**S UBSTANCE**  **P ROFILES** 



## T

etrafluoroethylene CAS No. 116-14-3

Reasonably anticipated to be a human carcinogen First Listed in the Ninth Report on Carcinogens (2000)



### Carcinogenicity
Tetrafluoroethylene (TFE) is reasonably anticipated to be a human carcinogen based on sufficient evidence of malignant tumor formation at multiple sites in multiple species of experimental animals (NTP 1997). When administered by inhalation to F344 rats, TFE induced renal tubule neoplasms, hepatocellular neoplasms, liver hemangiosarcoma, and mononuclear cell leukemia. When administered by inhalation to B6C3F 1 mice, TFE induced liver hemangiomas and hemangiosarcomas, hepatocellular neoplasms, and histiocytic sarcomas. No adequate human studies of the relationship between exposure to TFE and human cancer have been reported (IARC 1999). 

### Additional Information Relevant to Carcinogenicity
In prokaryotic systems, TFE was negative for the induction of gene mutations in Salmonella typhimurium with and without S9 activation. In mammalian systems in vitro , TFE was also negative for the induction of gene mutations in Chinese hamster ovary cells (HSDB 2001). No increases in the frequency of micronucleated erythrocyteswere observed in peripheral blood samples obtained from TFEexposed mice (NTP 1997). The frequency of H- ras codon 61 mutations observed in TFEinduced hepatocellular neoplasms (15%) was significantly less than the corresponding frequency (56 to 59%) in spontaneous liver neoplasms of B6C3F 1 mice, suggesting that TFE induces liver neoplasms via a ras -independent pathway (NTP 1997). The kidney-specific toxicity and carcinogenicity of TFE is most likely related to the selective uptake and subsequent processing of TFE-glutathione conjugates by renal β -lyase (Miller and Surh 1994, Anders et al. 1988). In rats, a TFE cysteine conjugate is bioactivated in the kidney to a difluorothionacetyl fluoride, the putative reactive metabolite for TFE-induced nephrotoxicity (NTP 1997). No data were available that would suggest that the mechanisms thought to account for tumor induction by TFE in experimental animals would not also operate in humans. 

### Properties
TFE is a colorless gas, is insoluble in water, and has a melting point of - 142.5°C (Kennedy 1990, Lewis 1992, IARC 1999). TFE is highly flammable when exposed to heat or flame. When heated to decomposition, it emits highly toxic fluorocarbon fumes. At ambient room temperature and pressure, air and TFE will form a flammable mixture when the TFE molar percentage is between 6.5 and 46% (Fiumara 1989) or the volume percentage is between 14 and 43%. It will explode at pressures above 2.7 bar (39.15 lb/in2 , 27,540 kg/m2 ) if a terpene inhibitor is not added. Examples of terpene inhibitors used

are d -limonene and terpene B (Gangal 1980). TFE will also react violently with oxygen (Lewis 1992). In the absence of oxygen, the violent thermal decomposition of TFE produces carbon and carbon tetrafluoride (Gangal 1980). 

### Use TFE is used primarily in the synthesis of polytetrafluoroethylene (Kennedy 1990). It is also used to produce copolymers with monomers such as hexafluoropropylene and ethylene (Carson et al. 1986).


### Production
TFE is primarily produced by the pyrolysis of chlorodifluoromethane or trifluoromethane (NTP 1997). In 1996, there were two producers of TFE (SRI 1996). No current production volumes have been found. Chem Sources (2001) listed four current U.S. suppliers for TFE. 

### Exposure
The primary route of exposure to TFE is inhalation. TFE has been reported to be present, along with several other low-molecular weight halogenated compounds, in volcanic emissions (Gribble 1994). Environmental exposure may occur due to releases of TFE through various waste streams; these releases may occur during its production and use in the production of fluoropolymers, nitroso rubbers, and low molecular mass compounds and intermediates (HSDB 2001). Potential occupational exposure to TFE may occur with workers involved in the production of polymers and copolymers of products containing the chemical. The National Occupational Exposure Survey (NOES), conducted by NIOSH between 1981 to 1983, listed a total of 14,963 employees, including 325 females, potentially exposed to TFE in 870 facilities (NIOSH 1990). The National Occupational Hazard Survey (NOHS), conducted between 1972 to 1974, estimated that 5,326 workers were potentially occupationally exposed to the chemical in 622 facilities. Of the total, 224 employees were in 28 plants reporting under industrial classification for the manufacture of chemicals and allied products (SIC Code 28), and 365 workers were in 99 plants reporting under industrial classification for manufacture of rubber and plastics products (SIC Code 30) (NIOSH 1976). 

### Regulations
DOT Tetrafluoroethylene 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 lb


### Guidelines

ACGIH Threshold Limit Value - Time-Weighted Average Limit (TLV-TWA) = 2 ppm

R EFERENCES
Anders, M. W., L. Lash, W. Dekant, A. A. Elfarra and D. R. Dohn. 1988. Biosynthesis and biotransformation of glutathione S-conjugates to toxic metabolites. Crit Rev Toxicol 18(4): 311-41. Carson, B. L., M. D. Erickson and J. l. McCann. 1986. Literature Review of Pyrolysis and Combustion Products of Selected Utility Materials. Palo Alto, CA: Electric Power Research Institute. 4 pp. ChemSources. 2001. Chemical Sources International, Inc. http://www.chemsources.com. Fiumara, A. 1989. Poly(tetrafluoroethylene): Flammability Problems in Monomer-Manufacturing Plants. In Proceedings of the 13th International Symposium on the Prevention of Occupational Accidents and Diseases in the Chemical Industry [in German]. p. 299-309. Gangal, S. V. 1980. Fluorine Compounds, Organic. In Kirk-Othmer Encyclopedia of Chemical Technology, 3rd. ed., vol. 11. M. Grayson, ed. New York, New York: John Wiley and Sons. p. 1-24. Gribble, G. W. 1994. The natural production of chlorinated compounds. Environ Sci Technol 28: 310A-319A.HSDB. 2001. Hazardous Substances Data Base. National Library of Medicine. http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?HSDB. IARC. 1999. Re-evaluation of Some Organic Chemicals, Hydrazine, and Hydrogen Peroxide. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 71. Lyon, France: International Agency for Research on Cancer. 1589 pp. Kennedy, G. L., Jr. 1990. Toxicology of fluorine-containing monomers. Crit Rev Toxicol 21(2): 149-70. Lewis, R. J. 1992. Sax's Dangerous Properties of Industrial Materials, 8th ed., vol. 3. New York, NY: Van Nostrand Reinhold. Miller, J. A. and Y. J. Surh. 1994. Historical perspectives on conjugation-dependent bioactivation of foreign compounds. Adv Pharmacol 27: 1-16. NIOSH. 1976. National Occupational Hazard Survey (1972-74). Cincinnati, OH: Department of Health, Education and Welfare. NIOSH. 1990. National Occupational Exposure Survey (1981-83). Unpublished provisional data as of 7/1/90. Cincinnati, OH: U. S. Department of Health and Human Services. NTP. 1997. Toxicology and Carcinogenesis Studies of Tetrafluoroethylene (CAS No. 116-14-3) in F344 Rats C C

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**LEVENTH E**  **DITION** and B6C3F1 Mice (Inhalation Studies). Technical Report Series No 450. NIH Publication No. 97-3366. Research Triangle Park, NC: National Toxicology Program. 321 pp. SRI. 1996. Directory of Chemical Producers, United States, 1996. Stanford Research Institute, Menlo Park, CA: SRI International.