Trichloroethylene (EHC 50, 1985)

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

ENVIRONMENTAL HEALTH CRITERIA 50

TRICHLOROETHYLENE

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experts and does not necessarily represent the decisions or the stated
policy of the United Nations Environment Programme, the International
Labour Organisation, or the World Health Organization.

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the International Labour Organisation,
and the World Health Organization

World Health Orgnization
Geneva, 1985

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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR TRICHLOROETHYLENE

1. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH

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
elimination
1.1.6. Effects on experimental animals
1.1.7. Effects on man
1.2. Recommendations for further research

2. IDENTITY, PROPERTIES AND ANALYTICAL METHODS

2.1. Identity
2.2. Physical and chemical properties
2.2.1. Pure trichloroethylene
2.2.1.1 Chemical reactivity
2.2.1.2 Chemical degradation
2.2.1.3 Photochemical degradation
2.2.2. Commercial trichloroethylene
2.3. Analytical methods
2.3.1. Identification and purity assessment
2.3.1.1 Colorimetry tests
2.3.1.2 Infra-red spectroscopy
2.3.1.3 Gas-liquid chromatography
2.3.2. Determination in environmental media
2.3.2.1 Soil
2.3.2.2 Water
2.3.2.3 Air
2.3.2.4 Foodstuffs
2.3.3. Determination in human tissues and fluids
2.3.3.1 Trichloroethylene
2.3.3.2 Trichloroacetic acid
2.3.3.3 Trichloroethanol
2.3.3.4 Total trichloro derivatives
2.3.4. Sensitivity

3. SOURCES IN THE ENVIRONMENT, USES, AND SAFE HANDLING

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
3.2.1.1 Fire, explosion, and thermal decomposition
3.2.1.2 Chemical reactivity
3.2.2. Handling precautions
3.2.2.1 Personal safeguards
3.2.2.2 Storage

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

4. ENVIRONMENTAL LEVELS, TRANSPORT AND DISTRIBUTION

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
4.2.2.1 Air
4.2.2.2 Soils and sediments
4.2.2.3 Water
4.2.2.4 Biota

5. KINETICS AND METABOLISM

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. EFFECTS ON ANIMALS AND CELL SYSTEMS

6.1. Effects on animals
6.1.1. Acute toxicity
6.1.2. Short-term exposures
6.1.2.1 Oral exposures
6.1.2.2 Inhalation exposure
6.1.2.3 Parenteral exposure
6.1.3. Long-term exposure
6.1.3.1 Oral exposure
6.1.3.2 Inhalation exposure
6.1.3.3 Parenteral exposure
6.1.4. Interactions
6.1.5. Immunotoxicity
6.1.6. Effects on cell systems
6.1.7. Carcinogenicity
6.1.7.1 Conclusions

6.1.8. Mutagenicity
6.1.8.1 Gene mutation
6.1.8.2 Chromosome aberrations
6.1.8.3 DNA damage
6.1.8.4 Mammalian cells (in vitro)
6.1.8.5 Mutagenic activity of trichloroethylene
metabolites
6.1.8.6 Conclusions
6.1.9. Reproduction, embryo/fetotoxicity, and teratology
6.1.9.1 Avian embryo system
6.1.9.2 Mouse
6.1.9.3 Rat
6.1.9.4 Rabbit

7. EFFECTS ON THE ENVIRONMENT

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. EFFECTS ON MAN

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. EVALUATION OF THE HEALTH RISKS FOR MAN

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
9.3.1.1 General points
9.3.1.2 Ingestion
9.3.1.3 Inhalation
9.3.1.4 Dermal exposure
9.3.1.5 Eye exposure

REFERENCES

APPENDIX I

REFERENCES TO APPENDIX I

TASK GROUP ON TRICHLOROETHYLENE

Members

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,
Italy

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,
USSR

Representatives from Other Organizations

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

Secretariat

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

Observers

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

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all users of the environmental health criteria documents, readers
are kindly requested to communicate any errors found to the Manager
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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 -
985850).

ENVIRONMENTAL HEALTH CRITERIA FOR TRICHLOROETHYLENE

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
trichloroethylene.

The draft criteria document was developed by the ISTITUTO
SUPERIORE DI SANITA, Rome, Director PROFESSOR F. POCCHIARI; the
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. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH

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
environment.

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
concentrations.

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
hepatocytes.

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, LC₅₀values in rodent test species range from 45 to
260 mg/m³, and oral LD₅₀values 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/m³for 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/m³by
inhalation or oral adiministration of 700 - 1200 mg/m³body 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/m³by 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
outcome.

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
conditions.

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
dermatitis.

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
studied.

2. IDENTITY, PROPERTIES AND ANALYTICAL METHODS

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-chloro-2,2-dichloroethylene,
1,1-dichloro-2-chloroethylene,
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.

2.2.1.1. 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).

2.2.1.2. 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).

2.2.1.3. 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 10⁶molecules/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.
(1976)

-87.1 Kirk & Othmer
(1979)

-73.0 CRC (1980)

Boiling point (°C) 86.7 (760 mm Hg) Windholz et al.
(1976)

-43.8 (1 mm Hg) Windholz et al.
(1976)
--------------------------------------------------------------------------

Table 1. (contd.)
--------------------------------------------------------------------------
Specific gravity 1.46 (25/25 °C) Snell & Hilton
(1967)

1.4904 (4/4 °C) Windholz et al.
(1976)

(vapour density; air = 1) 4.53 (25 °C) Windholz et al.
(1976)

(vapour, g/litre) 4.45 (86.7 °C) Kirk & Othmer
(1979)

Vapour pressure (torr) 5.4 (-20 °C) Snell & Ettre
(1970a)
20.1 (0 °C) Snell & Ettre
(1970a)
57.8 (20 °C) Snell & Ettre
(1970a)
305.7 (60 °C) Snell & Ettre
(1970a)
Other properties:

Refraction index (n_D) 1.4782 (20 °C) Kirk & Othmer
(1979)

(vapour) 1.001784 (0 °C) Kirk & Othmer
(1979)

Viscosity (cP) 0.58 (20 °C) Kirk & Othmer
(1979)

(vapour) 10 300 (60 °C) Kirk & Othmer
(1979)

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
(1979)

Critical temperature (°C) 271.0 Kirk & Othmer
(1979)

Critical pressure (atm) 49.7 Kirk & Othmer
(1979)

Dipole moment (debye) 0.90 Kirk & Othmer
(1979)
--------------------------------------------------------------------------

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
(1979)

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)

Solubility:

in water (g/litre) 1.07 (20 °C) Kirk & Othmer
(1979)

1.24 (60 °C) Kirk & Othmer
(1979)

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

in oil miscible Windholz et al.
(1976)
--------------------------------------------------------------------------

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

Organic carbon partition K^o/w x 0.6 Karickhoff et al.
coefficient, K_oc (1979)

Bioconcentration factor, K^o/w x 0.048 Mackay (1982)
K_B
--------------------------------------------------------------------------
^aSee section 3.2.1.1.

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 epichlorohydrin^a
bromodichloromethane
benzene
------------------------------------------------------
^aNow 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
methods.

2.3.1.1. 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).

2.3.1.2. 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).

2.3.1.3. 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

2.3.2.1. 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).

2.3.2.2. 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.

2.3.2.3. 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.

2.3.2.4. 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.

2.3.3.1. 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.

2.3.3.2. 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).

2.3.3.3. 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).

2.3.3.4. 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
trichloroethanol.

3. SOURCES IN THE ENVIRONMENT, USES, AND SAFE HANDLING

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

3.2.1.1. 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.

3.2.1.2. 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

3.2.2.1. 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.

3.2.2.2. 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
agents.

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
eliminated.

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/m³with a ceiling limit value of 1000 mg/m³for
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
countries^a
--------------------------------------------------------
Country Exposure Limit Category
(ppm) (mg/m³) of limit
--------------------------------------------------------
Australia 100 535 TWA^b

Austria 50 260 TWA

Belgium 100 535 TWA

Bulgaria 2 10 TWA

Czechoslovakia 47 250 TWA
235 1250 CV^c

Egypt 50 267 TWA

Finland 50 260 TWA

France 75 405 TWA
200 1080 CV

German Democratic 47 250 TWA
Republic 141 750 ST^d(30 min)

Germany, Federal 50 260^e 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

USA

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

b) ACGIH^g 100 535 TWA
150 800 ST (15 min)

USSR 2 10 CV

Yugoslavia 50 200 TWA
--------------------------------------------------------
^aFrom: ILO (1980) and IRPTC (1984).
^bTWA (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.
^cCV (ceiling value): a maximum allowable concentration
that must not be exceeded at any time.
^dST (short-term exposure limit): a maximum
concentration allowed for a short specified duration.
^eSuspected carcinogen.
^fIDLH (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.
^gNotice 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
comparisons.

4. ENVIRONMENTAL LEVELS, TRANSPORT AND DISTRIBUTION

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-
1940s.

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
reported.

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/m³range (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/m³range, 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 foodstuffs^a
------------------------------------------------
Foodstuff Concentration
(µg/kg)
------------------------------------------------
Dairy foods:

fresh milk 0.3
Cheshire cheese 3
English butter 10
eggs 0.6

Meat:

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

Drinks:

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

Cereals:

fresh bread 7
------------------------------------------------
^aFrom: 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 P_o/wto 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.

4.2.2.1. 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 2.4/10¹²cm³per molecule per second at 25 °C
(Howard, 1976). This leads to a calculated reaction rate of
approximately 4/10³per 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.

4.2.2.2. 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 2/10⁴per 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).

4.2.2.3. Water

Wakeham et al. (1982) measured a trichloroethylene exponential
decay rate in a sea-water mesocosm of approximately 2.5/10²per day
at 8 - 16 °C, which is equivalent to a rate of about 1/10³per 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.

4.2.2.4. 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 6/10³per h, which is about 10
times the microbial decay rates.

5. KINETICS AND METABOLISM

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- Rats^b Human beings^a
tissues pigs^a ^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 - - -
----------------------------------------------------------
^aFrom: Fabre & Truhaut (1952), 6045 mg/m³(1120 ppm)
x 5 h per day x 19 days.
^bFrom: Savolainen et al. (1977), 1080 mg/m³(200 ppm)
x 6 h/day x 5 days).
^cCerebellum value.
^dFrom: McConnell et al. (1975). Mean of 8 subjects aged
48 - 52 years.
^eFrom: Bauer (1981). Mean of 15 subjects (Figures in
parentheses are maximum values).
^fFat 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/m³for 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 V_maxwas
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
metabolized.

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,
1979).

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. EFFECTS ON ANIMALS AND CELL SYSTEMS

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 2.6.1.1) 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 2.6.1.1), alanine aminotransferase (EC 2.6.1.2), and ornithine
carbamoyltransferase (OCT) (EC 2.1.3.3) 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
weeks

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

35^a 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)
histology
--------------------------------------------------------------------------------------------------------

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

mouse^b 5500 20 min anaesthesia Gehring (1968)

5500 100 min liver injury (elevated SGPT) Gehring (1968)
5500 300 min mortality Gehring (1968)
---------------------------------------------------------------------------------------------------------
^aKalashmikova et al. (1976) reported that rats exposed to 50 mg/m³for 5 h per day, for 90 days, showed
damage to parenchyma in liver and kidney.
^bKjellstrand 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 3.1.1.8) 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)
LC_L0^a 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)
LC_L0^a 3000 16.0 2 Lazarev (1929)
LC₅₀ 40 4 Lazarev & Gadaskina
(1977)

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

Cat LC_L0^a 6074 32.5 2 Lehmann & Schmidt-Kehl
(1936)

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)
--------------------------------------------------------------------
^aLC_LO= 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.,
1976).

6.1.2. Short-term exposures

6.1.2.1. 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)
weight)
--------------------------------------------------------------------------
Rat 4920¹ 2725²

Dog 5680³ 2.800⁴ 150^5,a

Mouse 2850^6,b 3210^7,b 1440¹⁰ 34¹¹
2400¹² 3150^8,b
3000^9,c
1.200^6,b

Rabbit 20¹
--------------------------------------------------------------------------
¹From: Smyth et al. (1969). ^aLD_L0.
²From: Rigaud et al. (1977). ^bIn 24 h.
³From: Christensen et al. (1974). ^cIn 14 day.
⁴From: Klaassen & Plaa (1967).
⁵From: Barsoum & Saad (1934).
⁶From: Aviado et al. (1976).
⁷From: Klaassen & Plaa (1966).
⁸From: Gehring (1968).
⁹From: Gradiski et al. (1974).
¹⁰From: Plaa et al. (1958).
¹¹From: NIOSH (1977b).
¹²From: 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,
1983).

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).

6.1.2.2. 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/m³administered 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.
(1976).

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
fat.

Doses of 250, 500, 800, and 1200 mg/m³administered for 15 -
90 h resulted in increases in intracellular lipids (Verne et al.,
1959).

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 3.1.1.8) 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
sexes.

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 1.6.99.3) 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).

6.1.2.3. 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

6.1.3.1. 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
dilation.

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.

6.1.3.2. Inhalation exposure

Studies on