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    World Health Orgnization
    Geneva, 1985

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    1.1. Summary
         1.1.1. Properties and analytical methods
         1.1.2. Uses and sources of exposure
         1.1.3. Industrial exposure
         1.1.4. Environmental transport and distribution
         1.1.5. Absorption, distribution, biotransformation, and 
         1.1.6. Effects on experimental animals
         1.1.7. Effects on man
    1.2. Recommendations for further research


    2.1. Identity
    2.2. Physical and chemical properties
         2.2.1. Pure trichloroethylene
        Chemical reactivity
        Chemical degradation
        Photochemical degradation
         2.2.2. Commercial trichloroethylene
    2.3. Analytical methods
         2.3.1. Identification and purity assessment
        Colorimetry tests
        Infra-red spectroscopy
        Gas-liquid chromatography
         2.3.2. Determination in environmental media
         2.3.3. Determination in human tissues and fluids
        Trichloroacetic acid
        Total trichloro derivatives
         2.3.4. Sensitivity


    3.1. Production processes, levels, and uses
         3.1.1. Production processes and levels
         3.1.2. Uses
    3.2. Handling hazards, and precautions
         3.2.1. Handling hazards
        Fire, explosion, and thermal decomposition 
        Chemical reactivity
         3.2.2. Handling precautions
        Personal safeguards

         3.2.3. Recovery
         3.2.4. Disposal
         3.2.5. Emergency measures in case of accidental spills
         3.2.6. Occupational exposure


    4.1. Environmental levels
         4.1.1. Soils and sediments
         4.1.2. Water
         4.1.3. Air
         4.1.4. Biota
         4.1.5. Food
    4.2. Environmental distribution and transport
         4.2.1. Equilibrium distribution
         4.2.2. Transformation in the environment
        Soils and sediments


    5.1. Absorption
         5.1.1. Inhalation exposure
         5.1.2. Oral exposure
         5.1.3. Dermal exposure
    5.2. Distribution and storage
    5.3. Metabolic transformation
         5.3.1. Animals
         5.3.2. Human beings
         5.3.3. Drug and other interactions
    5.4. Elimination
         5.4.1. Studies on animals
         5.4.2. Studies on man
    5.5. Biological monitoring of exposure


    6.1. Effects on animals
         6.1.1. Acute toxicity
         6.1.2. Short-term exposures
        Oral exposures
        Inhalation exposure
        Parenteral exposure
         6.1.3. Long-term exposure
        Oral exposure
        Inhalation exposure
        Parenteral exposure
         6.1.4. Interactions
         6.1.5. Immunotoxicity
         6.1.6. Effects on cell systems
         6.1.7. Carcinogenicity

         6.1.8. Mutagenicity
        Gene mutation
        Chromosome aberrations
        DNA damage
        Mammalian cells  (in vitro)
        Mutagenic activity of trichloroethylene 
         6.1.9. Reproduction, embryo/fetotoxicity, and teratology 
        Avian embryo system


    7.1. Aquatic organisms
    7.2. Uptake, distribution, storage, metabolism, and elimination 
         in plant and animal organisms 
    7.3. Effects on the stratospheric ozone layer


    8.1. General symptoms and signs
         8.1.1. Acute effects
         8.1.2. Chronic effects
    8.2. Effects on organs and systems
         8.2.1. Effects on the nervous system
         8.2.2. Effects on the cardiovascular system
         8.2.3. Effects on the respiratory system
         8.2.4. Effects on the urinary tract
         8.2.5. Effects on the skin
         8.2.6. Effects on the eye
         8.2.7. Carcinogenicity


    9.1. Levels of exposure
         9.1.1. General population
         9.1.2. Occupational exposure
    9.2. Evaluation of human health risks
         9.2.1. Acute effects
         9.2.2. Chronic effects
    9.3. Treatment of poisoning in human beings
         9.3.1. Emergency measures
        General points
        Dermal exposure
        Eye exposure






Dr R.F. Addison, Department of Fisheries and Oceans, Bedford
   Institute of Oceanography, Dartmouth, Nova Scotia, Canada

Dr O. Axelson, Department of Occupational Medicine, University
   Hospital, Linköping, Sweden

Dr A. Di Domenico, High Institute of Health, Rome, Italy

Prof S.D. Gangolli, British Industries Biological Research
   Association, Carshalton, Surrey, United Kingdom

Prof M. Ikeda, Department of Environmental Health, Tohoku 
   University School of Medicine, Sendai, Japan 

Dr S.E. Jaggers, Central Toxicology Laboratory, ICI, Macclesfield, 
   Cheshire, United Kingdom 

Prof N. Loprieno, Laboratory of Genetics, University of Pisa, Pisa, 

Dr C. Maltoni, Oncology Institute and Tumour Centre "Felice 
   Addari", Bologna, Italy 

Dr J.H. Mennear, National Institute of Environmental Health 
   Sciences, Research Triangle Park, North Carolina 

Dr A.C. Monster, Coronel Laboratory, University of Amsterdam,
   Amsterdam, The Netherlands

Prof I.V. Sanotsky, Research Institute of Industrial Hygiene and 
   Occupational Diseases, USSR Academy of Medical Sciences, Moscow, 

 Representatives from Other Organizations

Mr J. Wilbourn, International Agency for Research on Cancer, Lyons, 


Dr E.M. Smith, International Programme on Chemical Safety, World 
   Health Organization, Geneva, Switzerland 


Prof E. Malizia, Emergency Toxicological Service, Antivenom Center, 
   Umberto the First Polyclinic, La Sapienza University, Rome, 


    Every effort has been made to present information in the 
criteria documents as accurately as possible.  In the interest of 
all users of the environmental health criteria documents, readers 
are kindly requested to communicate any errors found to the Manager 
of the 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. 

    In addition, experts in any particular field dealt with in 
the criteria documents are kindly requested to make available to 
the WHO Secretariat any important published information that may 
have inadvertently been omitted and which may change the evaluation 
of health risks from exposure to the environmental agent under 
examination, so that the information may be considered in the event 
of updating and re-evaluation of the conclusions contained in the 
criteria documents. 

                          *    *    *

    A detailed data profile and a legal file can be obtained from 
the International Register of Potentially Toxic Chemicals, Palais 
des Nations, 1211 Geneva 10, Switzerland (Telephone no. 988400 - 


    Following the recommendations of the United Nations Conference 
on the Human Environment held in Stockholm in 1972, and in response 
to a number of resolutions of the World Health Assembly (WHA23.60, 
WHA24.47, WHA25.58, WHA26.68), and the recommendation of the 
Governing Council of the United Nations Environment Programme, 
(UNEP/GC/10, 3 July 1973), a programme on the integrated assessment 
of the health effects of environmental pollution was initiated in 
1973.  The programme, known as the WHO Environmental Health 
Criteria Programme, has been implemented with the support of the 
Environment Fund of the United Nations Environment Programme.  In 
1980, the Environmental Health Criteria Programme was incorporated 
into the International Programme on Chemical Safety (IPCS).  The 
Programme is responsible for a series of criteria documents. 

    A WHO Task Group on Environmental Health Criteria for 
Trichloroethylene was held in Rome from 10 to 15 December, 1984.  
Dr E.M. Smith opened the meeting on behalf of the Director-General.  
The Task Group reviewed and revised the draft criteria document and 
made an evaluation of the health risks of exposure to 

    The draft criteria document was developed by the ISTITUTO 
principal author was DR A. DI DOMENICO. 

    The efforts of all who helped in the preparation and 
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.  The United Kingdom Department of Health and Social 
Security generously covered the costs of printing. 


1.1.   Summary

1.1.1.  Properties and analytical methods

    Trichloroethylene is a colourless liquid with a characteristic, 
slightly sweet odour.  It is used as a solvent in a variety of 
applications.  There are a number of techniques suitable for 
the determination of trichloroethylene including colorimetry, 
infra-red spectroscopy, gas-liquid chromatography (GLC), and gas 
chromatography/mass spectrometry.  In GLC, the use of flame 
ionization detection gives good sensitivity; however, electron 
capture detection is markedly more sensitive.  Methods are 
available for the determination of trichloroethylene in blood, fat, 
other tissues, food, water, etc. 

1.1.2.  Uses and sources of exposure

    A major use of trichloroethylene is in metal degreasing; 
other significant uses are in textile cleaning, solvent extraction 
processes, and as a carrier solvent.  It is no longer used as a 
grain fumigant and is now only occasionally used in anaesthesia.  
For practical use, trichloroethylene requires the addition of 
stabilizers (up to 2%). 

    There may be exposure to both the vapour and the liquid in the 
workplace, the highest atmospheric concentrations occurring in open 
degreasing processes.  Trichloroethylene may be emitted from 
industrial plants in the form of a vapour and in aqueous effluent. 

    The major part of the annual world production of trichloro-
ethylene (estimates range from 60 to 90%) is released into the 

1.1.3.  Industrial exposure

    Exposure in the workplace is mainly through inhalation of 
trichloroethylene vapour, but skin contamination with the liquid 
also occurs.  The highest levels of occupational exposure occur 
in metal cleaning processes.  Atmospheric trichloroethylene 
concentrations up to several hundred mg/m3 have been recorded.  
Exposure during the actual production of trichloroethylene is 
relatively low because of the nature of the process.  Oral intake 
is insignificant in occupational terms. 

1.1.4.  Environmental transport and distribution 

    Contamination of water has been reported but, with the 
exception of contamination of water supplies through accidental 
spillage, levels have been very low.  Trichloroethylene is probably 
widely distributed in the environment, but usually only at fairly 
low levels, i.e., in the µg/kg range in sediments, in the low 
µg/litre range in natural waters, in the low µg/m3 range in air, 
and in the µg/kg range in aquatic biota.  The limited toxicity data 

available show LC50 values for aquatic biota in the mg/litre range. 
Trichloroethylene is degraded in biological  and abiotic systems; 
in air (where most environmental trichloroethylene is expected to 
occur), its lifetime is about 10 days.  It seems unlikely that the 
present rate of release of trichloroethylene into the environment 
would contribute significantly to depletion of the stratospheric 
ozone layer. 

1.1.5.  Absorption, distribution, biotransformation, and elimination

    The most significant uptake of trichloroethylene is through 
inhalation of the vapour, but uptake can also take place through 
the skin or via the gastrointestinal tract.  Inhalation exposure 
is monitored by determining time-weighted average atmospheric 

    Following absorption, trichloroethylene is rapidly distributed 
and accumulates in the adipose tissue.  It easily crosses the 
placental barrier.  Trichloroethylene is eliminated unchanged in 
exhaled air and, to a lesser extent, in faeces, sweat, and the 
saliva.  It is rapidly metabolized, mainly in the liver. 

    At least 4 mammalian metabolites of trichloroethylene have 
been identified:  trichoroethanol, trichloroacetic acid, 
2-hydroxyacetylethanolamine, and oxalic acid; dichloroacetic acid 
appears to be specific to mice.  The major metabolites in human 
beings, trichloroethanol and trichloroacetic acid, are excreted 
in the urine.  Estimations of levels of these major urinary 
metabolites or total trichloro compounds in urine may be used for 
the biological monitoring of exposure. 

    There are species differences in the rate of metabolism of 
trichloroethylene to trichloroacetic acid, the rate in the mouse 
being more rapid than that in the rat.  Isolated hepatocytes 
obtained from the mouse and the rat accurately reflect the  in 
 vivo metabolic rates.  Isolated human hepatocytes metabolize 
trichloroethylene to trichloroacetic acid at a slower rate than rat 

    In man, the metabolism of trichloroethylene decreases when 
ethanol has been ingested, and intolerance may occur. 

1.1.6.  Effects on experimental animals

    Trichloroethylene is a moderately toxic substance.  In terms of 
acute toxicity, LC50 values in rodent test species range from 45 to 
260 mg/m3, and oral LD50 values range from 2400 to 4920 mg/kg body 
weight.  The toxic effects of exposure are related to a depressant 
action on the central nervous system.  Central nervous system 
depression can lead to coma and death.  Liquid trichloroethylene 
has an irritant effect on the skin and eyes; trichloroethylene 
vapour is irritant to the respiratory tract.  Toxic effects on the 
kidneys are produced in rats by long-term oral administration.  
Minimal changes in the kidneys can occur after oral administration 
of 100 mg/kg body weight per day for 13 weeks and nephrotic changes 

can be found following oral administration of 500 mg/kg body weight 
per day, for 2 years.  In mice, toxic effects on the kidney occur 
after oral administration of 3000 mg/kg per day, for 13 weeks, and 
mild nephrotic changes following 1000 mg/kg per day, for 2 years.  
Also, in mice, oral administration of 6000 mg/kg body weight per 
day for 13 weeks produced necrotic changes in the liver.  
Continuous exposure of mice by inhalation to 810 mg/m3 
trichloroethylene for 2 days resulted in an increased relative 
liver weight, which decreased following cessation of exposure. 

    Some immunological changes have been observed in rodents 
exposed to trichloroethylene by inhalation at concentrations 
between 10 and 1000 mg/m3 for several weeks and also in those given 
trichloroethylene in their drinking-water (0.1 - 5 g/litre) for a 
similar period. 

    Trichloroethylene does not cause any biologically significant 
embryotoxic or teratogenic effects. 

    The evidence for mutagenic effects is inconclusive. 

    There is clear evidence that trichloroethylene is carcinogenic 
in mice with lifetime (2-year) exposures to 1620 mg/m3 by 
inhalation or oral adiministration of 700 - 1200 mg/m3 body weight 
per day.  There is some evidence that trichloroethylene causes 
tumours in rats; a low incidence of renal tumours occurred in rats 
exposed for 2 years to levels of 3240 mg/m3 by inhalation or 500 - 
1000 mg/kg per day by the oral route.  There are species and strain 
differences in carcinogenic response and the purity of the 
trichloroethylene and the nature of any additives affect the 

1.1.7.  Effects on man

    The signs and symptoms of over-exposure in human beings are 
mainly related to the central nervous system; for example, 
headache, drowsiness, hyperhydrosis, tachycardia, and, in more 
severe cases, stupor and coma.  Trichloroethylene is analgesic and 
anaesthetic; inhalation of concentrations between 27 000 mg/m3 
(5000 ppm) and 108 000 mg/m3 (20 000 ppm) have been used in 
anaesthetic procedures. 

    Fatalities have been reported through accidental or suicidal 
over-exposure to trichloroethylene.  In general, the lethal oral 
dose for an adult is of the order of 7000 mg/kg body weight, but a 
death has occurred following a single dose of 50 ml (75 g).  Deaths 
have been reported following inhalation of trichloroethylene, 
including a number that have occurred during anaesthetic 
procedures.  While respiratory depression cannot be excluded, 
it is more likely that cardiac arrest, related to the arrhythmic 
properties of trichloroethylene, was the cause of death. 

    In laboratory and work-place studies, demonstrable psychomotor 
impairment was found following inhalation exposure to 5400 mg/m3 

(1000 ppm) for 2 h, and reaction time was increased by exposure to 
a concentration of 1320 mg/m3 (245 ppm), under work-place 

    Effects on the respiratory and gastrointestinal tracts 
are related to the irritant properties of trichloroethylene.  
Irritation of mucous membranes occurs with exposure to 
trichloroethylene vapour at concentrations of 810 - 3510 mg/m3 
(150 - 650 ppm).  At autopsy, following fatal ingestion, lesions 
of the gastrointestinal tract have been found. 

    Liquid trichloroethylene and its vapour at anaesthetic 
concentrations (27 500 - 108 000 mg/m3) cause eye irritation and 
superficial corneal damage, which normally recovers completely.  
Liquid trichloroethylene is mildly irritating to the skin but, if 
it is held in contact for any length of time, for example, by 
clothing or footwear, it can produce marked skin irritation with 
blistering.  Repeated contact produces defatting of the skin and 

    High oral doses (200 - 300 ml or more), taken suicidally or 
through misuse, have produced toxic effects on the liver and 
kidneys.  Hepatic necrosis and nephropathy have been found at 
autopsy.  The use of trichloroethylene in a confined unventilated 
space for 3 - 4 h has also resulted in liver and kidney damage.  
Addiction to trichloroethylene ("vapour sniffing") has produced 
liver and kidney damage, and deaths have occurred. 

    Chronic neurotoxic effects may occur, and a "psychoorganic 
syndrome", with lassitude and depression, has been described but 
has not been found consistently in studies on groups of 
trichloroethylene workers.  It is probable that many of the effects 
described were due to the metabolites of trichloroethylene. 

    Degeneration of cranial nerves has occurred following short-
term exposures to high levels of trichloroethylene, generally in 
enclosed spaces.  However, it is considered that the cranial 
neuropathy is probably due to breakdown products, mainly 
dichloroacetylene, rather than to trichloroethylene itself.  
Polyneuropathies have been reported following long-term exposure. 

    Data from epidemiological studies on carcinogenicity in 
occupationally exposed groups are inconclusive. 

1.2.   Recommendations for Further Research

1.  The toxic action and thresholds for toxic effects of 
    trichloroethylene in human beings and experimental animals, at 
    low levels of short- and long-term exposure, need to be defined 
    in more detail. 

2.  Studies are required for a full evaluation of the genotoxicity 
    of trichloroethylene.  Trichloroethylene samples of high purity 
    (with full data on the nature and the amount of any impurities) 
    should be used as well as trichloroethylene samples stabilized 
    with non-mutagenic compounds (e.g., amines). 

3.  The significance for human beings of the effects seen in 
    rodents with long-term exposures requires further study.  The 
    role of metabolism in carcinogenesis, both the rates and the 
    metabolites formed, and the production of biochemical responses 
    that may be the mechanisms of carcinogenic responses in target 
    tissues require further study and interspecies comparison. 

4.  In view of the equivocal evidence for mutagenicity in bacterial 
    and mammalian cell systems, there is an implication that 
    epigenetic mechanisms may be involved in the carcinogenic 
    effects observed in experimental animals. 

    It should be noted that trichloroacetic acid produced by the 
    metabolism of trichloroethylene has induced peroxisome 
    proliferation, with differences in response in isolated 
    hepatocytes from the mouse, rat, and human beings.  Peroxisome 
    proliferation has been implicated in the epigenetic induction 
    of hepatocellular carcinoma in mice and rats. 

5.  The pathological significance of trichloroethylene-induced 
    cytomegaly and karyomegaly of renal tubular cells and the 
    incidence in untreated laboratory rodents of tubular renal 
    carcinoma should be investigated. 

6.  There should be further epidemiological studies to investigate 
    the possible carcinogenic effects of trichloroethylene exposure.  
    Additional cohort studies should be initiated.  Registers of 
    TCA-monitoring data should be organized with epidemiological 
    studies in mind.  Case-control studies, particularly of 
    haemolymphatic, pancreatic, and genito-urinary tract cancers, 
    should specifically consider exposure to trichloroethylene in 
    industry, dry-cleaning operations, and via food, such as 
    decaffeinated coffee. 

7.  Biological monitoring should be extended and more attention 
    paid to interindividual differences in toxicokinetics and to 
    the factors responsible for these, such as anthropometric 
    parameters, sex, genetic make-up, use of drugs and alcohol, and 
    interactions with certain chemicals in the environment. 

8.  Workers with moderate levels of exposure to trichloroethylene 
    tend to have an increased incidence of subjective symptoms.  
    There should be a systematic approach to the clearer 
    identification, analysis, and evaluation of such symptoms and 
    their correlation with levels of occupational exposure in 
    different industrial environments. 

9.  Although, at present, trichloroethylene does not appear to be 
    a major environmental problem, this assessment is based on 
    relatively few data describing its distribution in the 
    environment, and its rates and routes of degradation.  More 
    comprehensive data should be obtained, and an assessment of 
    geographical or temporal changes in trichloroethylene 
    distribution should be made. 

    There should be studies on controlling the input of 
    trichloroethylene into the environment, and the provision of 
    disposal methods other than incineration should also be 


2.1  Identity

    Trichloroethylene is an aliphatic substance of the organic 
halogen and halogen-derivative families. 

Chemical structure:

                              H           Cl
                               \         /
                                C ===== C
                               /         \
                              Cl          Cl

Molecular formula:            C2HCl3

IUPAC and CAS name:           trichloroethene

Common synonyms:              acetylene trichloride, ethinyl 
                              trichloride, ethylene trichloride, 
                              1,1,2-trichloroethylene, TCE, TRI

Common trade names:           Algylen, Anamenth, Benzinol, 
                              Blacosolv, Blancosolv, Cecolene, 
                              Chlorilen, Chlorylen, Circosolv, 
                              Densin-fluat, Dow-Tri, Dukeron, 
                              Fleck-Flip, Flock-Flip, Fluate, 
                              Gemalgene, Germ-algene, Lanadin, 
                              Lethurin, Narcogen, Narkosoid, Nialk, 
                              Perm-a-Chlor, Pet-zinol, Philex, 
                              Threthylen, Threthylene, Trethylene, 
                              Triad, Trial, Triasol, Trichloran, 
                              Trichloren, Triclene, Trielene, 
                              Trielin, Trielina, Triklone, Trilen, 
                              Trilene, Triline, Trimar, Triol, Tri-
                              Plus, Tri Plus M, Vestrol, Vitran

CAS registry number:          79-01-6

Relative molecular mass:      131.40

Conversion factor             1 ppm trichloroethylene = 5.4 mg/m3

2.2.  Physical and Chemical Properties

2.2.1.  Pure trichloroethylene

    In its pure state, trichloroethylene is a colourless liquid 
with a characteristic, slightly sweet odour; the odour threshold 
for human beings is 540 mg/m3 (100 ppm) (Torkelson & Rowe, 1982). 

    Some physical and chemical properties of pure trichloroethylene 
are listed in Table 1.  Chemical reactivity

    Trichloroethylene oxidizes to yield acids, including 
hydrochloric acid (Aviado et al., 1976).  Its reactivity increases 
with rise in temperature and with exposure to ultraviolet radiation 
(UVR).  Under pressure, at 150 °C, it reacts with alkalis to 
produce glycolic acid.  With sulfuric acid, it reacts to produce 
monochloroacetic acid (Kirk & Othmer, 1964).  In the presence of 
alkali, dehydrochlorination may occur in solution as well as in the 
vapour phase, with the formation of dichloroacetylene, which is 
highly neurotoxic and carcinogenic for animals and probably for man 
(Henschler et al., 1970a).  Chemical degradation

    The chemical degradation of trichloroethylene in water is very 
slow.  In contact with red-hot metals or a direct flame, liquid or 
vapour-phase trichloroethylene decomposes to form phosgene and 
hydrogen chloride (Waters et al., 1977).  Photochemical degradation

    Photochemical reactions initiate the degradation of 
trichloroethylene in the environment.  When exposed to UVR and 
humidity, the compound decomposes to form acids that have mean 
half-lives ranging from 6 to 12 weeks (Correia et al., 1977).  With 
an OH- concentration of the order of 106 molecules/cm3 (accepted 
mean value), a calculated half-life of trichloroethylene is around 
5 days (De More et al., 1983).  Trichloroethylene exposure to xenon 
arc lamp radiation with a wavelength greater than 290 nm, at 
constant temperature, produces carbon monoxide, carbon dioxide, 
water, hydrogen chloride, dichloroacetyl chlorides, and phosgene; 
the phosgene hydrolyses to produce carbon dioxide and hydrogen 
chloride.  Dichloroacetyl chlorides enter the hydrosphere as 
dichloroacetate anions (McConnell et al., 1975). 

Table 1.  Physical and chemical properties of trichloroethylene
Melting point (°C)         -84.8 (freeze)               Windholz et al. 

                           -87.1                        Kirk & Othmer 

                           -73.0                        CRC (1980)

Boiling point (°C)         86.7            (760 mm Hg)  Windholz et al. 

                           -43.8           (1 mm Hg)    Windholz et al. 

Table 1.  (contd.)
Specific gravity           1.46            (25/25 °C)   Snell & Hilton 

                           1.4904          (4/4 °C)     Windholz et al. 

(vapour density; air = 1)  4.53            (25 °C)      Windholz et al. 

(vapour, g/litre)          4.45            (86.7 °C)    Kirk & Othmer 

Vapour pressure (torr)     5.4             (-20 °C)     Snell & Ettre 
                           20.1            (0 °C)       Snell & Ettre 
                           57.8            (20 °C)      Snell & Ettre 
                           305.7           (60 °C)      Snell & Ettre 
Other properties:

Refraction index (nD)      1.4782          (20 °C)      Kirk & Othmer 

 (vapour)                  1.001784        (0 °C)       Kirk & Othmer 

Viscosity (cP)             0.58            (20 °C)      Kirk & Othmer 

 (vapour)                  10 300          (60 °C)      Kirk & Othmer 

Dielectric constant        3.42            (16 °C)      Kirk & Othmer 
 (epsilon)                                              (1979)

Coefficient of cubic       0.00119         (0 - 40 °C)  Kirk & Othmer 
 expansion                                              (1979)

Surface tension (dyn/cm)   26.4            (20 °C)      Kirk & Othmer 

Critical temperature (°C)  271.0                        Kirk & Othmer 

Critical pressure (atm)    49.7                         Kirk & Othmer 

Dipole moment (debye)      0.90                         Kirk & Othmer 

Table 1.  (contd.)
Heat of combustion         1.751                        Kirk & Othmer 
 (kcal/g)                                               (1979)

Heat of formation          0.999                        Kirk & Othmer 
 (kcal/mole)                                            (1979)        
 (vapour)                  -7.00                        Kirk & Othmer 

Latent heat of             57.4            (86.7 °C)    Kirk & Othmer 
 vaporization (cal/g)                                   (1979)        
Flammability flash point (°C)

under various conditions   Non-flammable under normal   Kirk & Othmer 
                           working conditions; Vapours  (1979)
                           (12.5 - 90% v/v) in poorly-  CRC (1967)
                           ventilated rooms at          
                           temperatures between 30 and  ASCHIMICI (1980)
                           82 °C may ignite if in 
                           contact with high-
                           temperature heat sources; 
                           Vapour ignites (t>25.5 °C)   Aviado et al. 
                           if mixed with pure oxygen    (1976)
                           (10.3-64.5% v/v)

ignition temp. (°C)        410                          ASCHIMICI (1980)

danger of explosion:

 limits (% v/v in air)a    8.0 - 10.5      (25.5 °C)    Kirk & Othmer 
                           8.0 - 52.0      (100 °C)     (1979)

oxidizing properties       none                         ASCHIMICI (1980)


in water (g/litre)         1.07            (20 °C)      Kirk & Othmer 

                           1.24            (60 °C)      Kirk & Othmer 

in organic solvents        completely                   Windholz et al.
                           miscible with                (1976)
                           several organic

in oil                     miscible                     Windholz et al. 

Table 1.  (contd.)
 n-octanol/water partition  Log Ko/w 2.42                Banerjee et al.
 coefficient (log)                                      (1980)

Organic carbon partition   Ko/w x 0.6                   Karickhoff et al.
 coefficient, Koc                                       (1979)

Bioconcentration factor,   Ko/w x 0.048                 Mackay (1982)
a See section

2.2.2.  Commercial trichloroethylene

    Trichloroethylene produced for chemical reagent uses has a 
minimum purity of 99.85%.  The commercial product can contain 
impurities and stabilizers as shown in Table 2. 
Table 2.  Commercial trichloroethylene: examples of 
impurities and commonly-used stabilizers
Impurities                   Stabilizers
carbon tetrachloride         pentanol-2                              
chloroform                   thymol                                  
1,2-dichloroethane           triethanolamine                         
trans 1,2-dichloroethylene   triethylamine                           
cis 1,2-dichloroethylene     2,2,4-trimethylpentene-1                
pentachloroethane            cyclohexene oxide                       
1,1,1,2-tetrachloroethane     n-propanol                              
1,1,2,2-tetrachloroethane    iso-butanol                             
1,1,1-trichloroethane         n-methyl morpholine                     
1,1,2-trichloroethane        diisopropylamine                        
1,1-dichloroethylene          n-methyl pyrrole                        
bromodichloroethylene        methyl ethyl ketone                     
perchloroethylene            epichlorohydrina                        
a Now used to a much lesser extent commercially.

    Possible impurities depend on the manufacturing route, the type 
and quality of feed stock used, the type of distillation equipment, 
and the technical specification being met.  It is uncommon for any 
individual impurity to be present at a level in excess of 100 mg/kg 
and for the total impurities to exceed 1000 mg/kg; not all the 
impurities listed would be detected in any sample. 

    Stabilizers, in the form of antioxidants or acid-receptors 
(such as phenolic, olephinic, pyrrolic, and/or oxiranic derivatives 
and aliphatic amines), are usually added in concentrations that 
normally range from 20 to 600 mg/kg.  However, in some cases, for 
limited quantities and special uses, concentrations as high as 
5000 mg/kg are added.  The stabilizers used will depend on patent 
ownership and the technical specification being met. 

2.3.  Analytical Methods

2.3.1.  Identification and purity assessment

    The degree of purity of trichloroethylene can be established by 
a number of methods, described by Snell & Ettre (1970a).  Some 
spectral features of trichloroethylene are shown in Fig. 1 - 3. 

    Trichloroethylene can be determined by the following analytical 

FIGURE 1  Colorimetry tests

    In the Fujiwara test, trichloroethylene is treated with 
pyridine in an alkaline environment.  Solution absorbance is then 
determined at 535 or 470 nm (absorptivity: 18 - 32 litre/g x cm) 
with a sensitivity of about 1 mg/kg.  This test is suitable for 
other aliphatic halogenated compounds, and so is not substance-
specific.  Other complementary colorimetric tests that may enable 
trichloroethylene to be differentiated from other similar compounds 
have been reported by Snell & Ettre (1970b). 

FIGURE 2  Infra-red spectroscopy

    In the gaseous phase, quantities are determined by measuring 
the optical density of the mixture at the selected wavelength of 
11.8 µm (847/cm).  This corresponds to a detection sensitivity of 
not less than 0.5 µg/litre (Fishbein, 1973). 

    In solutions of carbon disulfide, trichloroethylene can be 
measured, even in the presence of similar chloro derivatives, using 
the specific band at 10.8 µm (926/cm) (Snell & Ettre, 1970b; 
Fishbein, 1973).  Detection thresholds of some µg/litre can be 
attained (Fishbein, 1973).  Gas-liquid chromatography

    Generally, either packed or capillary columns (low-resolution 
or high-resolution chromatography, respectively) are used; the 
latter are recommended for complex mixtures containing substances 
similar to trichloroethylene.  A number of stationary phases can 
be used, such as paraffinic hydrocarbons (squalene, hexadecane, 
paraffin), Apiezon L, Carbowax (600, 4000, 20M), silicones (SE-30, 
550, SF-96-350), and arylphosphates.  In general, detectors such as 
argon ionization or flame ionization detectors (sensitivity: ~10 ng) 
are suitable for several types of analyses; the thermoconductivity 
detector is little used, because it is less sensitive (sensitivity: 
~250 ng).  The detection threshold drops considerably (~0.02 ng in 
air) with electron-capture detectors (ECD).  ECD response can be 
improved slightly by adding small quantities of oxygen to the 
carrier gas (Miller & Grimsrud, 1979). 

    Gas chromatography combined with mass spectrometry (GC/MS) is 
both highly selective and sensitive (Snell & Ettre, 1970b). 


2.3.2.  Determination in environmental media  Soil

    High-resolution GC (hrGC-ECD) has been used for determining 
trichloroethylene in soil (De Leon et al., 1980).  The hrGC/MS 
combination has been used as a confirmatory technique, with a 
detection threshold of ~10 mg/kg (10 ppm).  Water

    Levels of trichloroethylene in water can be determined by 
hrGC/MS (Dowty et al., 1975), by GC with an electron-capture 
detector or an electrolytic conductivity detector (Nicholson et 
al., 1977; Dietz & Singley, 1979), and by various other techniques 
such as HPLC, hrGC, GC, and GC/MS (Eklund et al., 1978; Jungclaus 
et al., 1978).  Where specified, detection thresholds are in the 
region of 1.0 µg/litre, or lower.  Air

    GC/MS can be used to measure trichloroethylene levels in the 
urban atmosphere (Ioffe et al., 1977).  Herbolsheimer et al. 
(1972), Sawicki et al. (1975), NIOSH (1977a), Heil et al. (1979), 
and Makide et al. (1979) describe sampling and sample enrichment 
techniques.  Detection capacity may be as low as some ng/m3. 

    Fujiwara's test can be used to measure trichloroethylene levels 
in air (Rush, 1970). 

    Gas detector tubes (Kitagawa, 1961), activated carbon tubes 
(NIOSH, 1977a; Shipman & Whim, 1980), and activated carbon felt 
badges (Hirayama & Ikeda, 1979) are available for use in work-place 
environments.  Gas detector tubes are suitable for spot sampling, 
while activated carbon tubes and felt are suitable for time-
weighted average concentration determinations.  Foodstuffs

    High- and low-resolution GLC can be used for the determination 
of trichloroethylene and other aliphatic chloro derivatives in 
various foodstuffs (Entz & Hollifield, 1982).  The head-space 
technique is used in all cases.  The sensitivity of the method 
appears to be higher (< 1 µg/kg) for water-rich samples than for 
fat-rich foodstuffs (10 -50 µg/kg).  The coefficient of variation 
can be lower than 20%. 

2.3.3.  Determination in human tissues and fluids

    The methods described in this section are those normally 
used to determine the levels of trichloroethylene or its major 
metabolites (trichloroacetic acid and trichloroethanol) in 
blood and urine.  These methods can be used to obtain indirect 
measurements of exposure.  There are methods for the determination 
of trichloroethylene and trichloroethanol in expired air.  Trichloroethylene

    Blood or urine is distilled or aerated.  Any trichloroethylene 
vapour present is collected in pyridine, which is then subjected to 
Fujiwara's colour test (Seto & Schultze, 1956; Tada, 1969). 

    Trichloroethylene detection and determination in blood and 
urine samples are now generally performed by GC, which has largely 
replaced colorimetric reactions.  Samples are first extracted with 
solvents, and trichloroethylene concentrations are then determined 
in the extract.  There are various modifications of this technique 
(Stewart et al., 1962; Stewart & Dodd, 1964; Kylin et al., 1967; 
Stewart et al., 1970; Ertle et al., 1972).  Because of its 
volatility, trichloroethylene can be sampled using the head-space 
method (Monster & Boersma, 1975; Triebig et al., 1976; Astrand & 
Ovrum, 1976).  This method has also been successfully coupled with 
GC/MS (Balkon & Leary, 1979). 

    GLC alone (Monster & Boersma, 1975; Astrand & Ovrum, 1976) 
and GC/MS (Barkley et al., 1980) have been used to determine 
trichloroethylene in exhaled air.  The same methods, with suitable 
sampling techniques, may also be used for the determination of 
trichloroethylene in alveolar air.  Trichloroacetic acid

    Fujiwara's colorimetry test is performed on the blood or urine 
sample extract or, in the case of urine, directly on the sample 
itself (Abrahamsen, 1960; Soucek & Vlachová, 1960; Bartonícek, 
1962; Fawns, 1968; Tanaka & Ikeda, 1968; Tada, 1969; Weichardt & 
Bardodej, 1970; Ertle et al., 1972; Kimmerle & Eben, 1973; Mantel & 
Nothmann, 1977). 

    Trichloroacetic acid can also be determined by gas 
chromatography of the extract after methylation (Ehrner-Samuel 
et al., 1973; Ogata & Saeki, 1974; Nomiyama et al., 1978; 
van der Hoeven et al., 1979), by direct methylation of the 
specimen followed by head-space sampling and GC (Monster & Boersma, 
1975; Triebig et al., 1976), or by inducing trichloroacetic acid 
decarboxylation and measuring the chloroform thus formed (Müller 
et al., 1972; Buchet et al., 1974).  Ziglio (1979) determined 
trichloroacetic acid in subjects who had absorbed trichloroethylene 
in drinking-water.  The extraction and methylation method, as well 
as the method of inducing thermal decarboxylation and then 
injecting the chloroform thus formed according to the head-space 
method, were used (sensitivity of extraction and methylation 
methods is better than 10 µg/litre).  Trichloroethanol

    Trichloroethanol is found in the free state and as the 
glucuronide (urochloralic acid) in both blood and urine.  For 
total trichloroethanol determination, the glucuronide is 
hydrolysed.  The trichloroacetic acid originally present is then 
removed and the trichloroethanol is oxidized quantitatively to 
trichloroacetic acid (Vlachov, 1957).  The trichloroacetic acid 
thus formed is then measured by one of the methods previously 
described.  Alternatively, trichloroethanol can be distilled in a 
vapour stream and measured colorimetrically on the basis of the 
condensate resulting from the reaction with pyridine and alkalis 
(Bardodej, 1962).  The colour test can also be carried out without 
prior separation of trichloroethanol from trichloroacetic acid.  
The two compounds are measured by determining absorbance at 367 or 
440 nm, and at 530 nm (Cabana & Gessner, 1967; Ogata et al., 1970; 
Mantel & Nothmann, 1977).  Trichloroethanol can also be measured by 
determining the difference between the figure obtained for the 
trichloroacetic acid level and that obtained for all trichloro-
derivatives present after quantitative oxidation to trichloroacetic 
acid (Seto & Schulze, 1956; Tanaka & Ikeda, 1968). 

    Trichloroethanol can be measured by gas chromatography after 
quantitative hydrolysis of the glucuronide (Ogata et al., 1970; 
Ertle et al., 1972; Kimmerle & Eben, 1973; Ogata & Saeki, 1974; 
Buchet et al., 1974; Nomiyama et al., 1978).  The technique of 
head-space sampling has been used by Monster & Boersma (1975), 
Triebig et al. (1976), and Balkon & Leary (1979). 

    Trichloroethanol in exhaled air can be measured directly
(Monster & Boersma, 1975).  Total trichloro derivatives

    In the Imamura & Ikeda (1973) method, urine samples are 
oxidized with chromium trioxide in heated nitric acid, allowed to 
cool, and made alkaline; pyridine is added followed by mild heating 
(Fujiwara test).  Solution absorbance is then determined at 530 nm. 

2.3.4.  Sensitivity

    Generally speaking, colorimetric test detection thresholds 
range between 0.1 and 1 mg/kg.  Greater sensitivity is provided by 
gas chromatography, which has detection thresholds of between 10 
and 100 µg/kg for trichloroethylene, trichloroacetic acid, and 


    Trichloroethylene does not occur naturally. 

    It was first synthesized by Fisher in 1864 and became 
commercially available for the first time in 1908 in Austria and in 
the United Kingdom (Kirk & Othmer, 1964). 

3.1.  Production Processes, Levels, and Uses

3.1.1.  Production processes and levels

    Trichloroethylene is produced by three processes:  the 
dehydrochlorination of  sym-tetrachloroethane, the high-temperature 
oxychlorination of chlorinated products with one or two carbon 
atoms, or the chlorination of ethylene. 

    In Western Europe, production was approximately 250 000 tonnes 
in 1978.  The major producing countries are the Federal Republic of 
Germany, France, whose individual production capacity is of the 
order of 100 000 tonnes, Italy, and the United Kingdom.  Sweden 
and Spain are smaller producers.  In the USA the production of 
trichloroethylene in 1979 was 130 000 tonnes (US ITC, 1980).  In 
Japan, the annual production was approximately 74 500 tonnes in 
1981 and 67 500 tonnes in 1982 (Japanese Yearbook of Chemical 
Industries Statistics, 1983). 

3.1.2.  Uses

    Trichloroethylene is an industrial solvent mainly (85 - 90%) 
used for the vapour degreasing and cold cleaning of fabricated 
metal parts.  Trichloroethylene has also been used as a carrier 
solvent for the active ingredients of insecticides and fungicides; 
as a solvent for waxes, fats, resins, and oils; as an anaesthetic 
for medical and dental use; and as an extractant for spice 
oleoresins and for caffeine from coffee.  Trichloroethylene has 
been used in printing inks, varnishes, adhesives, paints, lacquers, 
spot removers, rug cleaners, disinfectants, and cosmetic cleansing 
fluids.  It may also be used as a chain terminator in polyvinyl 
chloride production and as an intermediate in the production of 
pentachloroethane (Defalque, 1961; Kirk & Othmer, 1963, 1979; 
Wetterhahn, 1972; Valle-Riestra, 1974; US CFR, 1976; Waters et al., 
1977; IARC, 1979). 

3.2.  Handling Hazards, and Precautions

3.2.1.  Handling hazards  Fire, explosion, and thermal decomposition

    At normal handling temperatures, trichloroethylene behaves 
as a non-flammable, non-burnable substance.  Under normal 
conditions, it is virtually impossible to induce an explosion with 
trichloroethylene.  In the presence of air, at temperatures above 
400 °C, it produces phosgene, hydrochloric acid, and carbon 

monoxide.  In the vicinity of arc welding, phosgene and hydrogen 
chloride can be produced from trichloroethylene.  In vapour 
degreasing, using combustion heaters, precautions must be taken to 
prevent solvent fumes from entering the combustion air.  Containers 
of trichloroethylene exposed to fire should be cooled by sprinkling 
with water.  Chemical reactivity

    Trichloroethylene is practically non-reactive with water at 
room temperature, under normal storage conditions, and the 
stabilized product does not undergo any changes in the presence of 
air, humidity, light, or in contact with metals.  It is, however, a 
wise precaution not to expose the product to temperatures exceeding 
130 °C. 

    In the presence of strong alkalis, particularly if heated, 
trichloroethylene produces dichloroacetylene (Reichert et al., 
1980a), which is highly reactive and acutely neurotoxic to both 
animals and man (Reichert & Henschler, 1978).  Dichloroacetylene 
is also potentially carcinogenic (Reichert et al., 1980b).  Under 
normal circumstances in industrial use, this reaction is unlikely.  
However, under occasional laboratory conditions and closed-circuit 
anaesthesia, in the presence of soda lime, some dichloroacetylene 
may be produced. 

    Dichloroacetylene may be formed from trichloroethylene by a 
reaction catalysed by ionic halides in the presence of certain 
epoxides, including epichlorohydrin (Dobinson & Green, 1972). 

    Non-stabilized trichloroethylene can react violently with 
aluminium (especially in the form of dust or filings) giving off 
hydrogen chloride and hexachlorobutene vapour (McNeill, 1979).  
Not all stabilizers are effective in preventing the reaction with 
aluminium; therefore, a suitably-stabilized product should be used 
when cleaning aluminium, especially ultrasonically or where 
aluminium particles are present. Suitable products are identified 
in manufacturers' literature or in specifications. 

3.2.2.  Handling precautions  Personal safeguards

    Accidental exposure to trichloroethylene under occupational 
conditions is more frequently associated with the generation of 
dense trichloroethylene vapour, e.g., misoperation of vapour-
degreasing apparatus (Sagawa et al., 1973) or the use of liquid 
trichloroethylene for cleaning the inside of a tank. 

    Individual protective measures should be related to the type 
and level of exposure.  When significant skin contact is likely, 
suitable protective clothing should be worn, bearing in mind the 
limitations of such clothing and the need to maintain it properly 
and replace it regularly.  To control exposure through inhalation, 
the use of full face masks with filters for organic vapours 

(basically for short-term or emergency use), self-contained 
breathing apparatus, or masks with air-line supply systems may be 
necessary.  Self-contained breathing apparatus should always be 
available for use in emergencies.  Storage

    Trichloroethylene can be safely stored in carbon steel or 
stainless steel containers.  It should not be kept in aluminium, 
aluminium alloy, or galvanized iron containers; plastic containers 
should not be used unless they are known to be suitable for the 
storage of trichloroethylene.  Storage areas should be cool, well-
ventilated, flame-proof, and shielded from direct sunlight, high-
temperature surfaces, or sparks.  Trichloroethylene should not be 
stored near food-stuffs, strong acids, alkalis, or oxidizing 

3.2.3.  Recovery

    Used trichloroethylene can readily be recovered by 
distillation.  Trichloroethylene vapours in the aspiration ducts 
of plants can be recovered by adsorption on activated carbon and 
subsequent desorption. 

3.2.4.  Disposal

    Where trichloroethylene is not recovered and recycled, it may 
be disposed of by incineration.  Incinerators must be properly 
operated, at a sufficiently high temperature and for an adequate 
period of time, to ensure complete combustion and prevent the 
formation of other toxic chlorinated compounds.  The incinerator 
should incorporate a suitable scrubber to remove the acidic 
breakdown products. 

3.2.5.  Emergency measures in case of accidental spills

    The spilt liquid should be contained with earth, sand, or other 
inert adsorbent material to prevent it from spreading. 

    If possible, remove damaged containers to an isolated and well-
ventilated area, preferably outside, or transfer contents to 
another container by mechanical pumping. 

    Wash away small leaks with water, taking appropriate measures 
to avoid creating environmental pollution problems. 

    When necessary, the contaminated area should be marked off 
until the risk of dangerous concentrations in the air has been 

3.2.6.  Occupational exposure

    Trichloroethylene is a widely-used industrial solvent and 
degreasing agent.  During production, exposure is relatively low 
and can be controlled, but users of trichloroethylene may be 

exposed to higher levels and under relatively uncontrolled 
conditions depending on the type of operation involved.  A WHO 
Study Group has recommended a time-weighted average exposure not 
exceeding 135 µg/m3 with a ceiling limit value of 1000 mg/m3 for 
not more than 15 min (WHO Study Group on Recommended Health-Based 
Limits in Occupational Exposure to Selected Organic Solvents, 
1981).  Some national occupational exposure limits are listed in 
Table 3. 

Table 3.  Occupational exposure limits used in various 
Country            Exposure  Limit     Category
                   (ppm)     (mg/m3)   of limit
Australia          100       535       TWAb

Austria            50        260       TWA

Belgium            100       535       TWA

Bulgaria           2         10        TWA

Czechoslovakia     47        250       TWA
                   235       1250      CVc

Egypt              50        267       TWA

Finland            50        260       TWA

France             75        405       TWA
                   200       1080      CV

German Democratic  47        250       TWA
 Republic          141       750       STd (30 min)

Germany, Federal   50        260e      TWA(MAK)
 Republic of

Hungary            10        50        TWA

Italy              75        400       TWA
                   200       1000      skin irritation

Japan              50        268       TWA

Netherlands        35        190       TWA

Poland             10        50        CV

Romania            37        200       TWA
                   55        300       CV

Spain              100       535       TWA

Table 3.  (contd.)
Country            Exposure  Limit     Category
                   (ppm)     (mg/m3)   of limit
Sweden             20        110       TWA
                   50        250       ST (15 min)

Switzerland        50        260       TWA

United Kingdom     100       535       TWA


 a) OSHA/NIOSH     100       536       TWA
                   200       1072      ST (5 min)
                   300       1608      CV
                   1000      5350      IDLHf

 b) ACGIHg         100       535       TWA
                   150       800       ST (15 min)

USSR               2         10        CV

Yugoslavia         50        200       TWA
a From:  ILO (1980) and IRPTC (1984).
b TWA (time-weighted average):  a mean exposure limit 
  averaged generally over a working day whereby, within 
  prescribed limits, excursions above the level 
  specified are permitted, provided they are compensated 
  for by excursions below the limit specified.
c CV (ceiling value):  a maximum allowable concentration 
  that must not be exceeded at any time.
d ST (short-term exposure limit):  a maximum 
  concentration allowed for a short specified duration.
e Suspected carcinogen.
f IDLH (immediately dangerous to life and health):  a 
  maximum level from which escape is possible within 
  30 min without escape-impairing symptoms or any 
  irreversible health effects.
g Notice of intended change to TWA 270 mg/m3 (50 ppm) 
  and ST 805 mg/m3 (150 ppm).

 Note:  Occupational exposure levels and limits are derived in 
       different ways, possibly using different data and expressed 
       and applied in accordance with national practices.  These 
       aspects should be taken into account when making 


4.1.  Environmental Levels

4.1.1.  Soils and sediments

    Trichloroethylene has been found in concentrations exceeding 
100 µg/kg in soils and sediments near production sites (IARC, 
1979).  However, samples taken further away from production sites 
show lower levels:  for example, in Liverpool Bay, United Kingdom, 
which is near an urban and industrialized area, concentrations in 
sediments ranged from a few ng/kg to 10 µg/kg (Pearson & McConnell, 
1975).  An organic-rich anoxic marine sediment from the 
Pettaquamscutt River in Rhode Island, USA, where there were no 
obvious local sources of trichloroethylene, contained 
concentrations ranging from undetectable to 70 µg/kg dry weight 
(Whelan et al., 1983).  Trichloroethylene was concentrated in the 
upper part of the sediment core, corresponding to the period from 
about 1940 to the present (determined by 210Pb dating).  The 
authors noted that the compound had been in use only since the mid-

    No relationship between trichloroethylene concentration and 
particle size or organic matter in sediments, as noted for higher 
hydrocarbons such as the DDT group (Pierce et al., 1974), has been 

4.1.2.  Water

    Trichloroethylene is widely distributed in surface water, 
rain-water, well water, and drinking-water from various sources.  
Chemical industry discharges may contain concentrations up to 
200 µg/litre (Eurocop-Cost, 1976); some Milan well waters contain 
high concentrations (80 µg/litre) because of pollution (Cavallo & 
Grassi, 1976; Ziglio et al., 1983).  However, most reported levels 
in water are below this, and are usually in the range of 10 - 
100 µg/litre (Rook et al., 1975; Ewing et al., 1977).  Rain-water 
has been reported to contain concentrations in the µg/litre range 
(McConnell et al., 1975) and sea water from Liverpool Bay, United 
Kingdom contained a mean concentration of 0.3 µg/litre (Pearson & 
McConnell, 1975).  This lower range has also been reported in some 
Japanese rivers (EAJ, 1983) and in some well water in the USA 
(Coleman et al., 1976).  Even lower concentrations (7 - 11 
ng/litre) have been reported for northeast Atlantic surface water 
(Murray & Riley, 1973). 

    While trihalomethanes are produced during the chlorination of 
natural waters containing humic substances, there are no data 
indicating that trichloroethylene is produced in this way (Bellar 
et al., 1979; Bauer & Selenka, 1982; Otson et al., 1982).  However, 
treatment of sewage effluent resulted in a small increase in the 
trichloroethylene level (Bellar et al., 1979).  Trichloroethylene 
was found in drinking-water when the original raw water source was 
contaminated or when the liquid chlorine used for water treatment 

contained trichloroethylene as an impurity.  It is also an 
intermediate in the breakdown of tetrachloroethylene in some 
groundwater systems (Parsons et al., 1984). 

    Because data for carcinogenicity are inadequate for evaluation, 
a tentative guideline value of 30 µg/litre in drinking-water has 
been recommended by the World Health Organization (WHO, 1984). 

4.1.3.  Air

    The distribution of trichloroethylene in the atmosphere has 
been studied intensively, because of its possible contribution to 
depletion of the ozone layer (Lovelock, 1974) (section 7.3). 

    Air concentrations are in the µg/m3 range (Lovelock, 1974; 
Pearson & McConnell, 1975; Cronn et al., 1977; Singh et al., 1977; 
Rasmusson et al., 1983).  Murray & Riley (1973) reported much lower 
concentrations, in the ng/m3 range, in rural areas or from sea 
stations; one urban sample (Liverpool) contained 0.85 µg/m3.  In 
general, higher levels are found near industrialized areas (Pearson 
& McConnell, 1975; Ohta et al., 1976; Correia et al., 1977; Ziglio 
et al., 1983). 

    Data describing the partition of trichloroethylene between the 
gaseous and particulate phases in the atmosphere are not available. 

4.1.4.  Biota

    Pearson & McConnell (1975) have described trichloroethylene 
concentrations in marine organisms from Liverpool Bay, United 
Kingdom which is fairly close to an urban and industrialized 
region.  Concentrations ranged from a few ng/g to about 100 ng/g 
wet weight.  There was no obvious correlation between concentration 
and trophic level.  Typical background concentrations are probably 
around 10 ng/g wet weight. 

    Other studies have shown the presence of trichloroethylene in 
marine organisms such as invertebrates (1 µg/kg wet weight), fish 
muscle (10 µg/kg), sea-bird eggs (50 µg/kg), and seal fat 
(50 µg/kg) (Pearson & McConnell, 1975). 

    Pearson & McConnell (1975) analysed samples of marine organisms 
mainly, but not exclusively, from areas near a region where major 
organochlorine production plants were situated.  Less than 15 µg/kg 
wet weight was found in fish muscle (plaice, dab, mackerel).  
Values in sea-bird eggs ranged from 2.4 µg/kg for  Phalacrocorax 
 aristotelis (shag) to around 30 (23 - 33) µg/kg for  Alca torda  
(razorbill),  Uria aalge (guillemot), and  Rissa tridactyla  
(kittiwake).  Seal  (Halichaerus grypus) blubber and liver from the 
Faroe Islands had values ranging from 2.5 to 7.2 µg/kg. 

4.1.5.  Food

    Trichloroethylene may be present in foodstuffs as a residue 
from its use as a solvent in food processing or as the result of 
environmental contamination.  A study conducted by McConnell et al. 
(1975) provided a table of the trichloroethylene contents of some 
common foodstuffs (Table 4). 

Table 4.  Trichloroethylene in major foodstuffsa
Foodstuff                  Concentration
Dairy foods:

 fresh milk                0.3
 Cheshire cheese           3
 English butter            10
 eggs                      0.6


 shin of beef              16
 adipose tissue of beef    12
 pig liver                 22

Oils and fats:

 margarine                 6
 olive oil (Spanish)       9
 cod liver oil             19
 vegetable oil for frying  7


 fruit juices              5
 light beer                0.7
 freeze-dried coffee       4
 tea in bags               60
 wine (Yugoslav)           0.02

Fruit and vegetables:

 potatoes                  3
 apples                    5
 pears                     5


 fresh bread               7
a From:  McConnell et al. (1975).

    In some cases, upper tolerable limits for trichloroethylene 
concentrations have been set; for instance, 25 mg/kg dry weight 
in powdered decaffeinated coffee, 10 mg/kg dry weight in instant 
coffee, and 30 mg/kg dry weight in spice oleoresins.  The US FDA 
has proposed the prohibition of the use of trichloroethylene in 
foodstuffs.  The progress of this proposal depends on the 
completion of long-term toxicology and carcinogenicity studies 
that are being carried out.  Before 1976, the US FDA prescribed 
tolerance level for trichloroethylene in decaffeinated ground 
coffee was 25 mg/kg dry weight (US CFR, 1976). 

    Trichloroethylene has been reviewed on a number of occasions 
by the Joint FAO/WHO Expert Committee on Food Additives, most 
recently in 1983.  An acceptable daily intake (ADI) has not been 
allocated.  The Joint Expert Committee recommended that the use of 
trichloroethylene as an extraction solvent should be limited, in 
order to ensure that its residues in food are as low as practicable 
(Joint FAO/WHO Expert Committee on Food Additives, 1983). 

4.2.  Environmental Distribution and Transport

4.2.1.  Equilibrium distribution

    The distribution of trichloroethylene, which is observed in 
various environmental "compartments", is similar to that which 
would be expected from a consideration of its physical and chemical 
properties (cf. Appendix I).  The relatively high vapour pressure 
at normal environmental temperatures should lead to appreciable 
atmospheric concentrations; this tendency will balance the tendency 
of relatively high water solubility and low Po/w to lead to high 
water, biota, or sediment concentrations through either partition 
or adsorption.  The tendency of trichloroethylene to enter the 
atmosphere is demonstrated further by its rapid evaporation from 
water; its evaporation half-life is approximately 20 min at 25 °C 
(Dilling, 1977). 

4.2.2.  Transformation in the environment

    Recent studies on the degradation of trichloroethylene in 
various environmental compartments are discussed below.  Air

    The main removal reaction appears to be that of attack by the 
tropospheric hydroxyl radical (Penkett, 1982), the steady-state 
concentrations of which are around 4 x 105/cm3 (Graedel, 1978).  
The decay of trichloroethylene is a function of the rate of its 
(bimolecular) reaction with the hydroxyl radical (Graedel, 1978), 
which is about 2.4/1012 cm3 per molecule per second at 25 °C 
(Howard, 1976).  This leads to a calculated reaction rate of 
approximately 4/103 per h, with the calculated lifetime of 
trichloroethylene in the atmosphere of around 11 days (Graedel, 
1978).  A half-life of the order of 5 days has been calculated by 

(De More et al., 1983).  Singh et al. (1977) reported a half-life 
of less than 2 days in a smog chamber.  Pearson & McConnell (1975), 
using unrealistically high concentrations of trichloroethylene in 
quartz flasks, estimated its half-life to be 11 weeks.  Soils and sediments

    When methanogenic bacterial batch cultures were exposed to 
low concentrations of trichloroethylene (simulating conditions in 
an organic-rich sediment or in a sewage treatment system), at 
35 °C, for 8 weeks, trichloroethylene concentrations were reduced 
by about 40% (Bouwer & McCarty, 1983).  If it is assumed that the 
reaction rate is halved with every 10 °C drop in temperature, this 
corresponds to an exponential decay rate (first order with respect 
to trichloroethylene) of about 2/104 per h at 15 °C.

    In a study on a laboratory fresh water-sediment system, it was 
concluded that trichloroethylene, formed by biotransformation from 
tetrachloroethylene, was itself biotransformed to chloroethane, 
cis- and trans-1,2-dichloroethene, and dichloromethane (Parsons et 
al., 1984).  Water

    Wakeham et al. (1982) measured a trichloroethylene exponential 
decay rate in a sea-water mesocosm of approximately 2.5/102 per day 
at 8 - 16 °C, which is equivalent to a rate of about 1/103 per h.  
This is similar to the rate described by Bouwer & McCarty (1983) 
for microbial degradation.  Pearson & McConnell (1975) measured a 
chemical degradation rate, in sealed bottles, which led to a half-
life estimate of 2.5 years.  Biota

    The only data available refer to the degradation of 
trichloroethylene in a soil-plant system (Klozskowski et al., 
1981) in which the rate of trichloroethylene loss was 10% per week.  
This was accounted for mainly by conversion to carbon dioxide, but 
with some evaporation of organic compounds.  This corresponds to an 
exponential decay rate of about 6/103 per h, which is about 10 
times the microbial decay rates. 


5.1.  Absorption

    Trichloroethylene absorption in mammals can take place by the 
respiratory, oral, and/or dermal routes.  Intraperitoneal uptake 
has been demonstrated experimentally. 

5.1.1.  Inhalation exposure

    In all the mammalian species studied, trichloroethylene uptake 
is high during the first minutes of exposure.  It then decreases 
until equilibrium is reached between uptake by the blood and 
release from the blood to tissues, and by metabolism.  After 
equilibrium is reached, uptake remains constant for the remainder 
of exposure (Fernandez et al., 1975; Monster et al., 1976). 

    In human beings, the blood/air partition coefficient ranges 
from 9 to 15.  Daily body uptake has been estimated to be 
approximately 6 mg/kg body weight, for an exposure of 4 h at 
378 mg/m3 (70 ppm), and does not seem to be greatly influenced 
by the quantity of adipose tissue (Monster et al., 1976, 1979; 
Monster, 1979).  Trichloroethylene retention varies according to 
physical activity.  Under laboratory conditions, when human 
volunteers at rest were exposed to concentrations of 540 or 
1080 mg/m3 (100 or 200 ppm), for 30 min, 50% of the quantity 
inhaled was retained.  The percentage retained decreased from 50 
to 25%, when activity rose from rest to a 150-watt work load, but, 
because of increased ventilation, the absolute amount absorbed 
still increased (Astrand & Ovrum, 1976). 

5.1.2.  Oral exposure

    Uptake via the oral route is high because of the ease with 
which trichloroethylene penetrates the gastrointestinal barrier.  
In man, oral intake is a frequent cause of acute poisoning (Waters 
et al., 1977). 

5.1.3.  Dermal exposure

    In the mouse, dermal absorption increases linearly at a 
constant rate with duration of exposure.  For exposure periods of 
between 15 min and 5 h, absorption rates ranged from 59.8 to 
92.4 nmol/min per cm2 (Tsuruta, 1978). 

    Trichloroethylene applied to the backs of guinea-pigs (glass 
depot containing at least 1.0 ml) was absorbed and produced blood 
concentrations of 0.79 mg/litre after 0.5 h and decreased to 
0.46 mg/litre after 6 h, in spite of continuing exposure (Jakobson 
et al., 1982). 

    When one hand of each of 4 human male volunteers was immersed 
in trichloroethylene for 30 min, Sato & Nakajima (1978) found blood 
concentrations of trichloroethylene (samples taken from unexposed 
arm) of 2 mg/litre, immediately after the end of immersion, 

0.34 mg/litre, after 30 min, and 0.22 mg/litre, after 60 min.  
The trichloroethylene concentration in the expired air was 
0.28 mg/litre, 5 min after the end of immersion, 0.06 mg/litre, 
30 min after, and 0.024 mg/litre 60 min after. 

    On the basis of these data and the results of earlier studies 
by Stewart & Dodd (1964), it is thought unlikely that 
trichloroethylene would be absorbed in toxic quantities through 
intact skin during normal industrial use. 

5.2.  Distribution and Storage

    After absorption, trichloroethylene is concentrated in the 
cellular components but disappears rapidly (Fabre & Truhaut, 1952).  
This rapid disappearance occurs because substantial amounts of 
trichloroethylene are metabolized during and after exposure 
(Monster, 1979).  Trichloroethylene reaches the tissues via the 
blood system and accumulates, particularly in adipose tissue, 
because of its high liposolubility.  The oil/blood partition 
coefficient is approximately 750 (Droz & Fernandez, 1977; Sato & 
Nakajima, 1979).  Trichloroethylene crosses the placental barrier 
readily and has been found in fetal blood (Laham, 1970).  It 
was detectable in the fetus in 2 min, and a fetal/maternal 
concentration equilibrium ratio of 1:1 was reached in 6 min (La Du 
et al., 1971).  Data on the distribution of trichloroethylene in 
the tissues of some animal species (including human beings) are 
available but, because of the differences in treatment, comparative 
conclusions are not possible.  Trichloroethylene concentrations 
found in various organs and tissues from guinea-pigs, rats, and 
human beings are listed in Table 5. 

5.3.  Metabolic Transformation

5.3.1.  Animals

    Trichloroethylene is metabolized primarily in the liver and, 
to a much lesser extent, in other tissues.  Metabolism is by the 
mixed-function oxidase system and is dependent on cytochrome P 450.  
Qualitative differences between species do not seem particularly 
significant with the exception of dichloroacetic acid formation, 
which appears to be specific for the mouse (Hathway, 1980; Green & 
Prout, in press).  The major mammalian metabolites are free and 
conjugated trichloroethanol and trichloroacetic acid.  Other 
metabolites include 2-hydroxyacetylethanolamine and oxalic acid 
(Dekant & Henschler, 1982; DeKant et al., 1984).  Metabolism is 
illustrated in Fig. 4. 

    Quantitative differences in the rates of metabolism in 
different species are much more significant.  Mice metabolize 
trichloroethylene to a much greater extent than rats (Stott et 
al., 1982).  It is possible to saturate the metabolism of 
trichloroethylene in the rat, but not in the mouse, at doses up to 
2000 mg/kg body weight (Anderson et al., 1980).  Mice also produce 
more reactive tissue-binding metabolites than rats in the liver and 
the kidney (Stott et al., 1982). 

Table 5.  Tissue distribution of trichloroethylene in 
(A) guinea-pigs and rats following exposure to the 
compound, and (B) in human tissues obtained at autopsy
(levels of exposure not specified)
                    (A)                     (B)                   
Organs or   Guinea-  Ratsb         Human beingsa
tissues     pigsa                  d          e
            (mg/kg)  (mg/kg)          (µg/kg)
adrenals    22       -             -          -
blood       5        0.9           -          -
brain       9        1.0 (1.2)c    1          -
fat         39       9.9           8.2 (32)   4.9 (11.7)
            -        -             -          7.8 (42.2)f
kidney      14       -             2.0        -
liver       10       0.3           4.1 (5.8)  2.5
lung        7        0.7           -          2.2
muscle      2        -             -          2.4 (156.6)
ovary       23       -             -          -
spleen      13       -             -          -
a From:  Fabre & Truhaut (1952), 6045 mg/m3 (1120 ppm) 
  x 5 h per day x 19 days.
b From:  Savolainen et al. (1977), 1080 mg/m3 (200 ppm) 
  x 6 h/day x 5 days).
c Cerebellum value.
d From: McConnell et al. (1975). Mean of 8 subjects aged 
  48 - 52 years.
e From: Bauer (1981). Mean of 15 subjects (Figures in 
  parentheses are maximum values).
f Fat from kidney capsule.


    Metabolically activated trichloroethylene binds covalently to 
the hepatic microsomal proteins and DNA,  in vitro.  This finding 
supports the formation of an epoxide intermediate (Banerjee & Van 

Duuren, 1978), though this has not been demonstrated  in vivo  
(Parchman & Magee, 1982; Stott et al., 1982). 

5.3.2.  Human beings

    As originally suggested by Powell (1945), the formation of the 
epoxide, an intermediate reactive metabolite that binds covalently 
with proteins (Bolt & Filher, 1977), has been confirmed by indirect 
spectral evidence (Uehleke et al., 1977).  The epoxide may undergo 
intramolecular rearrangement in 2 different ways (Henschler & Hoos, 
1982; DeKant & Henschler, 1983).  One pathway leads to chloral 
(Henschler, 1977a,b), which is further oxidized to trichloroacetic 
acid (TCA), or reduced to trichloroethanol (Leibman, 1965).  After 
oral administration, trichloroethanol is also partly metabolized 
into TCA (Müller et al., 1974).  Trichloroethanol is rapidly 
conjugated with glucuronic acid to form the respective glucuronide.  
The other pathway leads to the formation of dichloroacetyl chloride 
which, under  in vitro conditions, can lead to the formation of 
dichloroacetic acid.  However, under normal  in vivo conditions, 
dichloroacetic acid is not found, except in mice following the 
administration of very high doses of trichloroethylene.  Under 
these conditions, an "overspill" mechanism may operate (Henschler 
et al., 1979; Hathway, 1980; Henschler et al., 1983).  The 
excretion of chloroform in expired air and monochloroacetic acid in 
urine have also been proposed as minor routes of metabolism (Ogata 
& Saeki, 1974; Bartonicek, 1962).  Miller & Guenrich (1982) 
suggested that an epoxide was not an obligatory intermediate step 
and proposed an alternative model in which chlorine migration 
occurs in an oxygenated trichloroethylene P 450 transition state. 

    Trichloroacetic acid binds well with plasma proteins and its 
concentration in plasma is approximately double that in whole blood 
(Müller et al., 1972). 

5.3.3.  Drug and other interactions

    A number of commonly-used drugs might be expected to modify the 
extent of metabolism of trichloroethylene during human exposure.  
Although largely undocumented in man, the induction of the hepatic 
microsomal mixed-function oxidase system by drugs, taken for 
therapeutic reasons, or by exposure to certain environmental 
chemicals (e.g., phenobarbital, toluene, PCBs) can bring about an 
increased rate of trichloroethylene metabolism (Ikeda & Imamura, 
1973; Ikeda, 1974). 

    In human beings, the simultaneous administration of ethanol and 
trichloroethylene (100 mg/m3 for 6 h) causes an increase in 
trichloroethylene levels in both plasma (2.4 times the normal 
value) and in exhaled air (3.4 times), and a decrease in the levels 
of trichloroacetic acid and trichloroethanol (Müller et al., 1975). 

5.4.  Elimination

5.4.1.  Studies on animals

    The kinetics of the distribution and elimination of 
trichloroethylene, administered intravenously in Wistar rats at 
dose levels of 6, 9, 12, or 15 mg/kg body weight show that the 
blood concentration exhibits a first order, 2-compartment model 
exponential disappearance, and it has been suggested that a dose 
of 15 mg trichloroethylene/kg body weight is within the hepatic 
metabolic capacity in the rat (Withey & Collins, 1980).  Daniel 
(1963) showed that when trichloroethylene was administered orally 
to rats, the ratio of pulmonary to urinary elimination varied with 
the dose and that as dose increased, pulmonary excretion increased 
while urinary elimination decreased.  Further evidence showing that 
the metabolism of trichloroethylene is saturable in Wistar rats was 
obtained by Filser & Bolt (1979) who showed that the saturation 
point occurred at 350 mg/m3 (65 ppm), that the zero order Vmax was 
210 µmol/h per kg body weight and that the first order clearance at 
a dose of 350 mg/m3 (65 ppm) was 77 µmol/h per kg body weight.  
Stott et al. (1982) found that the pulmonary elimination of 
unchanged trichlorethylene in Osborn Mendel rats was only 2% of the 
dose at 54 mg/m3 (10 ppm), but 21% at a dose of 3240 mg/m3 
(600 ppm).  In contrast to these findings of a saturable process in 
the rat, The same authors showed that in the mouse, doses of 
trichloroethylene up to 3240 mg/m3 (600 ppm) were completely 

    In dogs, exposed through inhalation, for 1 h, to 
trichloroethylene at 3780, 8100, and 10 800 mg/m3 (700, 1500, and 
2000 ppm), the excretion of trichloroethylene and trichloroacetic 
acid was correlated with the trichloroethylene concentration.  The 
rate of trichloroacetic acid excretion was higher than that for 
trichloroethanol.  One hour after exposure ended, the percentage 
of trichloro compounds in the urine was 0.7% of the total 
trichloroethylene absorbed (Hobara et al., 1983). 

5.4.2.  Studies on man

    It has been shown that man metabolizes trichloroethylene 
extensively.  Ikeda et al. (1972) showed that the capacity of 
workers to metabolize trichloroethylene was nonlimiting, at least 
up to a daily exposure level of 945 mg/m3 (175 ppm) for 8 h. 

    In human beings, trichloroethylene is eliminated unchanged 
through the lungs and is eliminated in the urine in the form of 
metabolites.  Elimination by other routes (e.g., faeces, sweat, and 
saliva) accounts for less than 10% of the total (Bartonicek, 1962). 

    After inhalation exposure, about 10% of the amount absorbed is 
expired unchanged, about 30 - 50% is excreted as trichloroethanol 
in urine, and about 10 - 30% as trichloroacetic acid in urine 
(Soucek & Vlachova, 1960; Bartonicek, 1962; Monster et al., 1976, 

    The half-life of trichloroethylene in exhaled air and in the 
blood depends on the length of exposure and on the time of sampling 
after exposure.  The concentration follows a multi-exponential 
curve, compatible with at least 3 compartments:  lungs, blood and 
most other tissues, and adipose tissue.  After a single exposure 
to trichloroethylene, trichloroethanol reaches its maximum 
concentration in blood and urine almost directly after exposure.  
Thereafter, the concentration decreases, with a half-life of 
about 10 - 15 h (Müller et al., 1974; Monster et al., 1976, 
1979; Vesterberg et al., 1976).  After a single exposure to 
trichloroethylene, the concentration of trichloroacetic acid in 
both the blood and the urine increases for up to 20 - 40 h after 
exposure.  Thereafter, the concentration decreases with a half-life 
of about 70 - 100 h (Müller et al., 1974; Monster et al., 1979).  
Trichloroacetic acid, as such, has a shorter half-life of about 
50 h. 

    In a group of workers with long-term exposure to 
trichloroethylene at a concentration of 270 mg/m3 (50 ppm), median 
values of trichloroethanol and trichloroacetic acid of 330 and 
319 g/kg creatinine, respectively, were found at the end of a 
working shift; during the work-free periods, the metabolites of 
trichloroethylene were eliminated slowly (Triebig et al., 1976). 

    In a study on factory workers exposed to trichloroethylene, 
Ikeda & Imamura (1973) observed a half-life of 41 h for the 
urinary excretion of total trichloro-compounds (i.e., a combination 
of trichloroacetic acid and trichloroethanol).  This half-life is 
somewhat longer with oral administration of trichloroethylene and 
of chloral hydrate and is about 85 - 99 h after repeated exposure 
to trichloroethylene, because of the delayed formation of 
trichloroacetic acid from trichloroethylene and the 
trichloroethanol still available from the tissues (Müller et al., 
1974).  Thus, trichloroacetic acid will be found in the urine, even 
when trichloroethanol is no longer detectable (Ikeda et al., 1971).  
Trichloroacetic acid accumulates in the blood and urine during 
daily exposures to trichlorethylene (Monster et al., 1979; Müller 
et al., 1975). 

5.5.  Biological Monitoring of Exposure

    Droz & Fernandez (1978) used a mathematical model to study the 
effects of hourly and daily variations in exposure concentrations 
on alveolar air trichloroethylene concentrations and on the urinary 
excretion of trichloroethanol and trichloroacetic acid.  The 
determination of trichloroethanol in urine appeared to be more 
sensitive than the determination of trichloroethylene in exhaled 
air.  The excretion of trichloroacetic acid can be used for the 
qualitative evaluation of the preceding day's exposure.  In 
practice, blood analysis would be preferable to analysis of urine, 
because of the smaller individual variations generally observed 
with the former.  In studies concerning repeated exposure to 
constant concentrations, the smallest inter-individual variation 
was found in the concentrations in blood (Monster et al., 1979). 

    The measurement of total trichloro compounds in urine was 
described by Takana & Ikeda (1968).  The urinary trichloroethanol 
is oxidized to trichloroacetic acid and the total amount of 
trichloroacetic acid is then measured with the Fujiwara reaction.  
In the case of exposure to relatively steady concentrations, this 
has the advantage of being able to indicate small-scale inter-
personal variations.  It may be used as an index of exposure 
intensity, especially when the urine samples are collected at, 
or close to, the end of the workshift at the end of the work week 
(Ikeda et al., 1972).  However, other studies have demonstrated 
poor individual correlation between trichloroethylene exposure and 
the urinary elimination of the major metabolites, trichloroacetic 
acid and trichloroethanol (Boudène et al., 1983).  Separate 
measurement of urinary metabolites provides more information on 
exposure to daily fluctuating concentrations, because relatively 
high concentrations of trichloroethanol indicate recent high 
exposure, whereas relatively high concentrations of trichloroacetic 
acid indicate long-term exposure to high concentrations (Monster et 
al., 1979). 

    Trichloroethylene concentrations in alveolar air and in blood, 
shortly after exposure, indicate recent exposure concentrations, 
while the concentration several hours after exposure indicates the 
average exposure over the preceding days (Stewart et al., 1974). 


6.1.  Effects on Animals

    Data from acute, short-term repeated dose, and long-term 
toxicity studies on laboratory animals are summarized in Table 6. 

6.1.1.  Acute toxicity

    Acute toxicity data on common laboratory animals are shown in 
Tables 7 and 8. 

    Acute toxicity levels following inhalation exposure to 
trichloroethylene are summarized in Table 7.  Table 8 includes data 
on acute oral, dermal, intraperitoneal (ip), subcutaneous (sc), and 
intravenous (iv) LD50s for the mouse, rat, rabbit, and dog. 

    Von Oettingen (1955) reported that oral acutely toxic doses in 
rats produced gastrointestinal irritation.  Moderate increases in 
aspartate aminotranferase (EC levels were observed in rats 
24, 48, and 72 h after a single 6-h exposure to trichloroethylene 
vapour at concentrations of 54 mg/m3 (10 ppm) and 540 mg/m3 
(100 ppm) (Deguchi, 1972); the increase at 5400 mg/m3 (1000 ppm) 
was small (Deguchi, 1972), presumably due to inactivation of P-450.  
According to Rigaud et al. (1977), intraperitoneal administration 
resulted in a significant increase in aspartate aminotransferase 
(EC, alanine aminotransferase (EC, and ornithine 
carbamoyltransferase (OCT) (EC in the rat, whereas 
Wirtschafter & Cronyn (1964), administering 500 mg/kg body weight, 
detected only minor hepatic effects over the 12 - 24-h period 
following administration.  No evidence of kidney dysfunction was 
observed in mice following intraperitoneal administration of 
trichloroethylene at 0.004M/kg body weight.  Application of 2 ml 
trichloroethylene (7800 mg/kg), under an occlusive dressing, on the 
skin of 20 guinea-pigs, did not produce any deaths but, during the 
35-day observation period, there were reductions in body weight at 
1 week ( P < 0.001), 2 and 3 weeks ( P < 0.01), and 4 weeks 
( P < 0.05) (Wahlberg & Boman, 1979). 

     Skin irritation

    Trichloroethylene (purity 99.5%), applied (0.5 ml) to the 
shaved (non-abraded) skin of rabbits, for 24 h, under an occlusive 
dressing, produced severe skin irritation (Duprat et al., 1976).  
In another study, trichloroethylene (1.0 ml) was applied, 
occluded in a "skin depot", to the clipped skin of guinea-pigs.  
Histological examinations were performed at 15 min, 1, 4, and 16 h.  
Degenerative changes (pyknotic nuclei) were observed in the 
epidermis after 15 min and were progressive (pyknosis, karyolysis, 
junctional separation of the epidermis) up to the end of the study 
at 16 h (Kronevi et al., 1981). 

Table 6.  Concentrations of trichloroethylene at which no effects were observed in experimental animals 
exposed through inhalation
Species     Concentration     Duration             Biological endpoints          Reference
            (mg/m3) at                             being investigated
            which no effects
            were observed
rat         3000              7 h                  mortality                     Adams et al. (1951)

            6400              1.4 h                mortality                     Adams et al. (1951)

            12 000            0.6 h                mortality                     Adams et al. (1951)

            20 000            0.4 h                mortality                     Adams et al. (1951)

            200               7 h per day, 5 days  mortality                     Adams et al. (1951)
                              per week, for 26

            400               8 h per day for      mortality; body weight;       Battig et al. (1963)
                              5 days               learning capacity

            730               8 h per day, 5       mortality; body weight;       Prendergast et al.
                              days per week for    haematology; histology of     (1967)
                              6 weeks              heart, liver, lung, spleen,
                                                   and kidneys

            35a               90 days              mortality; body weight;       Prendergast et al.
                                                   haematology; histology of     (1967)
                                                   heart, liver, lung, spleen,
                                                   and kidneys

guinea-pig  730               8 h per day, 5       mortality; body weight;       Prendergast et al.
                              days per week for    haematology; histology        (1967)
                              6 weeks

            35                90 days              mortality; body weight;       Prendergast et al.
                                                   haematology; histology        (1967)

Table 6.  (contd.)
Species     Concentration     Duration             Biological endpoints          Reference
            (mg/m3) at                             being investigated
            which no effects
            were observed
guinea-pig  100               7 h per day, 5       mortality                     Adams et al. (1951)
 (contd.)                     days per week for
                              26 weeks

monkey      730               8 h per day, 5       mortality; body weight;       Prendergast et al.
 (squirrel)                   days per week for    haematology; histology of     (1967)
                              6 weeks              heart, liver, lung, spleen,
                                                   and kidneys

            35                90 days              mortality; body weight;       Prendergast et al.
                                                   haematology; histology of     (1967)
                                                   heart, liver, lung, spleen,
                                                   and kidneys

monkey      400               7 h per day, 5       mortality                     Adams et al. (1951)
 (Rhesus)                     days per week for
                              26 weeks

rabbit      730               8 h per day, 5       mortality; body weight;       Prendergast et al.
                              days per week for    haematology; histology of     (1967)
                              6 weeks              heart, liver, lung, spleen,
                                                   and kidneys

            35                90 days              mortality; body weight;       Prendergast et al.
                                                   haematology; histology of     (1967)
                                                   heart, liver, lung, spleen,
                                                   and kidneys

            200               7 h per day, 5       mortality                     Adams et al. (1951)
                              days per week for
                              6 weeks

dog         730               8 h per day, 5       mortality; body weight;       Prendergast et al.
                              days per week for    haematology; histology of     (1967)
                              6 weeks              heart, liver, lung, spleen,
                                                   and kidneys

Table 6.  (contd.)
Species     Concentration     Duration             Biological endpoints          Reference
            (mg/m3) at                             being investigated
            which no effects
            were observed
dog         35                90 days              mortality; body weight;       Prendergast et al.
 (contd.)                                          haematology; histology of     (1967)
                                                   heart, liver, lung, spleen,
                                                   and kidneys

mouseb      5500              20 min               anaesthesia                   Gehring (1968)

            5500              100 min              liver injury (elevated SGPT)  Gehring (1968)
            5500              300 min              mortality                     Gehring (1968)
a Kalashmikova et al. (1976) reported that rats exposed to 50 mg/m3 for 5 h per day, for 90 days, showed 
  damage to parenchyma in liver and kidney.
b Kjellstrand et al. (1983) reported that male NMRI mice 
continuously exposed to 200 mg/m3 (37 ppm) for 
  30 days showed increased plasma butyrylcholinesterase (BuChE) (EC activity; female mice did 
  not show any increase in BuChE activity; there was a significant increase in liver weight at 200 mg/m3 
  (37 ppm) in both sexes.
Table 7.  Acute toxicity of trichloroethylene administered via
inhalation to laboratory animals
Species  Toxicity         Exposure            Reference
         index     ------------------------
                   level           duration
                   (ppm)   (mg/litre)  (h)
Rat      LC100     20 000  107         0.4    Adams et al. (1951)
         LC100     12 000  64.2        1.4    Adams et al. (1951)
         LC100     2500    13.4        7.0    Adams et al. (1951)
         LC50      26 300  140.7       1      Vernot et al. (1977)
         LC50      12 500  66.9        4      Siegel et al. (1971)
         LCL0a     8000    42.8        4      Smyth et al. (1969)

Mouse    LC100     8000    42.7        2      Von Oettingen (1955)
         LC100     5600    30.0        9.75   Gehring (1968)
         LC50      8450    45.1        4      Kylin et al. (1962)
         LC50      41 122  220         0.33   Aviado et al. (1976)
         LC50      49 000  262         0.50   Vernot et al. (1977)
         LCL0a     3000    16.0        2      Lazarev (1929)
         LC50              40          4      Lazarev & Gadaskina

Guinea-  LC100     37 000  197.8       0.67   Von Oettingen (1955)

Cat      LCL0a     6074    32.5        2      Lehmann & Schmidt-Kehl

Rabbit   LC        5000    26.75       14.28  McCord (1932)
         LC        10 000  53.5        2.5    McCord (1932)
         LC        20 000  107         2      McCord (1932)
a LCLO = lowest published lethal concentration.

     Eye irritation

    Instillation of 0.1 ml of trichloroethylene (purity 99.5%) 
into rabbit eyes produced mild to moderate conjunctivitis with 
superficial epithelial abrasion.  At 7 days, there was a resolving 
keratitis with complete recovery within 2 weeks (Duprat et al., 

6.1.2.  Short-term exposures  Oral exposures

    In a US NTP study (1983), groups of 10 male and 10 female 
F344/N rats were administered trichloroethylene (in corn oil, by 
gavage) at doses ranging from 125 to 2000 mg/kg body weight (males) 
and 625 to 1000 mg/kg (females), 5 times per week, for 13 weeks.  
All rats survived the 13-week study, but males receiving the 
2000 mg/kg dose exhibited a 24% decrease in body-weight gain.  At 
the 1000 mg/kg dose, final body weights for males and for females 
were similar to those of the controls. 

Table 8.  Acute oral, dermal, intraperitoneal, subcutaneous, and
intravenous LD50s for trichloroethylene in laboratory animals
Species  Oral         Dermal   Intraperitoneal  Subcutaneous  Intravenous
         (mg/kg body  (ml/kg   (mg/kg body      (mg/kg body   (mg/kg body
         weight)      body     weight)          weight)       weight)
Rat      49201                 27252

Dog      56803                 2.8004                         1505,a

Mouse    28506,b               32107,b          144010        3411
         240012                31508,b

Rabbit                201
1 From:  Smyth et al. (1969).                 a LDL0.     
2 From:  Rigaud et al. (1977).                b In 24 h.  
3 From:  Christensen et al. (1974).           c In 14 day.
4 From:  Klaassen & Plaa (1967).
5 From:  Barsoum & Saad (1934).
6 From:  Aviado et al. (1976).
7 From:  Klaassen & Plaa (1966).
8 From:  Gehring (1968).
9 From:  Gradiski et al. (1974).
10 From:  Plaa et al. (1958).
11 From:  NIOSH (1977b).
12 From:  Tucker et al. (1982).
    Histopathological examination of tissues from animals receiving 
the highest doses showed minimal or mild cytomegaly and karyomegaly 
of the renal tubular epithelial cells in the inner cortex in 8/9 
males dosed with 2000 mg/kg per day, and the same effect, graded as 
equivocal or mild, was seen in 5/10 females that had received the 
1000 mg/kg per day dose. 

    The results of this 13-week study in F344/N rats were 
essentially similar to those of an earlier 8-week study conducted 
on Osborne-Mendel rats (NCI, 1976).  In this study, only doses in 
excess of 5000 mg/kg per day were lethal for rats.  Doses of 
1000 mg/kg per day had no effect on body-weight gains in males, 
but depressed weight gains in females by approximately 15%. 

    Groups of 10 male and 10 female B6C3F1 mice received 
trichloroethylene (by gavage in corn oil) at doses ranging from 
375 to 6000 mg/kg body weight, 5 times per week for 13 weeks.  All 
males and 9/10 females receiving 6000 mg/kg, 7/10 males and 1/10 
females receiving 3000 mg/kg, and 2/10 males and 1/10 females 
receiving 1500 mg/kg died.  Mean body weights of male mice dosed 
with 750, 1500, or 3000 mg/kg were depressed by 11%, 19%, and 17%, 
respectively, relative to the controls.  Mean body weights of 
control and treated groups of female mice were similar (US NTP, 

    Liver weights (both absolute and as percentage body weight) 
increased in a dose-related fashion.  Liver weights were increased 
by more than 10% relative to the controls for males receiving 
750 mg/kg body weight or more and for females receiving 1500 mg/kg 
or more. 

    Histopathological examination showed hepatic centrilobular 
necrosis (6/10 males and 1/10 females administered 6000 mg/kg).  
This lesion was not seen in either males or females administered 
3000 mg/kg, but 2/10 males had multifocal areas of calcification 
scattered throughout their livers.  Multi-focal calcification was 
also seen in the liver of the single female mouse that survived the 
6000 mg/kg dosage regimen.  One female in the 3000 mg/kg dose group 
developed a hepatocellular adenoma, an extremely rare lesion in 
female mice of this age (20 weeks). 

    Examination of renal tissues showed the presence of mild to 
moderate cytomegaly and karyomegaly of the renal tubular epithelial 
cells of the inner cortex.  These changes were found in only 1 of 
the 23 mice (13 males and 10 females) that died after receiving 
doses of 3000 or 6000 mg/kg for up to 6 weeks.  However, the 
changes were found in all 4 of the males that died after receiving 
the 3000 mg/kg dose for 7 - 13 weeks, and in all animals that 
survived the 6000 mg/kg (1/10 females) and the 3000 mg/kg doses 
(3/10 males and 9/10 females).  Tissues from mice receiving lower 
doses of trichloroethylene were not examined. 

    Trichloroethylene administered orally to mice at doses in 
excess of 500 mg/kg for 10 days produced proliferation of hepatic 
peroxisome as demonstrated by increased cyanide-insensitive 
palmitoyl CoA oxidation (PCO) and electron microscopy.  In the 
rat, trichloroethylene did not have any effect on peroxisome 
proliferation.  Trichloroacetic acid administered for 10 days 
increased hepatic peroxisome proliferation in both species (Elcombe 
et al., 1982).  It is possible that the rapid rate of 
trichloroethylene metabolism in the mouse, together with the 
enterohepatic circulation of trichloroacetic acid, leads to 
high steady-state blood levels of trichloracetic acid and the 
concomitant proliferation of peroxisomes. 

    Primary cultures of isolated mouse and rat hepatocytes have 
been found to metabolize trichloroethylene to trichloroacetic acid 
at rates comparable to those in intact animals.  Similarly, the 
isolated hepatocytes respond to exposure to trichloroacetic acid 
by peroxisome proliferation.  Isolated human hepatocytes have been 
found to produce trichloracetic acid from trichloroethylene at a 
lower rate than that in the rat.  Trichloroacetic acid does not 
induce peroxisome proliferation in human hepatocytes (Elcombe, 
1985).  Inhalation exposure

    In the rat, exposure to 81 000 mg/m3 (15 000 ppm) for a period 
of 2 - 4 min produced complete anaesthesia within 9 min (Schumacher 
& Grandjean, 1960).  In a study on mice, exposure to 36 7000 mg/m3 
(6800 ppm) for 10 - 11 min or 64 800 mg/m3 (12 000 ppm) for 5 - 
6 min produced complete anaesthesia (Friberg et al., 1953).  In 
another study on mice, exposure to 29 700 mg/m3 (5500 ppm) produced 
anaesthesia in 46 min (Gehring, 1968). 

    Studies conducted on rats by Vissarionova et al. (1975) showed 
that concentrations of 5000 mg/m3 administered for 5 h a day, for 
1 week, resulted in an increase in liver and kidney weight (21.6% 
and 18%, respectively), and a decrease in alkaline phosphatase and 
RNA-dependent hepatic dehydrogenase.  Histological changes have also 
been noted in hepatic and renal parenchyma by Kalashnikova et al. 

    With doses of 1080 mg/m3 (200 ppm) administered for 6 h daily 
for 4 days, Savolainen et al. (1977) found that rats exhibited 
greater motor activity and less cerebral RNA, 5 days after the last 
exposure, and an accumulation of trichloroethylene in perirenal 

    Doses of 250, 500, 800, and 1200 mg/m3 administered for 15 - 
90 h resulted in increases in intracellular lipids (Verne et al., 

    No effects were noticed in rats administered 1080 mg/m3 (200 
ppm) for 4 h a day for 4 days (Grandjean, 1960). 

    Continuous exposure of rats, mice, and gerbils by inhalation to 
trichloroethylene at 810 mg/m3 (150 ppm), for periods ranging from 
2 to 30 days, produced liver enlargement in all species; the mouse 
was the most severely affected.  After the end of exposure, the 
liver weights of the mice decreased rapidly.  An increased kidney 
weight was noted in gerbils (Kjellstrand et al., 1981a). 

    In another study in which 7 different strains of mice (wild, 
C57BL, DBA, B6CBA, A/su, NZB, and NMRI) were continuously exposed 
to a trichloroethylene concentration of 810 mg/m3 (150 ppm), 
Kjellstrand et al. (1983a) reported large increases in liver weight 
in all strains with minimal changes in kidney and spleen weights.  
Plasma butyrylcholinesterase (BuChE) (EC activity 
increased in males of all strains and in females of strains A/su 
and NZB, but to a lesser extent than in the corresponding males.  
In a further study, with continuous exposure to concentrations of 
200 - 1620 mg/m3 (37 - 300 ppm), plasma BuChE increased in male 
mice in a time- and concentration-dependent manner.  Liver weight 
increased in a time- and concentration-dependent manner in both 

    Exposure of rats, guinea-pigs, rabbits, dogs, and monkeys to 
3825 mg/m3, for 8 h per day, 5 days per week, for 6 weeks, resulted 
in a loss of overall body weight in dogs and monkeys.  There were 
no changes in haematological or liver enzyme parameters 
(Prendergast et al., 1967). 

    Groups of male Swiss Webster mice were exposed to 54 000 mg/m3 
(10 000 ppm) for 1 or 4 h, daily, for 5 consecutive days.  In the 
4-h group, the NADPH cytochrome c reductase (EC activity 
in the lung decreased, but that in the liver increased.  In the 
lungs of this group, there were platelet thrombi and vacuolization 
of bronchial epithelial cells.  There were no changes in the liver.  
It was concluded that the reduced activity of the pulmonary mixed-
function oxidase system reflected injury to the lungs (Lewis et 
al., 1984). 

    Rabbits exposed to 15 000 mg/m3 (2790 ppm) for 4 h per day, 
6 days a week for 45 days, developed severe normocytic anaemia, 
leukopenia, and thrombocytopenia due to toxic effects on the bone 
marrow (Mazza & Brancaccio, 1967). 

    In rats, urinary levels of trichloro-substituted metabolites 
and the activity of drug-metabolizing enzymes (cytochrome P-450) 
were related to the duration of trichloroethylene anaesthesia 
(Moslen et al., 1977).  Trichloroethylene hepatotoxicity in the rat 
produces increased levels of serum transaminases.  Hetaptotoxicity 
increases the activity of drug-metabolizing enzymes (cytochrome 
P-450) (correlation coefficient: 0.95) and the urinary excretion of 
trichloro-metabolites (correlation coefficient: 0.88) (Moslen et 
al., 1977). 

    Cytotoxic effects have been observed in the kidney and liver of 
dogs subjected to 81 000 mg/m3 (1.5%; 15 000 ppm) trichloroethylene 
anaesthesia (Kiseleva & Korolenko, 1971). 

    Studies on rats exposed by inhalation to trichloroethylene 
concentrations of 2160, 4320, or 8640 mg/m3 (400, 800, or 1600 ppm) 
for 6 h revealed no effects at the first concentration, a decrease 
in swimming activity at 4320 mg/m3, and a further decrease at 
8640 mg/m3 (Grandjean, 1963).  Other rats exposed to 1944 - 
2268 mg/m3 (360 - 420 ppm) for 8 h a day, 5 days a week for 
46 weeks, exhibited no effects (Bättig & Grandjean, 1963).  After 
43 weeks at 2160 mg/m3 (400 ppm), rats in another set of tests by 
Bättig (1964) exhibited greater maze skills.  Mice exposed 
intermittently to trichloroethylene showed a decrease in motor 
activity at 4500 mg/m3 (900 ppm), but, at 19 440 mg/m3, it was 
considerably increased (Kjellstrand et al., 1983b). 

    In Mongolian gerbils, continuously exposed to trichloroethylene 
at 1.72 mg/m3 (320 ppm) for 9 months, there was no effect on 
spatial memory, but subsequent maze performance test results were 
interpreted as indicating an irreversible effect on the central 
nervous system (Kjellstrand et al., 1980).  In another study, 2 
groups of Mongolian gerbils were continuously exposed to 810 mg 
trichloroethylene/m3 (150 ppm) for 71 and 106 days, respectively.  
In a series of maze tests following the end of exposure, the 
treated groups performed less well than the unexposed controls 
(Kjellstrand et al., 1981b).  Parenteral exposure

    When male Swiss Webster mice were injected ip with 3 doses of 
330 mg trichloroethylene/kg body weight (vehicle 0.2 ml of 25% 
Tween 80 in saline) on alternate days, the activity of hepatic 
microsomal NADPH cytochrome c reductase was increased.  There 
were no morphological changes in the liver (Lewis et al., 1984). 

    Studies conducted on rabbits showed that intramuscular 
administration of 3 ml trichloroethylene, 3 times weekly for 
29 days, induced neuronal damage (Bartonécek & Brun, 1970). 

6.1.3.  Long-term exposure  Oral exposure

    The US NTP (1983) studied the effects of orally-administered 
(in corn oil, by gavage) epichlorohydrin-free trichloroethylene in 
male and female F344/N rats and B6C3F1 mice.  Doses (500 and 
1000 mg/kg body weight for rats and 1000 mg/kg for mice) were 
administered 5 days per week for 103 weeks.  The survival of 
treated male rats and male mice was significantly reduced in 
relation to that of corn-oil control animals.  Mean body weights 
of treated rats (both sexes) were lower than those of corn-oil 
controls and the reduction in body weight gain was dose-related.  
The body weights of treated female mice were similar to those of 
vehicle controls. 

    Toxic nephrosis was found in 96/98 (98%) of the treated male 
rats, in 97/97 of the treated female rats, in 45/50 (90%) of the 
treated male mice, and in 48/49 (98%) of the treated female mice, 
but was not found in any of the corn-oil control rats or mice.  
Initially noted in rats that died early, the lesions were diagnosed 
as frank enlargement of the nucleus and cytoplasm of scattered 
individual tubular cells with brush borders, located near the 
cortico-medullary junction.  Progression of the lesions was 
evident.  As exposure time increased, affected tubular cells 
were larger and additional tubules and tubular cells were affected.  
Some tubules were enlarged or dilated to the extent that they were 
difficult to identify as tubules.  Eventually, there was loss of 
some enlarged cells.  Corresponding tubules became dilated and 
portions of the basement membrane had a stripped appearance.  In 
the most advanced stage, the lesion had progressed to the sub-
capsular cortex, with enlarged tubular cells. 

    In mice, the pathological development of the renal lesion was 
basically similar to that observed in rats, but it was relatively 
less severe and did not develop to a stage where there was 
extensive loss of cytomegalic epithelial cells and tubular 

    When trichloroethylene was given in the drinking-water (0.1, 
1.0, 2.5, and 5.0 g/litre) to CD-1 mice for 4 - 6 months, a 
significant reduction in body weight (males and females at 
5.0 g/litre), enlarged liver (males at 1.0, 2.5, and 5.0 g/litre; 

females at 5.0 g/litre), and increase in kidney weight (males and 
females at 5.0 g/litre) were observed.  However, pathology at 4 and 
6 months was unremarkable.  Inhalation exposure

    Studies on rats showed that exposure to concentrations below 
1080 mg/m3 (200 ppm) for 6 h a day, 5 days a week for 6 months, did 
not induce any visible effects.  At concentrations of 10 800 mg/m3 
(2000 ppm), narcosis and loss of appetite were observed.  At 
16 200 mg/m3 (3000 ppm), only 33% of the test animals survived 
(Taylor, 1936). 

    When NMRI mice were exposed to trichloroethylene at 700 mg/m3 
(130 ppm) continuously for 30 days, liver weight increased by 1.5 
and 1.9 times in males and females, respectively (Kanje et al., 

    When rats were exposed to trichloroethylene at 1945 - 
2270 mg/m3 (360 - 420 ppm), for 8 h a day, 5 days a week for 
46 weeks, there were no changes in conditioned reflexes or reaction 
time, but there was an increase in spontaneous climbing activity 
(Bättig & Grandjean, 1963). 

    Rats exposed to 50 mg/m3 (0.05 mg/litre) for 5 h daily, for 
3 months, showed damage to hepatic and renal parenchyma 
(Kalashnikova et al., 1976). 

    Long-term exposure to concentrations of 100 - 200 mg/m3 
(0.1 - 0.2 mg/litre) reduced the phagocytic activity of rat 
leukocytes (Pelts, 1962). 

    In female Mongolian gerbils, exposed continuously to 270 and 
810 mg/m3 (50 and 150 ppm) for 12 months, there were small changes 
in the lipid composition of the cerebral cortex and hippocampus.  
While protein content and lipid class distribution were virtually 
unaffected, the cholesterol to phospholipid ratio in the cortex 
decreased (Kyrklund et al., 1983).  Parenteral exposure

    Of 6 rabbits given trichloroethylene at 200 mg/kg body weight 
intramuscularly for 55 - 100 days, 2 died from renal failure 
(Bartonécek & Brun, 1970).  Rabbits given 2 ml (2.92 g) 
intramuscularly twice a week for 41 - 247 days exhibited 
neuronal damage (Bartonécek & Sovcek, 1959). 

6.1.4.  Interactions

    Studies on rats showed that trichloroethylene was more toxic in 
animals on a high-carbohydrate diet than in those on a high-protein 
diet (Kalashnikova et al., 1974).  In rats (Cornish & Adefuin, 
1966), rabbits (Desoille et al., 1962), and human beings (Sbertoli 
& Brambilla, 1962; Ferguson & Vernon, 1970; Pardys & Brotman, 
1974), the presence of ethanol increased trichloroethylene 

toxicity.  Trichloroethylene and carbon tetrachloride acted 
synergistically in producing hepatotoxicity (Deguchi, 1972; 
Pessayre et al., 1982). 

    When trichloroethylene was administered intraperitoneally with 
toluene, there was a decrease in the side-chain oxidation of the 
toluene (Ikeda, 1974). 

    In studies by White & Carlson (1979), trichloroethylene 
caused spontaneous, and potentiated epinephrine-induced, cardiac 
arrhythmias in rabbits.  A series of studies was conducted to 
examine the effects of metabolic-inhibitors, enzyme-inducing 
agents, or pre-treatment with ethanol or caffeine, on the 
sensitivity of rabbits to epinephrine-induced cardiac arrythmias 
(White & Carlson, 1979, 1981a, 1982).  Rabbits treated with 
metabolic-inhibiting agents developed more arrhythmias after 
shorter exposure times in response to lower doses of epinephrine 
than controls.  Phenobarbitone and Aroclor 1254(R), and in a later 
study benzo( a)pyrene (Carlson & Shite, 1983), were used as enzyme-
inducing agents.  Phenobarbitone-treated rabbits developed 
fewer cardiac arrhythmias and had lower blood levels of 
trichloroethylene.  Rabbits treated with benzo( a)pyrene developed 
more cardiac arrhythmias and at lower doses of epinephrine when 
exposed by inhalation to a trichloroethylene concentration of 
43 500 mg/m3 (8100 ppm).  Aroclor 1254(R) did not induce any 
effects on trichloroethylene metabolism nor on the development of 
epinephrine-induced cardiac arrhythmias.  Rabbits pre-treated with 
ethanol (1000 mg body weight, intravenously or orally) or caffeine 
(10 mg/kg body weight, intraperitoneally) 30 min before exposure to 
trichloroethylene at 32 400 mg/m3 (6000 ppm) by inhalation showed 
an increased senstivity to epinephrine-induced cardiac arrhythmias. 

    Male New Zealand rabbits exposed to trichloroethylene at 
10 800, 21 600, 32 400, or 43 200 mg/m3 (2000, 4000, 6000, or 
8000 ppm) by inhalation for 1 h showed a concentration-related 
sensitivity to epinephrine-induced cardiac arrhythmias.  The blood 
levels of the trichloroethylene metabolites (trichloroethanol and 
trichloroacetic acid) were measured.  Rabbits given chloral 
hydrate (50 mg/kg body weight, intravenously), a trichloroethylene 
intermediate metabolite, had blood levels of trichloroethanol and 
trichloroacetic acid that were 40 - 100 times higher than those of 
rabbits exposed to a trichloroethylene level of 43 200 mg/m3 (8000 
ppm) but showed no increase in sensitivity to epinephrine-induced 
cardiac arrhythmias (White & Carlson, 1981b).  It is concluded that 
trichloroethylene, rather than its metabolites, sensitizes the 
rabbit myocardium. 

6.1.5.  Immunotoxicity

    Changes in some components of antibody production (7S), cell-
mediated immunity (haemagglutination), and bone marrow stem cell 
colonization have been observed in rodents (female mice were more 
sensitive than males in one study; chinchillas were used in the 
other) exposed to low-to-moderate levels (10 - 1000 mg/m3) by 

inhalation or to 0.1 - 5 g/litre per day in the drinking-water for 
periods ranging from a few weeks to 6 - 10 months (Shmuter, 1972; 
Sanders et al., 1982). 

6.1.6.  Effects on cell systems

     In vitro incubation of nerve-fibre membranes from rat spinal 
cord with 10 µM trichloroethylene reduced the low relative 
molecular mass protein fraction (Savolainen & Seppalainen, 1979). 

    A trichloroethylene concentration of 1.3/108 moles per ml was 
the LD50 for HeLa (human cervix carcinoma) cells on the third day 
of treatment (Gradiski et al., 1974). 

    Exposure of rabbit trachea cultures to trichloroethylene vapour 
at 27 000 mg/m3 (5000 ppm) for 129 min and 216 000 (40 000 ppm) for 
13 min, induced ciliostasis (Tomenius et al., 1979).  The isolated 
guinea-pig heart exposed to trichloroethylene at 530 mg/litre, 
developed transitory arrhythmia.  At a concentration of 1.06%, 
there was evidence of a reduction in contractile force and coronary 
flow, and arrhythmia (Bianchi et al., 1963; Matturro et al., 1963). 

6.1.7.  Carcinogenicity

    Groups of 50 male and 50 female Osborne-Mendel rats, 7 weeks 
old, were administered trichloroethylene (99% trichloroethylene 
stabilized with 0.19% 1,2-epoxybutane and 0.09% epichlorohydrin) in 
corn oil, by gavage, 5 days a week for 78 weeks.  High-dose animals 
received varying dose schedules of 1000 - 1500 mg/kg body weight 
per day, and low-dose animals received 500 - 750 mg/kg body weight 
per day.  All surviving animals were killed 110 weeks after the 
start of treatment.  The time-weighted average doses were 549 and 
1097 mg/kg body weight per day.  A group of 20 male and 20 female 
vehicle-treated rats served as controls.  Of the males, 17/20 
controls, 42/50 low-dose, and 47/50 high-dose animals died before 
the end of the study; of the females, 12/20 controls, 35/48 low-
dose, and 37/50 high-dose animals died early.  Median survival 
times were approximately 60 weeks for high-dose males, 85 weeks 
for low-dose males, and 70 weeks for high- and low-dose females.  
Of the males, 5/20 controls, 7/50 low-dose, and 5/50 high-dose rats 
developed tumours; of the females, 7/20 controls, 12/48 low-dose, 
and 12/50 high-dose rats developed tumours.  There were no liver-
cell tumours.  Tumours occurred in various other organs in treated 
and control animals and were mainly reticulum-cell sarcomas, 
lymphosarcomas or malignant lymphomas, fibroadenomas of the 
mammary gland, haemangiosarcomas at various sites, follicular 
adenocarcinomas of the thyroid, chromophobe adenomas of the 
pituitary, and renal hamartomas.  Toxic nephropathy was observed 
in rats of both sexes treated with high and low doses of 
trichloroethylene (NCI, 1976). 

    Groups of 50 male and 50 female B6C3F1 mice, 5 weeks old, 
were given trichloroethylene (99% trichloroethylene stabilized 
with 0.19% 1,2-epoxybutane and 0.09% epichlorhydrin) in corn oil 
by gavage, 5 days a week, for 78 weeks.  High-dose males received 

2000 - 2400 mg/kg body weight per day, and females 1400 - 1800 
mg/kg body weight per day; low-dose males and females received 
1000 - 1200 mg/kg body weight per day and 700 - 900 mg/kg body 
weight per day, respectively.  All surviving animals were observed 
until they reached 95 weeks of age.  Time-weighted average doses 
were 1169 and 869 mg/kg body weight per day, respectively, in low-
dose males and females and 2339 and 1739 mg/kg body weight per day, 
respectively, in high-dose males and females.  Groups of 20 male 
and 20 female mice served as vehicle-treated matched controls.  
Survival was reduced in high-dose males and control males.  
Hepatocellular carcinomas occurred in 1/20 control males and 0/20 
control females; in 26/50 low-dose males and 4/50 low-dose females, 
and in 31/48 high-dose males and 11/47 high-dose females. 
Metastases of the liver-cell tumours to the lung were found in 
7/98 treated males and in 1 control male.  The first hepatocellular 
carcinoma was observed in a mouse which had been treated with the 
high dose of trichloroethylene and which died during week 27.  
Lung tumours occurred in treated animals of both sexes:  5/50 (5 
adenomas) in males and 4/50 (2 adenomas, 2 carcinomas) in females 
in the low-dose group, and 2/48 (1 adenoma, 1 carcinoma) in males 
and 7/47 (5 adenomas, 2 carcinomas) in females treated with the 
high dose of trichloroethylene.  Among controls, only one lung 
adenoma was reported in a female (NCI, 1976). 

    In a study by Maltoni & Maioli (1977) and Maltoni et al. (in 
press), groups of 30 male and 30 female, 13-week-old Sprague Dawley 
rats were given trichloroethylene (highly purified and epoxide-
free, and stabilized with 20 ppm of butyl-hydroxytoluene) in olive 
oil by gavage, 5 days a week, for 52 weeks.  Two doses of 
trichloroethylene were tested. The high-dose animals received 
250 mg/kg body weight, and the low-dose animals 50 mg/kg body 
weight; 30 males and 30 females received olive oil alone and served 
as controls.  The animals were kept until their spontaneous death 
(the study lasted 140 weeks).  There was no increase in specific 
tumours. Abnormalities (cytokaryomegaly) in cells of the renal 
tubules were observed in high-dose male rats.  These changes were 
not observed in females. 

    Groups of 30 female ICR Swiss mice and a group of 30 male 
and 30 female mice of the same strain, were treated with 
trichloroethylene dermally (1 mg in acetone), 3 times weekly, for 
83 weeks, subcutaneously (0.5 mg in trioctanoin) once weekly for 
89 weeks, and by gavage (0.5 mg in trioctanoin), once weekly, for 
89 weeks.  Similar-sized groups of animals served as controls.  No 
tumours were observed at the site of application (Van Duuren et 
al., 1979).  Similar negative findings were obtained following 
thrice-weekly skin applications and once-weekly subcutaneous 
injections of trichloroethylene oxide for life in a group of 
70 female mice of the same strain (Van Duuren et al., 1983) 

    Groups of 30 male and 30 female Wistar rats, NMRI mice, and 
Syrian hamsters were exposed by inhalation to trichloroethylene 
(purified, with no detectable epoxides, and containing 15 ppm 
triethanolamine as stabilizer) at 540 and 2700 mg/m3 (100 and 
500 ppm).  The animals were exposed for 6 h per day, 5 days per 

week, for 78 weeks.  The studies were terminated by killing the 
surviving mice and hamsters after 130 weeks, and rats after 156 
weeks.  No carcinogenic effects were observed in rats, hamsters, 
and male mice.  A moderate increase in lymphomas was found in 
treated female mice (18/28 at 2700 mg/m3; 17/30 at 540 mg/m3, and 
9/29 in controls).  The authors concluded that, on the basis of 
these findings, there were no indications of carcinogenicity 
(Henschler et al., 1980). 

    Groups of 49 - 50 female ICR mice, 4 weeks of age, were exposed 
by inhalation to trichloroethylene (purity 99.8% with 0.128% carbon 
tetrachloride, 0.019% benzene, 0.019% epichlorohydrin, and 0.01% 
1,1,2-trichloroethane) at 0.270, 810, or 2430 mg/m3 (0, 50, 150, 
or 450 ppm), 7 h per day for 5 days per week, for 104 weeks.  The 
surviving animals were killed 107 weeks after the start of the 
study.  Mortality was similar in control and treated groups.  
Lung adenomas were found in 5, 2, 5, and 4 mice in the control, 
low-dose, mid-dose, and high-dose groups, respectively.  However, 
it was reported that adenocarcinomas (none of which gave rise to 
metastases) occurred in 1/49, 3/50, 8/50, and 7/46 mice in the 
control, low-dose, mid-dose, and high-dose groups, respectively, 
and that increased incidences in the mid- and high-dose groups, 
were statistically significant compared with controls.  In similar 
studies on Sprague Dawley rats, no statistically-increased 
incidence of tumours was detected; one clear-cell carcinoma of the 
kidney was observed in the high-dose group (Fukuda et al., 1983). 

    In a large series of inhalation studies, highly purified 
epoxy-free trichloroethylene (stabilized with 20 ppm butyl-
hydroxytoluene) was studied under controlled exposure conditions 
in male and female Sprague Dawley rats and Swiss and B6C3F1 mice.  
Treatment was for 7 h per day, 5 days per week for 8, 78, or 104 
weeks.  After the end of the treatment, all animals were kept under 
observation until spontaneous death.  The following 7 studies were 
performed (Maltoni & Maioli, 1977; Maltoni et al., in press): 

     Study 1

    Groups of 60 - 90 male and 60 - 90 female Sprague Dawley rats 
were exposed to 0, 540, or 3240 mg trichloroethylene/m3 (0, 100, or 
600 ppm) for 8 weeks.  No increase in tumours related to treatment 
was observed.  Cytomegaly and karyomegaly of tubular cells in the 
kidney were not observed at either dose. 

     Study 2

    Groups of 60 - 100 male and 60 - 100 female Swiss mice were 
exposed to trichloroethylene at 0, 540, or 3240 mg/m3 (0, 100, or 
600 ppm) for 8 weeks.  No increase in tumours related to treatment 
was observed. 

     Studies 3 and 4

    Groups of 90 - 95 male and 90 - 105 female Sprague Dawley rats 
were exposed to trichloroethylene at 0, 540, 1620, 3240 mg/m3 (0, 
100, 300, or 600 ppm) for 104 weeks.  Further groups of 40 males 
and 40 females were started on the same treatment 4 - 5 weeks later 
(Study 4).  The method and results of the 2 studies were similar 
and the combined data are described.  No increase in mortality was 
observed in the treated animals.  Cytomegaly and karyomegaly of 
renal tubular cells were observed in males in the mid- and high-
dose groups and the incidence was dose-related; no such lesions 
were observed in males in the low-dose group or in females at 
any of the 3 dose levels, or in the controls.  Five tubular 
adenocarcinomas were observed in 4/130 males and 1/130 females 
at the high-dose level.  Leydig cell tumours of the testis were 
observed in 6/135 controls, and in 16/130, 30/130, and 31/130 
male rats, respectively, in the low-, mid-, and high-dose treated 
groups.  The average time of appearance of the tumours, from the 
start of the study, was 113 weeks in controls and from 109 to 
113 weeks in treated animals.  A higher incidence of immunoblastic 
lymphosarcomas was detected in male and female treated animals: 
1/280 in controls, 9/260 at the low dose, 5/260 in the mid-dose 
group, and 3/260 in the high-dose group. 

     Study 5

    Groups of 90 male and 90 female Swiss mice were exposed to 
trichloroethylene at 0, 540, 1620, or 3240 mg/m3 (0, 100, 300, 
or 600 ppm) for 78 weeks.  The incidence of hepatocellular 
carcinomas in males was 4/90 in controls compared with 2/90 at the 
low dose, 8/90 at the mid dose, and 13/90 at the high dose.  One 
hepatocellular carcinoma occurred in a female at the high dose.  
The incidences of lung adenomas and adenocarcinomas were 25/180 
in controls, 26/180 in low-dose groups, 36/180 in mid-dose, and 
47/180 in the high-dose groups (males and females combined).  Two 
adenocarcinomas were seen in the control groups and 3 in the high-
dose group. 

     Studies 6 and 7

    For study 6, groups of 90 male and 90 female B6C3F1 mice were 
exposed to trichloroethylene at 0, 540, 1620, or 3240 mg/m3 (0, 
100, 300, or 600 ppm) for 78 weeks.  Because of excess mortality 
due to fighting in the male groups, study 7 was started in which 
trichloroethylene was tested in the same way in equal numbers of 
male mice.  In females, the incidence of pulmonary tumours (all 
adenomas except one adenocarcinoma in the low-dose group) were 4/90 
in controls compared with 6/90, 10/90, and 15/90 in the low-, mid-, 
and high-dose groups, respectively.  Hepatocellular carcinomas were 
observed in 3/90 controls compared with 4/90, 4/90, and 9/90 in the 
low-, mid-, and high-dose groups, respectively.  In the males in 
study 7, the incidence of pulmonary tumours was not affected by the 
treatment.  Hepatocellular carcinomas were observed in 14/90 
controls compared with 19/90, 27/90, and 21/90 in the 3 treated 
groups, respectively.  Cytomegaly and karyomegaly were not observed 
in either study (Maltoni et al., in press). 

    Groups of 50 male and 50 female rats (F344) and mice 
(B6C3F1) were treated, by corn-oil gavage, with epichlorohydrin-
free trichloroethylene at 500 and 1000 mg/kg body weight (rats), 
and 1000 mg/kg body weight (mice), 5 times weekly, for 103 weeks.  
Similar-sized groups of male and female rats and mice treated with 
corn oil alone, or without any treatment, served as controls.  The 
animals were killed between 103 and 107 weeks from the start of the 
study.  Trichloroethylene significantly reduced the survival of 
male rats and mice.  In male rats treated with trichloroethylene, 
the incidence of tubular-cell neoplasms was increased (0/49, 
untreated; 0/48, corn-oil control; 2/49, low dose; 3/49, high 
dose).  There was one tubular-cell tumour in a high-dose female 
rat.  Five low-dose male rats also had malignant peritoneal 
mesotheliomas, compared with 1/50 untreated control, 1/50 vehicle 
control, and 0/49 high-dose animals.  Trichloroethylene also 
produced nephrosis in both sexes of both species.  In mice, the 
administration of trichloroethylene increased the incidence of 
hepatocellular carcinoma (males: 8/48, controls; 30/50, treated; 
females:  2/48, controls; 13/49, treated).  The incidence of 
hepatocellular adenomas was also increased in male mice (3/48, 
controls; 8/50, dosed) and in female mice (2/48, controls; 8/49, 
dosed) (US NTP, 1983). 

    Groups of 50 male and 50 female Swiss mice were treated 
by corn-oil gavage with daily doses of different samples of 
trichloroethylene, initially at 2400 mg/kg body weight (males) 
and 1800 mg/kg body weight (females), 5 days a week, for 78 weeks.  
Due to toxicity, dosing and dose levels were reduced during the 
study.  The animals were kept under observation until 
spontaneous death.  The samples included:  (a) highly purified 
trichloroethylene stabilized with 0.0015% triethanolamine, (b) 
industrial trichloroethylene (99.4% pure), (c) highly purified 
trichloroethylene stabilized with 0.8% epichlorohydrin, (d) highly 
purified trichloroethylene, with 0.8% 1,2-epoxybutane, and (e) 
highly purified trichloroethylene with 0.25% epichlorohydrin and 
0.25% epoxybutane.  Similar-sized groups of each sex, treated with 
corn oil alone, served as controls.  Mortality was increased in 
treated males and some treated female groups.  No increase in 
tumour incidence was observed except in groups (c) and (d) where 
there was an increased incidence of forestomach cancers, attributed 
to the direct alkylating properties of one of the two stabilizers 
(Henschler et al., 1984).  Conclusions

    Trichloroethylene (with or without epoxide stabilizers) caused 
an increased incidence of hepatocellular carcinomas in 2 different 
strains of mice, either when given by oral administration or by 

    Trichloroethylene also produced lung tumours in Swiss ICR mice 
and in female, but not male, B6C3F1 mice. 

    Trichloroethylene, with added epichlorohydrin, administered by 
gavage, caused an increased incidence of forestomach cancers in 
WMRI mice. 

    Trichloroethylene (epoxide stabilizer-free) produced a low 
incidence of renal tubular tumours in 2 different strains of mice 
(mainly in males) following long-term oral or inhalation exposure.  
These tumours occur very rarely in untreated rats of these strains. 

    A dose-related increase in Leydig (interstitial) cell tumours 
of the testis was observed in one study on male Sprague Dawley rats 
following long-term inhalation exposure. 

    In one strain of mice and one strain of rats, epoxide 
stabilizer-free trichloroethylene produced some increases in the 
incidence of lymphomas.  However, these data are insufficient to 
draw any conclusions. 

    Thus, there is clear evidence that trichloroethylene is 
carcinogenic in mice.  There is also some evidence that 
trichloroethylene causes tumours in rats. 

    It was noted in the evaluations by IARC (1979, 1982) that 
it was considered that there was limited evidence for the 
carcinogenicity of trichloroethylene for experimental animals. 

    The significance of these findings needs to be evaluated in 
the context of further studies on the mechanism of action of 

6.1.8.  Mutagenicity  Gene mutation

    (a)   Bacteria and fungi

    Pure trichloroethylene induced revertants (gene-mutations) in 
the K-12 strain of  Escherichia coli in the presence of fortified 
mouse Arochlor(R)-induced microsomal preparations for only one gene 
out of four analysed.  In the positive case, the induced effect was 
the doubling of spontaneous background (Greim et al., 1975). 

    Trichloroethylene (of unspecified purity) in vapour form was 
slightly mutagenic for the TA-100 strain of  Salmonella typhimurium,  
in the presence of S9 mix obtained from mouse liver (control 
value = 140 revert./plate; treated values:  240 revert./plate) 
(Simmon et al., 1977). 

    Technical grade trichloroethylene (containing 1900 ppm of 
1,2-epoxybutane and 900 ppm of epichlorohydrin) was mutagenic for 
the TA-100 strain of  S. typhimurium in a desiccator, in the absence 
of a metabolic activation system (untreated 161 - 187 revert./plate; 
treated:  567 - 651 revert./plate).  Trichloroethylene of high 
purity was not mutagenic for the TA 100 strain of  S. typhimurium 
in the presence of 0.5 ml of S9 mix obtained from mouse, rat, and 

hamster liver; it was, however, mutagenic for this strain of 
 S. typhimurium in the presence of 50 - 150 µl of S9 mix from 
Arochlor-treated rat liver (untreated series:  160 - 180 
revert./plate; treated series:  350-379 revert./plate) (Crebelli 
et al., 1982). 

    High-purity trichloroethylene was not mutagenic for the TA 100 
strain of  S. typhimurium in a plate assay, with and without 
addition of S9 mixture (Henschler et al., 1977). 

    Trichloroethylene containing no traces of 1,2-epoxybutane or 
epichlorohydrin was tested as a gas in a desiccator on the TA 1535 
and TA 100 strains of  S. typhimurium.  Concentrations of 1 - 3% 
produced a 30% increase (less than a doubling) in revertants in 
strain TA 100 in the presence of a metabolic activation system from 
Arochlor(R)-induced rat liver (Baden et al., 1979). 

    The exposure of  S. typhimurium strains TA 98 and TA 100 to 
0.5 - 10% vapour concentrations of trichloroethylene in sealed 
vials for 48 h did not produce an increase in revertants either in 
the presence or absence of rat liver homogenate (Waskell, 1978). 

    Trichloroethylene of high purity (99.5%) was mutagenic for the 
TA-100 strain of  S. typhimurium when used as a gas in a desiccator 
in the presence of S9 mix (Bartsch et al., 1979).  However, it 
should be noted that the increase in revertants in the treated 
series was less than twice that of the untreated series, but this 
slight effect was consistent in repeated experiments. 

    Trichloroethylene of unspecified purity was reported to double 
the spontaneous frequency of reverse mutations in the D-7 strain of 
the yeast  Saccharomyces cerevisiae, at one concentration, in the 
presence of an endogenous metabolic activation system (Callen et 
al., 1980). 

    Trichloroethylene containing impurities, which were not 
specified, was mutagenic for  S. cerevisiae, strain XV185-14C 
(reverse mutations) in the presence of S9 mix.  These results 
were obtained at a level of yeast cell % survival of < 1 (1 h of 
treatment) and of < 0.1 (4 h of treatment).  These conditions are 
unusual for the detection of mutagenic effects, since, at these 
toxic values, selection of different cells (wild type and mutants) 
is very efficient (Shahin & von Borstel, 1977).  One of the authors 
(von Borstel, personal communication, 1984) stated that, when these 
studies were repeated with a pure trichloroethylene sample, it was 
not mutagenic for yeast cells. 

    Trichloroethylene of high purity (99.8%), as well as 
trichloroethylene containing stabilizers such as 1,2-epoxy-butane 
(0.19%) and epichlorohydrin (0.09%), were not mutagenic for the 
yeast  S. pombe (forward mutations), with or without a metabolic 
system obtained from rats and mice treated with phenobarbital and 
beta-naphthoflavone.  Using intraperitoneal or intrasanguineous, 
host-mediated assay techniques with male mice inoculated with the 
yeast  S. pombe and treated orally with 2 g/kg body weight for  

4 or 16 h, both pure trichloroethylene and the stabilized 
trichloroethylene were found not to be mutagenic (Rossi et al., 

    A slightly mutagenic action for cells of  S. cerevisiae strain 
D7 (reverse mutation at  his locus) was found for trichloroethylene 
of unspecified purity in the presence of a metabolic activation 
system obtained from mice (untreated series:  0.79 - 0.89  his, 
rev/106; treated series:  3.00 - 3.60  his rev/106 with 40 mol).  
For this experiment, no survival values were reported, nor were the 
actual number of revertants counted, and therefore the observed 
effect cannot be definitely assigned to trichloroethylene 
(Bronzetti et al., 1978).  The same authors administered 
trichloroethylene (unspecified purity) orally to mice (400 mg/kg 
body weight) that were also inoculated with yeast cells intra-
sanguineously; a mutagenic effect was found on yeast cells (reverse 
mutations at the  his locus) collected from liver, lung, and kidney 
but, again, the survival level was not reported nor was the number 
of revertants counted (Bronzetti et al., 1978). 

    Trichloroethylene of high purity and containing known 
contaminants (~80 ppm) was found to be active for the production 
of reverse mutations (suppressor mutations) on  Aspergillus 
 nidulans sumeth A1 strain at a dose of 27 000 mg/m3 (5000 ppm) 
applied in a desiccator containing the plates inoculated with the 
fungal conidia (Crebelli et al., in press). 

    (b)   Mammalian cells (in vitro)

    A pure sample of trichloroethylene, stabilized with thymol, 
did not induce mutations (forward mutations) at the HPRT locus of 
Chinese hamster V-79 cell line treated  in vitro with or without 
metabolic activation (S9 mix) (Loprieno & Abbondandolo, 1980). 

    (c)   Mammals (in vivo)

    Trichloroethylene (purity 99.5%) was evaluated for its ability 
to induce somatic gene mutations  in vivo in embryonic fibroblasts 
of mice (spot test).  Pregnant mice were injected 12 days after 
copulation with a dose of 140 mg/kg body weight (50 females), or 
350 mg/kg (26 females).  The results observed were 2/145 (1.4%) 
and 2/51 (3.9%) of progeny with "spots", respectively, whereas 
the untreated series produced 0/146, 3/182 (1.6%), 6/794 (0.75%).  
These results were considered by the authors to indicate a 
mutagenic effect (Fahrig, 1977); however, positive data such as 
those observed for trichloroethylene are among spontaneous values 
for this test system.  Chromosome aberrations

    (a)   Mammals (in vivo)

    Trichloroethylene (purity not given), repeatedly administered 
intraperitoneally to ICR mice for 5 days at a dose equivalent to 
half of the LD50, did not induce a significant increase in 

chromosome aberration frequency in bone marrow cells from animals 
killed 6, 24, and 48 h after the last treatment (Cerna & Kjpenova, 

    A single dose of trichloroethylene of 1000 mg/kg body weight 
(stabilized with thymol), administered orally to Swiss albino 
mice, did not induce a significant increase in the frequency of 
chromosome aberrations in bone marrow, 24 h after treatment 
(Loprieno & Abbondandolo, 1980). 

    The exposure of male mice (NMRI-Han/BGA) to trichloroethylene 
vapour (99.5% purity) for 24 h at concentrations of 272, 1090, and 
2430 mg/m3 (50, 202, and 450 ppm) did not induce dominant lethal 
mutations (Slacik-Erben et al., 1980). 

    CDI male mice were treated orally with 3000, 2250, 1500, 
1125, 750, or 375 mg/kg body weight (2 treatments in 24 h) with a 
trichloroethylene sample of high purity (99.5%) and sacrificed 6 h 
following the second treatment, for the analysis of the frequency 
of micronucleated erythrocytes in the bone marrow cells.  The 
results indicated a positive dose-related effect of 
trichloroethylene (Duprat & Gradiski, 1980). 

    Using high purity (99.8%) trichloroethylene, B6C3F1 mice (10 
female and 10 male) were treated by inhalation with 3240 mg/m3 
(600 ppm), for 7 h a day, 5 days a week, for a total of 52 days.  
The animals were killed 6 h and 24 h after the last treatment.  The 
cytogenetic analysis showed the presence only of gaps without any 
indication of induced chromosomal aberrations (Loprieno, personal 
communication, 1984). 

    When trichloroethylene of high purity (99.8%) was administered 
to B6C3F1 male mice, by gavage, in a single dose of 1200 mg/kg 
body weight, an increased frequency (4 times) of micronucleated 
erythrocytes in the bone marrow cells compared with control animals 
was observed, 42 h after dosing (Sbrana et al., 1984).  DNA damage


    Trichloroethylene (unspecified purity) was positive for 
the induction of mitotic gene conversion at the  trp locus and 
mitotic recombination in the D7 strain of  S. ceverisiae, under 
endogenous metabolic activation conditions (Callen et al., 1980).  
Trichloroethylene (unspecified purity) was also found to be 
positive for the induction of mitotic gene conversion at the  trp 
locus of  S. cerevisiae D7 strain treated  in vitro in the presence 
of a metabolic activation system obtained from rat liver.  Using 
the host-mediated assay technique, and a single oral dose of 
400 mg/kg body weight, given to mice inoculated with yeast cell 
D4 strain of  S. cerevisiae, a positive effect on the induction of 
mitotic gene conversion at the  trp 5 and  ade 2 loci was observed 
in the yeast cells recovered from the kidney.  Repeated oral 
administration of trichloroethylene to male mice, with a total 

dose of 3700 mg/kg body weight, induced a positive effect (mitotic 
recombination) in yeast cells recovered from the liver and kidney. 
In all these studies, the actual numbers of the convertant or 
recombinant colonies were not given, and the significance of the 
results is questionable (Bronzetti et al., 1978). 

    Trichloroethylene (stabilized with thymol) was considered 
inactive for the induction of mitotic recombinations in the D4 
strain of  S. cerevisiae following  in vitro and  in vivo (host-
mediated assay) studies (Loprieno & Abbondandolo, 1980). 

    Trichloroethylene of high purity (99.9%) induced somatic 
segregants in  A. nidulans strain 35 x 17, at concentrations of 
40 500 and 81 000 mg/m3 (7500 and 15 000 ppm), in a desiccator 
containing the plates inoculated with the fungal conidia; under 
identical doses and conditions, no mitotic recombinant colonies 
were induced in this strain of  A. nidulans by trichloroethylene 
(Crebelli et al., in press).  Mammalian cells ( in vitro)

    Trichloroethylene of high purity (99.9%) induced morphological 
transformations,  in vitro, in rat embryo cell cultures (Price et 
al., 1978). 

    Stabilized with thymol, trichloroethylene did not stimulate 
unscheduled DNA synthesis in an HeLa human cell line grown  in 
 vitro, in the presence or absence of a metabolic activation 
system (S9 mix) (Loprieno & Abbondandolo, 1980).  Trichloroethylene 
(unspecified purity) elicited DNA repair synthesis in human 
lymphocytes in the presence of S9 mix (Perocco & Prodi, 1981). 

    Exposure of Chinese hamster ovary cells (CHO) to 
trichloroethylene bubbled into the growth medium for 2 min, 
corresponding to a dose of 0.17% v/v for 1 h treatment time, 
did not induce sister-chromatid exchange (White et al., 1979). 

    Trichloroethylene bound covalently to calf thymus DNA  in vitro  
in the presence of a rat liver metabolic activation system (Di 
Renzo et al., 1982; Bergman, 1983). 

    When given ip to NMRI mice, twice daily for 5 days 
(33.6 mg/kg), trichloroethylene bound to RNA and DNA of brain, 
lung, liver, kidney, spleen, pancreas, and testis (Bergman, 1983).  Mutagenic activity of trichloroethylene metabolites

    Trichloroethylene oxide was not mutagenic for the TA 1535 
strain of  S. typhimurium or the WP2 UVRA strain of  E. coli (plate 
test), but was positive in the DNA repair test on  E. coli (Kline 
et al., 1982). 

    The same compound was found to be a direct mutagen for the 
yeast  S. pombe (forward mutation) and for mammalian cells grown 
 in vitro (V-79 cell line) (forward mutation) (Loprieno & 
Abbondandolo, 1980). 

    Syrian golden hamster embryo cells were exposed to 
trichloroethylene oxide (1.1, 2.5, and 5.0 µM) at 37 °C for 30 min.  
After 5 days, the number of transformed colonies was scored.  A low 
but dose-related increased frequency of transformed cells was 
induced (Di Paolo & Doniger, 1982). 

    Chloral hydrate has been reported to have direct genotoxic 
activity in  S. typhimurium (Waskell, 1978) and in  A. nidulans 
(Bignami et al., 1980). 

    At doses of 82.7, 165.4, or 4135 mg/kg body weight, chloral 
hydrate, administered intraperitoneally, induced chromosome non-
disjunction in the secondary spermatocytes of mice (Russo et al., 
1984).  Conclusions

    Pure trichloroethylene acts as a weak mutagen in  S. typhimurium 
in the presence of a metabolic activation system.  However, in all 
cases, the induced effect was never more than twice the spontaneous 
value.  Technical grade trichloroethylene containing stabilizers 
such as 1,2-epoxybutane epichlorohydrin, is mutagenic in 
 S. typhimurium in the absence of a metabolic activation system. 

    Pure trichloroethylene is not mutagenic for the yeast  S. pombe,
with or without metabolic activation,  in vitro or  in vivo (host-
mediated assay). 

    Thymol-stabilized trichloroethylene is not mutagenic for V-75 
hamster cells, with or without metabolic activation. 

    Trichloroethylene (99.5% pure) is a weak mutagen for the 
induction of somatic mutations in mouse embryo. 

    In mice, a single oral dose of trichloroethylene (1 g/kg body 
weight) or repeated exposure to 3240 mg/m3 (600 ppm) for 52 days, 
7 h/day, through inhalation, did not increase chromosome 
aberration frequency in bone-marrow cells.  A half-LD50 dose 
of trichloroethylene, administered ip to mice, did not increase 
chromosomal aberration frequency in bone-marrow cells.  In a 
micronucleus test, a single oral treatment with 1200 mg/kg body 
weight or repeated (twice) oral treatment with a series of doses 
ranging from 375 to 3000 mg/kg body weight increased the frequency 
of induced micronucleated erythrocytes in the bone-marrow cells of 
mice.  Trichloroethylene bound to DNA  in vitro and  in vivo to 
mouse tissues. 

    Dominant lethal mutations were not induced in mice exposed 
through inhalation to trichloroethylene vapours. 

    Trichloroethylene induces mitotic gene conversion in yeast 
cells grown under conditions allowing an endogenous metabolic 
activation system to function.  The same effect reported in yeast 
in the presence of an exogenous metabolic activation system 

(S9 mix), or in the host-mediated assay, is questionable, because 
of inadequate data and the fact that other studies produced 
negative data. 

    A positive effect for the induction of unscheduled DNA 
synthesis (UDS) in human lymphocytes, treated  in vitro, was 
reported by Perocco & Prodi (1981), whereas a negative response 
for the same biological effect (UDS) in a human fibroblast cell 
line (HeLa) grown  in vitro was observed by Loprieno & Abbondandolo 

    Trichloroethylene induces morphological transformation in rat 
embryo cells. 

    The available results, shown in Table 9, are not adequate 
for a complete evaluation of the genotoxic potential of 
trichloroethylene.  Only a few mutagenicity studies have indicated 
the grade and purity of the trichloroethylene sample employed.  
The confusing results could be due either to the use of 
trichloroethylene samples stabilized with mutagenic compounds or to 
the use of pure trichloroethylene samples which, unstablized, can 
rapidly decompose to chemicals with mutagenic activity. 

6.1.9.  Reproduction, embryo/fetotoxicity, and teratology

    The embryo/fetal toxicity and teratogenic potential of 
trichloroethylene have been evaluated in the avian embryo system, 
the mouse, rat, and rabbit.  Reproductive function has been 
examined in male rats.  Avian embryo system

    Exposing avian embryos to 1% trichloroethylene (10 g/litre) 
caused a significant increase in embryonic death and a slight 
increase in anomalies (Fink, 1968).  These observations were made 
on the 3rd day of development, a time at which frank malformations 
would be difficult to observe or evaluate.  Elovaara et al. (1979) 
reported the results of a comparative study of the teratogenic 
potential of trichloroethylene and other aliphatic chlorinated 
hydrocarbons in the chick embryo.  Trichloroethylene (reagent 
grade) in doses ranging from 5 to 1000 µmoles in olive oil (25 µl) 
was injected into the air space of fertilized eggs on the 2nd and 
6th days of incubation and examined on the 14th day.  The LD50 for 
trichloroethylene was between 50 and 100 µmoles/egg.  Macroscopic 
embryonic malformations occurred in 9 out of 55 surviving embryos, 
5 times the incidence in the vehicle control eggs. 

    In another study, injection of low doses of trichloroethylene 
(1, 5, 10, and 25 µmol/egg), on days 1 and 2 of embryogenesis, 
resulted in embryotoxicity, growth defects, and morphological 
anomalies (Bross et al., 1983). 

Table 9.  Summary of the mutagenicity data reported for trichloroethylene
Organism                                 Genotoxic effects                               
             Gene                    Chromosome                       DNA
             mutation                anomalies                        damage
prokaryotes  weak
fungi        negative ( in vitro)     positive                         negative ( in vitro)
             negative (hma)          mitotic                          weak (hma)
             positive? ( in vitro)    segregation                      positive (yeast
             positive  (A. nidulans)  A. nidulans                      metabolism)
mammalian    negative                                                 negative (SCE)
cells                                                                 negative (DNA
( in vitro)                                                            repair synthesis)
                                                                      positive (covalent
mammals      weak                    negative (1 dose) (1 g/kg body
( in vivo)                            weight, oral) 
                                     negative (52 doses) (3240 mg/m3, 
                                     negative (5 doses) (1/2 LD50, ip) 
                                     positive (micronuclei) 1200 mg/kg 
                                     positive (micronuclei) (375 - 
                                     3000 mg/kg)
                                     negative (dominant lethals) (270, 
                                     1090, 2430 mg/m3, inhalation)
For human cases, see Table 10.  Mouse

    Swiss-Webster mice were exposed by inhalation to 
trichloroethylene at 1620 mg/m3 (300 ppm), for 7 h daily, on days 
6 - 15 of gestation (Day 0 = vaginal plug).  The mice were observed 
daily throughout pregnancy.  Maternal body weights were recorded on 
days 6, 10, and 18 of gestation as an index of maternal toxicity.  
On day 18, no effect was observed on the average number of 
implantation sites/litter, litter size, the incidence of fetal 
resorptions, fetal sex ratios, or fetal body measurements (Schwetz 
et al., 1975).  The incidence of gross anomalies observed by 
external examination was not significantly greater than that among 
the control litters.  Trichloroethylene exposure did not exert any 
effect on the incidence of skeletal anomalies in mice, and 
microscopic examination did not reveal any abnormalities in organs, 
tissues, or cells (Leong et al., 1975; Schwetz et al., 1975).  Rat

    In studies similar to the preceding mouse study, exposure to 
trichloroethylene at 1620 mg/m3 (300 ppm) did not produce any 
evidence of maternal toxicity or teratogenicity in Sprague Dawley 

rats (Leong et al., 1975; Schwetz et al., 1975) or Charles River 
strain rats (Bell, 1977). 

    Exposing Sprague Dawley rats to trichloroethylene at 2700 mg/m3 
(500 ppm) for 7 h per day, 5 days per week, during a 3-week 
pregestational period, and 7 h per day each day for days 0 - 18 and 
days 6 - 18 of gestation did not cause maternal or embryo/fetal 
toxicity.  Beliles et al. (1980) concluded that the frequency and 
the character of the macro- or microscopic findings in the treated 
groups did not indicate either adverse fetal effects or that 
trichloroethylene, at the dose used, was teratogenic. 

    Dorfmueller et al. (1979) reported that female Long-Evans rats 
exposed to trichloroethylene at 9720 mg/m3 (1800 ppm) before 
mating, for 6 h per day, 5 days per week, for 2 weeks and/or during 
pregnancy, for 6 h per day, each day, for 0 - 20 days of gestation) 
did not exhibit any signs of maternal toxicity.  There was no 
indication of embryotoxicity, and no significant treatment effects 
or interactions were found in the number of corpora lutea or 
implantation sites/litter, fetal body weights, resorbed 
fetuses/litter, or sex ratios.  No significant treatment effects 
were observed in the analysis of total soft-tissue anomalies.  
However, prenatal exposure to trichloroethylene at 9720 mg/m3 
(1800 ppm) caused an increase in minor anomalies of the offspring 
(incomplete ossification of the sternum) indicative of development 
delays in maturation, but not of major malformation. 

    While the study did not indicate any treatment-related effects 
on general post-natal behaviour, there was a small but significant 
regression in post-natal weight gain in offspring in the pre-mating 
exposure group. 

    In groups of male rats dosed by gavage with trichloroethylene 
at 10, 100, or 1000 mg/kg body weight 5 days per week, for 6 weeks, 
there was no evidence of spermatotoxic effects.  Trichloroethylene-
related effects of reduced weight gain and elevated liver/body 
weight ratios were seen primarily in the 1000 mg/kg group.  
Copulatory behaviour was initially diminished by the narcotic 
properties of trichloroethylene, but was normal by the 5th week 
(Zenick et al., 1984).  Rabbit

    Female New Zealand white rabbits were exposed by inhalation to 
trichloroethylene at 2700 mg/m3 (500 ppm), for 7 h per day, 5 days 
per week, during a 3-week pregestation period, and daily, for days 
0 - 21 and days 7 - 21 of gestation (Day 0 = mating day).  There 
was no evidence of maternal toxicity or embryotoxicity.  The 
occurrence of hydrocephalus in a few fetuses in one of the study 
groups was reported (4 fetuses in 2 litters), but no definitive 
conclusion was drawn from these findings (Beliles et al., 1980). 


7.1.  Aquatic Organisms

    There is little information on the toxicity of 
trichloroethylene for fish.  The US Registry of Toxic Effects of 
Chemical Substances (Christensen & Lugenbyhl, 1975) reports, for an 
unidentified species, that exposure to a concentration range of 
100 - 1000 mg/litre produced toxic effects in 96 h.  Toxicity tests 
carried out on salt-water flatfish,  Limanda limanda (sole), 15 - 
20 cm long, in a continuous water flow, established a 96-h LC50 
of 16 mg/litre (Pearson & McConnell, 1975).  A 96-h LC50 of 
approximately 40 mg/litre (static) or 67 mg/litre (continuous flow) 
has been reported for the minnow  Pimephales promelas (Alexander et 
al., 1978). 

    Verschueren (1977) established an LC100 of 600 mg/litre for 
 Daphnia magna.  The LC50 for the balanide salt-water crustacean 
nauplius (larva)  (Elminius modestus) was 20 mg/litre after 46 h 
(Pearson & McConnell, 1975), and the LC50 for the protozoon 
 Entosiphon sulcatum was established as 1200 mg/litre (Bringmann 
& Kuhn, 1980). 

    Various LC50 values have been established for algae including 
63 mg/litre for  Microcystis aeruginosa, (Verschueren, 1977); a 
concentration of 1000 mg/litre did not have any observable effect 
on  Scenedesmus quadricauda (Bringmann & Kuhn, 1980).  A short-term 
photosynthesis efficiency test gave an LC50 of 8 mg/litre 
(Pearson & McConnell, 1975) and, finally, in tests carried out on 
 Thalassiosira pseudonana and  Dunaliella tertiolecta, there were 
observable effects at 50 and 100 µg/litre, in a mixed culture 
(Biggs et al., 1979). 

7.2.  Uptake, Distribution, Storage, Metabolism, and Elimination in 
Plant and Animal Organisms

    Bioaccumulation of trichloroethylene in a marine environment 
has been studied by Pearson & McConnell (1975); concentration 
levels were determined for a wide variety of marine organisms, 
mostly in the Bay of Liverpool. 

    The greatest increase in trichloroethylene concentrations in 
the tissues of animals that are relatively high up in the food 
chain (birds' eggs, fish liver, and seal fat) was nearly 100 times 
the level in water (from 0.5/109 µg/litre in water to 50/109 µg/kg 
in tissues). 

    These data agree with the laboratory findings of Barrows et 
al. (1980) who, in a 14-day test, noted that trichloroethylene 
accumulation in the sunfish species,  Lepomis macrochirus was 17 
times that of the aquatic medium with a halving time of less than 
one day.  A low bioconcentration factor (concentration in organism 
divided by  concentration in environment) (Uehleke et al., 1977) 
has been derived using water solubility and the equation proposed 
by Kenaga (1980) and Kenaga & Goring (1980). 

7.3.  Effects on the Stratospheric Ozone Layer

    Consideration has been given to the possibility that 
trichloroethylene, together with other halocarbons in the 
atmosphere, may contribute to the depletion of the stratospheric 
ozone layer, which would lead to atmospheric heating and increased 
exposure of terrestrial biota to ultraviolet radiation (Molina & 
Rowland, 1974).  Atmospheric trichloroethylene concentrations seem 
to be about one-fifth to one-tenth of those of other chlorocarbons 
such as CH3CCl3, CH2Cl2, CCl4, or C2Cl4 or the major chlorofluoro- 
carbons (Cronn et al., 1977; Penkett, 1982).  The reason for this 
is that while trichloroethylene emissions into the atmosphere are 
of the same order as those of other halocarbons (Jesson, 1980), 
trichloroethylene is efficiently scavenged by hydroxyl radicals 
in the troposphere, and the reaction rate for this process is 
appreciably faster for trichloroethylene than for other halocarbons 
(Penkett, 1982).  Thus, the predicted atmospheric lifetime for 
trichloroethylene is short (about 10 - 11 days) (Derwent & 
Eggleton, 1978; Graedel, 1978) compared with those for the 
chlorofluorocarbons, which may be 10 years or more (Jesson, 1980).  
It is not clear whether trichloroethylene is even present in the 
stratosphere (Cronn et al., 1977).  However, the data suggest that 
trichloroethylene is unlikely to be involved in the possible 
depletion of the ozone layer. 


8.1.  General Symptoms and Signs

8.1.1.  Acute effects

    Sorgo (1976) reported a lethal oral dose for trichloroethylene 
to be 7 g/kg body weight, and Lazarev et al. (1977) reported a 
fatality after the oral ingestion of less than 50 ml. 

    At exposure concentrations of 270 - 540 mg/m3 (50 - 100 ppm), 
the most common symptoms are headache, sluggishness, sleepiness 
(especially at the end of the workshift), dulling of senses, 
dizziness, nausea, and vomiting (Rubino et al., 1959; Lilis et 
al., 1969; Governa, 1981).  At narcotic doses, vomiting may occur. 

    Trichloroethylene has been used as an analgesic and as an 
anaesthetic on its own or in mixtures.  It is now much less used 
for this purpose, as safer and more effective alternatives are 
available.  Inhalation of 27 000 mg/m3 (5000 ppm) produces light 
anaesthesia; concentrations of up to 108 000 mg/m3 (20 000 ppm) 
have been used for deeper anaesthesia (Wade, 1977). 

    Clinical signs are not very specific.  There can be enhanced 
responsiveness to caloric stimulation of the labyrinth and some EEG 
anomalies may be detected (Chiesura, 1980) (section 8.2).  Acute 
hepatic and renal toxicity has been reported (Sucui & Olinici, 

    A particular intolerance to ethanol may occur after ingesting 
even small amounts of alcoholic beverages.  This intolerance is 
characterized by intense cutaneous vasodilatation, particularly in 
the face, often called "degreaser's flush" (Stewart et al., 1974). 

    Non-specific effects on the digestive system (e.g., dyspepsia, 
gastritis, and diarrhoea) have been reported in cases of suicidal 
or accidental ingestion of trichloroethylene (Bozza Marrubini et 
al., 1978; Governa, 1981). 

8.1.2.  Chronic effects

    The existence of a condition of chronic trichloroethylene 
poisoning is not clear (Chiesura, 1980; Boudène et al., 1983).  
However, chronic effects in human beings can occur following 
prolonged exposure to moderate concentrations of trichloroethylene 
of about 540 mg/m3 (100 ppm).  The clinical picture is mainly 
related to the central nervous system (CNS), and consists of 
asthenia, anorexia, headache, loss of memory, moodiness, 
depression, insomnia, paraesthesia, and disturbances of the 
autonomic nervous system such as hyperhydrosis, tachycardia, and 
dermographism (Ahlmark & Forssman, 1951a,b; Bardodej & Viskocil, 
1956; Rubino et al., 1959; Lerza et al., 1963; Castellino, 1969). 

    The role of trichloroethylene in inducing liver damage in 
occupationally-exposed human beings is not clear (Parmeggiani, 
1956; Capellini & Grisler, 1958; Rubino et al., 1959; Tolot et al., 
1964; Schuttmann, 1970; Lachnit, 1971; Thiele, 1982; Sucui & 
Olinici, 1983; Svabova & Mencik, 1983). 

    Human subjects with high repeated, but non-occupational, 
exposure may exhibit toxic effects on the liver (e.g., elevated 
aspartate (EC and alanine aminotransferase (EC, 
renal insufficiency, and abnormal EEG patterns (Baerg & Kimberg, 
1970).  Following accidental or suicidal ingestion (e.g., doses of 
100 - 300 ml), hepatic necrosis and nephropathy have been found in 
autopsy cases (Keinfeld & Tabershaw, 1954; Graovac-Leposavic 
et al., 1964; Priest & Horn, 1965; Beisland & Wannag, 1970; 
Clearfield, 1970).  A decrease in sexual potency has been reported 
in industrial workers exposed to trichloroethylene (Bardodej & 
Vyskocil, 1956; Lazarev & Gadaskiva, 1977). 

    Trichloroethylene is one of the volatile solvents inhaled 
("sniffed") for its euphoric effect (Hayden et al., 1976), and 
abuse by oral self-administration has been reported (Wells, 1982).  
Centrilobular hepatic necrosis and renal toxicity have occurred in 
addicts (Baerg & Kimberg, 1970; Clearfield, 1970), and deaths have 
been reported (James, 1963; Musclow & Awen, 1971).  Some mixtures 
sold commercially as trichloroethylene may contain other solvents, 
including carbon tetrachloride, which can contribute to the toxic 
manifestations (Bouyges et al., 1980; Conso et al., 1980).  
Dependent patients may show withdrawal symptoms (Ikeda et al., 

8.2.  Effects on Organs and Systems

8.2.1.  Effects on the nervous system

    Acute effects on the central nervous system (CNS) are 
characterized by two sequential phases (i.e., excitation and 
depression), and are usually reversible.  These symptoms generally 
prevail over those of other systems (Stewart et al., 1962; 
Chiesura, 1980; Governa, 1981). 

    In the early phase of excitation, euphoria and inebriation are 
present.  The subsequent phase of CNS depression is characterized 
by various degrees of narcosis culminating in coma (Caccuri, 1976; 
Chiesura, 1980).  Muscular hypotony, muscular spasms, reduced 
tendon reflexes, and loss of co-ordination may occur (Huff, 1971). 

    Changes in EEG patterns may vary considerably.  The EEG may 
be normal in some cases, while substantial alterations, regressing 
after a few days, may be observed in others.  The most frequently 
observed change is a decrease in alpha activity, which is often 
irregular.  Widespread rapid rhythms or low theta activity may also 
be present (Chiesura, 1980). 

    Exposure to trichloroethylene at a concentration of 540 mg/m3 
(100 ppm) produces various results on the CNS.  Though there may 
not be any evidence of effects on psychomotor capacities (Stewart 
et al., 1970), reductions in mental performance evidenced by the 
test for perception, past recall, answering speed, and response 
and manual dexterity tests have been reported (Ferguson & Vernon, 
1970).  Visual and auditory evoked potentials were affected at 
exposure levels ranging between 270 and 540 mg/m3 (50 and 100 ppm), 
for 3 1/2 - 7 1/2 h (Winneke, 1982). 

    The behavioural effects of exposure to trichloroethylene have 
been studied under laboratory and work-place conditions. Laboratory 
exposure to 540 or 1080 mg/m3 (100 or 200 ppm), for 70 min, had no 
effect on reaction time or short-term memory (Gamberale et al., 
1976).  Volunteers exposed to 540, 1620, or 5400 mg/m3 (100, 300, 
or 1000 ppm), for 2 h, showed significant impairment in a number 
of psychomotor tests at 5400 mg/m3 but not at 1620 or 540 mg/m3 
(Vernon & Ferguson, 1969).  In a further study (Ferguson & Vernon, 
1970), effects were again found at 5400 mg/m3 and marginal effects 
at 1620 mg/m3.  In another study, exposure of volunteers to 810 
or 1620 mg/m3 (150 or 300 ppm), for 2 1/2 h, did not produce 
any significant impairment in behavioural test results (Ettema 
& Zielhuis, 1975).  With repeated exposure under work-place 
conditions, no behavioural effects were observed with mean 
atmospheric levels of 270 mg/m3 (50 ppm) (Triebig et al., 1977a,b).  
In a study of complex reaction time in an occupational group with a 
mean exposure of 1320 mg/m3 (245 ppm), reaction time was increased 
in comparison with that in a control group (Gun et al., 1978).  
Motor nerve conduction velocity was not affected in a group 
occupationally exposed to mean atmospheric levels of less than 
270 mg/m3 (50 ppm) (Triebig et al., 1982). 

    A study on 122 exposed workers (Ahlmark & Forssman, 1951a) 
showed that symptoms of toxicity in human beings were correlated 
with urinary levels of metabolic trichloroacetic acid.  With 
urinary concentrations of up to 20 mg trichloroacetic acid/litre, 
no particular symptoms were noted.  With urinary levels ranging 
between 45 and 75 mg/litre, headache, fatigue, increased need for 
sleep, irritability, and alcohol intolerance were reported in 50% 
of workers.  When urinary levels of trichloroacetic acid exceeded 
300 mg/litre, these symptoms were found in 100% of subjects.  
Initial nervous-system signs of toxicity were reported to be 
associated with the urinary excretion of trichloroacetic acid 
at 75 mg/litre and 30 mg/litre (Lazarev & Gadaskiva, 1977). 

    Two types of irreversible neurotoxic effects have been reported 
in man.  One is the specific degeneration of the cranial nerves, in 
particular the trigeminal, the olfactory, and the facial nerves 
(Goldblatt, 1956; James, 1963; Kjellstrand et al., 1980; Barrett 
et al., 1982).  However, it is considered that this effect is 
not produced by trichloroethylene itself but by its decomposition 
product, dichloroacetylene (Henschler et al., 1970a).  In addition, 
polyneuropathies involving the whole peripheral nervous system have 
been described after long-term exposure to trichloroethylene 
(Szulc-Kuberska, 1972). 

8.2.2.  Effects on the cardiovascular system

    Several cases of sudden death due to cardiac arrest have been 
reported in subjects exposed to trichloroethylene, either medically 
or occupationally (Ostelere, 1953; Norris & Stuart, 1957; Meyer, 
1966; Wiecko, 1966; Clearfield, 1970; Tomasini, 1976).  It has 
been suggested that these deaths might be due to an increased 
sensitivity of the myocardium to endogenous and exogenous 
catecholamines.  The event would entail irregular cardiac 
rhythm due to the onset of ectopic foci with atrioventricular 
dissociation.  A range of alterations in cardiovascular function 
(e.g., atrial and ventricular extrasystole, tachycardia, and 
ventricular fibrillation) has been reported (Bardodej & Viskocil, 
1956; Anderson, 1957; Lilis et al., 1969; Tomasini, 1976; Governa, 

8.2.3.  Effects on the respiratory system 

    Under normal conditions of exposure, trichloroethylene did not 
induce any effects on the respiratory tract but, at high exposure 
levels of 810 - 3510 mg/m3 (150 - 650 ppm), there may be effects 
due to local irritation (Bardodej & Viskocil, 1956; Jouglard & 
Vincent, 1971; Meyer, 1973; Gaultier et al., 1974; Tomasini, 1976).  
Breakdown products are of more importance than trichloroethylene 
with respect to the effects on the respiratory system (Castellino, 

8.2.4.  Effects on the urinary tract

    Altered renal function has been described in both acute and 
chronic trichloroethylene poisoning (Nomura, 1962; Graovac-
Leposavic et al., 1964; Clearfield, 1970).  The nephropathy 
observed could be due to impurities rather than to the 
trichloroethylene; technical grade trichloroethylene might have 
contained nephrotoxic chlorinated hydrocarbons (e.g., 1,1,2,2-
tetrachloroethane) as impurities (Chiesura, 1980). 

8.2.5.  Effects on the skin

    When applied to the skin, trichloroethylene causes erythema 
(Wahlberg, 1984).  It is only mildly irritating to human skin 
providing it is not held in contact (e.g., by clothing or 
footwear).  Chemical burning of the skin has been reported 
following prolonged contact (Maloof, 1949; Tomasini, 1976).  There 
is a considerable difference in individual susceptibility to the 
effects of repeated exposure.  The reaction to repeated contact 
(which will defat the skin) may take the form of an erythematous, 
exudative, vesicular, eczematous, or exfoliative dermatitis (Roche 
et al., 1958; Stopps & McLaughlin, 1967; Ettema et al., 1975).  
Secondary infection of the skin may complicate the dermatitis. 
"Degreaser's flush", a reddening of the skin in some individuals 
ingesting ethanol after exposure to trichloroethylene, can occur 
(section 8.1.1). 

8.2.6.  Effects on the eye

    Liquid trichloroethylene in the eye produces pain and 
discomfort and superficial damage to the cornea, but complete 
recovery occurs within a few days (Grant, 1974).  Exposure to high 
concentrations of vapour (anaesthetic levels of 27 500 - 108 000 
mg/m3) also causes eye irritation and superficial damage to the 
cornea, but again with complete recovery (Grant, 1961). 

8.2.7.  Carcinogenicity

    A number of epidemiological studies have been conducted to 
examine the possible carcinogenic effects of trichloroethylene in 
occupationally-exposed populations, and the major findings are 
summarized in Tables 10 and 11.  Some of these studies have 
followed groups with specified exposure to trichloroethylene 
(Axelson et al., 1978, 1984; Tola et al., 1980) (Table 10), whereas 
others have involved workers in laundry and dry cleaning with more 
or less mixed exposures including trichloroethylene (Blair et al., 
1979; Malek et al., 1979; Katz & Jowett, 1981) (Table 11).  Other 
studies are of a case-reporting or a case-referent (case-control) 
type, concerning pancreatic (Lin & Kessler, 1981) and liver tumours 
(Novotna et al., 1979; Paddle, 1983) or other conditions and, also, 
involving exposure to other solvents (Lin & Kessler, 1981).  Some 
case-control studies of lymphomas, both of the Hodgkin and non-
Hodgkin type (Olsson & Brandt, 1980; Hardell et al., 1981) and of 
liver cancer (Hernberg et al., 1984) have mentioned exposure to 
trichloroethylene as a factor in a few cases, but the numbers are 
too small for any conclusions to be drawn about trichloroethylene 
as a risk factor. 
Table 10.  Summary of epidemiological studies on carcinogenicity with specific reference 
to trichloroethylene exposure
Type of study/cohort        Remarks                                       Reference
Mortality in a cohort   1.  Exposure intensity had been monitored since   Axelson et al.
of 518 male workers         1950 in terms of urinary excretion of         (1978)
(7688 person-years)         trichloroacetic acid (TCA).

                        2.  No significant excess of cancer mortality 
                            either in the high-dose group (> 100 mg 
                            TCA/litre urine) or the low-dose group 
                            (< 100 mg TCA/litre urine).

                        3.  Results of first update, see Axelson (1984) 

Table 10.  (contd.)
Type of study/cohort        Remarks                                       Reference
Mortality in a cohort   1.  Exposure information was based on TCA         Tola et al. 
of 1148 male workers        determinations in the urine, permitting       (1980)     
and 969 female workers      latency requirements of 6 - 13 years.  Loss 
(4269 person-years for      to follow-up was 9%.
                        2.  Trichloroethylene was not carcinogenic 
                            (given a latency period of 6 to 13 years) 
                            among those exposed at low levels (100 mg 
                            TCA/litre urine in 91% of the cohort).

                        3.  Cohort to be updated at 5-year intervals.

Mortality and           1.  Extension and update of the first-mentioned   Axelson et al.
incidence in a              study, 65% with exposure from 1970 to 1975    (1984)
cohort of 1424 men          and with more than 90% having TCA levels 
                            < 100 mg/litre.

                        2.  Deficit found in mortality from cancers (22 
                            versus 36.9 expected), but a significant 
                            excess of urinary tract (11 versus 4.85) and 
                            haematolymphatic tumours (5 versus 1.20).

                        3.  Specifically, there were 3 urinary bladder 
                            cancers versus 0.83 expected, 4 cancers of 
                            the prostrate versus 2.35 expected and 2 
                            lymphomas versus 0.27 expected, requiring
                            2 years or more of exposure and 10 years of 

Table 11.  Summary of epidemiological studies and case reports on carcinogenicity of 
mixed exposures involving trichloroethylene or trichloroethylene production
Type of study/cohort        Remarks                                       Reference
Cohort of 330 laundry   1.  Significant increase in lung and cervical     Blair et al.
and dry-cleaning            cancer, and a slight excess of leukaemia and  (1979)
workers                     liver cancer detected.

                        2.  Exposed also to other chemicals such as 
                            benzene and carbon tetrachloride.

                        3.  To be extended to a prospective study of 
                            2 - 5 x 103 workers.

Cohort of 37 male       1.  Exposure intensity was such that TCA in       Malek et al.
dry-cleaning workers        urine was less than 100 mg/litre in over 60%  (1979)
                            of the cohort.                         

                        2.  6 cases of cancer, none of which were in the 

Table 11.  (contd.)
Type of study/cohort        Remarks                                       Reference
Cohort of 671 female    1.  Death certificates were employed.             Katz & Jowett
laundry/dry-cleaning                                                      (1981)
workers (controls:      2.  Elevated risks of genital (unspecified) and 
entire female working       kidney cancers were detected, along with a 
population and other        smaller excess of bladder and skin cancer and 
low-wage occupations)       lymphoma.

109 pancreatic cancer   1.  Hospital records were employed.               Lin & Kessler
patients, case-control                                                    (1981)
study                   2.  An association was observed between 
                            pancreatic cancer and exposure to dry-
                            cleaning chemicals and gasoline fumes, as 
                            well as to drinking of decaffeinated (by 
                            means of trichloroethylene) coffee.

                        3.  No information was available on extent or 
                            type of exposure.

95 liver cancers,       1.  Cancer registry data on liver cancer in the   Paddle (1983)
case-study                  area of a production plant were employed.

                        2.  No case could be definitely tied to 
                            trichloroethylene production.
    While some of these studies are continuing as prospective 
studies to cover larger populations, they suffer, in general, from 
one or more of the following factors:  (a) small cohort population, 
(b) young age of the cohort, (c) a rather short follow-up period, 
(d) relatively few cases, (e) inaccurate or uncertain estimation 
of intensity and duration of exposure to trichloroethylene, (f) 
possible exposure to other chemicals, even in the more specific 
studies, including potential carcinogens, and (g) inadequate 
information on other general risk factors for cancer, such as 
smoking, even if the influence of uncontrolled confounding is 
likely to be limited in this respect. 

    At present, it is not possible to draw definite conclusions 
from the existing epidemiological data on the carcinogenic 
potential of trichloroethylene.  However, the appearance of an 
excess of haematolymphatic malignancies in several of the studies, 
possibly associated with trichloroethylene exposure (Blair et al., 
1979; Hardell et al., 1981; Katz & Jowett, 1981; Axelson et al., 
1984) deserves attention.  Furthermore, genito-urinary tumours were 
over-represented in 3 studies (Blair et al., 1979; Katz & Jowett, 
1981; Axelson et al., 1984), though the picture is less consistent 
with regard to the specific sites involved (bladder, kidney, 
prostrate, and cervix). 

    It was noted that IARC (1979, 1982) concluded that 
epidemiological studies on human beings were inadequate to make an 


9.1.  Levels of Exposure

9.1.1.  General population

    The general population is exposed to very low levels of 
trichloroethylene in air, water, and food (Table 12).  The move 
away from the use of trichloroethylene in anaesthesia, the solvent 
extraction and fumigation of foodstuffs, and the dry-cleaning 
of textiles has reduced exposure from these sources.  
Trichloroethylene does not accumulate significantly in the food 
chain.  It is degraded by both biotic and abiotic processes and 
its persistence in various environmental compartments is relatively 
short, of the order of days or months rather than years.  In ground 
water, the absence of actinic radiation means that the rate of 
degradation is slower, and trichloroethylene contamination may be 
relatively prolonged (e.g., half-life of 2 1/2 years). 

Table 12.  Maximum observed concentrations of trichloroethylene
in environmental media
Media                       Maximum observed concentration
Open water reservoir        220 µg/litre

Industrial discharge water  200 µg/litre
Rain water                  ~ 1 µg/litre

Atmosphere                  ~ 40 µg/m3

Dairy foods                 10 µg/kg

Meat                        22 µg/kg

Fats and oil                19 µg/kg

    Accidental or suicidal ingestion by adults occurs, but is 
influenced by the limited availability of trichloroethylene for 
domestic use in many countries. 

9.1.2.  Occupational exposure

    Exposure during the actual production of trichloroethylene is 
relatively low because of the nature of the process.  Subsequent 
uses in, for example, metal degreasing and the dry-cleaning of 
textiles, can involve higher exposures.  The respiratory route is 
the principal route of exposure with dermal exposure as an 
additional route.  Oral intake is insignificant in occupational 

9.2.  Evaluation of Human Health Risks

9.2.1.  Acute effects

    The predominant effect of trichloroethylene in human beings 
is on the central nervous system; liver and kidney damage can also 
occur.  Central nervous system depression can result in coma and 
death.  A lethal dose as low as 50 ml (75 g) has been reported 
but, in general, the lethal dose for an adult is approximately 
7000 mg/kg body weight.  The threshold for demonstrable behavioural 
effects, resulting from inhalation exposure, is approximately 1350 
mg/m3 (250 ppm); less well-defined subjective complaints have been 
reported with exposure to concentrations of 270 - 540 mg/m3 (50 -
100 ppm) for a few hours. 

    Cardiac arrhythmia has been reported during anaesthesia 
involving trichloroethylene at inhaled concentrations of 27 000 - 
54 000 mg/m3 (5000 - 10 000 ppm) (blood levels 60 - 120 mg/litre). 

    It should be noted that ethanol potentiates the central nervous 
system effects of trichloroethylene.  Exposure to trichloroethylene 
at 1080 mg/m3 (200 ppm) with blood ethanol levels of 300 - 450 
mg/litre produces demonstrable behavioural effects. 

    Irreversible neurotoxic effects on the trigeminal nerve have 
been described in anaesthesia with trichloroethylene, using a 
closed-circuit system with soda lime.  This effect is attributed to 
the generation of dichloroacetylene and not to trichloroethylene. 

9.2.2.  Chronic effects

    The main chronic effects of trichloroethylene in human beings 
are disturbances in the central nervous system, as well as effects 
on the kidney and liver. 

    Nervous system symptoms (headache, fatigue, irritability, and 
alcohol intolerance) begin to occur when levels of trichloroacetic 
acid in urine are about 30 - 75 mg/litre.  No symptoms have been 
reported at concentrations of 20 mg/litre in urine, which 
corresponds to a concentration of trichloroethylene in air of about 
50 mg/m3. 

    For effects on other organs, there is no clear-cut quantitative 
information on dose response.  There are insufficient data on 
possible effects on human chromosomes. 

    Epidemiological data on the carcinogenicity of trichloro-
ethylene are inconclusive, but a slight excess of genito-urinary 
cancers and lymphomas in some studies on dry cleaners and metal 
degreasers deserves further attention. 

    The results of long-term exposure studies on rodents have shown 
that the liver and kidney are the critical organs.  Cytomegaly and 
karyomegaly of renal tubular cells was observed in male rats 

exposed to pure trichloroethylene at 1620 mg/m3 (300 ppm), for 7 h 
per day, 5 days per week, for 104 weeks, but not at 540 mg/m3 (100 

    No embryotoxic or teratogenic effects have been observed in 
mice and rats with inhalation of trichloroethylene at levels of 
1620 mg/m3 (300 ppm). 

    Data on the genetic effects of trichloroethylene are 

    Lifetime exposure of mice to trichloroethylene at 1620 mg/m3 
(300 ppm) through inhalation or to oral doses of 700 - 1200 mg/kg 
body weight per day produced lung and liver tumours.  A low 
incidence of renal tumours was found in rats exposed to a 
trichloroethylene concentration of 3240 mg/m3 (600 ppm) by 
inhalation or to 500 - 1000 mg/kg body weight per day by gavage. 

    A dose-related increase in Leydig (interstitial) cell tumours 
of the testis was observed in one study on male Sprague Dawley rats 
following long-term inhalation exposure to trichloroethylene 
concentrations of > 540 mg/m3 (> 100 ppm). 

    Thus, there is clear evidence that trichloroethylene is 
carcinogenic in mice.  There is also some evidence that 
trichloroethylene causes tumours in rats.  The significance of 
these findings needs to be evaluated in the context of further 
studies on the mechanism of action of trichloroethylene. 

9.3.  Treatment of Poisoning in Human Beings

9.3.1.  Emergency measures  General points

    In the treatment of trichloroethylene poisoning, pressor amines 
should not be used because of the risk of producing arrhythmias in 
the trichloroethylene-sensitized myocardium (Bozza Marrubini et 
al., 1978).  Hypotension may be treated by transfusion.  If 
necessary, anti-arrhythmic and beta-blocking agents can be 
administered.  Haemodialysis, haemoperfusion, or plasmapheresis 
have been reported to be useful (Zaffiri et al., 1968; Roessler 
& Morawiec-Borowiac, 1973; Malizia et al., 1984).  Medical advice 
should always be obtained in cases of over-exposure to, or frank 
poisoning by, trichloroethylene.  Ingestion

    Vomiting should not be induced, because of the danger of 
aspiration into the larynx and lungs and consequent risks of 
vagal inhibition or chemical pneumonitis.  Gastric lavage can be 
effective if performed within 4 h.  Adsorbents such as activated 
charcoal or liquid paraffin (medicinal grade) reduce intestinal 
absorption; saline laxatives will speed elimination (Bothe et al., 
1973).  If the patient is in a state of stupor or coma, intubation 
must be performed before gastric lavage.  Inhalation

    The victim should be removed from the polluted area and placed 
in a semi-prone position ensuring that the airway is clear.  If 
the victim is in a state of stupor or coma, oxygen should be 
administered.  If spontaneous respiration is absent or very weak, 
artifical respiration should be applied.  Dermal exposure

    All contaminated clothing should be removed and the affected 
parts of the body washed thoroughly with soap and plenty of water.  Eye exposure

    The eyes should be thoroughly irrigated with water for at least 
15 min, and ophthalmological advice obtained on the possible need 
for further treatment. 


ABRAHAMSEN, A.M.  (1960)  Quantitative estimation of 
trichloroacetic acid in the urine and serum in trichloroethylene 
poisoning.  Acta pharmacol. toxicol., 17: 288-294. 

ACGIH  (1982)  TLVs -  Threshold limit values for chemical 
 substances in workroom air adopted by ACGIH for 1982, Cincinnati, 
Ohio, American Conference of Governmental Industrial Hygienists, 
p. 32. 

D.D.  (1951)  Vapor toxicity of trichloroethylene determined by 
experiments on laboratory animals.  Arch. ind. Hyg. occup. Med., 
4: 469-481. 

AHLMARK, A. & FORSSMAN, S.  (1951a)  Evaluating trichloroethylene 
exposures by urinalyses for trichloroacetic acid.  Arch. ind. Hyg. 
 occup. Med., 3: 386-398.

AHLMARK, A. & FORSSMAN, S.  (1951b)  The effect of 
trichloroethylene on the organism.  Acta physiol. scand., 
22: 326-339. 

ALEXANDER, H.C., MCCARTHY, W.M., & BARTLETT, E.A.  (1978)  Toxicity 
of perchloroethylene, trichloroethylene, 1,1,1-trichloroethane, 
and methylene chloride to fathead minnows.  Bull. environ. Contam. 
 Toxicol., 20: 344-352. 

(1980)  Determination of the kinetic constants for metabolism of 
inhaled toxicants  in vivo using gas uptake measurements.  Toxicol. 
 appl. Pharmacol., 54(1): 100-116. 

ANDERSSON, A.  (1957)  [Health hazards in industry on exposure to 
trichloroethylene: a clinical, experimental, and technical hygienic 
investigation.]  Acta med. scand., 157(Suppl. 323): 1-220 (in German). 

ASCHIMICI  (1980)   Report for Italian Working Group for 

ASTRAND, I. & OVRUM, P.  (1976)  Exposure to trichloroethylene. 
I. Uptake and distribution in man.  Scand. J. Work Environ. Health,
2: 199-211. 

AVIADO, D.M., ZAKHARI, S., SIMAAN, J.A., & ULSAMER, A.G.  (1976)  
In: Golberg, L., ed.  Methyl chloroform and trichloroethylene in 
 the environment, Cleveland, Ohio, CRC Press Inc., pp. 47-89. 

& DE VERDIER, A.  (1978)  A cohort study on trichloroethylene 
exposure and cancer mortality.  J. occup. Med., 20: 194-196. 

Cancer morbidity and exposure to trichloroethylene. In:  ICOST, 
 International Conference on Organic Solvent Toxicity, Stockholm, 
15-17 November 1984 (Abstract in:  Arbete och Halsa, 29: 126). 

BADEN, J.M., KELLEY, M., MAZZE, R.I., & SIMMON, V.F.  (1979)  
Mutagenicity of inhalation anaesthetics:  trichloroethylene, 
divinyl ether, nitrous oxide and cyclopropane.  J. Anaesth., 51: 417. 

BAERG, R.D. & KIMBERG, D.V.  (1970)  Centrilobular hepatic necrosis 
and acute renal failure in "solvent sniffers".  Ann. intern. Med., 
73: 713-720. 

BALKON, J. & LEARY, J.A.  (1979)  An initial report on a 
comprehensive, quantitative, screening procedure for volatile 
compounds of forensic and environmental interest in human biofluids 
by GC/MS.  J. anal. Toxicol., 3: 213-215. 

BANERJEE, S. & VAN DUUREN, B.L.  (1978)  Covalent binding of the 
carcinogen trichloroethylene to hepatic microsomal proteins and to 
endogenous DNA  in vitro. Cancer Res., 38: 776-780. 

BANERJEE, S., YALKOWSKY, S.H., & VALVANI, S.C.  (1980)  Water 
solubility and octanol/water partition coefficients of organics. 
Limitations of the solubility-partition coefficient correlation. 
 Environ. Sci. Technol., 14: 1227-1229.

BARDODEJ, Z.  (1962)  [Value and use of exposure test. VIII. 
Volatile organic chloride test in urine.]  Cesk. Hyg., 7: 234-239 (in 

BARDODEJ, Z. & VISKOCIL, J.  (1956)  The problem of 
trichloroethylene metabolism and its effects on the nervous system 
as a means of hygienic control.  Am. Med. Assoc. Arch. ind. Health, 
13: 581-592. 

TOMER, K.B., WAGNER, R., & ZWEIDINGER, R.A.  (1980)  Gas 
chromatography mass spectrometry computer analysis of volatile 
halogenated hydrocarbons in man and his environment: a multimedia 
environmental study.  Biomed. mass Spectrom., 7: 139-147. 

REYMOND, F.  (1982)  Evoked trigeminal nerve potential in chronic 
trichloroethylene intoxication.  J. Toxicol. clin. Toxicol., 19: 

(1980)  Bioconcentration and elimination of selected water 
pollutants by bluegill sunfish  (Lepomis macrochirus). In: Hague, 
R., ed.  Dynamics, Exposure and Hazard Assessment of Toxic 
 Chemicals, Ann Arbor, Michigan, Ann Arbor Science Publishers, 
pp. 379-392. 

BARSOUM, G.S. & SAAD, K.  (1934)  Relative toxicity of certain 
chlorine derivatives of the aliphatic series.  Q. J. Pharm. 
 Pharmacol., 7: 205-214. 

BARTONICEK, V.  (1962)  Metabolism and excretion of 
trichloroethylene after inhalation by human subjects.  Br. J. ind. 
 Med., 19: 134-141. 

BARTONICEK, V. & BRUN, A.  (1970)  Subacute and chronic 
trichloroethylene poisoning: a neuropathological study in rabbits. 
 Acta pharmacol. toxicol., 28: 359-369. 

BARTONICEK, V. & SOUCEK, B.  (1959)  Metabolism of 
trichloroethylene in rabbits.  Arch. Gewerbepathol. Gewerbehyg., 17: 

Mutagenic and alkylating metabolites of haloethylenes, 
chlorobutadienes and dichlorobutenes produced by rodent or human 
liver tissues.  Arch. Toxicol., 41: 249-277. 

BATTIG, K.  (1964)  Comparison of the effects of trichloroethylene 
with the effects of drugs on exploratory behaviour in the rat. In: 
 14th International Congress on Occupational  Health, Madrid, 1963,  
Vol. 2, pp. 887-889. 

BATTIG, K. & GRANDJEAN, E.  (1963)  Chronic effects of 
trichloroethylene on rat behaviour.  Arch. environ. Health, 7: 

BAUER, U.  (1981)  [Human exposure to environmental chemicals. 
Investigations on volatile organic halogenated compounds in water, 
air, food, and human tissues.]  Zbl. Bakt. I. Abt. Orig., B174: 200-237 
(in German). 

BAUER, U. & SELENKA, F.  (1982)  [Exposure of the population to 
haloforms and chlorinated solvents in drinking water compared to 
air and food.]  Von Wasser, 59: 7-16 (in German). 

BEISLAND, H.O. & WANNAG, S.A.  (1970)  [Trichloroethylene sniffing: 
acute liver and kidney damage.]  Tidsskr. Nor. Laegeforen., 90: 285-288 
(in Norwegian). 

BELILES, R.P., BRUSICK, D.J., & MECLER, F.J.  (1980)   Teratogenic-
 mutagenic risk of workplace contaminants: trichloroethylene, 
 perchloroethylene, and carbon disulfide, Washington DC, US 
Department of Health, Education and Welfare, pp. 234 (Report for US 
DHEW Contract No. 210-77-0047) (Govt Rep. Announce. Index (US), 
1982: 2728). 

BELL, Z.  (1977)   Written communication with contractor reports of: 
 (a) Dominant lethal study with trichloroethylene in albino rats 
 exposed via inhalation (February 1977); and (b) Teratogenic study 
 via inhalation with trichlor 132, trichloroethylene in albino rats 
 (March 1977), Washington DC, US Environmental Protection Agency 

BELLAR, T.A., BUDDE, W.L., & EICHELBERGER, J.S.  (1979)  The 
identification and measurement of volatile organic compounds in 
aqueous environmental samples. IV. In: Schuetzle, D., ed. 
 Monitoring toxic substances, Washington DC, American Chemical 
Society (ACS Symposium Series No. 94). 

BERGMAN, K.  (1983)  Application and results of whole-body 
autoradiography in distribution studies of organic solvents.  Crit. 
 Rev. Toxicol., 12(1): 59-118. 

BIANCHI, A., DE NATALE, G., & MATTURRO, F.  (1963)  [Comparative 
research on some pharmacological effects of fluothane and other 
volatile narcotics.]  G. Ital. Chir., 19: 327-349 (in Italian). 

BIGGS, D.C., ROWLAND, R.G., & WURSTER, C.F.  (1979)  Effects of 
trichloroethylene, hexachlorobenzene, and polychlorinated biphenyls 
on the growth and cell size of marine phytoplankton.  Bull. environ. 
 Contam. Toxicol., 21: 196-201. 

Mutagenicity of halogenated aliphatic hydrocarbons in  Salmonella 
 typhimurium, Streptomyces coelicolor, and  Aspergillus nidulans. 
 Chem.-biol. Interact., 30: 9-23. 

BLAIR, A., DECOUFLE, P., & GRAUMAN, D.  (1979)  Causes of death 
among laundry and dry cleaning workers.  Am. J. public Health, 69: 

BOLT, H.M. & FILSER, J.G.  (1977)  Irreversible binding of 
chlorinated ethylenes to macromolecules.  Environ. Health Perspect., 
21: 107-112. 

BOTHE, J., BRAUN, W., & DONHARDT, A.  (1973)  [Effect of mineral 
oil in hydrocarbon poisoning in mice.]  Arch. Toxikol., 30: 243-250 (in 

BOUDENE, C., TURBIAUX, M., CLUET, J.-L., & TRUHAUT, R.  (1983)  
Contribution à la fixation d'une concentration limite tolérable de 
trichloroéthylène dans l'atmosphère des locaux de travail.  Arch. 
 Mal. prof. Méd. Trav. Sécur. soc., 44(2): 75-91. 

BOUWER, E.J. & MCCARTY, P.L.  (1983)  Transformations of 1- and 2-
carbon halogenated aliphatic organic compounds under methanogenic 
conditions.  Appl. environ. Microbiol., 45: 1286-1294. 

(1980)  Hépatite au trichloroéthylène. Action synergique du 
tétrachlorure de carbone?  Nouv. Presse méd., 9(43): 3277. 

 [Acute intoxication: clinical diagnosis and  treatment,] Milan, 
Italy, Medico-Farmaceutica Organization Editore, p. 470 (in 

BRINGMANN, G. & KUHN, R.  (1980)  Comparison of the toxicity 
thresholds of water pollutants to bacteria, algae, and protozoa in 
the cell multiplication inhibition test.  Water Res., 14: 231-241. 

BRONZETTI, G., ZEIGER, E., & FREZZA, D.  (1978)  Genetic activity 
of trichloroethylene in yeast.  J. environ. Pathol. Toxicol., 1: 

BROSS, G., DI FRANCEISCO, D., & DESMOND, M.E.  (1983)  The effects 
of low dosages of trichloroethylene on chick development. 
 Toxicology, 28: 283-294. 

(1974)  Le dosage par chromatographie en phase gazeuse des 
métabolites urinaires du trichloréthylène: l'acide trichloro- 
acétique et le trichloroéthanol.  Arch. Mal. prof. Méd. Trav. Sécur. 
 soc., 35(3): 395-402. 

CABANA, B.E. & GESSNER, P.K.  (1967)  Determination of chloral 
hydrate, trichloroacetic acid, trichlorethanol, and urochloralic 
acid in the presence of each other and in tissue homogenates.  Anal. 
 Chem., 39: 1449-1452. 

CACCURI, S.  (1976)   [Labour medicine,] 3rd ed., Napoli, Italy, 
Idelson, pp. 343-352 (in Italian). 

CALLEN, D.F., ROLAND WOLF, C., & PHILPOT, R.M.  (1980)  Cytochrome 
P-450 mediated genetic activity and cytotoxicity of seven 
halogenated aliphatic hydrocarbons in  Saccharomyces cerevisiae. 
 Mutat. Res., 77: 55-63. 

CAPELLINI, A. & GRISLER, R.  (1958)  [Studies on liver function in 
a group of workers chronically exposed to trichloroethylene.]  Med. 
 Lav., 49: 167-172 (in Italian). 

CARLSON, G.P. & WHITE, J.F.  (1983)  Cardiac arrythmogenic action 
of benzo( a)pyrene in the rabbit.  Toxicol. Lett., 15: 43-48. 

CASTELLINO, N.  (1969)   [Trichloroethylene:  technology, 
 pathological manifestations and prevention,] Milano, Italy, Franco 
Angeli Editore, p. 117 (in Italian). 

CAVALLO, A. & GRASSI, P.  (1976)  Determination of chlorinated 
hydrocarbons in potable waters.  Boll. chim. Union Ital. Lab. prov., 
27: 337-350. 

CEFIC  (1982)   Chlorinated solvents: trichloroethylene in metal 
 cleaning and other industrial applications, Brussels, Conseil 
Européen des Fédérations des Industries Chimiques. 

CERNA, M. & KJPENOVA, H.  (1977)  Mutagenic activity of 
chloroethylenes analyzed by screening system tests.  Mutat. Res., 46: 

CHIESURA, P.  (1980)  [Halogenated aliphatic hydrocarbons.] In: 
Crepet, M., ed.  [Occupational medicine,] Torino, Italy, Utet (in 

CHIESURA, P. & CORSI, G.  (1961)  [Acute trichloroethylene 
poisoning in man followed by liver disease and hyperglycaemic 
glycosuria.]  Folia med., 44: 121-135 (in Italian). 

CHRISTENSEN, H.E., LUGINBYHL, T.T., & CARROLL, B.B., ed.  (1974)  
 The toxic substances list 1974, Washington DC, National Institute 
of Occupational Safety and Health, p. 353. 

CHRISTENSEN, H.E. & LUGINBYHL, T.T.  (1975)   Registry of toxic 
 effects of chemical substances 1975, Washington DC, US Department 
of Health, Education and Welfare. 

CLEARFIELD, H.R.  (1970)  Hepatorenal toxicity from sniffing spot-
remover (trichloroethylene): Report of 2 cases.   Am. J. dig. Dis., 
15: 851-856. 

COLEMAN, W.E., LINGG, R.D., MELTON, R.G., & KOPFLER, F.C.  (1976)  
The occurrence of volatile organics in five drinking water supplies 
using gas chromatography/mass spectrometry. Identification and 
analysis of organisms in polluted water. In: Keith, L.H., ed. 
 Proceedings of the First Chemical Congress of the North American 
 Continent, 1975, Ann Arbor, Michigan, Ann Arbor Science, 
pp. 305-327. 

Interêt de la toxicovigilance: example de certains 
trichloréthylènes du commerce.  Arch. Mal. prof. Méd. Trav., 41: 

CORNISH, H.H. & ADEFUIN, J.  (1966)  Ethanol potentiation of 
halogenated aliphatic solvent toxicity.  Am. Ind. Hyg. Assoc. J., 27: 

CORREIA, Y., MARTENS, G.J., VAN MENSCH, F.H., & WHIM, B.P.  (1977)  
The occurrence of trichloroethylene, tetrachloroethylene and 1,1,1-
trichloroethane in Western Europe in air and water.  Atmos. 
 Environ., 11: 1113-1116. 

CREBELLI, R., BIGNAMI, M., CONTI, L., & CARERE, A.  (1982)  
Mutagenicity of trichloroethylene in  Salmonella typhimurium TA 100. 
 Ann. Ist. Super. Sanità, 18: 117-122. 

CREBELLI, R., CONTI, G., CONTI, L., & CARERE, A.  (in press)  
Mutagenicity of trichloroethylene, trichloroethanol, and chloral 
hydrate in  Aspergillus nidulans. Mutat. Res. 

Halogenated compound identification and measurement in the 
troposphere and lower stratosphere.  J. geophys. Res., 82: 5935-5944. 

DALBEY, W. & BINGHAM, E.  (1978)  Metabolism of trichloroethylene 
by the isolated perfused lung.   Toxicol. appl. Pharmacol., 43: 267-277. 

DANIEL, J.W.  (1963)  The metabolism of 36Cl-labelled 
trichloroethylene and tetrachloroethylene in the rat.  Biochem. 
 Pharmacol., 12: 795-802. 

DEFALQUE, R.J.  (1961)  Pharmacology and toxicology of 
trichloroethylene: A critical review of the world literature.  Clin. 
 Pharmacol. Ther., 2: 665-688. 

DEGUCHI, T.  (1972)  Threshold limit values for solvent mixtures in 
the air. Effects of single and mixed chlorinated hydrocarbons upon 
the level of serum transaminases in rats.  Osaka Shiritsu Daigaku 
 Igaku Zasshi, 21: 187-209. 

DEKANT, W. & HENSCHLER, D.  (1982)  Dechlorination reactions in the 
course of the metabolism of trichloroethylene.  Naunyn-Schmiedeb 
 Arch. Pharmacol., 319: R16. 

DEKANT, W. & HENSCHLER, D.  (1983)  New pathways of 
trichloroethylene metabolism.  Dev. Toxicol. environ. Sci., 11: 

DEKANT, W., METZLER, M., & HENSCHLER, D.  (1984)  Novel metabolites 
of trichloroethylene through dechlorination reactions in rats, 
mice, and humans.  Biochem. Pharmacol., 33(13): 2021-2027. 

P.C., STEELE, C.F., WARREN, V.L., & LASETER, J.L.  (1980)  Rapid 
gas chromatographic method for the determination of volatile and 
semivolatile organochlorine compounds in soil and chemical waste 
disposal site samples.  J. chromatogr. Sci., 18: 85-88. 

R.T., HOWARD, C.J., GOLDEN, D.M., & RAVISHANKARA, A.R.  (1983)  
 Chemical kinetics and photochemical data for use in stratospheric 
 modeling evaluation number 6, Washington DC, National Aeronautics 
and Space Administration (NASA JPL Publication No. 83-62, 
15 September, 1983). 

DERWENT, R.G. & EGGLETON, A.E.J.  (1978)  Halocarbon lifetimes and 
concentration distributions calculated using a two-dimensional 
tropospheric model.  Atmos. Environ., 12: 1261-1268. 

Intoxication expérimentale aiguë par le trichloroéthylène. Effets 
aggravants de l'intoxication éthylique chronique associée. Etude 
expérimentale électroencéphalographique chez le lapin.  Arch. Mal. 
 prof. Méd. Trav. Sécur. soc., 23: 653-664. 

DIETZ, E.A., Jr & SINGLEY, K.F.  (1979)  Determination of 
chlorinated hydrocarbons in water by headspace gas chromatography. 
 Anal. Chem., 51: 1809-1814. 

DILLING, W.L.  (1977)  Interphase transfer processes. II. 
Evaporation rates of chloromethanes, ethanes, ethylenes, propanes, 
and propylenes from dilute aqueous solutions. Comparisons with 
theoretical predictions.  Environ. Sci. Technol., 11: 405. 

DI PAOLO, J.A. & DONIGER, J.  (1982)  Neoplastic transformation of 
Syrian hamster cells by putative epoxide metabolites of 
commercially-utilized chloroalkenes.  J. Natl Cancer Inst., 69(2): 

DI RENZO, A.B., GANDOLFI, A.J., & SPIES, I.G.  (1982)  Microsomal 
bioactivation and covalent binding of aliphatic halides to DNA. 
 Toxicol. Lett., 11: 243-252. 

DMS  (1967)   UV atlas of organic compounds, London, Dortmund, 
Butterworths-Verlag Chemie, Vol. 3 (Spectrum No. A1/6). 

DOBINSON, B. & GREEN, G.E.  (1972)  Formation of dichloroacetylene 
from trichloroethylene in the presence of epoxides.   Chem. Ind., 5: 

MANSON, J.M.  (1979)  Evaluation of teratogenicity and behavioural 
toxicity with inhalation exposure of maternal rats to 
trichloroethylene.  Toxicology, 14: 153-166. 

DOWTY, B.J., CARLISLE, D.R., & LASETER, J.L.  (1975)  New Orleans 
drinking water sources tested by gas chromatography-mass 
spectrometry.  Environ. Sci. Technol., 9: 762-765. 

DROZ, P.O. & FERNANDEZ, J.G.  (1977)  Solubility of organic 
solvents. I. Gas chromatographic determination of olive oil/gas 
partition coefficient.  Helv. Chim. Acta, 60: 454. 

DROZ, P.O. & FERNANDEZ, J.G.  (1978)  Trichloroethylene exposure. 
Biological monitoring by breath and urine analyses.  Br. J. ind. 
 Med., 35: 35. 

DUPRAT, P. & GRADISKI, D.  (1980)  Cytogenic effect of 
trichloroethylene in the mouse as evaluated in the micronucleus 
test.  IRCS med. Sci. soc. occup. Med., 8: 182. 

DUPRAT, P., DELSAUT, L., & GRADISKI, D.  (1976)  Pouvoir irritant 
des principaux solvants chlorés aliphatiques sur la peau et les 
muqueuses oculaires du lapin.  Eur. J. Toxicol., 9(3): 171-177. 

EAJ  (1983)   Environmental monitoring of chemicals: environmental 
 survey report of F.Y. 1980 and 1981, Japan, Office of Health 
Studies, Department of Environmental Health, Environmental Agency 
Japan, p. 144. 

Determination of trichloroacetic acid in urine by a gas 
chromatographic method.  Am. Ind. Hyg. Assoc. J., 34: 93-96. 

EKLUND, G., JOSEFFSON, B., & ROOS, C.  (1978)  Determination of 
volatile halogenated hydrocarbons in tapwater.  J. High Res. Chrom. 
 & Chrom. Comms., July, pp. 34-40. 

ELCOMBE, C.R.  (in press)  Species differences in carcinogenicity 
and peroxisome proliferation due to trichloroethylene: a 
biochemical human hazard assessment.  Arch. Toxicol. 

ELCOMBE, C.R., PRATT, I.S., & GREEN, T.  (1982)  The rate of 
trichloroacetic acid (TCA) formation determines two species 
differences in hepatic peroxisome proliferation due to 
trichloroethylene (TRI).  Toxicologist, 2: 173. 

ELOVAARA, E., HEMMINKI, K., & VAINIO, H.  (1979)  Effects of 
methylene chloride, trichloroethane, trichloroethylene, 
tetrachloroethylene, and toluene on the development of chick 
embryos.  Toxicology, 12: 111-119. 

ENTZ, R.C. & HOLLIFIELD, H.C.  (1982)  Headspace gas 
chromatographic analysis of foods for volatile hydrocarbons. 
 J. agric. food Chem., 30: 84-88. 

Metabolism of trichloroethylene in man.  Arch. Toxikol., 29: 171-188. 

ETTEMA, J.J., KLEEREKOPER, L., & DUBA, W.C.  (1975)  Mental 
stresses during short-term inhalation of trichloroethylene. 
 Staub-Reinhalt. Luft, 35: 409-410. 

EUROCOP-COST  (1976)   A comprehensive list of polluting substances 
 which have been identified in various fresh waters, effluent 
 discharges, aquatic animals and plants, and bottom sediments, 2nd 
ed., Luxembourg, Commission of the European Community, p. 57 
(EUCO/MDU/73/76, XII/476/76). 

(1977)   Monitoring to detect previously unrecognized pollutants in 
 surface waters - appendix: organic analysis data, Springfield, 
Virginia, US NTIS, pp. 304 (PB Report PB-273350) (Govt Rep. 
Announce. Index, 1978: 199). 

FABRE, R. & TRUHAUT, R.  (1952)  Toxicology of trichloroethylene. 
II. Results of experimental animal studies.  Br. J. ind. Med., 9: 

FAHRIG, R.  (1977)  The mammalian spot test (Fellfleckenstest) with 
mice.  Arch. Toxicol., 38: 87-98. 

FAWNS, H.T.  (1968)  Trichloroacetic acid in the urine of workers 
using trichloroethylene.  Proc. Assoc. Clin. Biochem., 5: 110-114. 

FERGUSON, R.K. & VERNON, R.J.  (1970)  Trichloroethylene in 
combination with CNS drugs: effects on visual-motor tests.  Arch. 
 environ. Health, 20: 462-467. 

Exposition au trichloroéthylene. Bilan de l'absorption, de 
l'excrétion, et du métabolisme sur des sujets humains.  Arch. Mal. 
 prof. Méd. Trav. Sécur. soc., 36(7-8): 397-407. 

Trichloroethylene exposure: simulation of uptake, excretion, and 
metabolism using a mathematical model.  Br. J. ind. Med., 34: 43-55. 

FILSER, J.G. & BOLT, H.M.  (1979)  Pharmacokinetics of halogenated 
ethylenes in rats.  Arch. Toxicol., 42: 123-136. 

FINK, R.  (1968)   Toxicity of anaesthetics, Baltimore, Maryland, 
Williams & Williams, pp. 270. 

FISHBEIN, L.  (1973)   Chromatography of environmental hazards, 
New York, Elsevier Scientific Publishing Company, Vol. 2, 
pp. 471-490. 

FOOD CHEMICAL NEWS  (1978)  Preliminary report on TCE study shows 
no carcinogenicity in rats.  Food chem. News, 20: 41-42. 

FOSSA, A.A., WHITE, J.F., & CARLSON, G.P.  (1982)  Anti-arrhythmic 
effects of disulfiram on epinephrine-induced cardiac arrthythmias 
in rabbits exposed to trichloroethylene.  Toxicol. appl. Pharmacol., 
66: 109-117. 

FRIBERG, G.L., KYLIN, B., & NYSTROM, A.  (1953)  Toxicities of 
trichloroethylene and tetrachloroethylene and Fujiwara's pyridine 
reaction.  Acta pharmacol. toxicol., 9: 303-312. 

FUKUDA, K., TAKEMOTO, K., & TSURATA, H.  (1983)  Inhalation 
carcinogenicity of trichloroethylene in mice and rats.  Ind. Health, 
21: 243-245. 

GAMBERALE, F., ANNWALL, G., & OLSON, B.A.  (1976)  Exposure to 
trichloroethylene. III. Psychological functions.  Scand. J. Work 
 environ. Health, 4: 220-224. 

GAULTIER, M.  (1974)   [Clinical toxicology,] Rome, Italy, Società 
Editrice Demi (in Italian). 

GEHRING, P.J.  (1968)  Hepatoxic potency of various chlorinated 
hydrocarbon vapours relative to their narcotic and lethal potencies 
in mice.  Toxicol. appl. Pharmacol., 13: 287-298. 

(1964)  Effect of repeated inhalation of vapours of industrial 
solvents on animal behaviour. I. Evaluation of nine solvent vapours 
on pole-climb performance in rat.  Am. Ind. Hyg. Assoc. J., 25: 369-375.

GOLDBLATT, M.W.  (1956)   Industrial medicine and hygiene, London, 
Merewether, Vol. 3. 

GOVERNA, M.  (1981)  [Occupational diseases due to chlorine 
derivatives of the aliphatic hydrocarbons.] In: Sartorelli, E., ed. 
 [Textbook of occupational medicine,] Padova, Italy, Vol. 1, 
pp. 483-502 (in Italian). 

M.B.  (1974)  Toxicité comparée des principaux solvants chlorés 
aliphatiques.  J. eur. Toxicol., 7: 247-254. 

J.M.  (1978)  Toxicité aiguë comparée par inhalation des principaux 
solvants aliphatiques chlorés.  Arch. Mal. prof. Méd. Trav. Sécur. 
 soc., 39: 249-257. 

GRAEDEL, T.E.  (1978)   Chemical compounds in the atmosphere, 
New York, Academic Press. 

GRANDJEAN, E.  (1960)  Trichloroethylene effects on animal 
behaviour.  Arch. environ. Health, 1: 106-108. 

GRANDJEAN, E.  (1963)  The effects of short exposures to 
trichloroethylene on swimming performances and motor activity of 
rats.  Am. Ind. Hyg. Assoc. J., 24: 376-379. 

H.K., & ROSENMUND, H.  (1955)  Investigations into the effects of 
exposure to trichloroethylene in mechanical engineering.  Br. J. 
 ind. Med., 12: 131-142. 

GRANT, M.W.  (1961)  Trichoroethylene in the eye.  J. Am. Med. 
 Assoc., 178: 359. 

GRANT, M.W.  (1974)   Toxicology of the eye, 2nd ed., Springfield, 
Illinois, Charles C. Thomas, pp. 1034-1045. 

[Liver function in workers exposed to trichloroethylene.]  Arh. Hig. 
 Rad. Toksikol., 15: 93-97 (in Yugoslavian). 

GREEN, T. & PROUT, M.S.  (in press)  Species differences in 
response to trichloroethylene. II. Biotransformation in rats and 
mice.  Arch. Toxicol. 

GREEN, T., PROUT, M.S., & PROVAN, W.M.  (in press)  Species 
differences in response to trichloroethylene. I. Pharmacokinetics 
in rats and mice.  Arch. Toxicol. 

(1975)  Mutagenicity  in vitro and potential carcinogenicity of 
chlorinated ethylenes as a function of metabolic oxirane formation. 
 Biochem. Pharmacol., 24: 2013-2017. 

C., CHMARA, D., & FAURE, J.  (1981)  Induction of sister chromatid 
exchanges by trichloroethylene and its metabolites.  Toxicol. Eur. 
 Res., 3: 63-67. 

GUN, R.T., GRYGORCENICZ, D., & NETTELBECK, T.J.  (1978)  Choice 
reaction time in workers using trichloroethylene.  Med. J. Aust., 1: 

Malignant lymphoma and exposure to chemicals, especially organic 
solvents, chlorophenols, and phenoxy acids: a case-control study. 
 Br. J. Cancer, 73: 169-176. 

HATHWAY, D.E.  (1980)  Consideration of the evidence for mechanisms 
of 1,1,2-trichloroethylene metabolism including new identification 
of its dichloroacetic acid and trichloroacetic acid metabolites in 
mice.  Cancer Lett., 8: 263-269. 

HAYDEN, J.W., COMSTOCK, E.G., & COMSTOCK, B.S.  (1976)  The 
chemical toxicology of solvent abuse.  Clin. Toxicol., 9: 169-184. 

HEIL, E., OESER, H., HATZ, R., & KELKER, H.  (1979)  [Gas 
chromatographic determination of traces of C- and C-fluoro- and 
chlorohydrocarbons in air.]  Fresenius Z. Anal. Chem., 297: 357-364 
(in German). 

HENSCHLER, D.  (1977a)  Metabolism and mutagenicity of halogenated 
olefuis: a comparison of structure and activity.  Environ. Health 
 Perspect., 21: 61-64. 

HENSCHLER, D.  (1977b)  Metabolism of chlorinated alkenes and 
alkanes as related to toxicity.  J. environ. Pathol. Toxicol., 1: 

HENSCHLER, D. & HOOS, R.  (1982)  Metabolic activation and 
deactivation mechanisms of di-, tri-, and tetrachloroethylenes. 
In: Snyder, Parke, Kocsis, Jollow, Gibson, & Witmer, ed.  Biological 
 reactive intermediates. II. Part A., New York, Plenum Publishing 
Corporation, pp. 659-666. 

HENSCHLER, D., BONSE, G., & GREIM, H.  (1970a)  [Cranial nerve 
neuritis due to poisoning with chlorinated acetylenes when handling 
vinylidene chloride copolymers.]  Arch. Toxikol., 26: 62-75 (in 

HENSCHLER, D., BROSER, F., & HOPF, H.C.  (1970b)   Environmental 
 Pollution and Carcinogenic Risks, Lyons, International Agency for 
Research on Cancer, pp. 171-175 (IARC Scientific Publications 
No. 13). 

Carcinogenicity of trichloroethylene: fact or artifact?   Arch. 
 Toxicol., 37: 233-236. 

(1979)  Reactions of trichloroethylene epoxide in aqueous systems. 
 Biochem. Pharmacol., 28: 543-548. 

RADWAN, Z.  (1980)  Carcinogenicity study of trichloroethylene by 
long-term inhalation in three animal species.  Arch. Toxicol., 43: 

HENSCHLER, D., BONSE, G., & DEKANT, W.  (1983)  Mechanisms and 
reactions of electroplulic intermediates of halogenated ofefins. 
In:  Proceedings of the 13th International Cancer Congress. Part B. 
 Biology of Cancer, New York, Alan R. Liss, Inc., Vol. 1, 
pp. 175-183. 

HENSCHLER, D., ELSASSER, H., ROMEN, W., & EDER, E.  (1984)  
Carcinogenicity study of trichloroethylene, with and without 
epoxide stabilizers, in mice.  J. Cancer Res. clin. Oncol., 107: 

HERBOLSHEIMER, R., FUNK, L., & DRASCHE, H.  (1972)  Use of 
activated carbon as an adsorbent in the determination of 
trichloroethylene in the air.  Staub-Reinhalt. Luft, 32: 407-409. 

Primary liver cancer and exposure to solvents.  Int. Arch. occup. 
 environ. Health, 54: 147-153. 

HIRAYAMA, T. & IKEDA, M.  (1979)  Applicability of carbon felt to 
the dosimetry of solvent vapour mixture.  Am. Ind. Hyg. Assoc. J., 
40: 1091-1096. 

T.  (1983)  [Experimental studies of trichloroethylene toxicity. 
II. Changes in trichloroethylene in blood serum and in urine during 
and after exposure to trichloroethylene.]  Nippon Eiseigaku Zasshi, 
38(4): 772-779 (in Japanese with English summary). 

HOWARD, C.J.  (1976)  Rate constants for the gas-phase reactions of 
OH radicals with ethylene and halogenated ethylene compounds. 
 J. Chem. Phys., 65: 4771. 

HUFF, J.E.  (1971)  New evidence on the old problems of 
trichloroethylene.  Ind. Med. Surg., 40: 25-33. 

IARC (1979)   Trichloroethylene, Lyons, International Agency for 
Research on Cancer, pp. 545-572 (IARC Monographs on the Evaluation 
of the Carcinogenic Risk of Chemicals to Humans, Vol. 20). 

IARC  (1982)   Chemicals, industrial processes, and industries 
 associated with cancer in humans, Lyons, International Agency for 
Research on Cancer, pp. 247-249 (IARC Monographs on the Evaluation 
of the Carcinogenic Risk of Chemicals to Humans, Supplement 4). 

IKEDA, M.  (1974)  Reciprocal metabolic inhibition of toluene and 
trichloroethylene  in vivo and  in vitro. Int. Arch. Arbeitsmed., 33: 

IKEDA, M. & IMAMURA, T.  (1973)  Biological half-life of 
trichloroethylene and tetrachloroethylene in human subjects.  Int. 
 Arch. Arbeitsmed., 31: 209-224. 

IKEDA, M., OHTSUJI, H., KAWAI, H., & KUNIYOSHI, M.  (1971)  
Excretion kinetics of urinary metabolites in patient addicted to 
trichloroethylene.  Br. J. ind. Med., 28: 203-206. 

Urinary excretion of total trichloro-compounds, trichloroethanol, 
and trichloroacetic acid as a measure of exposure to 
trichloroethylene and tetrachloroethylene.  Br. J. ind. Med., 29: 

ILO  (1980)   Occupational exposure limits for airborne toxic 
 substances, 2nd (revised) ed., Geneva, International Labour 
Office, pp. 206-207 (Occupational Safety and Health Series No. 37). 

IMAMURA, T. & IKEDA, M.  (1973)  A time-saving procedure for the 
determination of total trichloro-compounds in human urine samples. 
 Int. Arch. Arbeitsmed., 31: 333-338. 

IOFFE, B.V., ISIDOROV, V.A., & ZENKEVICH, I.G.  (1977)  Gas 
chromatographic-mass spectrometric determination of volatile 
organic compounds in an urban atmosphere.  J. Chromatogr., 142: 

IRPTC  (1984)   IRPTC legal file, Geneva, International Register of 
Potentially Toxic Chemicals, United Nations Environment Programme. 

JAMES, W.R.L.  (1963)  Fatal addiction to trichloroethylene.  Br. J. 
 ind. Med., 20: 47-49. 

Uptake via the blood and elimination of 10 organic solvents 
following epicutaneous exposure of anaesthetized guinea-pigs. 
 Toxicol. appl. Pharmacol., 63: 181-187. 

Ministry of International Trade and Industry. 

JESSON, J.P.  (1980)  Release of industrial halocarbons and 
tropospheric budget. In:  Proceedings of the NATO Advanced Study 
 Institute on Atmospheric Ozone: Its Variation and Human Influences,  
Washington DC, US Department of Transportation, Federal Aviation 

 Evaluation of certain food additives: 27th report, Geneva, World 
Health Organization (Technical Report Series No. 696). 

JOUGLARD, J. & VINCENT, V.  (1971)  Pulmonary signs of ingestions 
of solvents.  Marseille Med., 108: 696-697. 

JUNGCLAUS, G.A., LOPEZ-AVILA, V., & HITES, R.A.  (1978)  Organic 
compounds in an industrial waste water: a case study of their 
environmental impact.  Environ. Sci. Technol., 12: 88-96. 

B.K., & KARANTIROVA, O.V.  (1974)  [Influence of different diets on 
the course of chronic experimental trichloroethylene poisoning.] 
 Vopr. Pitan., No.6: 43-47 (in Russian). 

[Evaluation of the toxic effects of trichloroethylene according 
to morphological and some biochemical indexes.]  Gig. i Sanit., No. 2: 
107-108 (in Russian). 

Neurotransmitter metabolizing enzymes and plasma 
butyrylcholinesterase in mice exposed to trichloroethylene.  Acta 
 pharmacol. toxicol., 49: 205-209. 

KARICKHOFF, S.W., BROWN, D.S., & SCOTT, T.A.  (1979)  Sorption of 
hydrophobic pollutants on natural sediments.  Water Res., 13: 241-248. 

KATZ, R.M. & JOWETT, D.  (1981)  Female laundry and dry cleaning 
workers in Wisconsin: a mortality analysis.  Am. J. public Health, 
71: 305-307. 

KEINFELD, M. & TABERSHAW, I.R.  (1954)  Trichloroethylene toxicity: 
report of 5 fatal cases.  AMA Arch. ind. Hyg. occup. Med., 10: 134-141. 

KENAGA, E.E.  (1980)  Predicted bioconcentration factors and soil 
sorption coefficients of pesticides and other chemicals. 
 Ecotoxicol. environ. Saf., 4: 26-38.

KENAGA, E.E. & GORING, C.A.I.  (in press)  Relationship between 
water solubility, soil sorption, octanol-water partitioning, and 
bioconcentration of chemicals in biota. In: Eaton, J.C., Parrish, 
P.R., & Hendricks, A.C., ed.  Aquatic toxicology ASTM STP, 707,  
Philadelphia, Pennsylvania, American Society for Testing and 

KIMMERLE, G. & EBEN, A.  (1973)  Metabolism, excretion, and 
toxicology of trichloroethylene after inhalation. II. Experimental 
human exposure.  Arch. Toxicol., 30: 127-138. 

KIRK, R.E. & OTHMER, D.F., ed.  (1963)  Anesthetics. In: 
 Encyclopedia of chemical technology, 2nd ed., New York, John Wiley 
and Sons, Vol. 2, pp. 393-410. 

KIRK, R.E. & OTHMER, D.F., ed.  (1964)  Chlorocarbons and 
chlorohydrocarbons. In:  Encyclopedia of chemical technology, 2nd 
ed., New York, John Wiley and Sons, Vol. 5, pp. 183-195. 

KIRK, R.E. & OTHMER, D.F., ed.  (1979)  Chlorocarbons and 
chlorohydrocarbons. In:  Encyclopedia of chemical technology, 3rd 
ed., New York, John Wiley and Sons, Vol. 5, pp. 745-753. 

KISELEVA, A.F. & KOROLENKO, A.M.  (1971)  Histoenzymic changes in 
liver and kidneys during the experimental effect of anesthetic 
doses of fluorothan and trylen.  Eksp. Khir. Anesteziol., 16: 81-84. 

KITAGAWA, T.  (1961)  The rapid measurement of toxic gases and 
vapour. In:  Proceedings of the 13th International Congress on 
 Occupational Health, New York, pp. 506-512. 

MANSSON, L.  (1980)  Irreversible effects of trichloroethylene 
exposure on the central nervous system.  Scand. J. Work environ. 
 Health, 6: 40-47. 

MORTENSEN, I., LANKE, J., & HOLMQUIST, B.  (1981a)  
Trichloroethylene: effects on body and organ weights in mice, 
rats, and gerbils.  Toxicology, 21: 105-115.

I., LANKE, J., & HOLMQUIST, B.  (1981b)  Effects of long-term 
exposure to trichloroethylene on the behaviour of Mongolian gerbils 
 (Meriones unguiculatus).  J. Toxicol. environ. Health, 8: 787-793. 

(1983a)  Effects of continuous trichloroethylene inhalation on 
different strains of mice.  Acta pharmacol. toxicol., 53: 369-374. 

JONSSON, I., MANSSON, L., & BJERKEMO, M.  (1983b)  
Trichloroethylene: further studies of the effects on body and organ 
weights and plasma butyrycholinesterase activity in mice.  Acta 
 pharmacol. toxicol., 53: 375-384. 

KLAASSEN, C.D. & PLAA, G.L.  (1966)  Relative effects of various 
chlorinated hydrocarbons on liver and kidney function in mice. 
 Toxicol. appl. Pharmacol., 9: 139-151. 

KLAASSEN, C.D. & PLAA, G.L.  (1967)  Relative effects of various 
chlorinated hydrocarbons on liver and kidney function in dogs. 
 Toxicol. appl. Pharmacol., 10: 119-131. 

(1982)  Mutagenicity of chloroalkene epoxides in bacterial systems. 
 Mutat. Res., 101: 115-125. 

Laboratory screening of distribution, conversion, and 
mineralisation of chemicals in the soil-plant-system and comparison 
to outdoor experimental data.  Chemosphere, 10: 1089-1090. 

WEICHARDT, H.  (1978)  [Chromosome studies on trichloroethylene 
workers.]  Arch. Toxicol., 40: 201-206 (in German). 

KRONEVI, T., WAHLBERG, J.E., & HOLMBERG, B.  (1981)  Skin pathology 
following epicutaneous exposure to seven organic solvents.  Int. J. 
Tiss. React., 111(1): 21-30. 

KYLIN, B., REICHARD, H., SUMEGI, I., & YLLNER, S.  (1962)  
Heptatoxic effect of tri- and tetrachloroethylene on mice.  Nature 
 (Lond.), 193: 395. 

Effect of inhaled trichloroethylene on the CNS.  Arch. environ. 
 Health, 15: 48-52. 

influence of trichloroethylene during labour process in women in 
comparison with the results  in vitro.]  Pol. Tyg. Lek., 18: 
1333-1338 (in Polish). 

Chronic exposure to trichloroethylene: lipid and acyl group 
composition in gerbil cerebral cortex and hippocampus. 
 Neurotoxicology, 4(4): 35-42. 

LACHNIT, V.  (1971)  Halogenated hydrocarbons and the liver.  Wein. 
 Klin. Wochenschr., 83: 734-737. 

LA DU, B.N., MANDEL, H.G., & WAY, E.L., ed.  (1971)   Fundamentals 
 of drug metabolism and drug disposition, Baltimore, Maryland, 
Williams and Wilkins. 

LAHAM, S.  (1970)  Studies on placental transfer: 
trichloroethylene.  Ind. Med. Surg., 39: 46-49. 

LAZAREV, N.V.  (1929)  [The narcotic efficacy of the vapours of the 
chlorine derivatives of methane, ethane and ethylene.]  Naunyn-
 Schmiedeb. Arch. exp. Pathol. Pharmacol., 141: 19-24 (in German). 

LAZAREV, N.V. & GADASKINA, I.D.  (1977)   [Harmful substances 
 in industry,]  Leningrad, Medecine, Vol. 3 (in Russian).

LEHMANN, K.B. & SCHMIDT-KEHL, L.  (1936)  [Thirteen most important 
chlorohydrocarbons of the paraffin series from the standpoint of 
industrial hygiene.]  Arch. Hyg. Bakt., 116: 131-268 (in German). 

LEIBMAN, K.C.  (1965)  Metabolism of trichloroethylene in liver 
microsomes.  Mol. Pharmacol., 1: 239-246. 

LEONG, B.K.J., SCHWETZ, B.A., & GEHRING, P.J.  (1975)  Embryo- and 
fetotoxicity of inhaled trichloroethylene, perchloroethylene, 
methylchloroform, and methylene chloride in mice and rats.  Toxicol. 
 appl. Pharmacol., 33: 136. 

LERZA, P., LOMBARDI, F., & VIOTTI, G.  (1963)  [Health and hygiene 
considerations regarding work in dry-cleaning establishments using 
trichloroethylene.]  Lav. Um., 15: 459-478 (in Italian). 

LEWIS, G.D., REYNOLDS, R.C., & JOHNSON, A.R.  (1984)  Some effects 
of trichloroethylene on mouse lungs and livers.  Gen. Pharmacol., 
15(2): 139-144. 

LILIS, R., STANESCU, D., MUICA, N., & ROVENTA, A.  (1969)  Chronic 
effects of trichloroethylene exposure.  Med. Lav., 60: 595-601. 

LIN, R.S. & KESSLER, I.I.  (1981)  A multifactoral model for 
pancreatic cancer in man.  J. Am. Med. Assoc., 245: 147-152. 

LOPRIENO, N. & ABBONDANDOLO, A.  (1980)  Comparative mutagenic 
evaluation of some industrial compounds. In:  Proceedings of the 
 Symposium on Short-Term Test Systmes and the Detection of 
 Carcinogenesis, Berlin, Heidelberg, New York, Springer-Verlag, 
pp. 333-356. 

LOPRIENO, N., SBRANA, I., & LASCIALFARI, D.  (in press)  [Study on 
the  in vivo potential mutagenic effect of trichloroethylene 
evaluated by cytogenetic analysis in mice treated by inhalation for 
52 days.] (in Italian). 

LOVELOCK, J.E.  (1974)  Atmospheric halocarbons and stratospheric 
ozone.  Nature (Lond.), 252: 292-294. 

MACKAY, D.  (1982)  Correlations of bioconcentration factors. 
 Environ. Sci. Technol., 10: 274-278. 

MCCONNELL, G., FERGUSON, D.M., & PEARSON, C.R.  (1975)  Les 
hydrocarbures chlorés et l'environnement.  Endeavour, 34: 13-18. 

MCCORD, C.P.  (1932)  Toxicity of trichloroethylene.  J. Am. 
 Med. Assoc., 99: 409.

MACKAY, D. & PATERSON, S.  (1981)  Calculating fugacity.  Environ. 
 Sci. Technol., 15: 1006-1014. 

MCNEILL, W.C.  (1979)  Chlorocarbons and chlorohydrocarbons. 
Trichloroethylene. In:  Kirk-Othmer's encyclopedia of chemical 
 technology, 3rd ed., New York, Wiley Interscience, Vol. 5, 
pp. 745-753. 

MAKIDE, Y., TOMINAGA, K., & ROWLAND, F.S.  (1979)  Gas 
chromatographic analysis of halogenated hydrocarbons in air over 
Japan.  Chem. Lett., 1979: 355-358. 

MALEK, B., KRCMAROVA, B., & RODOVA, O.  (1979)  [Epidemiological 
study of hepatic tumour incidence in subjects working with 
trichloroethylene: II. Negative result of retrospective studies in 
dry cleaners.]  Pracov. Lek., 31(4): 124-126 (in Czech). 

MALIZIA, E., PELAIA, P., & PIROVINE, C.  (1984)  Experience in the 
emergency treatment of acute intoxication by trichloroethylene. 
 Riv. Toss. Speriment Clin., 14: 437. 

MALOOF, C.C.  (1949)  Burns of the skin produced by 
trichloroethylene vapours at room temperature.  J. ind. Hyg. 
 Toxicol., 31: 295-296. 

MALTONI, I.C. & MAIOLI, P.  (1977)  [Long-term bioassay of 
carcinogenicity of trichloroethylene. Preliminary results.] 
 Osp. Vita, 4: 108-110 (in Italian). 

MALTONI, C., LEFEMINE, G., & COTTI, G.  (in press)  Experimental 
research on trichloroethylene carcinogenesis. In: Maltoni, C. & 
Mehlman, M.A., ed.  Archives of research on industrial 
 carcinogenesis, Vol. 5.

MANTEL, M. & NOTHMANN, R.  (1977)  Rapid determination of 
trichloroethanol and trichloroacetic acid in urine.  Analyst, 102: 

MATTURRO, F.  (1963)  [Effects of some volatile narcotics on 
isolated guinea-pig heart.]  G. Ital. Chir., 19: 95-99 (in Italian). 

MAZZA, V. & BRANCACCIO, A.  (1967)  [Behaviour of the formed 
elements of the blood and the marrow in experimental intoxications 
with Tri.]  Folia med., 50: 318-324 (in Italian). 

MELINO, C., MESSINEO, A., & PACELLI, E.  (1979)  Risk from 
trichloroethylene in a factory producing electrical condensers. 
 Riv. Med. Lab. Ig. Ind., 3: 67-81. 

MEYER, H.-J.  (1966)  [Trichloroethylene poisoning by the oral 
route.]  Arch. Toxikol., 21: 225-234 (in German). 

MEYER, H.-J.  (1973)  Bronchopulmonary alterations induced by 
trichloroethylene and other halogenated hydrocarbons.  Bronches, 23: 

MILLER, D.A. & GRIMSRUD, E.P.  (1979)  Correlation of electron 
capture response enhancements caused by oxygen with chemical 
structure for chlorinated hydrocarbons.  Anal. Chem., 51: 851-859. 

MILLER, R.E. & GUENGERICH, F.P.  (1982)  Oxidation of 
trichloroethylene by liver microsomal cytochrome P-450: evidence 
for chlorine migration in a transition state not involving 
trichloroethylene oxide.  Biochemistry, 21: 1090-1097. 

MOLINA, M.J. & ROWLAND, F.S.  (1974)  Stratospheric sink for 
chlorofluoromethanes: chlorine atom-catalysed destruction of ozone. 
 Nature (Lond.), 294: 810-812. 

MONSTER, A.C.  (1979)  Differences in uptake, elimination, and 
metabolism in exposure to trichloroethylene, 1,1,1-trichloroethane, 
and tetrachloroethylene.  Int. Arch. occup. environ. Health, 42: 

MONSTER, A.C. & BOERSMA, G.  (1975)  Simultaneous determination of 
trichloroethylene and metabolites in blood and exhaled air by gas 
chromatography.  Int. Arch. occup. environ. Health, 35: 155-163. 

MONSTER, A.C., BOERSMA, G., & DUBA, W.C.  (1976)  Pharmaco- 
kinetics of trichloroethylene in volunteers: influence of workload 
and exposure concentration.  Int. Arch. occup. environ. Health, 38: 

MONSTER, A.C., BOERSMA, G., & DUBA, W.C.  (1979)  Kinetics of 
trichloroethylene in repeated exposure of volunteers.  Int. Arch. 
 occup. environ. Health, 42: 283-292. 

MOSLEN, M.T., REYNOLDS, E.S., & SZABO, S.  (1977)  Enhancement of 
the metabolism and hepatoxicity of trichloroethylene and 
perchloroethylene.  Biochem. Pharmacol., 26: 369-375. 

Trichloroethylene exposure and trichloroethylene metabolites in 
urine and blood.  Arch. Toxicol., 29: 335-340. 

MULLER, G., SPASSOVSKI, M., & HENSCHLER, D.  (1974)  Metabolism of 
trichloroethylene in man. II. Pharmacokinetics of metabolites. 
 Arch. Toxicol., 32: 283-295. 

MULLER, G., SPASSOVSKI, M., & HENSCHLER, D.  (1975)  Metabolism of 
trichloroethylene in man. III. Interaction of trichloroethylene and 
ethanol.  Arch. Toxicol., 33: 173-189. 

MURRAY, A.J. & RILEY, J.P.  (1973)  Occurrence of some chlorinated 
aliphatic hydrocarbons in the environment.  Nature (Lond.), 242: 37-38. 

MUSCLOW, C.E. & AWEN, C.F.  (1971)  Glue sniffing: report of a 
fatal case.  Can. Med. Assoc. J., 104: 315-319. 

NCI  (1976)   Carcinogenesis bioassay of trichloroethylene. CAS No. 
79-01-6, Washington DC, National Cancer Institute (US DHEW 
Publication No. (NIH) 76-802). 

NEELY, W.B. & MACKAY, D.  (1982)  In: Dickson, K.L., Maki, A.W., & 
Cairns, J., ed.  Modelling the fate of chemicals in the aquatic 
 environment, Ann Arbor, Michigan, Ann Arbor Science Publications. 

NICHOLSON, A.A., MERESZ, O., & LEMYK, B.  (1977)  Determination of 
free and total potential haloforms in drinking-water.  Anal. Chem., 
49: 814-819. 

NIOSH  (1977a)   Manual of analytical methods, 2nd ed., Cincinnati, 
Ohio, National Institute of Occupational Safety and Health, Vol. 3, 
pp. S336-1 to S336-9 (US DHEW Publication No. (NIOSH) 77-157-C). 

NIOSH  (1977b)   National occupational hazard survey. III. Survey 
 analyses and supplemental tables, Cincinnati, Ohio, National 
Institute of Occupational Safety and Health, pp. 2864-2866. 

NIOSH  (1978)   Special occupational hazard review of 
 trichloroethylene, Washington DC, National Institute of 
Occupational Safety and Health (US DHEW Publication No. (NIOSH) 

NOMIYAMA, H., NOMIYAMA, K., & UCHIKI, H.  (1978)  Gas-liquid 
chromatographic determination of trichloroethylene metabolites in 
urine.  Am. Ind. Hyg. Assoc. J., 39: 506-510. 

NOMURA, S.  (1962)  Health hazards in workers exposed to 
trichloroethylene vapour. I. Trichloroethylene poisoning in an 
electroplating plant.  Kumamoto med. J., 15: 29-37. 

NORRIS, W. & STUART, P.  (1957)  Cardiac arrest during 
trichloroethylene anaesthesia.  Br. med. J., 1: 860-863. 

NOVOTNA, E., DAVID, A., & MALEK, B.  (1979)  [An epidemiological 
study on hepatic tumour incidence in subjects working with 
trichloroethylene. I. Negative result of retrospective 
investigations in subjects with primary liver carcinoma.]  Pracov. 
 Lek., 31(4): 121-123 (in Czech). 

ODUM, E.P.  (1971)   Fundamentals of ecology, 3rd ed., 
Philadelphia, Pennsylvania, W.B. Saunders Co. 

OGATA, M. & SAEKI, T.  (1974)  Measurement of chloral hydrate, 
trichloroethanol, trichloroacetic acid, and monochloroacetic acid 
in the serum and the urine by gas chromatography.  Int. Arch. 
 Arbeitsmed., 33: 49-58. 

OGATA, M., TAKATSUKA, Y., TOMUKUNI, K., & MUROI, K.  (1970)  Simple 
method for the quantitative analysis of urinary trichloroethanol 
and trichloroacetic acid as an index of trichloroethylene exposure. 
 Br. J. ind. Med., 27: 378-381. 

OHTA, T., MORITA, M., & MIZOGUCHI, I.  (1976)  Local distribution 
of chlorinated hydrocarbons in the ambient air in Tokyo.  Atmos. 
 Environ., 10: 557-560. 

OLSSON, H. & BRANDT, L.  (1980)  Occupational exposure to organic 
solvents and Hodgkin's disease in men.  Scand. J. Work environ. 
 Health, 6: 302-305. 

OSTELERE, G.  (1953)   Trichloroethylene anaesthesia, Edinburgh, 
Scotland, Livingstone. 

OTSON, R., WILLIAMS, D.T., & BIGGS, D.C.  (1982)  Relationships 
between raw water quality treatment and the occurrence of organics 
in Canadian potable water.  Bull. environ. Contam. Toxicol., 28: 

PADDLE, G.M.  (1983)  Incidence of liver cancer and 
trichloroethylene manufacture: joint study by industry and a cancer 
registry.  Br. med. J., 286: 876.

PARCHMAN, L.G. & MAGEE, P.N.  (1982)  Metabolism of 
14C-trichloroethylene to 14CO2 and interaction of a metabolite 
with liver DNA in rats and mice.  J. Toxicol. environ. Health, 9: 

PARDYS, S. & BROTMAN, M.  (1974)  Trichloroethylene and alcohol: a 
straight flush.  J. Am. Med. Assoc., 229:: 521-522. 

PARMEGGIANI, L.  (1956)  [A case of chronic trichloroethylene 
poisoning.]  Med. Lav., 47: 639-646 (in Italian). 

PARSONS, F., WOOD, P.R., & DE MARCO, J.  (1984)  Transformation of 
tetrachloroethene and trichloroethene in microcogus and ground 
water.  J. Am. Water Works Assoc., 76(2): 56-59. 

PEARSON, C.R. & MCCONNELL, G.  (1975)  Chlorinated C and C 
hydrocarbons in the marine environment.  Proc. R. Soc. London 
 Ser. B, 189: 305-332. 

PELTS, D.G.  (1962)  [Effect of trichloroethylene and 
tetrachloroethylene on the phagocytic activity of blood 
leukocytes.]  Gig. i Sanit., 27(7): 96-99 (in Russian). 

PENKETT, S.A.  (1982)  Non-methane organics in the remote 
troposphere. In: Goldberg, E.D., ed.  Atmospheric chemistry, Berlin, 
Springer, pp. 329-355. 

PEROCCO, P. & PRODI, G.  (1981)  DNA damage by haloalkanes in human 
lymphocytes cultered  in vitro. Cancer Lett., 13: 213-218. 

ARTIGOU, J-Y., & BENHAMOU, J-P.  (1979)  Inhibition, activation, 
destruction, and induction of drug-metabolizing enzymes by 
trichloroethylene.  Toxicol. appl. Pharmacol., 49: 355-363. 

Hepatotoxicity of trichloroethylene-carbon tetrachloride mixtures 
in rats.  Gastroenterology, 63: 761-772. 

PIERCE, R.H., OLNEY, C.E., & FELBECK, G.T.  (1974)  p-p'-DDT 
adsorption to suspended particulate matter in sea water.  Geochim. 
 cosmochim. Acta, 38: 1060-1073. 

PLAA, G.L., EVANS, E.A., & HINE, C.H.  (1958)  Relative 
hepatoxicity of seven halogenated hydrocarbons.  J. Pharmacol. exp. 
 Ther., 123: 224-229. 

POWELL, J.F.  (1945)  Trichloroethylene: absorption, elimination, 
and metabolism.  Br. J. ind. Med., 2: 142-145. 

(1967)  Effects on experimental animals of long-term inhalation of 
trichloroethylene, carbon tetrachloride, 1,1,1-trichloroethane, 
dichlorodifluoromethane, and 1,1-dichloroethylene.  Toxicol. appl. 
 Pharmacol., 10: 270-289. 

PRICE, P.J., HASSETT, C.M., & MANSFIELD, J.I.  (1978)  Transforming 
activities of trichloroethylene and proposed industrial 
alternatives.  In Vitro, 14: 290-293. 

PRIEST, R.J. & HORN, R.C., Jr  (1965)  Trichloroethylene 
intoxication: a case of acute hepatic necrosis possibly due to this 
agent.  Arch. environ. Health, 11: 361-365. 

RASMUSSEN, R.A. & KHALIL, M.A.K.  (1983)  Natural and anthropogenic 
trace gases in the lower troposphere of the Arctic.  Chemosphere, 12: 

REICHERT, D. & HENSCHLER, D.  (1978)  Nephrotoxic and hepatotoxic 
effects of dichloroacetylene.  Food Cosmet. Toxicol., 16: 227-235. 

REICHERT, D., METZLER, M., & HENSCHLER, D.  (1980a)  Decomposition 
of the neuro- and nephrotoxic compound dichloroacetylene in the 
presence of oxygen: separation and identification of novel 
products.  J. environ. Pathol. Toxicol., 4: 525-532. 

Carcinogenic potential of dichloroacetylene.  Dev. Toxicol. environ. 
 Sci., 8: 269-272. 

RIGAUD, M., CHALABREYSSE, J., PROST, G., & TOLOT, F.  (1977)  Etude 
expérimentale de la toxicité hépatique du trichloroéthylène. 
 Arch. Mal. prof. Méd. Trav. Sécur. soc., 38: 263-265. 

ROCHE, L., GENEVOIS, M., & MARIN, A.  (1958)  Trichloréthylène et 
eczéma de la face.  Arch. Mal. prof. Méd. Trav. Sécur. soc., 19: 

ROESSLER, R. & MORAWIEC-BOROWIAK, D.  (1973)  [Use of hemodialysis 
in acute trichloroethylene poisoning.]  Wiad. Lek., 26(13): 1271-1275 (in 

ROOK, J.J., MEIJERS, A.P., GRAS, A.A., & NOORDSIJ, A.  (1975)  
[Headspace analysis of volatile trace compounds in the Rhine.]  Vom 
 Wasser, 44: 23-30 (in German). 

ROSSI, A.M., MIGLIORE, L., BARALE, R., & LOPRIENO, N.  (1983)   In 
 vivo and  in vitro mutagenicity studies of a possible carcinogen, 
trichloroethylene, and its two stabilizers, epichlorohydrin and 
1,2-epoxybutane.  Teratog. Carcinog. Mutagen., 3: 75-87. 

RUBINO, G.F., SCANSETTI, G., & TROMPEO, G.  (1959)  [Chronic 
trichloroethylene poisoning. II. Absorption of trichloroethylene.] 
 Med. Lav., 50(12): 733-742 (in Italian). 

RUSH, W.E.  (1970)   Quantitative analysis of gaseous pollutants,  
London, Ann Arbor-Humphrey Science Publishers, Inc., pp. 229-232. 

RUSSO, A., PACCHIELOTTI, F., & METALLI, P.  (1984)  Nondysfunction 
induced in mouse spermatogenesis by chloral hydrate, a metabolite 
of trichloroethylene.  Environ. Mutagen., 6(5): 695-703. 

SADTLER STANDARD SPECTRA  (1961)   25 frequently-used spectra for 
 the infrared spectroscopist, London, Heyden & Son, Ltd. 

SAGAWA, K., NISHITANI, Y., KAWAI, H., KUGE, Y., & IKEDA, M.  (1973)  
Transverse lesion of spinal cord after accidental exposure to 
trichloroethylene.  Int. Arch. Arbeitsmed., 31: 257-264. 

(1982)  Humoral and cell-mediated immune status in mice exposed to 
trichloroethylene in the drinking water.  Toxicol. appl. Pharmacol., 
62: 358-368. 

SATO, A. & NAKAJIMA, T.  (1978)  Differences following skin or 
inhalation exposure in the absorption and excretion kinetics of 
trichloroethylene and toluene.  Br. J. ind. Med., 35: 43-49. 

SATO, A. & NAKAJIMA, T.  (1979)  A structure-activity relationship 
of some chlorinated hydrocarbons.  Arch. environ. Health, 34: 69. 

SAVOLAINEN, H. & SEPPALAINEN, A.M.  (1979)  Biochemical and 
physiological effects of organic solvents on rat axon membranes 
isolated by a new technique.  Neurotoxicology, 1: 467-477. 

Trichloroethylene and 1,1,1-trichloroethane: effects on brain and 
liver after five days intermittent inhalation.  Arch. Toxicol., 38: 

RASMUSSEN, R.A., RIPPERTON, L.A., & WHITE, L.D.  (1975)  Organic 
solvent vapours in air: analytical method.  Health Lab. Sci., 12: 

SBERTOLI, C. & BRAMBILLA, G.  (1962)  [Three cases of 
trichloroethylene poisoning presenting with intolerance to alcohol 
as the only symptoms.]  Med. Lav., 53: 353-358 (in Italian). 

SBRANA, I., LASCIALFARI, N., & LOPRIENO, N.  (1984)  [Analysis of 
the cytogenetic effects of trichloroethylene.]  AHI AGI/ABCD/SIBBM,  
21-25 October, p. 93 (in Italian). 

SCHUMACHER, H. & GRANDJEAN, E.  (1960)  Comparative investigations 
on the anaesthetic effects and acute toxicity of nine solvents. 
 Arch. Gewerbepathol. Gewerbehyg., 18: 109-119. 

SCHUTTMANN, W.  (1970)  Liver damage after occupational exposure to 
trichloroethylene.  Dtsch. Z. Verdau Stoffwechselkr., 30: 43-45. 

SCHWETZ, B.A., LEONG, B.K.J., & GEHRING, P.J.  (1975)  The effect 
of maternally-inhaled trichloroethylene, perchloroethylene, methyl 
chloroform, and methylene chloride on embryonal and fetal 
development in mice and rats.  Toxicol. appl. Pharmacol., 32: 84-96. 

SEBA, D.B. & PROSPERO, J.M.  (1971)  Pesticides in the lower 
atmosphere of the northern equatorial Atlantic Ocean.  Atmos. 
 Environ., 5: 1043-1050. 

J.  (1972)  Interaction of chloral hydrate and ethanol in man. II. 
Hemodynamics and performance.  Clin. Pharmacol. Ther., 13: 50-58. 

SETO, T.A. & SCHULTZE, M.O.  (1956)  Determination of 
trichloroethylene, trichloroacetic acid, and trichloroethanol in 
urine.  Anal. Chem., 28: 1625-1629. 

SHAHIN, M.M. & VON BORSTEL, R.C.  (1977)  Mutagenic and letal 
effects of alpha-benzene hexachloride, dibutyl phthalate, and 
trichloroethylene in  Saccharomyces cerevisiae. Mutat. Res., 48: 

SHANKS, C.A.  (1964)  The compatibility of octapressin with 
cyclopropane, trichloroethylene, and halothane.  N.Z. med. J., 63: 

SHIPMAN, A.J. & WHIM, B.P.  (1980)  Occupational exposure to 
trichloroethylene in metal cleaning processes and to 
tetrachloroethylene in the dry-cleaning industry in the U.K.  Ann. 
 occup. Hyg., 23: 197-204. 

SHMUTER, L.M.  (1972)  [The effect of the chronic action of low 
concentrations of chlorinated hydrocarbons on the production of 
various classes of immunoglobulins.]  Gig. i Sanit., 37(2): 32-35 (in 

SIEGEL, J., JONES, R.A., COON, R.A., & LYON, J.P.  (1971)  Effects 
on experimental animals of acute, repeated, and continuous 
inhalation exposures to dichloroacetylene mixtures.  Toxicol. appl. 
 Pharmacol., 18: 168-174. 

SIMMON, V.F., KAUHANEN, K., & TARDIFF, R.G.  (1977)  Mutagenic 
activity of chemicals identified in drinking-water.  Dev. Toxicol. 
 environ. Sci., 2: 249-258. 

SINGH, H.B., SALAS, L.J., & CAVANAGH, L.A.  (1977)  Distribution, 
sources, and sinks of atmospheric halogenated compounds.  J. Air 
 Pollut. Control Assoc., 27: 332-336. 

Tichloroethylene vapours do not produce dominant lethal mutations 
in mice.  Arch. Toxicol., 45: 37. 

STRIEGEL, J.A., & NYCUM, J.S.  (1969)  Range-finding toxicity data. 
VII.  Am. Ind. Hyg. Assoc. J., 30: 470-476. 

SNELL, F.D. & ETTRE, L.S., ed.  (1970a)  Chlorocarbons. In: 
 Encyclopedia of industrial chemical analysis, New York, John Wiley 
and Sons, Vol. 9, pp. 373-410. 

SNELL, F.D. & ETTRE, L.S., ed.  (1970b)  Chlorocarbons. In: 
 Encyclopedia of industrial chemical analysis, New York, John Wiley 
and Sons, Vol. 9, pp. 454-459. 

SNELL, F.D. & HILTON, C.L., ed.  (1967)  Anesthetics. In: 
 Encyclopedia of industrial chemical analysis, New York, John Wiley 
and Sons, Vol. 5, pp. 357, 366-367, 420-421. 

SORGO, G.  (1976)  [Trichloroethylene, carbon tetrachloride, and 
gasoline intoxication as etiological factors in the developement of 
arterio- and coronary sclerosis.]  Arch. Toxicol., 35: 295-318 (in German). 

SOUCEK, B. & VLACHOVA, D.  (1960)  Excretion of trichloroethylene 
metabolites in human urine.  Br. J. ind. Med., 17: 60-64. 

STEERE, N.V., ed.  (1967)   Handbook of laboratory safety, 
Cleveland, Ohio, The Chemical Rubber Co., pp. 544-545. 

 Registry of mass spectral data, New York, John Wiley and Sons, 
Vol. 1, p. 246. 

STEWART, R.D. & DODD, H.C.  (1964)  Absorption of carbon 
tetrachloride, tetrachloroethylene, methylene chloride, and 
1,1,1-trichloroethane through the human skin.  Am. Ind. Hyg. Assoc. 
 J., 25: 439-446. 

(1962)  Observations on the concentrations of trichloroethylene in 
blood and expired air following exposures of humans.  Am. Ind. Hyg. 
 Assoc. J., 23: 167-170. 

STEWART, R.D., DODD, H.C., GAY, H.H., & ERLEY, D.S.  (1970)  
Experimental human exposure to trichloroethylene.  Arch. environ. 
Health, 20: 64-71. 

STEWART, R.D., HAKE, C.L., & PETERSON, J.E.  (1974)  Use of breath 
analysis to monitor trichloroethylene exposures.  Arch. environ. 
 Health, 29: 6-13. 

STOPPS, G.J. & MCLAUGHLIN, M.  (1967)  Psychophysiological testing 
of humans exposed to solvent vapors.  Am. Ind. Hyg. Assoc. J., 28: 

STOTT, W.T., QUAST, J.F., & WATANABE, P.G.  (1982)  The 
pharmacokinetics and macromolecular interactions of 
trichloroethylene in mice and rats.  Toxicol. appl. Pharmacol., 62: 

SUCIU, I. & OLINICI, L.  (1983)  Hepato-renal involvement in acute 
occupational trichloroethylene intoxication.  Med. Lav., 74(2): 123-128. 

SVABOVA, K. & MENCIK, M.  (1983)  [Changes in the state of health 
of workers long-term exposed to halogenated hydrocarbons.]  Pracov. 
 Lek., 35: 105-111 (in Czech with English abstract). 

SZLUC-KUBERSKA, J.  (1972)  Chronic industrial trichloroethylene 
poisoning.  Folia med. Lodz., 16: 67-90. 

TADA, O.  (1969)  Evaluating the exposure to some chlorinated 
hydrocarbons.  J. Sci. Labour, Part 2, 45: 757-765. 

TANAKA, S. & IKEDA, M.  (1968)  A method for determination of 
trichloroethanol and trichloroacetic acid in urine.  Br. J. ind. 
 Med., 25: 214-219. 

TAYLOR, H.  (1936)  Experiments on the physiological properties of 
trichloroethylene.  J. ind. Hyg. Toxicol., 18: 175-193. 

THIELE, D.L., EIGENBRODT, E.E., & WARE, A.J.  (1982)  Cirrhosis 
after repeated trichloroethylene and 1,1,1-trichloroethane 
exposure.  Gastroenterology, 83: 926-929. 

TOLA, S., VILHUNEN, R., JARVINEN, E., & KORKALA, M.-L.  (1980)  A 
cohort study on workers exposed to trichloroethylene.  J. occup. 
 Med., 22: 737-740. 

(1964)  Toxicité hepatique au trichloroéthylène.  Arch. Mal. prof. 
 Méd. Trav., 25: 9-15. 

TOMASINI, M.  (1976)  [Cardiac arrythmias due to intoxication by 
trichloroethylene ("th").]  Med. Lav., 67: 163-169 (in Italian). 

& THOMASON, M.  (1979)  Effect of trichloroethylene on cilia 
activity in rabbit trachea.  Acta pharmacol. toxicol., 44: 65-70. 

TORKELSON, T.R. & ROWE, V.K.  (1981)  Trichloroethylene. In: 
 Patty's industrial hygiene and toxicology, 3rd (revised) ed., 
New York, John Wiley and Sons, Vol. 2B, pp. 3553-3586. 

TRIEBIG, G., GOSSLER, K., & SCHALLER, K.-H.  (1976)  [Simple and 
reliable gas-chromatographic determination of trichloroethylene and 
its metabolites in blood and urine.]  Fresenius Z. Anal. Chem., 279: 
115-116 (in German). 

SCHALLER, K.H.  (1977a)  [Psychopathometrical results of follow-up 
studies of trichloroethylene-exposed persons.]  Zbl. Bakt. Hyg. I. 
 Abt. Orig. B., 164: 314-327 (in German with English summary). 

Biochemical investigations and psychological studies of persons 
chronically exposed to trichloroethylene with regard to non-
exposure intervals.  Int. Arch. occup. environ. Health, 38: 149-162. 

(1982)  Investigations on neurotoxicity of chemical substances at 
the workplace. III. Determination of the motor and sensory nerve 
conduction velocity in persons occupationally exposed to 
trichloroethylene.  Int. Arch. occup. environ. Health, 51: 25-34. 

TSURUTA, H.  (1978)  Percutaneous absorption of trichloroethylene 
in mice.  Ind. Health, 16: 145-148. 

K.L., Jr, SAIN, L.E., BORZELLACA, J.F., & MUNSON, A.E.  (1982)  
Toxicology of trichloroethylene in the mouse.  Toxicol. appl. 
 Pharmacol., 62: 351-357. 

(1977)  Spectral evidence for 2,2,3-trichloro-oxirane formation 
during microsomal trichloroethylen oxidation.  Arch. Toxicol., 37: 

US CFR  (1976)  Code of Federal Regulations.  21 CFR, 8: 305. 

US ITC  (1980)   Production statistics, 1979, Washington DC, 
International Trade Commisssion. 

US NTP  (1983)   Technical report on the carcinogenesis studies of 
 trichloroethylene (without epichlorohydrin) in F344/n rats and BCF 
 mice, Research Triangle Park, NC, National Toxicology Program (NIH 
Publication No. 83-1979, NTP TR 243). 

VALLE-RIESTRA, J.F.  (1974)  Food processing with chlorinated 
solvents.  Food Technol., 28: 25-32. 

T.A., & PLOMP, G.J.J.  (1979)  Improved method for the electron-
capture gas chromatographic determination of trichloroacetic acid 
in human serum.  J. Chromatogr., 164: 106-108. 

VAN DUUREN, B.L. & BANERJEE, S.  (1976)  Covalent interaction of 
metabolites of the carcinogen trichloroethylene in rat hepatic 
microsomes.  Cancer Res., 36: 2419-2422. 

MELCHIONNE, S., SELDMAN, I., & ROTH, D.  (1979)  Carcinogenicity of 
halogenated olefinic and aliphatic hydrocarbons in mice.  J. Natl 
 Cancer Inst., 63: 1433-1439. 

(1983)  Chemical structure and carcinogenicity relationships of 
some chloroalkene oxides and their parent olefins.  Cancer Res., 43: 

VERNE, J., CECCALDI, P.F., HEBERT, S., & ROUX, J.M.  (1959)  
Hepatic steatosis during intoxication by volatile organic 
compounds. IV. Biochemistry and histochemistry of fatty livers 
produced by trichloroethylene poisoning.  Pathol. Biol. (Paris), 7: 

VERNON, R.J. & FERGUSON, R.K.  (1969)  Effects of trichloroethylene 
on visual-motor performance.  Arch. environ. Health, 18: 894-900. 

VERNOT, E.H., MACEWEN, J.D., HAUN, C.C., & KINKEAD, E.R.  (1977)  
Acute toxicity and skin corrosion data for some organic and 
inorganic compounds and aqueous solutions.  Toxicol. appl. 
 Pharmacol., 42: 417-423. 

VERSCHUEREN, K.  (1977)   Handbook of environmental data on organic 
 chemicals, New York, Van Nostrand Reinhold Company, pp. 607-610. 

VESTERBERG, O., GORCZAC, J., KRASTS, M.  (1976)  Exposure to 
trichloroethylene. II. Metabolites in blood and urine.  Scand. J. 
 Work environ. Health, 4: 212-219. 

O.V., & LAPRUN, I.B.  (1975)  [Comparative evaluation of indexes of 
rat liver functions in trichloroethylene poisoning.]  Gig. Tr. 
 Prof. Zabol., No.11: 56-58 (in Russian). 

VLACHOVA, D.  (1957)  Determination of trichloroethanol in the 
urine after exposure to trichloroethylene.  J. Hyg. Epidemiol. 
 Microbiol. Immunol., 1-2: 225-229. 

VON OETTINGEN, W.F.  (1955)   The halogenated aliphatic, olifinic, 
 cyclic, aromatic, and aliphatic-aromatic hydrocarbons including the 
 halogenated insecticides: their toxicity and potential dangers, 
Washington DC, US Government Printing Office. 

WADE, A., ed.  (1977)   Martindale: the extra pharmacopoeia, 27th 
ed., London, The Pharmaceutical Press, pp. 714-715. 

WAHLBERG, J.E.  (1984)  Erythema-inducing effects of solvents 
following epicutaneous administration to man: studied by Laser 
Doppler flowmetry.  Scand. J. Work environ. Health, 10: 159-162. 

WAHLBERG, J.E. & BOMAN, A.  (1979)  Comparitive percutaneous 
toxicity of ten industrial solvents in the guinea-pig.  Scand. J. 
 Work environ. Health, 5: 345-351. 

WAKEHAM, S.G., DAVIS, A.C., & GOODWIN, J.T.  (1982)  
Biogeochemistry of volatile organic compounds in marine 
experimental ecosystems and the estuarine environment: initial 
results. In: Grice, G.D. & Reeve, M.R., ed.  Marine Mesocosms, 
New York, Springer. 

WASKELL, L.  (1978)  A study of the mutagenicity of anesthetics and 
their metabolites.  Mutat. Res., 57: 141-153. 

WATERS, E.M., GERSTNER, H.B., & HUFF, J.E.  (1977)  
Trichloroethylene. I. An overview.  J. Toxicol. environ. Health, 2: 

WEAST, R.C., ed.  (1980)   Handbook of chemistry and physics, 61st 
ed., Boca Raton, Florida, CRC Press, Inc., p. C-317. 

WEICHARDT, H. & BARDODEJ, Z.  (1970)  Determination of 
trichloroacetic acid and trichloroethanol in the urine of 
trichloroethylene workers.  Zentralbl. Arbeitsmed. Arbeitsschutz.,
20: 219-221. 

WELLS, J.C.D.  (1982)  Abuse of trichloroethylene by oral self-
administration.  Anaesthesia, 37: 440-441. 

WETTERHAHN, J.  (1972)  Eye make-up. In: Balsam, M. & Sagarin, E., 
ed.  Cosmetics science and technology, New York, John Wiley and 
Sons, Inc., pp. 419. 

WHELAN, J.K., BLANCHETTE, M.A., & HUNT, J.M.  (1983)  Volatile C,-
C7 organic compounds in an anoxic sediment core from the 
Pettaquamscutt River (Rhode Island, USA).  Org. Geochem., 5: 29-33. 

(1979)  Sister-chromatid exchanges induced by inhaled anaesthetics. 
 Anaesthesiology, 50: 426. 

WHITE, J.F. & CARLSON, G.P.  (1979)  Influence of alterations in 
drug metabolism on spontaneous and epinephrine-induced cardiac 
arrhythmias in animals exposed to trichloroethylene.  Toxicol. appl. 
 Pharmacol., 47: 515-527. 

WHITE, J.F. & CARLSON, G.P.  (1981a)  Epinephrine-induced cardiac 
arrhythmias in rabbits exposed to trichloroethylene: potentiation 
by ethanol.  Toxicol. appl. Pharmacol., 60: 466-471. 

WHITE, J.F. & CARLSON, G.P.  (1981b)  Epinephrine-induced cardiac 
arrhythmias in rabbits exposed to trichloroethylene: role of 
trichloroethylene metabolites.  Toxicol. appl. Pharmacol., 60: 458-465. 

WHITE, J.F. & CARLSON, G.P.  (1982)  Epinephrine-induced cardiac 
arrhythmias in rabbits exposed to trichloroethylene: potentiation 
by caffeine.  Fundam. appl. Toxicol., 2: 125-129. 

WHO  (1984)   Guidelines for drinking-water quality. I. 
 Recommendations, Geneva, World Health Organization, 66 pp. 

 based limits in occupational exposure to selected organic solvents,  
Geneva, World Health Organization, 84 pp (Technical Report Series 
No. 664). 

WIECKO, W.  (1966)  [Oral poisoning with trichloroethylene.]  Wiad. 
 Lek., 19: 1117-1118 (in Polish). 

ed.  (1976)   The Merck index, 9th ed., Rahway, New Jersey, Merck & 
Co., Inc., p. 1238. 

WINNEKE, G.  (1982)  Acute behavioural effects of exposure to some 
organic solvents: psychophysiological aspects.  Acta neurol. scand., 
66(suppl. 92): 117-129. 

WITHEY, J.R. & COLLINS, B.T.  (1980)  Chlorinated aliphatic 
hydrocarbons used in the foods industry: the comparative 
pharmaocokinetics of methylene chloride, 1,2-dichloroethane, 
chloroform, and trichloroethylene after iv administration in the 
rat.  J. environ. Pathol. Toxicol., 3: 313-332. 

WIRTSCHAFTER, Z.T. & CRONYN, M.W.  (1964)  Relative hepato- 
toxicity: pentane, trichloroethylene, benzene, carbon 
tetrachloride.  Arch. environ. Health, 9: 180-185. 

ZAFFIRI, O., RUGGERINI, R., & FRANCESCATO, F.  (1968)  Anesthetics 
and adrenergic receptors.  Minerva Anestesiol., 34: 556-560. 

(1984)  Effects of trichloroethylene exposure on male reproductive 
function in rats.  Toxicology, 31: 237-250. 

ZIGLIO, G.  (1979)  [Gas-chromatographic determination of blood 
trichoroacetic acid concentration in subjects not occupationally 
exposed to trichloro- and tetrachloroethylene.]  Ig. Mod., 72: 876-900 
(in Italian). 

Human environmental exposure to trichloro- and tetrachloroethylene 
from water and air in Milan, Italy.  Arch. environ. contam. 
 Toxicol., 12: 57-64. 


    Predicting the Equilibrium Distribution of Trichloroethylene 

    On the basis of the physical and chemical data summarized 
in Table 1 of this document, it is possible to predict the 
approximate equilibrium distribution of trichloroethylene in major 
environmental "compartments".  The models used have been described 
by Mackay & Paterson (1981).  Essentially, these use physical and 
chemical data and realistic compartment volumes in a "model world" 
to calculate fugacity capacities and to predict the partitioning of 
a chemical between various compartments.  The following compartment 
volumes are assumed (Neely & Mackay, 1982) (Table I.1) in an 
environment, 1 km2 in area. 

Table I.1  Compartment volumes for trichloroethylene
Atmosphere         6 x 109 m3    1 km2 area x 6 km height

Water              7 x 106 m3    70% area x 10 m depth

Soil               4.5 x 104 m3  30% area x 15 cm depth

Sediment           2.1 x 104 m3  70% water x 3 cm depth

Suspended aquatic  35.0 m3       water volume x 5 ppm

Aquatic biota      7.0 m3        water volume x 1 ppm

    As an example, the input of trichloroethylene is assumed to be 
1000 moles/km2 per year, based on an annual production capacity of 
4 x 105 tonnes per year and an approximate land area of 106 km2.  
This leads to an actual production of approximately 3000 moles/km2, 
but it is assumed that land represents one-third of the total area. 

    Physical and chemical data for trichloroethylene are given in 
Table 1 (main text).  Environmental temperature is assumed to be 
25 °C (atmosphere) or 15 °C (land and water). 

    Additional compartments at appropriate volumes can be added with 
appropriate characteristics, e.g., atmospheric particulates at 
2 µg/m3 (Seba & Prospero, 1971) or terrestrial biota at 
approximately 1 kg/m2 (Odum, 1971). 

    The model predicts the distributions shown in Table I.2.  
These are remarkably close to the distributions observed in 
most compartments and, furthermore, the ratios of concentrations 
predicted to occur between compartments are remarkably similar to 
those that are observed.  The predicted and observed distributions 
of trichloroethylene are not surprising; as noted in section 4.2.1, 
its high vapour pressure would be expected to lead to high 
atmospheric concentrations, and this would offset the tendency of 

high water solubility and low partition coefficients (themselves 
related) to lead to high water, biota, or sediment concentrations, 
through either partition or adsorption. 

Table I.2  Predicted and observed distribution of 
trichloroethylene (TCE) in the environment using compartment 
volumes and approaches described in text
Compartment  Predicted  Predicted TCE   Observed TCE
             % TCE      Concentration   concentration
                                        (see text)
Air          99.7       22 µg/m3        0.01 - 10 µg/m3

Water        0.3        0.06 µg/litre   0.01 - 100 µg/litre

Sediment     < 0.01     0.4 µg/kg       1 - 10 µg/kg

Aquatic      < 0.01     0.7 ng/g        1 - 100 ng/g

    The value of a model like this is not that it predicts the 
"correct" distribution, but that it illustrates and identifies 
the compartments that are important as reservoirs or as sites of 
degradation of chemicals.  In the present case, the size of the 
atmospheric compartment and the high vapour pressure of 
trichloroethylene are such that the bulk of trichloroethylene 
released into the environment should be found in the atmosphere.  
Therefore, atmospheric degradation processes should be important in 
the eventual degradation of trichloroethylene. 

    This approach can be refined further by considering not only 
the distribution at equilibrium (assuming no degradation), but 
adding rates of degradation.  For these purposes, we have assumed 
the rates of degradation in the appropriate compartment, shown in 
section 4.2.2.  Although absolute trichloroethylene concentrations 
are predicted by this model to be appreciably lower in each 
compartment than those shown in Table I.2, the ratios of 
concentrations between compartments do not change appreciably 
(Table I.3).  However, the important point is that since most of 
the trichloroethylene is predicted to occur in the atmosphere, and 
since atmospheric degradation rates are similar to or faster than 
those in other compartments, most of the degradation should take 
place in the atmosphere (Table I.3).  Washout or fallout of 
atmospheric particulate material is not likely to be an important 
process; there seems to be little tendency for trichloroethylene to 
sorb to particles, because of its low Koc, and residence times of 
such particles are long compared to the the expected rate of 
degradation by OH radicals.  Total environmental lifetime is 
controlled by the atmospheric degradation rate, and should, 
therefore, be about 10 - 11 days.  Degradation in sediments and/or 
biota probably contribute in only a very minor way to overall 

Table I.3  Predicted distribution and compartmental 
degradation rates for trichloroethylene (TCE) as % 
of total environmental degradation using compartment 
volumes and degradation rates in text
Compartment    Predicted TCE    Total degradation 
               concentration    (%)
Air            0.6 µg/m3        99.9
Water          0.002 µg/litre   0.08

Sediment       0.01 µg/kg       < 0.01

Aquatic biota  0.02 ng/g        < 0.01


MACKAY, D. & PATERSON, S.  (1981)  Calculating fugacity.  Environ. 
 Sci. Technol., 15: 1006-1014. 

NEELY, W.B. & MACKAY, D.  (1982)  In: Dickson, K.L., Maki, A.W., & 
Cairns, J.,  Modelling the fate of chemicals in the aquatic 
 environment, Ann Arbor, Michigan, Ann Arbor Science Publications. 

ODUM, E.P.  (1971)   Fundamentals of ecology, 3rd ed., Philadelphia, 
Pennsylvania, W.B. Saunders Co. 

SEBA, D.B. & PROSPERO, J.M.  (1971)  Pesticides in the lower 
atmosphere of the northern equatorial Atlantic Ocean.  Atmos. 
 Environ., 5: 1043-1050. 

    See Also:
       Toxicological Abbreviations
       Trichloroethylene (ICSC)
       Trichloroethylene (WHO Food Additives Series 10)
       Trichloroethylene (FAO/PL:1968/M/9/1)
       Trichloroethylene (IARC Summary & Evaluation, Volume 63, 1995)