (2002)

Carcinogenicity

Vinyl fluoride is reasonably anticipated to be a human carcinogen based

on sufficient evidence of carcinogenicity in experimental animals. Both

male and female rats exposed to vinyl fluoride by inhalation showed

increased incidences of hepatic hemangiosarcoma, hepatocellular

adenoma or carcinoma, and Zymbal gland carcinoma. Both male and

female mice exposed to vinyl fluoride by inhalation showed increased

incidences of hepatic hemangiosarcoma, bronchiolar-alveolar adenoma

or adenocarcinoma, hepatocellular adenoma, and harderian gland

adenoma. Female mice also showed an increased incidence of

mammary gland adenocarcinoma (Bogdanffy et al. 1995, IARC 1995).

The tumor responses of laboratory animals to vinyl fluoride are

similar to their responses to vinyl chloride, a known human carcinogen

(IARC 1987), and to vinyl bromide, a probable human carcinogen

(IARC 1986). A unique feature of vinyl chloride carcinogenicity is that

vinyl chloride induces rare hepatic hemangiosarcomas in experimental

animals and is causally associated with excess risk of liver

hemangiosarcoma in epidemiological studies of exposed workers. The

fact that vinyl fluoride, vinyl chloride, and vinyl bromide all induce

rare hemangiosarcomas of the liver in experimental animals and induce

the formation of similar DNA adducts suggests a possible common

mechanism of carcinogenicity for all three of these chemicals.

No adequate human studies of the relationship between exposure

to vinyl fluoride and human cancer were found.

Additional Information Relevant to Carcinogenicity

Vinyl fluoride is mutagenic in Salmonella typhimurium with the

addition of a rat liver homogenate metabolic activation system. In

addition, vinyl fluoride induces gene mutations and chromosomal

aberrations in Chinese hamster ovary cells (with metabolic activation),

sex-linked recessive lethal mutations in Drosophila melanogaster, and

micronuclei in bone marrow cells of female mice (IARC 1995).

Vinyl fluoride likely is metabolized in a manner similar to vinyl

chloride: oxidation via cytochrome P450 to fluoroethylene oxide,

followed by rearrangement to 2-fluoroacetaldehyde, which is oxidized

to fluoroacetic acid. Human, rat, and mouse liver microsomes

metabolize vinyl fluoride at similar rates (Cantoreggi and Keller 1997).

Vinyl fluoride metabolites form covalent DNA adducts. Inhalation

exposure of rats and mice to vinyl fluoride produced a dose-related

increase in the formation of the promutagenic adduct N 2,3-

ethenoguanine in their liver DNA (Swenberg et al. 1995).

No available data suggest that mechanisms by which vinyl fluoride

induces tumors in experimental animals would not also operate in humans.

Properties

Vinyl fluoride is a colorless gas with a faint ether-like odor. It is

insoluble in water and soluble in alcohol, ether, and acetone. Vinyl

fluoride is extremely flammable and will form explosive mixtures with

air. It can form hazardous polymers when heated. A fire containing

vinyl fluoride can generate highly toxic hydrogen fluoride gas (HSDB

2001). Vinyl fluoride reacts with alkali and alkaline earth metals,

powdered aluminum, zinc, and beryllium (IARC 1995).

Use

Vinyl fluoride is used primarily in the production of polyvinyl

fluoride and other fluoropolymers. Polymers of vinyl fluoride are

resistant to weather and have great strength, chemical inertness, and

low permeability to air and water. Polyvinyl fluoride is laminated

with aluminum, galvanized steel, and cellulose materials and is used

as a protective surface for the exteriors of residential and commercial

buildings. Polyvinyl fluoride laminated with various plastics has been

used to cover walls, pipes, and electrical equipment and inside aircraft

cabins (IARC 1995).

Production

Vinyl fluoride was first prepared in the early 1900s by reaction of zinc

with 1,1-difluoro-2-bromoethane. Modern preparation of vinyl

fluoride involves reaction of acetylene and hydrogen fluoride in the

presence of a mercury-based or aluminum-based catalyst (IARC 1995).

Annual U.S. production is approximately 3.3 million lb (HSDB

2001). The U.S. Environmental Protection Agency (EPA), through the

Office of Pollution Prevention and Toxics, listed vinyl fluoride in the

high production volume chemical list in 1990, indicating that annual

production exceeded 1 million lb (EPA 1990). Only one U.S.

manufacturer of vinyl fluoride was identified (HSDB 2001).

Exposure

Exposure to vinyl fluoride in the environment will occur by

inhalation, because vinyl fluoride released into the environment exists

as a gas (IPCS 1993).

Occupational exposure to vinyl fluoride occurs primarily by

inhalation (HSDB 2001). Skin and eye contact can occur among

workers handling liquid vinyl fluoride. Handling liquid vinyl fluoride

also would cause frostbite (IPCS 1993).

Occupational exposure to vinyl fluoride was studied in a

manufacturing and polymerization facility in the United States. In

eight personal air samples taken at the manufacturing facility,

concentrations of vinyl fluoride generally were less than 2 ppm (3.76

mg/m3). In one personal sample, however, the concentration of vinyl

fluoride was 21 ppm (39.5 mg/m3). Vinyl fluoride concentrations in

seven personal samples taken in the polymerization facility ranged

from 1 to 4 ppm (1.88 to 7.52 mg/m3). In four general working areas,

the vinyl fluoride concentrations ranged from 1 to 5 ppm (1.88 to 9.4

mg/m3) (IARC 1995).

Regulations

DOT

Vinyl fluoride is considered a hazardous material and special requirements have been

set for marking, labeling, and transporting this material

EPA

Clean Air Act

Prevention of Accidental Release: Threshold Quantity (TQ) = 10,000 lbs

Guidelines

ACGIH

Threshold Limit Value - Time-Weighted Average Limit (TLV-TWA) = 1 ppm

NIOSH

Ceiling Recommended Exposure Limit = 5 ppm

Recommended Exposure Limit (REL) = 1 ppm

REFERENCES

Bogdanffy, M. S., G. T. Makovec and S. R. Frame. 1995. Inhalation oncogenicity bioassay in rats and mice

with vinyl fluoride. Fundam Appl Toxicol 26(2): 223-38.

Cantoreggi, S. and D. A. Keller. 1997. Pharmacokinetics and metabolism of vinyl fluoride in vivo and in

vitro. Toxicol Appl Pharmacol 143(1): 130-9.

EPA. 1990. Vinyl Fluoride (CAS # 75-02-5). U.S. Environmental Protection Agency, Office of Pollution

Prevention and Toxics. http://www.epa.gov/opptintr/chemrtk/opptsrch.htm and search CAS # 75-02-5.

HSDB. 2001. Hazardous Substances Data Base. National Library of Medicine. http://toxnet.nlm.nih.gov/

cgi-bin/sis/htmlgen?HSDB.

IARC. 1986. Some Chemicals Used in Plastics and Elastomers. Vinyl Fluoride. IARC Monographs on the

Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 39. Lyon, France: International Agency

for Research on Cancer. 147-154 pp.

IARC. 1987. Overall Evaluations of Carcinogenicity. IARC Monographs on the Evaluation of Carcinogenic

Risk of Chemicals to Humans, Supplement 7. Lyon, France: International Agency for Research on

Cancer. 440 pp.

IARC. 1995. Dry Cleaning, Some Chlorinated Solvents and Other Industrial Chemicals. IARC Monographs

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on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 63. Lyon, France: International

Agency for Research on Cancer. 558 pp.

IPCS. 1993. International Chemical Safety Cards. Vinyl Fluoride. International Programme on Chemical

Safety. http://www.cdc.gov/niosh/homepage.html.

Swenberg, J. A., D. K. La, N. A. Scheller and K. Y. Wu. 1995. Dose-response relationships for carcinogens.

Toxicol Lett 82-83: 751-6.

REPORT ON CARCINOGENS, ELEVENTH EDITION