Note: At OSHA's 1988 permissible exposure limit (PEL) hearing, NIOSH recommended that tetrachloroethylene (perchloroethylene) be labeled a potential occupational carcinogen.
The National Institute for Occupational Safety and Health (NIOSH) recommends
that it is prudent to handle tetrachloroethylene (perchloroethylene)
in the workplace as if it were a human carcinogen. The recommendation
is based on a recent study by the National Cancer Institute (NCI) indicating
that tetrachloroethylene causes liver cancer in laboratory mice.1 This
Bulletin is to advise you of the findings of the NCI study, other pertinent
data, their implications for occupational health, and precautions for handling tetrachloroethylene.
Animal studies are valuable in helping identify human carcinogens. Substances that cause cancer in experimental animals must be considered to pose a potential cancer risk in man. Safe levels of exposure to carcinogens have not been demonstrated, but the probability of cancer development is lowered with decreasing exposure to carcinogens. Thus NIOSH recommends that
occupational exposure to tetrachloroethylene be minimized and is providing
suggested industrial hygiene practices. This is an interim recommendation
while the carcinogenic potential of tetrachloroethylene in the workplace
is being further evaluated.
The current Occupational Safety and Health Administration (OSHA) standard
for occupational exposure to tetrachloroethylene is 100 ppm, (8-hour time-weighted
average). In July 1976 NIOSH 3 recommended an exposure limit
of 50 ppm (time-weighted average for up to a 10-hour workday, 40-hour
workweek). Neither of these levels may provide adequate protection from
potential carcinogenic effects because they were selected to prevent toxic
effects other than cancer.
Potential Occupational Exposures
Tetrachloroethylene is a volatile liquid with an odor detectable at about
50 ppm. It is a solvent widely used in dry cleaning, fabric finishing, metal
degreasing, and other applications. NIOSH estimates that approximately
500,000 workers are currently at risk of exposure to tetrachloroethylene
in the United States. Over 20,000 dry cleaning establishments and a large
number of other industries manufacture or use this substance. About 700
million pounds of tetrachloroethylene are currently produced in the United
States each year.
Two-thirds of the domestically consumed tetrachloroethylene is used for
dry cleaning and for the processing and finishing of textiles. Tetrachloroethylene is used by three-quarters of the dry cleaners in the United States because it is an excellent cleaner of most fabrics, is easily recycled, and is not flammable.
Metal cleaning accounts for approximately fifteen percent of the domestic
consumption of tetrachloroethylene, where exposures can occur during
degreasing and cold cleaning. Tetrachloroethylene also serves as a chemical
intermediate in the synthesis of trichlorotrifluoroethane (fluorocarbon
113), dichlorotetrafluoroethane (fluorocarbon 114), chloropentafluoroethane
(fluorocarbon 115), and hexafluoroethane (fluorocarbon 116). Tetrachloroethylene exposures may also occur in extraction processes, during its use as an industrial solvent, as a heat exchange fluid, and as a drug in treatment of internal parasite infestations.
Laboratory Animal Studies for Carcinogenicity
The long term animal study reported by NCI demonstrates tetrachloroethylene
to be carcinogenic in laboratory mice. In the study, B6C3F1 mice
were force fed tetrachloroethylene for 78 weeks. Male mice were treated
at two dose levels (536 or 1072 mg/kg/day) and female mice were treated
at two different dose levels (386 or 772 mg/kg/day). A significant increase
of hepatocellular carcinoma (liver cancer) was observed in both sexes of
treated mice when compared with control animals. At both dose levels
more than 50% of the male mice and 40% of the female mice (each from
groups of approximately 50 animals) developed liver cancer. By comparison,
cancer developed in 12% or less of the groups of untreated or vehicle-matched controls. This NCI report is the first definitive association of tetrachloroethylene with cancer. To relate some of the above information to the work environment a 70 kg man breathing a typical 10 cu m/day (over an 8-hour work shift) of air contaminated with 100 ppm of tetrachloroethylene would have an inhalation exposure of about 100 mg/kg/day.
In the same NCI report, Osborne-Mendel rats showed no significant increase
of liver cancer under the same experimental procedure. Because many
of the rats died early in the study, this bioassay was considered inadequate
for the carcinogenicity testing of tetrachloroethylene. However there
was a high incidence of kidney damage observed in both the rats and mice
treated with tetrachloroethylene.
A study by The Dow Chemical Company 2 found many tumors in Sprague-Dawley rats exposed by inhalation to 300 or 600 ppm tetrachloroethylene, but for most tumors there was no statistically significant difference in tumor incidence between exposed and control rats. Some tumors were found in higher incidence in control animals. The only tumor seen at higher incidence in exposed animals was adrenal pheochromocytoma in female rats at the lower exposure level only. Pheochromocytoma is a tumor which gives rise to high blood pressure and hyperglycemia due to release of adrenalin and noradrenalin into the blood. Increased mortality occurred in male rats exposed to 600 ppm tetrachloroethylene.
The liver is a principal target organ of tetrachloroethylene exposure in
animals. Typical toxic effects are fatty liver) liver enlargement and
abnormal liver function tests, Tetrachloroethylene has also been shown
to cause kidney damage in mice following intraperitoneal injection and
in rats and rabbits following inhalation.
Neurophysiological effects of tetrachloroethylene are reflected in the
distinct alterations of the electroencephalogram (EEG) in rats. Central
nervous system (CNS) depression including abnormal weakness, handling
intolerance intoxication, restlessness, irregular respiration, muscle incoordination, and unconsciousness have been observed in exposed animals.
Tetrachloroethylene has been shown to be a primary eye and skin irritant
in rabbits. Other effects of tetrachloroethylene exposure in laboratory
animals include lung damage (excessive fluid accumulation inflammation,
congestion, or hemorrhage, cardiac depression, decreased blood pressure
depressed respiration, decreased oxygen consumption, and depression in
growth rate.
One study suggests the teratogenic potential of tetrachloroethylene. Fetal
and maternal toxicity was observed in mice and rats exposed to tetrachloroethylene
on days 615 of gestation. In this study a decrease in the maternal
weight gain in rats, an increase in the relative weight of the liver in
pregnant mice, an increase of fetal reabsorption in rats, a decrease in
fetal body weight and an increase of subcutaneous edema in fetal mice,
were all associated with exposure to tetrachloroethylene. Delayed ossification
of skull bones and split sternebrae were possible teratogenic effects observed in mice.
Clinical evidence accumulated over the years clearly demonstrates that
tetrachloroethylene is toxic to the liver and kidneys in humans. Liver
impairment has been noted in cases of exposure to tetrachloroethylene
as evidenced by abnormal liver function tests. Also, toxic chemical hepatitis,
and enlargement of the liver and spleen have been associated with
exposure to tetrachloroethylene. Tetrachloroethylene vapor is irritating
to the eyes and upper respiratory tract, and may cause frontal sinus congestion
and headache. Direct contact with skin can cause burns, blistering,
and erythema due to the "degreasing" effect of tetrachloroethylene on
the skin. Over a period of time this can result in extreme skin dryness
with cracking and associated infection.
Altered physiological and behavioral responses observed in subjects exposed
to tetrachloroethylene include vague nonspecific complaints generally
attributed to CNS depression. These symptoms include vertigo, impaired
memory, confusion fatigue drowsiness irritability loss of appetite nausea
and vomiting. Motor coordination following tetrachloroethylene exposure
requires additional mental effort, which along with memory impairment
and fatigue have important implications for worker safety. Various disturbances
of the peripheral nervous system such as tremors and numbness
have also been associated with exposure to tetrachloroethylene. Excessive
absorption of tetrachloroethylene can cause severe depression of the CNS
leading to coma; ultimately death may occur from respiratory paralysis
or circulatory failure.
Tetrachloroethylene is most commonly absorbed through the lungs and
can be absorbed from the intestines if ingested. The skin is a less important
absorption site. Physical exercise can significantly increase the amount of
tetrachloroethylene absorbed through the lungs because of greater respiration
and increased blood flow.
Metabolism and elimination of tetrachloroethylene is relatively slow. It
is deposited in body fat and the biologic halflife of tetrachloroethylene
in man is estimated at six days.
NIOSH has contracted for a retrospective mortality study of persons
employed in dry cleaning establishments where there had been
exposure to tetrachloroethylene. The contract will be monitored
by the Biometry Section of the NIOSH Industry-wide Studies Branch.
The NIOSH Industrial Hygiene Section of the Industry-wide Studies
Branch plans an industrial hygiene assessment of dry cleaning workers
exposed to tetrachloroethylene.
The NIOSH Behavioral and Motivational Factors Branch is undertaking
a tetrachloroethylene behavioral teratology study. The study
results should be available in late 1978.
NIOSH has contracted for a control technology assessment of the
dry cleaning industry. The contract will be monitored by the NIOSH
Control Technology Research Branch.
NIOSH will coordinate research on tetrachloroethylene with the
National Cancer Institute (NCI) which is also examining the mortality
experience of persons employed in dry cleaning establishments.
NIOSH has contracted for a study to evaluate the potential
teratogenicity and the mutagenicity of tetrachloroethylene. This
contract will be monitored by the NIOSH Experimental Toxicology
Branch.
Currently available NIOSH publications on tetrachloroethylene include:
a) Criteria for a recommended standard .... Occupational Exposure
to Tetrachloroethylene (Perchloroethylene). HEW Publication
No. (NIOSH) 76-185.
b) Health and Safety Guide for Laundries and Dry Cleaners. HEW
Publication No. (NIOSH) 75-151.
c) Effects of Perchloroethylene/Drug Interaction on Behavior
and Neurological Function HEW Publication No. (NIOSH) 77-124
191.
d) A Behavioral and Neurological Evaluation of Dry Cleaners
Exposed Perchloroethylene. HEW Publication No. (NIOSH)
77-214.
[signature]
Edward J. Baier
Deputy Director
SUGGESTED PROCEDURES FOR MINIMIZING EMPLOYEE EXPOSURE TO TETRACHLOROETHYLENE (PERCHLOROETHYLENE)
Control of Overexposures
NIOSH recommends that it is prudent to handle tetrachloroethylene in
the workplace as if it were a human carcinogen and that occupational
exposure to tetrachloroethylene be minimized. Exposure to tetrachloroethylene should be limited to as few employees as possible while minimizing workplace exposure levels. The area in which it is used should be
restricted to those employees necessary to the process or operation.
Furthermore, consideration should be given to isolating the tetrachloroethylene exposure area so that adjacent workers are not also exposed.
Exposure monitoring
The NIOSH Occupational Exposure Sampling Strategy Manual, NIOSH publication #77-173,
may be helpful in developing efficient programs to monitor employee exposures to tetrachloroethylene.
The manual discusses determination of the need for exposure measurements, selection of appropriate
employees for sampling, and selection of sampling times.
Employee exposure measurement samples can be obtained and analyzed
using the guidelines in NIOSH method #P&CAM l27 in the second edition
of the NIOSH Manual of Analytical Methods, NIOSH publication #77-157.
Exposure measurements should consist of 8-hour TWA exposure estimates
calculated from personal or breathing zone samples (air that would most
nearly represent that inhaled by the employees).
Engineering controls
Engineering and work practice controls should be used to minimize employee
exposure to tetrachloroethylene.
To ensure that ventilation equipment is working properly, it is advised
that effectiveness be checked at least every three months (e.g., air velocity, static pressure or air volume). System effectiveness should also be checked within five days of any change in production, process, or control which might result in significant increases in airborne exposures to tetrachloroethylene.
Respiratory protection
Exposure to tetrachloroethylene should not be controlled with the use of respirators except:
During the time period necessary to install or implement engineering or
work practice controls; or
In work situations in which engineering and work practice controls are
technically not feasible; or
To supplement engineering and work practice controls when such controls
fail to adequately control exposure to tetrachloroethylene; or
For operations which require entry into tanks or closed vessels; or
In emergencies.
Respirators should be approved by the National Institute for Occupational
Safety and Health (NIOSH) or by the Mining Enforcement and Safety Administration (MESA). Refer to
NIOSH Certified Equipment, December 15, 1975, NIOSH publication #76-145 and Cumulative
Supplement June 1977, NIOSH Certified Equipment, NIOSH Publication #77-195. The use of
face seal coverlets or socks with any respirator voids NIOSH/MESA approvals.
Quantitative faceseal fit test equipment (such as sodium chloride or PDOP)
should be used. Refer to A Guide to Industrial Respiratory Protection,
NIOSH publication #76-189 for guidelines on appropriate respiratory protection programs.
Where respirators are used under the preceding guidelines, NIOSH recommends that for routine use the employer provide either a) Self-contained
breathing apparatus with a full facepiece operated in pressure-demand
for other positive pressure mode (30 CFR 11.70(a)) or b) A combination
respirator which includes a Type-C supplied-air respirator with a full facepiece operated in pressure-demand or other positive pressure or continuous flow mode and an auxiliary self-contained breathing apparatus operated in pressure-demand or positive pressure mode (30 CFR 11.70(b)). For firefighting, the employer should provide a) Self-contained breathing apparatus with a full facepiece operated in pressure-demand or other positive pressure mode (30 CFR 11.70(a)). For escape the employer should provide a) Any gas mask providing protection against organic vapors (30 CFR 11.90) or b) Any escape self-contained breathing apparatus (30 CFR 11.70(a)).
Personal Protective Equipment
Employers should provide impervious, gloves, face shields (8-inch minimum)
and other appropriate clothing necessary to prevent repeated or prolonged
skin contact with liquid tetrachloroethylene.
Employers should see that employee clothing wet with liquid tetrachloroethylene is
placed in closed containers for storage until it can be discarded or until the
employer provides for the removal of tetrachloroethylene from the clothing. If the clothing
is to be laundered or otherwise cleaned to remove the tetrachloroethylene, the employer
should inform the person performing the operation of the hazardous properties of
tetrachloroethylene including the fact that it is a possible human carcinogen.
Employers should see that permeable clothing which becomes contaminated
with liquid tetrachloroethylene be removed promptly and not reworn until
the tetrachloroethylene is removed from the clothing.
Personal Hygiene
Employers should see that employees who handle liquid tetrachloroethylene
wash their hands thoroughly with soap or mild detergent before eating,
smoking or using toilet facilities.
Employers should see that employees whose skin becomes contaminated
with liquid tetrachloroethylene promptly wash or shower with soap and
mild detergent and water to remove any tetrachloroethylene from the
skin.
Bibliography
Bioassay of Tetrachloroethylene for Possible Carcinogenicity, DHEW
Publication No. (NIH) 77-813. U.S. Department of Health,
Education, and Welfare, Public Health Service, National
Institutes of Health, National Cancer Institute, October,
1977.
Rampy, L. W., J. F. Quast, B.K.J. Leong and P.J. Gehring, Results
of longterm inhalation toxicity studies on rats of 1,1,
trichloroethane and perchloroethylene formulations.
Toxicology Research Laboratory, Dow Chemical, U.S.A., Poster
presentation International Congress of Toxicology, Toronto,
Canada, April, 1977.
Criteria for a recommended standard .... Occupational Exposure to
Tetrachloroethylene (Perchloroethylene). HEW Publication
No. (NIOSH) 76-185. U.S. Department of Health, Education,
and Welfare, Public Health Service, Center for Disease Control,
National Institute for Occupational Safety and Health, July,
1976.
Fishbein, L., Industrial mutagens and potential mutagens I.
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Fujii, T., Variation in the liver function of rabbits after
administration of chlorinated hydrocarbons, Jap. J. Ind.
Hlth., 17: 81-88, 1975.
Duprat, P., L. Delsaut and D. Gradiski, Irritant potency of the
principal aliphatic chloride solvents on the skin and ocular
mucous membranes of rabbits. Europ. J. Toxicol., 3:171-177,
1976.
Brancaccio, A., V. Mazza and R. Di Paolo, Renal function in
experimental tetrachloroethylene poisoning. Folia Med., 54:233-237, 197l.
Korn, J., How many more? Perchloroethylene intoxication in coin
drycleaning establishments. Ugeskr. laeg., 139: 303-304,
1977.
Weichardt, H., and J. Lindner, Health hazards due to
perchloroethylene in chemical drycleaning enterprises from
the viewpoint of occupational medicine and toxicology.
Staub Reinhalt Luft, 35: 416-420, 1975.
Medek, V., and J. Kovarik, The effect of perchloroethylene on the
health of workers. Pracovni lekarstvi, 25: 339-341, 1973.
Larsen, N. B. Nielsen, and A. RaynNielsen, Perchloroethylene
intoxication. A hazard in the use of coin laundries.
Ugeskr. Laeg., 139: 270-275, 1977.
Schwetz, B.A., KJ. Leong and P.J. Gehring, The effect of
maternally inhaled trichloroethylene, perchloroethylene,
methyl chloroform and methylene chloride on embryonal and
fetal development in mice and rats. Toxicol. Appl.
Pharmacol., 32: 84-96, 1975.
Ikeda, M., and T. Imamura, Biological halflife of trichloroethylene
and tetrachloroethylene in human subjects. Int. Arch. Arbeitsmed., 31: 209-224) 1973.
Copies of this and other NIOSH documents are available from:
or to the CDC home page.
