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    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


         The International Programme on Chemical Safety (IPCS) is a
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        ISBN 92 4 154091 5

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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 500C 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                  -22C
    boiling point                  121C
    water solubility               150 mg/litre, 20C
     n-octanol-water partition
     coefficient                   2.86
    density                        1.62 g/ml, 20C
    relative vapour density        5.8
    vapour pressure                1.9 kPa (14 mm Hg), 20C
    surface tension                32.32 dyne/cm2 20C

    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 g/m3                            Russell &
                 Porapak N         heating, gas                                             Shadoff
                                   chromatography,                                          (1977)
                                   combined with  
                                   electron capture              
                                   detection and    
                                   mass spectrometry

air     ambient                    gas chromatography  0.03 g/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 g/m3                      Bauer (1981)
        breath   sorption on       pentane-ether
                 XAD - 2

solids  food,    solid and liquid  elution by pentane  food: 0.2 g/kg
        tissues  samples: strip-   gas chromatography  wet-weight
                 ping by nitrogen, with electron
liquids water    sorption on XAD   capture detection   water: 0.001
                 - 2                                   g/litre

water                              gas chromatography  0.05 g/litre   direct headspace     Piet et al.
                                   with electron                       analysis             (1978)
                                   capture detection

water   drinking                   gas chromatography  0.5 g/litre    direct analysis      Nicholson et
                                   with electron                                            al. (1977)
                                   capture detection
                                            
food             extraction by     gas chromatography  2-5 g/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 g/litre, while the sediment 
contained 0.02-4.8g/litre (Pearson & McConnell, 1975).  Not 
surprisingly, marine organisms were also found to contain residues 

of tetrachloroethylene.  Pearson & McConnell measured 0.05-15 g/kg 
wet weight in vertebrates, 13-20 g/kg wet weight in algae, and 0-
19 g/kg wet weight in seal blubber and shrew.  Organs and eggs of 
birds contained 0.7-39 g/kg wet weight. 

    Surface water in Western Europe was found to contain 
tetrachloroethylene levels of 0.01-46 g/litre (Correia et al., 
1977; Bauer, 1981).  Maximum levels of 22 g/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 g/m3 in the urban atmosphere, 
35 g/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 g/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 g/m3 (Bauer, 1981; Dszeln et al., 
1982). 

    Municipal drinking-water in the Federal Republic of Germany, 
the United Kingdom, and the USA contained an average of 1.3 g of 
tetrachloroethylene per litre, or less (Pearson & McConnell, 1975; 
Saunders et al., 1975; Fujii, 1977; Dszeln et al., 1982).  In the 
Federal Republic of Germany, the maximum concentration found in a 
drinking-water survey in 100 cities was 35.3 g/litre in 1977, the 
average being 0.6 g/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 g per day (Zimmerli et al., 1982).  In the Federal Republic of 
Germany, the daily intake via food was calculated to be 160 g per 
day (Bauer, 1981) and 87 g per day (Dszeln et al., 1982) 

    The total human intake of tetrachloroethylene from air, water, 
and food was calculated by Bauer and Dszeln to be, respectively, 
113 and 144 g/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 g/kg wet weight were found, the average being 
approximately 14 g/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; Mnzer & 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 & Khn
            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

    Mnzer & 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 (Mnzer & 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 (Mnzer & 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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    See Also:
       Toxicological Abbreviations
       Tetrachloroethylene (HSG 10, 1987)
       Tetrachloroethylene (ICSC)
       TETRACHLOROETHYLENE (JECFA Evaluation)
       Tetrachloroethylene (UKPID)
       Tetrachloroethylene (IARC Summary & Evaluation, Volume 63, 1995)