Tetrachloroethylene (CASRN 127-18-4)
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0106
Tetrachloroethylene;
CASRN 127-18-4
Health assessment information on a chemical substance is included in IRIS
only after a comprehensive review of chronic toxicity data by U.S. EPA
health scientists from several Program Offices and the Office of Research
and Development. The summaries presented in Sections I and II represent
a consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Tetrachloroethylene
File First On-Line 01/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 03/01/1988 |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data |
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — Tetrachloroethylene
CASRN — 127-18-4
Last Revised — 03/01/1988
The oral Reference Dose (RfD) is based on the assumption that thresholds
exist for certain toxic effects such as cellular necrosis. It is expressed
in units of mg/kg-day. In general, the RfD is an estimate (with uncertainty
spanning perhaps an order of magnitude) of a daily exposure to the human
population (including sensitive subgroups) that is likely to be without
an appreciable risk of deleterious effects during a lifetime. Please refer
to the Background Document for an elaboration of these concepts. RfDs
can also be derived for the noncarcinogenic health effects of substances
that are also carcinogens. Therefore, it is essential to refer to other
sources of information concerning the carcinogenicity of this substance.
If the U.S. EPA has evaluated this substance for potential human carcinogenicity,
a summary of that evaluation will be contained in Section II of this file.
__I.A.1. Oral RfD Summary
Critical Effect |
Experimental Doses* |
UF |
MF |
RfD |
---|---|---|---|---|
Hepatotoxicity in 6-Week Mouse Gavage Buben and O'Flaherty, |
NOAEL: 20 mg/kg/day LOAEL: 100 mg/kg/day |
1000 |
1 |
1E-2 mg/kg/day |
*Conversion Factors: Doses have been adjusted for treatment schedule (5 days/week)
__I.A.2. Principal and Supporting Studies (Oral RfD)
Buben, J.A. and E.J. O'Flaherty. 1985. Delineation of the role of metabolism
in the hepatotoxicity of trichloroethylene and perchloroethylene: a dose-
effect study. Toxicol. Appl. Pharmacol. 78: 105-122.
Buben and O'Flaherty (1985) exposed Swiss-Cox mice to tetrachloroethylene in
corn oil by gavage at doses of 0, 20, 100, 200, 500, 1500, and 2000 mg/kg, 5
days/ week for 6 weeks. Liver toxicity was evaluated by several parameters
including liver weight/body weight ratio, hepatic triglyceride concentration,
DNA content, histopathological evaluation, and serum enzyme levels. Increased
liver triglycerides were first observed in mice treated with 100 mg/kg. Liver
weight/body weight ratios were significantly higher than controls for animals
treated with 100 mg/kg. At higher doses, hepatotoxic effects included
decreased DNA content, increased SGPT, decreased levels of G6P and
hepatocellular necrosis, degeneration and polyploidy.
A NOEL of 14 mg/kg/day was established in a second study, as well (Hayes et
al., 1986). Groups of 20 Sprague-Dawley rats of both sexes were administered
doses of 14, 400, or 1400 mg/kg/day in drinking water. Males in the high-dose
group and females in the two highest groups exhibited depressed body weights.
Equivocal evidence of hepatotoxicity (increased liver and kidney weight/body
weight ratios) were also observed at the higher doses.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — The uncertainty factor of 1000 results from multiplying factors of 10 to
account for intraspecies variability, interspecies variability and
extrapolation of a subchronic effect level to its chronic equivalent.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Other data support the findings of the principal studies. Exposure of mice
and rats to tetrachloroethylene by gavage for 11 days caused hepatotoxicity
(centrilobular swelling) at doses as low as 100 mg/kg/day in mice (Schumann et
al., 1980). Mice were more sensitive to the effects of tetrachloroethylene
exposure than rats. Increased liver weight was observed in mice at 250 mg/kg,
while rats did not exhibit these effects until doses of 1000 mg/kg/day were
reached. Relative sensitivity to man cannot be readily established but the
RfD of 1E-2 mg/kg/day is protective of the most mild effects observed in
humans [diminished odor perception/modified Romberg test scores in volunteers
exposed to 100 ppm for 7 hours; roughly equivalent to 20 mg/kg/day (Stewart et
al., 1961)].
The principal studies are of short duration. Inhalation studies have been
performed which indicate that the uncertainty factor of 10 is sufficient for
extrapolation of the subchronic effect to its chronic equivalent. Liver
enlargement and vacuolation of hepatocytes were found to be reversible lesions
for mice exposed to low concentrations of tetrachloroethylene (Kjellstrand et
al., 1984). In addition, elevated liver weight/body weight ratios observed in
animals exposed to tetrachloroethylene for 30 days were similar to those in
animals exposed for 120 days. Several chronic inhalation studies have also
been performed (Carpenter, 1937; NTP, 1985; Rowe et al., 1952). None are
inconsistent with a NOAEL of 14 mg/kg/day for tetrachloroethylene observed by
Buben and O'Flaherty (1985) and Hayes et al. (1986).
__I.A.5. Confidence in the Oral RfD
Study — Low
Database — Medium
RfD — Medium
No one study combines the features desired for deriving an RfD: oral exposure, large number of animals, multiple dose groups, testing in both sexes and chronic exposure. Confidence in the principal studies is low mainly because of the lack of complete histopathological examination at the NOAEL in the mouse study. The database is relatively complete but lacks studies of reproductive and teratology endpoints subsequent to oral exposure; thus, it receives a medium confidence rating. Medium confidence in the RfD follows.
__I.A.6. EPA Documentation and Review of the Oral RfD
U.S. EPA. 1985. Health Assessment Document for Tetrachloroethylene
(Perchloroethylene). Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Research Triangle
Park, NC for the Office of Air Quality Planning and Standards, Research
Triangle Park, NC. EPA 600/8-82/005F.
U.S. EPA. 1987. Quantification of Toxicological Effects for
Tetrachloroethylene. Prepared from the Health Assessment Document for
Tetrachloroethylene (Perchloroethylene). Office of Drinking Water,
Washington, DC.
Agency Work Group Review — 05/20/1985, 08/05/1986, 09/17/1987
Verification Date — 09/17/1987
__I.A.7. EPA Contacts (Oral RfD)
Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov(internet address).
_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)
Substance Name — Tetrachloroethylene
CASRN — 127-18-4
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Tetrachloroethylene
CASRN — 127-18-4
Not available at this time.
_VI. Bibliography
Substance Name — Tetrachloroethylene
CASRN — 127-18-4
Last Revised — 07/01/1989
_VI.A. Oral RfD References
Buben, J.A. and E.J. O'Flaherty. 1985. Delineation of the role of metabolism
in the hepatotoxicity of trichloroethylene and perchloroethylene: A dose-
effect study. Toxicol. Appl. Pharmacol. 78: 105-122.
Carpenter, C.P. 1937. The chronic toxicity of tetrachloroethylene. J. Ind.
Hyg. Toxicol. 19(7): 323-336.
Hayes, J.R., L.W. Condie, Jr. and J.F. Borzelleca. 1986. The subchronic
toxicity of tetrachloroethylene (perchloroethylene) administered in the
drinking water of rats. Fund. Appl. Toxicol. 7: 119-125.
Kjellstrand, P., B. Holmquist, M. Kanje, et al. 1984. Perchloroethylene:
Effects on body and organ weights and plasma butyrylcholinesterase activity in
mice. Acta Pharmacol. Toxicol. 54(5): 414-424.
NTP (National Toxicology Program). 1985. NTP Technical Report on the
Toxicology and Carcinogenesis Studies of Tetrachloroethylene
(perchloroethylene). U.S. Dept. Health and Human Services, NIH Publ. No. 85-
2567.
Rowe, V.K., D.D. McCollister, H.C. Spencer, E.M. Adams and D.D. Irish. 1952.
Vapor toxicity of tetrachloroethylene for laboratory animals and human
subjects. Arch. Ind. Hyg. Occup. Med. 5: 566-579.
Schumann, A.M., J.F. Quast and P.G. Watanabe. 1980. The pharmacokinetics and
macromolecular interaction of perchloroethylene in mice and rats as related to
oncogenicity. Toxicol. Appl. Pharmacol. 55: 207-219.
Stewart, R.D., H.H. Gay, D.S. Erley, C.L. Hake and A.W. Schaffer. 1961.
Human exposure to tetrachloroethylene vapor. Arch. Environ. Health. 2:
40-46.
U.S. EPA. 1985. Health Assessment Document for Tetrachloroethylene
(perchloroethylene). Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Research Triangle
Park, NC for the Office of Air Quality Planning and Standards, Research
Triangle Park, NC. EPA 600/8-82-005F. Office of Drinking Water, Washington,
DC.
U.S. EPA. 1987. Quantification of Toxicological Effects for
Tetrachloroethylene. Prepared from the Health Assessment Document for
Tetrachloroethylene (perchloroethylene). Office of Drinking Water,
Washington, DC.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Tetrachloroethylene
CASRN — 127-18-4
Date |
Section |
Description |
---|---|---|
12/23/1987 | I.A. | RfD withdrawn pending further review |
03/01/1988 | I.A. | Revised Oral RfD sumary added - RfD changed |
03/01/1988 | III.A. | Health Advisory added |
07/01/1989 | VI. | Bibliography on-line |
05/01/1990 | II. | Carcinogen assessment now under review |
06/01/1990 | IV.A.1. | Area code for EPA contact corrected |
06/01/1990 | IV.F.1. | EPA contact changed |
01/01/1992 | IV. | Regulatory actions updated |
04/01/1992 | IV. | Regulatory action section withdrawn |
08/01/1995 | II. | EPA's RfD/RfC and CRAVE workgroups were discontinued in May, 1995. Chemical substance reviews that were not completed by September 1995 were taken out of IRIS review. The IRIS Pilot Program replaced the workgroup functions beginning in September, 1995. |
04/01/1997 | III., IV., V. | Drinking Water Health Advisories, EPA Regulatory Actions, and Supplementary Data were removed from IRIS on or before April 1997. IRIS users were directed to the appropriate EPA Program Offices for this information. |
01/02/1998 | I., II. | This chemical is being reassessed under the IRIS Program. |
_VIII. Synonyms
Substance Name — Tetrachloroethylene
CASRN — 127-18-4
Last Revised — 01/31/1987
- 127-18-4
- Ankilostin
- Antisal 1
- Antisol 1
- Carbon bichloride
- Carbon dichloride
- Czterochloroetylen
- Dee-Solv
- Didakene
- Didokene
- Dowclene EC
- Dow-Per
- ENT 1,860
- Ethene, tetrachloro-
- Ethylene tetrachloride
- Ethylene, tetrachloro-
- Fedal-Un
- NCI-C04580
- Nema
- PCE
- PER
- Perawin
- PERC
- Perchloorethyleen, per
- Perchlor
- Perchloraethylen, per
- Perchlorethylene
- Perchlorethylene, per
- Perchloroethylene
- Perclene
- Percloroetilene
- Percosolv
- Percosolve
- PERK
- Perklone
- Persec
- Tetlen
- Tetracap
- Tetrachlooretheen
- Tetrachloraethen
- Tetrachlorethylene
- Tetrachloroethene
- Tetrachloroethylene
- 1,1,2,2-Tetrachloroethylene.
- Tetracloroetene
- Tetraguer
- Tetraleno
- Tetralex
- Tetravec
- Tetroguer
- Tetropil
- WLN: GYGUYGG