10th Report on Carcinogens.
Published 2002 by US National Institutes for Health. http://ehp.niehs.nih.gov/roc/tenth/profiles/s170tfe.pdf
(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 B6C3F1 mice,TFE induced
liver hemangiomas and hemangiosarcomas,
hepatocellular neoplasms, and histiocytic sarcomas.
adequate human studies of the relationship between exposure
to TFE and human cancer have been reported (IARC 1999).
INFORMATION RELEVANT TO CARCINOGENESIS OR POSSIBLE MECHANISMS
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 erythrocytes were observed in peripheral
blood samples obtained from TFE-exposed mice (NTP 1997).
frequency of H-ras codon 61 mutations observed in TFE-induced
hepatocellular neoplasms (15%) was significantly less than
the corresponding frequency (56 to 59%) in spontaneous liver
neoplasms of B6C3F1 mice, suggesting that TFE induces liver
neoplasms via a ras -independent pathway (NTP 1997).
kidney-specific toxicity and carcinogenicity of TFE is most
likely related to the selective uptake and subsequent processing
of TFE-glutathione conjugates by renal ¥-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).
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.
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).
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
regulates TFE under the Clean Air Act (CAA). It considers
the compound a regulated flammable substance and designates
a threshold quantity of 10,000 lb for accidental release
prevention. It has placed TFE in its list of toxic and reactive
highly hazardous chemicals that have a potential for a catastrophic
event at or above a designated threshold quantity (TQ);
for TFE, the TQ is 5,000 lb.
approves TFE polymers and copolymers for food-related uses.
American Conference of Governmental Industrial Hygienists
(ACGIH) recommends a threshold limit value (TLV)of 2 ppm
(8.2 mg/m 3 ). OSHA regulates the compound under the Hazard
Communication Standard and as a chemical hazard in laboratories.
Regulations are summarized in Volume II, Table 170.