INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
ENVIRONMENTAL HEALTH CRITERIA 31
TETRACHLOROETHYLENE
This report contains the collective views of an international group of
experts and does not necessarily represent the decisions or the stated
policy of the United Nations Environment Programme, the International
Labour Organisation, or the World Health Organization.
Published under the joint sponsorship of
the United Nations Environment Programme,
the International Labour Organisation,
and the World Health Organization
World Health Orgnization
Geneva, 1984
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toxicology. Other activities carried out by the IPCS include the
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coordination of laboratory testing and epidemiological studies, and
promotion of research on the mechanisms of the biological action of
chemicals.
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CONTENTS
PREFACE
1. SUMMARY
2. PROPERTIES AND ANALYTICAL METHODS
2.1. Chemical and physical properties of
tetrachloroethylene
2.2. Analytical methods
3. SOURCES IN THE ENVIRONMENT, ENVIRONMENTAL TRANSPORT
AND DISTRIBUTION
3.1. Natural occurrence
3.2. Production levels and processes, and uses
3.2.1. Production levels and processes
3.2.2. Uses
3.3. Occurrence and transport in the environment
3.3.1. Occurrence
3.3.2. Transport
4. ENVIRONMENTAL LEVELS AND EXPOSURES
4.1. Occupational exposure
4.2. General population exposure
5. CHEMOBIOKINETICS AND METABOLISM
5.1. Absorption
5.1.1. Animal studies
5.1.2. Human studies
5.2. Distribution
5.2.1. Animal studies
5.2.2. Human studies
5.3. Metabolic transformation
5.3.1. Animal studies
5.3.2. Human studies
5.4. Excretion
5.4.1. Animal studies
5.4.2. Human studies
6. EFFECTS ON ORGANISMS IN THE ENVIRONMENT
7. EFFECTS ON ANIMALS
7.1. Short-term studies
7.1.1. Oral exposure
7.1.2. Inhalation exposure
7.1.3. Exposure of eyes and skin
7.2. Long-term studies
7.2.1. Oral exposure
7.2.2. Inhalation exposure
7.3. Carcinogenicity
7.3.1. Oral exposure
7.3.2. Inhalation exposure
7.3.3. Dermal exposure
7.4. Mutagenicity
7.5. Reproduction and teratogenicity
8. EFFECTS ON MAN
8.1. Controlled human studies
8.2. Accidental exposures
8.3. Occupational exposure
8.4. Mortality studies
9. EVALUATION OF HEALTH RISKS FOR MAN
10. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
10.1. Occupational exposure
10.2. Ambient air levels
10.3. Drinking-water
10.4. Use
10.5. Labelling and packaging
10.6. Storage and transport
REFERENCES
WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR TETRACHLOROETHYLENE
Members
Dr C.M. Bishop, Health and Safety Executive, London, England
Dr V. Hristeva-Mirtcheva, Institute of Hygiene and
Occupational Health, Sofia, Bulgaria
Dr R. Lonngren, National Products Control Board, Solna, Sweden
(Chairman)
Dr M. Martens, Institute of Hygiene and Epidemiology,
Brussels, Belgium
Dr W.O. Phoon, Department of Social Medicine & Public Health,
Faculty of Medicine, University of Singapore, National
Republic of Singapore
Dr L. Rosenstein, Assessment Division, Office of Toxic
Substances, US Environmental Protection Agency, Washington
DC, USA
Mr C. Satkunananthan, Consultant, Colombo, Sri Lanka
(Rapporteur)
Dr G.O. Sofoluwe, Oyo State Institute of Occupational Health,
Ibadan, Nigeria
Dr A. Takanaka, Division of Pharmacology, Biological Safety
Research Center, National Institute of Hygienic Sciences,
Tokyo, Japan
Dr R.G. Tardiff, Life Systems, Inc., Arlington, VA, USA
Representatives of Other Organizations
Dr J.P. Tassignon, European Chemical Industry Ecology and
Toxicology Centre, Brussels, Belgium
Observers
Dr M. Nakadate, Division of Information on Chemical Safety,
National Institute of Hygienic Sciences, Tokyo, Japan
Dr R. McGaughy, Carcinogen Assessment Division, US
Environmental Protection Agency, Washington, DC, USA
Secretariat
Dr M. Gilbert, International Register of Potentially Toxic
Chemicals, United Nations Environment Programme, Geneva,
Switzerland
Dr K.W. Jager, Scientist, International Programme on Chemical
Safety, World Health Organization, Geneva, Switzerland
Dr M. Mercier, Manager, International Programme on Chemical
Safety, World Health Organization, Geneva, Switzerland
Dr F. Valic, Scientist, International Programme on Chemical
Safety, World Health Organization, Geneva, Switzerland
(Secretary)
Dr G.J. Van Esch, National Institute for Public Health,
Bilthoven, Netherlands (Temporary Adviser)
Dr T. Vermeire, National Institute for Public Health,
Bilthoven, Netherlands, (Temporary Adviser)
The WHO Task Group for the Environmental Health Criteria for
Tetrachloroethylene met in Brussels from 19 to 22 September, 1983.
Professor A. Lafontaine opened the meeting and welcomed the
participants on behalf of the host government, and Dr. M. Mercier,
Manager, IPCS, on behalf of the heads of the three IPCS co-
sponsoring organizations (ILO/WHO/UNEP). The Group reviewed and
revised the second draft criteria document and made an evaluation
of the health risks of exposure to tetrachloroethylene.
The efforts of Dr. G.J. Van Esch and Dr. T. Vermeire, who were
responsible for the preparation of the draft, and of all who helped
in the preparation and the finalization of the document are
gratefully acknowledged.
* * *
Partial financial support for the publication of this criteria
document was kindly provided by the United States Department of
Health and Human Services, through a contract from the National
Institute of Environmental Health Sciences, Research Triangle Park,
North Carolina, USA - a WHO Collaborating Centre for Environmental
Health Effects.
PREFACE
A partly-new approach to develop more concise Environmental
Health Criteria documents has been adopted with this issue.
While the document is based on a comprehensive search of the
available, original, scientific literature, only key references
have been cited. A detailed data profile and a legal file on
tetrachloroethylene can be obtained from the International Register
of Potentially Toxic Chemicals, Palais des Nations, 1211 Geneva 10,
Switzerland (Telephone No. 988400 - 985850).
The document focuses on describing and evaluating the risks of
tetrachloroethylene for human health and the environment.
While every effort has been made to present information in the
criteria documents as accurately as possible without unduly
delaying their publication, mistakes might have occurred and are
likely to occur in the future. In the interest of all users of the
environmental health criteria documents, readers are kindly
requested to communicate any errors found to the Manager,
International Programme on Chemical Safety, World Health
Organization, Geneva, Switzerland, in order that they may be
included in corrigenda, which will appear in subsequent volumes.
1. SUMMARY
Tetrachloroethylene is widely used as a dry-cleaning and
degreasing solvent under many different chemical, common, generic,
and code names. Assessment of the toxicity of commercial
tetrachloroethylene is frequently complicated by the presence of
minor amounts of stabilizers that may themselves be toxic.
Man is exposed mainly to the vapour of tetrachloroethylene.
Groups exposed to high concentrations include workers in dry-
cleaning shops and factories; people living near these
establishments may also be exposed to higher concentrations than
the rest of the community. The general population is exposed to
low levels of tetrachloroethylene in ambient air, food, and
drinking-water.
An estimated 85% of man-made tetrachlorethylene is released
into the ambient air, as a result of evaporation. In the
troposphere, photodegradation takes place, ultimately leading to
the formation of hydrogen chloride, trichloracetic acid, and carbon
dioxide, in the presence of water. The significance of these
findings for environmental conditions cannot be evaluated yet
because of lack of consistent data. In surface water, photo-
degradation does not appear to be important in view of rapid
volatilization. Available data concerning the process of
microbial degradation are inadequate. Tetrachloroethylene is
rather persistent in groundwater, which is one of the reasons for
the present concern about the increasing incidence of contamination
of groundwater through industrial spillage and waste dumps. No
data are available concerning the behaviour of tetrachloroethylene
in soil.
Tetrachloroethylene is absorbed via the skin, on direct
contact, and via the lungs, after inhalation. Uptake is
proportional to the exposure level and increases with exercise.
Limited bioconcentration occurs in the lipid-rich tissues of
both man and animals. All species are able to metabolize
tetrachloroethylene, principally to trichloroacetic acid and
sometimes also to trichloroethanol via the cytochrome P-450
mixed function oxidase system. However, the extent of metabolism
differs in different species. In rat and man, most absorbed
tetrachloroethylene is excreted unchanged via the lungs, whereas,
in the mouse, the compound is metabolized to a much greater extent.
In all species, metabolic capacity is limited, i.e., high exposures
will not lead to higher concentrations of metabolites in the urine.
Because of accumulation in lipid-rich tissues, removal of
tetrachloroethylene from blood and excretion in the breath are
slow, both being proportional to the exposure level but not to the
length of exposure. The concentrations of tetrachloroethylene in
blood and breath can be used for estimating exposure levels in man.
Adequate analytical methods are available.
Subjects exposed to tetrachloroethylene vapour will experience
eye irritation at approximately 500 mg/m3 and will begin showing
signs of central and autonomic nervous system depression, after
both single exposure and short-term repeated exposure to about
700 mg/m3. At this concentration, nose and throat irritation is
reported. These effects are reversible and increase in severity
with the concentration and length of exposure. Direct skin
exposure will result in irritation of the skin.
No effects were noted in man after repeated exposure (1, 3,
or 7.5 h/day, 5 days/week) to approximately 140 mg/m3, but rats
showed EEG changes at 100 mg/m3. In mice, liver and kidney damage
first occurred at 1360 mg/m3 with short-term repeated inhalation
exposure, and at 50 mg/kg body weight during long-term oral
exposure. In rats, short-term oral exposure to 16 mg/kg body
weight did not induce signs of liver toxicity. The level of
exposure at which effects on the liver and/or kidneys might occur
in man is not clear. Workers in dry-cleaning plants did not show
altered liver-enzyme activity at exposure levels up to 2700 mg/m3.
Embryotoxicity was observed in the progeny of experimental
animals exposed by inhalation to tetrachloroethylene concentrations
exceeding 2000 mg/m3. It is possible that similar effects might
occur in human beings. However, there was no indication of
reproduction injury and only slight evidence of teratogenicity in
the animal studies reported.
Tetrachloroethylene was found to be carcinogenic for mice but
not for rats. Evidence from epidemiological studies among dry-
cleaning and laundry workers is insufficient to conclude that
exposure to tetrachloroethylene causes cancer in human beings.
Tetrachloroethylene has been shown to be moderately toxic for
aquatic organisms in short-term studies and toxic in one long-term
study on fish.
2. PROPERTIES AND ANALYTICAL METHODS
2.1. Chemical and Physical Properties of Tetrachloroethylene
Tetrachloroethylene (C2Cl4) is a nonflammable compound that is
stable up to 500°C in the absence of catalysts, moisture, and
oxygen, but decomposes slowly in contact with moisture to yield
trichloroacetic acid and hydrochloric acid.
Chemical structure:
Cl Cl
\ /
\ /
C===C
/ \
/ \
Cl Cl
CAS registration number: 127-18-4
RTECS registration number: KX 385 0000
Common synonyms include: carbon dichloride, ethylene
tetrachloride, perchloroethylene, tetrachloroethene,
1,1,2,2-tetrachloroethylene
Common trade names include: Ankilostin, Antisal 1,
Antisol 1, Blancosolv No. 2, Dee Solve, Didakene, Dowper,
Ent 1860, Fedal Un, Mid Solv, NeMa, Per, Perawin, Perc,
Perclene, Per-Ex, Perk, Perklone, Perm-a-kleen, Persec,
Phillsolv, Tetlen, Tetracap, Tetraguer, Tetraleno,
Tetralex, Tetravec, Tetropil, Wacker-Per.
Some physical data on tetrachloroethylene
physical state liquid
colour colourless
odour ethereal
relative molecular mass 165.82
melting point -22°C
boiling point 121°C
water solubility 150 mg/litre, 20°C
n-octanol-water partition
coefficient 2.86
density 1.62 g/ml, 20°C
relative vapour density 5.8
vapour pressure 1.9 kPa (14 mm Hg), 20°C
surface tension 32.32 dyne/cm2 20°C
Conversion factor
tetrachloroethylene 1 ppm = 6.78 mg/m3
2.2. Analytical Methods
A summary of relevant methods of sampling and analysis is given
in Table 1.
Table 1. Sampling, preparation, analysis
---------------------------------------------------------------------------------------------------------
Medium Specifi- Sampling Analytical Detection Comments Reference
cation method method limit
---------------------------------------------------------------------------------------------------------
air occupa- sampling on char- desorption with recommended for White et
tional coal carbon disulphide, range 655-2749 al. (1970)
gas chromatography mg/m3
air occupa- photodetection 3-6 mg/m3 halide meters are Nelson &
tional not specific for Shapiro
tetrachloroethylene; (1971)
suitable for con-
tinuous monitoring
air occupa- direct reading a not specific, Saltzman
tional indicating tube cheap method to (1972)
estimate exposure
air occupa- continuous moni- infra-red Baretta et
tional toring and breath spectroscopy al. (1969)
analysis
air ambient sampling on desorption by 0.2 µg/m3 Russell &
Porapak N heating, gas Shadoff
chromatography, (1977)
combined with
electron capture
detection and
mass spectrometry
air ambient gas chromatography 0.03 µg/m3 direct analysis Grimarud &
with mass spectro- Rasmussen
metric detection (1975)
---------------------------------------------------------------------------------------------------------
Table 1. (contd.)
---------------------------------------------------------------------------------------------------------
Medium Specifi- Sampling Analytical Detection Comments Reference
ation method method limit
---------------------------------------------------------------------------------------------------------
air ambient, air, breath: elution by air: 0.01 µg/m3 Bauer (1981)
breath sorption on pentane-ether
XAD - 2
solids food, solid and liquid elution by pentane food: 0.2 µg/kg
tissues samples: strip- gas chromatography wet-weight
ping by nitrogen, with electron
liquids water sorption on XAD capture detection water: 0.001
- 2 µg/litre
water gas chromatography 0.05 µg/litre direct headspace Piet et al.
with electron analysis (1978)
capture detection
water drinking gas chromatography 0.5 µg/litre direct analysis Nicholson et
with electron al. (1977)
capture detection
food extraction by gas chromatography 2-5 µg/kg Zimmerli et
steam distilla- with electron wet weight al. (1982a)
tion in presence capture detection
of 25% sulfuric
acid
blood, gas chromatography 0.06 mg/litre head space analysis Monster &
breath with electron blood (blood) Boersma
capture detection 0.01 mg/m3 direct analysis (1975)
air (breath)
---------------------------------------------------------------------------------------------------------
3. SOURCES IN THE ENVIRONMENT, ENVIRONMENTAL TRANSPORT AND DISTRIBUTION
3.1. Natural Occurrence
Tetrachloroethylene is not known to occur as a natural product
(IARC, 1979).
3.2. Production Levels and Processes, and Uses
3.2.1. Production levels and processes
World production of tetrachloroethylene amounted to 680 kilo-
tonnes in 1972 (Fishbein, 1979) and to 1000 kilotonnes in 1974
(Fuller, 1976).
The annual production is estimated to be 50-100 kilotonnes in
Eastern Europe, about 55 kilotonnes in Japan (IARC, 1979), 100-250
kilotonnes in Western Europe (IARC, 1979), and about 350 kilotonnes
in the USA (USITC, 1981).
Tetrachloroethylene is produced mainly by oxyhydrochlorination,
perchlorination, and/or dehydrochlorination of hydrocarbons or
chlorinated hydrocarbons such as: 1,2 dichloroethane, methane,
ethane, propane, propylene, propylene dichloride, 1,1,2-tri-
chloroethane, and acetylene (Fuller, 1976; IARC, 1979).
Technical products contain stabilizers, believed to include
amines or mixtures of epoxides, esters, and other chemicals such
as acetone, acetylenic compounds, aniline, borate esters, n-butane,
2-cresol, diiosopropylamine, ethyl acetate, hydrazine derivatives,
isobutyl alcohol, lactones, 2-nitrophenol, pyrazoles, stearates,
and sulfur dioxide.
3.2.2. Uses
Tetrachloroethylene is mainly used as a solvent in dry cleaning
and metal cleaning. It is also used for processing and finishing
in the textile industry, as an extraction solvent, a veterinary
anthelminthic, a heat-exchange fluid, in grain fumigation, and in
the manufacture of fluorocarbons (IARC, 1979; NIOSH, 1976;
Umweltbundesamt, 1978).
3.3. Occurrence and Transport in the Environment
3.3.1. Occurrence
In addition to being present in the air over rural and urban
sites, tetrachloroethylene has also been found in the air over
oceans (Murray & Riley, 1973). The concentrations over the North
East Atlantic ocean ranged between 1 and 9 ng/m3, the concentration
in the water being 0.2-0.8 ng/litre. Bay water along the coast of
the United Kingdom contained 0.12-2.6 µg/litre, while the sediment
contained 0.02-4.8µg/litre (Pearson & McConnell, 1975). Not
surprisingly, marine organisms were also found to contain residues
of tetrachloroethylene. Pearson & McConnell measured 0.05-15 µg/kg
wet weight in vertebrates, 13-20 µg/kg wet weight in algae, and 0-
19 µg/kg wet weight in seal blubber and shrew. Organs and eggs of
birds contained 0.7-39 µg/kg wet weight.
Surface water in Western Europe was found to contain
tetrachloroethylene levels of 0.01-46 µg/litre (Correia et al.,
1977; Bauer, 1981). Maximum levels of 22 µg/litre, measured in
groundwater in the Netherlands, were probably caused by leaching
of tetrachloroethylene through the soil after industrial spillage
(Zoeteman et al., 1980).
3.3.2. Transport
About 85% of the tetrachloroethylene used annually in the USA
is lost to the atmosphere (Fuller, 1976), and the world-wide
emission of tetrachloroethylene has been estimated to be about 450
kilotonnes per year (Singh et al., 1975). Volatilization also
appears to be the major pathway by which tetrachloroethylene is
lost from water. Zoeteman et al. (1980) estimated the half-life of
tetrachloroethylene to be 3-30 days for river water and 30-300 days
for lake- and groundwater, on the basis of field experiments.
Photodegradation of tetrachloroethylene in water does not appear
to be important as a sink, in view of the rapid volatilization from
water. Hydrolysis also seems to be of minor importance (Dilling,
1975).
Once tetrachloroethylene enters the troposphere, hydroxyl
radicals can attack the double bond, yielding intermediate
products likely to be hydrolized in the aqueous phase mainly to
trichloroacetic acid, which, in turn, is slowly decomposed to
carbon dioxide and chloride ions (Pearson & McConnell, 1975).
Reports about microbial biodegradation are few and conflicting.
Bouwer et al. (1981) did not find aerobic or anaerobic degradation
using primary sewage effluent and a mixed methanogenic culture,
respectively. However, recently, Bouwer et al. (1983) reported
almost complete anaerobic transformation using a mixed methanogenic
culture. The first step appeared to be reductive dechlorination to
trichloroethylene. Tabak et al. (1981) found significant aerobic
degradation in water, inoculated by settled domestic waste water.
4. ENVIRONMENTAL LEVELS AND EXPOSURES
Tetrachloroethylene is mainly used in dry-cleaning and degreasing
operations. Consequently, the main human exposure is through vapour
inhalation, sometimes accompanied by skin and eye contact, at the
place of work. People living nearby may be exposed to higher levels
than the general population elsewhere. Maximum concentrations have
been found not to exceed about 50 µg/m3 in the urban atmosphere,
35 µg/litre in drinking-water, and about 3.5 mg/kg wet weight in
foodstuffs. A point of concern is the contamination of groundwater
through spillage, as tetrachloroethylene is remarkably persistent
in water.
4.1. Occupational Exposure
Exposures in dry-cleaning establishments can be as high as an
8-h time-weighted average of 4000 mg/m3 (Shipman & Whim, 1980).
However, in the United Kingdom, over 90% of 493 8-h measurements
in 131 dry-cleaning establishments revealed concentrations below
680 mg/m3, and over 50% of these samples revealed concentrations
below 200 mg/m3 (Shipman & Whim, 1980). Similar results were
obtained in a survey of 46 dry-cleaning establishments in the
Federal Republic of Germany (Franke & Eggeling, 1969). Between
1977 and 1979, breathing-zone air samples were collected from 144
workers at 44 out of an estimated 25 000 dry-cleaning establishments
in the USA (Anon, 1983). Machine-operators received the highest
exposures with 8-h time-weighted averages between 27 and 1010 mg/m3.
Machine-operators in 9 plants had 8-h time-weighted-average exposures
exceeding 340 mg/m3. In 7 plants, 15-min peak exposures exceeded
680 mg/m3. Other workers received a maximum 8-h time-weighted
average of 251 mg/m3. At railway works, where tetrachloroethylene
was used as a cleaning agent, 6% of 104 8-h measurements were below
680mg/m3 with peaks up to 1290 mg/m3 (Essing, 1975).
4.2. General Population Exposure
Individuals living near dry-cleaning shops can be exposed
to concentrations of tetrachloroethylene high enough to show
measurable uptake. The breath of residents, living above 12 dry-
cleaning shops in the Netherlands, was found to contain a mean
concentration of 5 mg/m3, while the breath of residents, living
adjacent to the shops, contained 1 mg/m3 (Verberk & Scheffers,
1979). People, living elsewhere, can also be exposed. However,
at rural sites, exposure will be low and air concentrations ranging
from 8 ng/m3 to 500 ng/m3 have been measured (Murray & Riley,
1973; Lillian et al., 1975). At a similar site, a concentration
of 337 ng/m3 was reported by Singh et al. (1982). Surveys of the
air in 9 cities in the USA showed concentrations between 0.2 and
51.55 mg/m3 with averages between 1.98 and 3.99 µg/m3 (Simmons
et al., 1974; Lillian et al., 1975; Singh et al., 1982). In 14
cities in the Federal Republic of Germany, average concentrations
were between 1.7 and 6.1 µg/m3 (Bauer, 1981; Düszeln et al.,
1982).
Municipal drinking-water in the Federal Republic of Germany,
the United Kingdom, and the USA contained an average of 1.3 µg of
tetrachloroethylene per litre, or less (Pearson & McConnell, 1975;
Saunders et al., 1975; Fujii, 1977; Düszeln et al., 1982). In the
Federal Republic of Germany, the maximum concentration found in a
drinking-water survey in 100 cities was 35.3 µg/litre in 1977, the
average being 0.6 µg/litre (Bauer, 1981).
In foodstuffs, McConnell et al. (1975) measured 0.01 - 19 mg/kg
wet weight. In milk (products) or meat (products), average
concentrations were recorded ranging from 0.003 to 3.49 mg/kg in
Switzerland, and a total daily intake via food was calculated of
160 µg per day (Zimmerli et al., 1982). In the Federal Republic of
Germany, the daily intake via food was calculated to be 160 µg per
day (Bauer, 1981) and 87 µg per day (Düszeln et al., 1982)
The total human intake of tetrachloroethylene from air, water,
and food was calculated by Bauer and Düszeln to be, respectively,
113 and 144 µg/day. When human tissues of 15 deceased persons from
an industrialized area in the Federal Republic of Germany were
analysed, maximum concentrations of tetrachloroethylene in fat of
up to 36.9 µg/kg wet weight were found, the average being
approximately 14 µg/kg (Bauer, 1981).
5. CHEMOBIOKINETICS AND METABOLISM
5.1. Absorption
5.1.1. Animal studies
Dermal absorption was rapid in both mice and guinea-pigs, peak
concentrations of tetrachloroethylene in the blood of guinea-pigs
being reached 30 min after application (Tsuruta, 1975; Jakobson et
al., 1982). The level of tetrachloroethylene in the blood of rats
reached a maximum 1 h after oral ingestion, or immediately after 6
h inhalation (Pegg et al., 1979).
5.1.2. Human studies
Dermal exposure to liquid tetrachloroethylene resulted in
measurable levels of the compound in the breath, reaching a maximum
10 min after exposure (Steward & Dodd, 1964). Absorption via the
lungs is also rapid. Within 3 h of exposure to tetrachloroethylene
vapour, concentrations in the blood appeared to reach equilibrium
(Steward et al., 1961a). The exposure level had a greater effect
on blood concentrations than the exposure time (Hake & Steward,
1977). The total uptake over 4 h increased 2.1 times when the
exposure concentration was doubled. Body mass influenced this
uptake more than respiratory minute volume or the amount of adipose
tissue. Due to decreased retention, the uptake decreased in the
course of the exposure to 60% of the initial uptake. Uptake
increased with exercise (Monster et al., 1979). The venous blood
concentration also increased during exercise (Hake & Steward,
1977).
5.2. Distribution
5.2.1. Animal studies
Seventy-two hours after either oral administration (once by
gavage, or for 12 h in the drinking-water) or 6-h inhalation of
labelled tetrachloroethylene by rats (Pegg et al., 1979; Frantz &
Watanabe, 1983) and mice (Schumann et al., 1980), less than 5% of
the radioactivity was retained by the body. Most radioactivity was
found in body fat, kidneys, and liver of rats. Some radioactivity
was also found in the lung, heart, and adrenals. Tetrachloroethylene
was bound irreversibly to liver macromolecules more rapidly, and to
a greater extent, in mice than in rats. No binding to DNA was
found (Schumann et al., 1980).
In short-term exposures of laying hens, via the feed,
tetrachloroethylene was mainly deposited in fat and fat-containing
tissues. The concentration of tetrachloroethylene in eggs and
tissues increased proportionally with the concentration in the feed
up to 575 mg/kg of feed (Zimmerli et al., 1982b).
5.2.2. Human studies
Evidence of limited accumulation of tetrachloroethylene in
the human body was found by Hake & Steward (1977). Exposure of
volunteers to 678 mg/m3 for 7.5 h per day, 5 days/week, resulted in
a slightly higher alveolar excretion after each daily exposure.
5.3. Metabolic Transformation
5.3.1. Animal studies
Tetrachloroethylene, ingested or inhaled by rats, is mainly
excreted unchanged via the lungs, particularly at high exposures.
Pegg et al. (1979) (section 5.2.1) recovered 60-70% of labelled
tetrachloroethylene in the breath after low oral and inhalation
exposures and about 90% after a high exposure. Mice metabolized
tetrachloroethylene to a greater extent than rats. After inhaling
a low concentration of the labelled compound, 12% was excreted
unchanged in the breath (Schumann et al., 1980), while 70% was
excreted unchanged after inhalation of a high concentration (Yllner,
1961). Most of the balance was found as metabolites in the urine.
At a very high oral dose (8300 mg/kg body weight), only 1.6% of the
radioactivity was found in the urine of rats (Daniel, 1963). The
above values indicate saturable metabolism.
The major metabolite, found in the urine of rats, mice, and
hamsters, was trichloroacetic acid (Yllner, 1961; Daniel, 1963;
Ikeda & Imamura, 1973; Moslen et al., 1977). Other metabolites
found were oxalic acid and ethylene glycol. Pegg et al. (1979)
found only oxalic acid in the urine of rats.
Yllner (1961) and Daniel (1963) suggested a metabolic pathway
in which epoxidation was the first step. After a chloride shift,
trichloroacetyl chloride could be formed, which hydrolyses to
trichloroacetic acid. The involvement of a mixed-function oxidase
was demonstrated in rats and hamsters, when inducers of these
enzymes increased the excretion of trichlorocompounds as much as
7 times (Ikeda & Imamura, 1973; Moslen et al., 1977). The results
of in vitro experiments showed that cytochrome P-450 binds
tetrachloroethylene and metabolizes it to mainly trichloroacetic
acid, stimulated by inducers of mixed-function oxidases. Binding
between metabolites and liver macromolecules (Schumann et al.,
1980) is believed to occur via an acylation reaction (Bonse et al.,
1975; Leibmann & Ortiz, 1977; Costa & Ivanetich, 1980). The
formation of radicals, presumably trichloroacetyl radicals, was
established in vivo in rats and mice (Schmid & Beuter, 1982).
5.3.2. Human studies
Trichlorocompounds in the urine of workers exposed to 70-
2710 mg/m3 for a few hours or repeatedly over several days were
identified as metabolites of tetrachloroethylene. Mainly
trichloroacetic acid was found (Weiss, 1969; Ikeda & Ohtsuji, 1972;
Ikeda et al., 1972; Ikeda & Imamura, 1973; Münzer & Hecter, 1973),
but also trichloroethanol (Ikeda & Ohtsuji, 1972; Ikeda et al.,
1972). After controlled exposures to tetrachloroethylene
concentrations of 488-1356 mg/m3 for 1-8 h, less than 2% of the
uptake was found as trichloroacetic acid in the urine (Fernandez et
al., 1976; Hake & Steward, 1977; Monster et al., 1979). Monster et
al. (1979) calculated that 80-100% of the uptake was excreted
unchanged via the lungs. Ikeda et al. (1972) found that the
trichloroacetic acid concentration in the urine reached a plateau
with repeated exposures above 340 mg/m3.
5.4. Excretion
5.4.1. Animal studies
Tetrachloroethylene was still detectable in the breath of
rats 16 h after a single exposure to levels of 339-3390 mg/m3
for 1 - 40 h. The excretion was proportional to the exposure
level and not directly to the exposure time (Boettner & Muranko,
1969). This excretion followed first-order kinetics with a
half-life of 7 h (Pegg et al., 1979; Frantz & Watanabe, 1983).
Excretion of tetrachloroethylene in cows' milk was found after
oral ingestion of 100 mg/day with the feed. One percent of the
intake was recovered in the milk (Wanner et al., 1982).
Tetrachloroethylene was also recovered in hen eggs at a rate
of 0.6%, when the hens were repeatedly exposed via the feed
(Zimmerli et al., 1982b).
5.4.2. Human studies
The elimination of tetrachloroethylene from the body has
been reported to be slow (Steward et al., 1970; Monster et
al., 1979). Excretion of tetrachloroethylene in breath was
proportional to the exposure level (Steward et al., 1961a;
Fernandez et al., 1976), but not to the length of exposure
(Fernandez et al., 1976). A prolonged exponential decay was
found (Steward et al., 1961a) with a biological half-life of
65 h (Ikeda & Imamura, 1973). Contrary to the rapid excretion
of tetrachloroethylene found by Steward et al. (1961a), Monster
et al. (1979) found a slow excretion. The excretion via blood
and lungs occurred at 3 different rate constants with half-
lives of 12-16 h, 30-40 h, and about 55 h, respectively, 20,
50, and 100 h after exposure. Trichloroacetic acid was excreted
from blood with a half-life of 75-80 h (Monster et al., 1979).
Ikeda & Imamura (1973) estimated the half-life of this metabolite
in urine to be about 6 days. One case was reported of excretion
of tetrachloroethylene in breast milk (Bagnell & Ellenberger,
1977).
6. EFFECTS ON ORGANISMS IN THE ENVIRONMENT
A summary of the acute toxicity of tetrachloroethylene for
aquatic organisms and plants is presented in Table 2.
In a 60-day study, 3 groups of black mollies (Poecilia
sphenops), each comprising 3 females and 3 males, were exposed,
respectively, to 0, 0.001, and 0.005 ml tetrachloroethylene per
litre water. Weights declined by 30 - 40% in the exposed groups
and increased in the control group. Survival was 100%, 17%, and 0%
at 0, 0.001, and 0.005 ml/litre, respectively. The livers of
exposed fish showed fatty degeneration (Loekle et al., 1983).
Pearson & McConnell (1975) estimated bioconcentration factors
from levels in sea water and biota (fish, birds' eggs, seal
blubber) to be less than 100. A steady-state bioconcentration
factor of 49 was found in bluegill sunfish with a half-life of less
than 1 day for depuration (Barrows et al., 1980).
Table 2. Acute aquatic toxicity
---------------------------------------------------------------------------------------------------------
Organism Description t(°C) pH Dissolved Hardness Flow/1 Parameter Concen- Reference
oxygen (mgCaCO3/ stat tration
(mg/litre) litre) mg/litre
---------------------------------------------------------------------------------------------------------
crustacea water flea, 22 6.7- 6.5-9.1 72 stat 48-h LC50 18 Le Blanc (1980)2
Daphnia magna 8.1 no-observed 10
adverse-
effect level
crustacea water flea, 20 8.0 >2 stat 24-h EC50 147 Bringmann & Kühn
Daphnia magna 24-h ECO 65 (1982)3
fish fathead minnow, 12 7.8- >5.0 stat 96-h LC50 21.4 Alexander et al.
Pimephales 8.0 (1978)4
promelas
fish fathead minnow, 12 7.8- >5.0 flow 96-h LC50 18.4 Alexander et al.
Pimephales 8.0 (1978)4
promelas
fish bluegill sun- 21-23 6.5- 9.7-0.3 32-48 stat 96-h LC50 13 Buccafusco et al.
fish, Lepomis 7.9 24-h LC50 46 (1981)5
macrochirus
fish rainbow trout, 12 7.1 44 stat 96-h LC50 5 Shubat et al.
Salmo gairdneri (1982)11
algae unicellular EC50 10.5 Pearson &
Phaeodactylum McConnell
tricornutum (1975)7
plankton phytoplankton 18 7.8 flow lowest 2.0 Erickson &
observable Hawkins (1980)8
effect
level
---------------------------------------------------------------------------------------------------------
Table 2. (contd.)
---------------------------------------------------------------------------------------------------------
Organism Description t(°C) pH Dissolved Hardness Flow/1 Parameter Concen- Reference
oxygen (mgCaCO3/ stat tration
(mg/litre) litre) mg/litre
---------------------------------------------------------------------------------------------------------
inverte- barnacle stat 48-h LC50 3.5 Pearson &
brate Elminius McConnell
modestus (1975)9
fish dab, Limanda flow 96-h LC50 5 Pearson &
limanda McConnell
(1975)10
fish sheepshead 25-31 stat 96-h LC50 >29, Heitmuller et
Cyprinodon <5 al. (1981)11
variegatus
---------------------------------------------------------------------------------------------------------
Notes
1) Flow through or static method.
2) 15 daphnias/concentration, < 24 h old.
3) 20 daphnias/concentration, < 24 h old; standardised synthetic medium was aerated up to saturation
before the test; the sum of calcium and magnesium ions was 2.5 mmol/litre.
4) dechlorinated, sterilised lake water.
5) 10 juvenile fish/concentration, deionized reconstituted fresh water; no aeration.
6) 20 fish/concentration; lake water.
7) 14C uptake inhibition during photosynthesis in sea water.
8) sea water; phytoplankton included Chlorophyceae, Cyanophyceae and Bacillariophyceae; salinity
1.6-1.7%.
9) Sea water.
10) Sea water; 5 fish/concentration.
11) Sea water; salinity 1.0-3.1%; 10 juvenile fish/concentration; no aeration.
7. EFFECTS ON ANIMALS
7.1. Short-term studies
7.1.1. Oral exposure
Fatty infiltration of the liver and heart was observed in dogs
after oral ingestion of tetrachloroethylene at 306-398 mg/kg body
weight along with depressed heart and respiration rates
(Christensen & Lynch, 1933).
Rats receiving 405 mg of tetrachloroethylene per kg body weight
in arachis oil, for 5 days per week, during 4 weeks, showed an
increased relative liver weight and increased liver aniline
hydroxylase activity. No histopathological abnormalities were
found. At 16 mg/kg body weight, no effects on the liver were noted
(de Vries et al., 1982).
7.1.2. Inhalation exposure
No macroscopic lesions were found in surviving rats at the
6-h LC50 value of 27 800 mg/m3, 14 days after exposure (Bonnet
et al., 1980). Inhalation by rats of tetrachloroethylene at
concentrations of 3390 mg/m3 or more caused increased activity
in the following enzymes in blood: serum glutamic oxaloacetic
transaminase (SGOT) (EC 2.6.1.1), serum glutamic pyruvic
transaminase (SGPT) (EC 2.6.1.2), glucose-6-phosphatase (EC
3.1.3.9), and ornithine carbamoyl-transferase (EC 2.1.3.3).
These changes are indicative of liver injury (Drew et al., 1978).
Neurotoxic effects were noted in rats following a single exposure
to 2000 mg/m3. Rats exhibited an intensified motor reaction and
there were distinct alterations in the EEG, an increased impedance
of the cerebral cortex and decreased biopotentials and EEG voltage.
Serum acetylcholinesterase (EC 3.1.1.7) activity was decreased
(Dmitrieva, 1966).
In mice, SGPT-activity increased by 100% after inhalation
of 25 100 mg/m3 for 7 h (Gehring, 1968). Moderate fatty
infiltration was noted in the livers of mice after a 4-h exposure
to a tetrachloroethylene concentration of 1366 mg/m3. Massive
infiltrations occurred at higher exposures. No liver necrosis was
found (Kylin et al., 1963).
After 8 weeks of exposure to 1356 mg/m3, for 4 h per day and 5
days per week, rats showed fatty infiltration in the liver and an
increase in extractable fat, but no cirrhosis or necrosis (Kylin et
al., 1965). The kidneys were not affected in this study.
Rats, rabbits, and monkeys did not exhibit any adverse effects,
including neurotoxic and behavioural effects during or after
repeated exposure to levels of tetrachloroethylene up to 2720 mg/m3
for about 200 days. Guinea-pigs, however, showed increased liver
weight and a few liver cells containing fat vacuoles at 680 mg/m3.
At levels of 1360 mg/m3 or more, fatty degeneration without
cirrhosis was found. Loss of equilibrium, coordination, and
strength were observed in rats at 10 900 mg/m3, and rabbits at 1700
mg/m3. Kidney damage appeared after 24 days of exposure to 17 000
mg/m3. The weight was increased and the tubular epithelium was
swollen (Rowe et al., 1952).
Rabbits exposed repeatedly to 15 000 mg/m3 for 45 days showed
increased SGOT, SGPT, and glutamate dehydrogenase (EC 1.4.1.2)
activity and signs of adrenal injury (Mazza & Brancaccio, 1971;
Mazza, 1972).
Neurotoxic effects were observed in rats exposed to 100 mg of
tetrachloroethylene per m3 air, for 5 h per day, for 5 months.
There were EEG changes together with an increased electrical
impedance of cerebral tissue. The protoplasm of some cortex cells
was swollen and there were isolated cells with vacuoles and
karyolysis. Acetylcholinesterase activity was reduced. Fatty
infiltration of the liver was also noted. At 10 mg/m3, only changes
in impedance and a slight decrease in acetylcholinesterase activity
were found (Dmitrieva & Kuleshov, 1971). In 1937, Carpenter did
not find any pathological changes in rats exposed repeatedly to
tetrachloroethylene at 475 mg/m3 for 7 months. At concentrations
of 1559 and 3187 mg/m3, congestion and swelling were the major
changes in liver and kidneys.
Relevant acute mortality data are shown in Table 3.
Table 3. Acute mortality after oral intake or inhalation of
tetrachloroethylene
---------------------------------------------------------------------------
Species Route Vehicle Parameter Value Reference
studied
---------------------------------------------------------------------------
rat oral none LD50 13 000 mg/kg Smyth et al.
body weight (1969)
rat inhalation - 6-h LC50 27 800 mg/m3 Bonnet et al.
(1980)
mouse oral herring LD50 10 300 mg/kg Dybing & Dybing
oil body weight (1946)
mouse oral none LD50 8400 mg/kg Dybing & Dybing
body weight (1946)
mouse inhalation - 4-h LC50 35 00 mg/m3 Friberg et al.
(1953)
mouse inhalation - 6-h LC50 20 200 mg/m3 Gradisky et al.
(1978)
---------------------------------------------------------------------------
The slope of the regression line giving the probability units
of the percentage mortality after inhalation as a function of the
logarithm of the concentration is rather steep for both rats and
mice, the difference between the LC10 and the LC90 being less than
14 000 mg/m3 (Gradiski et al., 1978; Bonnet et al., 1980).
7.1.3. Exposure of eyes and skin
Duprat et al. (1976) exposed New Zealand rabbits once, either
by ocular instillation or dermal application. The ensuing
conjunctivitis and epithelial abrasion of the eye was reversible
and qualified as slight. Severe erythema and oedema with necrosis
of the skin was noted. In a study on guinea-pigs, 1 ml (1.62 g) of
undiluted tetrachloroethylene applied to the skin caused severe
karyolisis, oedema, spongiosis, and pseudoeosinophilic infiltration
(Kronevi et al., 1981).
7.2. Long-term studies
7.2.1. Oral exposure
B6C3F1 mice and Osborn Mendel rats were given tetrachloroethylene
(more than 99% pure) in corn oil, by gavage, 5 days per week, for
78 weeks (NCI, 1977). Two groups each consisting of 50 male and 50
female animals received doses of approximately 500 and 1000 mg/kg
body weight, respectively. Treated and untreated control groups
were each made up of 20 male and 20 female animals. A dose-related
increase in mortality was found in both species. Kidney damage
observed at both dose levels, showing degenerative changes of the
convoluted tubules with cloudy swelling, fatty degeneration, and
necrosis of the tubular epithelium was not seen in the control
animals. No effects on behaviour were observed, but rats developed
a hunched appearance.
7.2.2. Inhalation exposure
Two groups each consisting of 96 male and 96 female Sprague
Dawley rats were exposed to 2100 and 4010 mg tetrachloroethylene
(96%) per m3 air, for 6 h per day, 5 days per week, during 12
months. A control group consisted of 192 male and 192 female rats
(Rampy et al., 1978). The rats were observed throughout their
lifetime. At the highest exposure, increased mortality in males
was related to an earlier onset of advanced chronic renal disease,
which was also noted in females and controls. No significant
effects were found on body weight, or on the gross- and
histopathology of major organs and tissues, other than the kidneys.
7.3. Carcinogenicity
7.3.1. Oral exposure
In the study by NCI (1977) (section 7.2.1), a significant
increase in the incidence of hepatocellular carcinomas was found in
mice at dose levels of both 500 and 1000 mg/kg body weight. No
other significant effects were observed in the liver.
No evidence of an increased incidence of tumours was found in
rats exposed to 500 and 1000 mg/kg body weight (NCI, 1977, section
7.2.1). However, survival was poor.
7.3.2. Inhalation exposure
There were no clear differences in the incidence of the
different tumour types between exposed and control animals in the
study by Rampy et al. (1978) (section 7.2.2) in which male and
female rats were exposed to tetrachloroethylene (96%) at 2100 and
4010 mg/m3 for 6 h/day, 5 days/week, for 12 months. The animals
were kept for their lifetime.
7.3.3. Dermal exposure
Two groups, each consisting of 30 male and 30 female Ha:ICR
Swiss mice, received 18 and 54 mg, respectively, of tetra-
chloroethylene in acetone applied to the shaven dorsal skin, 3
times per week for 440-594 days. In a third group, each mouse
received one application of 163 mg of tetrachloroethylene followed
after 2 weeks by a promotor in acetone, 3 times per week for 428-
576 days. There were 3 control groups, one for the promotor, one
for acetone, and one for no treatment. Tetrachloroethylene did not
initiate or induce dermal tumours (Van Duuren et al., 1979).
7.4. Mutagenicity
Tetrachloroethylene, of undisclosed purity, induced base
substitutions and frameshift mutations in plate tests with several
strains of Salmonella typhimurium without metabolic activation
(Cherna & Kypenova, 1977), but the response was dose-dependent only
in TA 100.
With Escherichia coli K12, tetrachloroethylene was non-
mutagenic in vitro, with or without metabolic activation (Greim et
al., 1975).
In a 2-h test with Saccharomyces cerevisiae D7, no mutagenic
alterations were found in vitro or in vivo, with or without
metabolic activation (Bronzetti et al., 1983). However, Callen et
al. (1980) did find dose-related mutagenic effects with strain D7
at the same loci and at similar concentrations without additional
metabolic activation in 1-h, but not in 4-h suspension tests.
Strain D4 did not show mutagenic activity in vitro. Both groups of
authors suggest a possible toxic effect on the cytochrome P-450
system. Strain D4 contains much less cytochrome P-450 than strain
D7.
In bone-marrow cells of mice and rats, no chromosomal
aberrations were induced after single, repeated, or long-term
exposure to tetrachloroethylene in vivo (Cherna & Kypenova, 1977;
Rampy et al., 1978).
In host-mediated assays with Salmonella typhimurium strains TA
1950, TA 1951, and TA 1952 and female ICR mice as hosts, an
increase in mutagenic effects was observed. No dose dependence was
found (Cherna & Kypenova, 1977).
7.5. Reproduction and Teratogenicity
Seventeen rats exposed to 2060 mg of tetrachloroethylene per m3
air on days 6-15 of pregnancy showed reduced body weight and a
slightly increased number of resorptions (Schwetz et al., 1975).
No teratogenic effects were found.
In the same study, pups of 17 mice, exposed to 2060 mg/m3
on days 6-15 of pregnancy showed a reduced body weight. Out of 17
litters, all showed delayed ossification of skull bones, 10 litters
showed an increase in the incidence of subcutaneous oedema, and 4,
split sternebrae. Tetrachloroethylene did not exhibit any
reproductive toxicity or teratogenic potential when rats and
rabbits were exposed to 3390 mg/m3 during pregnancy.
Histopathology and weight of maternal organs were also not affected
(Hardin et al., 1981). Several behavioural and neurochemical
effects were observed in the offspring of 75 rats, exposed to 6100
mg tetrachloroethylene per m3 air between the 7th and 13th day or
between the 14th and 20th day of pregnancy (Nelson et al., 1979).
Neuromuscular ability was affected. Decreased levels of
acetylcholine and dopamine were found in the brains of 21-day-old
pups but not in the newborn. At 680 mg/m3, no behavioural effects
were found in pups, but the mothers consumed less food and gained
less weight at both concentrations.
8. EFFECTS ON MAN
8.1. Controlled Human Studies
Rowe et al. (1952) exposed six volunteers to tetrachloroethylene.
Between exposure levels of 560 and 880 mg/m3, only eye irritation
was noted; from 1400 mg/m3 upwards, reversible signs of central
nervous system depression were observed, which increased in
severity with higher exposures. The most frequently reported
subjective complaints of central nervous system depression in this
study were, in order of severity: light-headedness, dizziness,
drowsiness, headache, nausea, fatigue, and impaired coordination.
Two groups of 6 male volunteers were exposed to concentrations
of tetrachloroethylene ranging from 508 to 1654 mg/m3. After
several min of exposure to 508 mg/m3, slight eye irritation was
reported and, after 30 min of exposure to 1425 mg/m3 the subjects
experienced slight light-headedness and impaired motor
coordination. No liver or kidney damage was found (Steward et al.,
1961a).
Irritation of the eyes, nose, or throat and central nervous
system depression were experienced by 17 subjects, exposed to 685
mg of tetrachloroethylene per m3 air. Coordination was impaired
within 3 h of exposure. No liver or kidney damage was found
(Steward et al., 1970).
Hake & Steward (1977) exposed 19 subjects for 1, 3, or 7.5 h
per day, for 5 days per week. At 136 mg/m3, no effects were found.
At 678 and 1017 mg/m3, coordination was slightly impaired in males.
No general relationship was found between subjective complaints and
exposure. Adaptation occurred for odour perception and the
subjective feelings reported earlier by Steward et al. (1970).
The odour threshold for tetrachloroethylene has been
established as 32 mg/m3 (Leonardos et al., 1969).
8.2. Accidental Exposures
A man accidentally exposed to 1860 mg/m3 for 3 h, followed
by 7460 mg/m3 for 30 min, experienced light-headedness and
eye irritation and finally became unconscious reversibly after
the first 3 h. Liver damage was indicated by the clinical report
(Steward et al., 1961b). Saland (1967) reported reversible
elevated SGOT values in 8 out of 9 men after accidental exposures.
Another accident resulted in unconsciousness in one man (Patel et
al., 1977). No liver damage was noted, but the principal clinical
feature was pulmonary oedema. It can be presumed that the oedema
was an effect secondary to hypoxia induced by circulatory failure.
A girl of 6 weeks was exposed to tetrachloroethylene through
excretion in breast milk. Jaundice was diagnosed. SGOT and
alkaline phosphatase activities and bilirubin were increased in the
serum of the baby, but not in that of the parents (Bagnell &
Ellenberger, 1977).
8.3. Occupational Exposure
Münzer & Heder (1972) carried out further studies on 40 workers
in dry-cleaning plants found to have more than 40 mg/litre of
trichloroacetic acid in the urine. Exposures ranged from 678 to
2712 mg/m3. Sixteen subjects showed signs of central nervous
system depression and, in 21 cases, the autonomic nervous system
was also affected. Liver malfunction was not observed.
Examination of 113 dry-cleaning workers (Franke & Eggeling,
1969), revealed that 35% of them experienced symptoms of central
nervous system depression, while the autonomic nervous system was
affected in 40%. Slight liver function disturbances were revealed.
Out of 326 measurements, 75% revealed average 8-h concentrations
below 678 mg/m3.
Neurotoxic effects, including differences in the proximal motor
latency of nerve cells and electrodiagnostic and neurological
rating scores, were found in 20 dry-cleaning workers, exposed for
an average of 7.5 years to time-weighted-average concentrations of
between 9 and 252 mg/m3. A correlation was found between years of
exposure and some behavioural variables (Tuttle et al., 1976).
Chmielewski et al. (1976) identified 6 pseudoneurotic syndrome
cases and 4 subjects with pathological EEG recordings among 16
factory employees exposed to tetrachloroethylene concentrations
ranging from 400 to 3000 mg/m3 for periods of 2 years to more than
20 years. The altered EEG was accompanied by a reduced choline-
sterase activity in the serum of 3 workers and an increased alanine
aminotransferase activity in the serum of 2 workers, which could
point to liver damage. Subjective complaints of irritation and
neurological disorders were related to length of exposure. Adrenal
gland damage was also noted.
Essing (1975) did not find significant differences in the
incidence of liver and kidney malfunctions between a group of 112
railway workers, exposed to tetrachloroethylene, and a control
group of 101 workers, over an average period of 11.5 years. Three-
quarters of all 8-h measurements revealed concentrations below 340
mg/m3. Liver dysfunction after short-term tetrachloroethylene
exposure was found in a number of case studies (Hughes, 1954;
Meckler & Phelps, 1966; Trense & Zimmerman, 1969). In two of these
cases, liver cell necrosis was found and, in one case, pulmonary
oedema. One case of liver cirrhosis was reported by Coler &
Rosmiller (1953). They examined a total of 7 men, exposed for 2-6
years. Three of the men, including the cirrhosis case, showed
significantly changed clinical chemistry measurements, indicative
of liver disease.
Cytogenic and cytokinetic studies of lymphocytes were performed
on 10 factory workers, who had been exposed to tetrachloroethylene
vapour concentrations between 68 and 270 mg/m3 air or between 200
and 1490 mg/m3 air for periods ranging from 3 months up to 18
years. No significant dose-related changes were found in chromosome
aberrations, sister-chromatid-exchange rates, the proportion of M2
+ M3 metaphases, and the mitotic index (Ikeda et al., 1980).
8.4. Mortality Studies
The causes of death of 330 laundry- and dry-cleaning workers in
the USA, deceased in the period 1957-77, were analysed by the
proportionate mortality method (Blair et al., 1979). The workers
had mainly been exposed to tetrachloroethylene, but also to carbon
tetrachloride, trichloroethylene, and other petroleum solvents,
including benzene. An excess of lung, cervical, and skin cancer
was the main cause of the increase in the observed number of deaths
due to carcinogenic effects, compared with the proportionate
mortality data of the USA population.
In another study, the death certificates of 671 female workers
in the laundry- and dry-cleaning industry, deceased in the period
1963-77, were examined for the causes of death (Katz & Jowett,
1981). These data were compared with the mortality data of working
females and with those of a population derived from low-wage
occupations. Results failed to show an overall increase in
malignant neoplasms, but an elevated risk of genital and kidney
cancer was observed, together with a smaller excess of bladder and
skin cancer and lymphosarcoma. Exposure data were not given.
9. EVALUATION OF HEALTH RISKS FOR MAN
On the basis of results of repeated short-term, human exposure
studies, it is considered that no acute effects will occur at
tetrachloroethylene concentrations of approximately 140 mg/m3 or
less (Hake & Steward, 1977).
The results of human exposure studies indicate that, after
single or short-term exposures to tetrachloroethylene, human beings
are likely to begin experiencing eye irritation at air concentrations
of approximately 500 mg/m3 (Rowe et al., 1952) and depression of
the central nervous system, and nose and throat irritation, at
approximately 700 mg/m3 (Steward et al., 1970). Such effects are
reversible on cessation of exposure, but increase in severity with
both increasing concentration and duration of exposure. Because
the excretion rate is relatively slow, a large dose in the target
tissue is likely to remain high for several days after exposure.
Direct skin exposure will result in irritation of the skin.
Observations after repeated exposure to tetrachloroethylene
over months or years indicate that human beings inhaling
tetrachloroethylene are likely to begin to exhibit depression of
the central- and autonomic nervous systems at concentrations
exceeding approximately 700 mg/m3 (Münzer & Heder, 1972; Hake &
Steward, 1977). Results of studies on rats indicate that
inhalation exposure to tetrachloroethylene concentrations of
approximately 1300 mg/m3 or more appears to be associated with
definable liver injury (Kylin et al., 1965). However, the level at
which similar effects in the liver might occur in human beings is
not clear. Workers in dry-cleaning plants, exposed to
concentrations up to 2700 mg/m3 did not show alterations in liver
enzyme activity (Münzer & Heder, 1972).
Embryotoxicity was observed in the progeny of experimental
animals exposed by inhalation to tetrachloroethylene concentrations
exceeding 2000 mg/m3 (Schwetz et al., 1975). It is possible that
similar effects might occur in human beings. However, there was no
indication of reproduction injury and only slight evidence of
teratogenicity in the animal studies reported.
Tetrachloroethylene was found to be carcinogenic for mice but
not for rats (NCI, 1977). Evidence from epidemiological studies
(Blair et al., 1979; Katz & Jowett, 1981) among dry-cleaning and
laundry workers is insufficient to conclude that exposure to
tetrachloroethylene can cause cancer in human beings.
10. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS
10.1. Occupational Exposure
Maximum allowable concentrationsa range from 10 mg/m3 (1.5 ppm,
ceiling value) in the USSR, 140 mg/m3 (20 ppm, TWA) in Sweden, and
250 mg/m3 (37 ppm) in Czechoslovakia to 340 mg/m3 (50 ppm) in the
Federal Republic of Germany, Japan, and the USA. Short-term
exposure limits range from 340 mg/m3 (50 ppm) in Sweden to 1250
mg/m3 (183 ppm) in Czechoslovakia and 1340 mg/m3 (200 ppm) in the
USA. The acceptable limit in Brazil is 525 mg/m3 (78 ppm) for 48 h
per week (IRPTC, 1983).
10.2. Ambient Air Levels
Maximum allowable concentrations are 1.0 mg/m3 average per day
or 4.0 mg/m3 average per 0.5 h in Czechoslovakia and 0.06 mg/m3
average per day in the USSR (IRPTC, 1983).
10.3. Drinking-Water
The WHO recommended guideline value in drinking-water is 10
mg/litre (WHO, 1983).
10.4. Use
The European Economic Commission prohibits the use of
tetrachloroethylene in cosmetic products (IRPTC, 1983).
10.5. Labelling and Packaging
The European Economic Commission regulations state that the
label should read that tetrachloroethylene is harmful if inhaled or
swallowed, and should be kept out of reach of children. Contact
with the eyes must be avoided (IRPTC, 1983).
10.6. Storage and Transport
The United Nations Committee of Experts (1977) on the
Transportation of Dangerous Goods qualifies tetrachloroethylene as
a toxic substance (Class 6.1) with minor danger for packing
purposes (Packing Group III). Packing methods and a label are
recommended. The Inter-governmental Maritime Consultative
Organization (1981) also qualifies tetrachloroethylene as a toxic
substance (Class 6.1) and recommends packing, storage, and
labelling methods for maritime transport in glass bottles, cans,
and metal drums. The label recommended by both organizations is:
--------------------------------------------------------------------
a Values quoted from national lists.
References with cross-references to IRPTC data-profile
(< Coden, page number>)
--------------------------------------------------------------------
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