| 1.1 Substance|
| 1.2 Group|
| 1.3 Synonyms|
| 1.4 Identification numbers|
| 1.4.1 CAS number|
| 1.4.2 Other numbers|
| 1.5 Brand names, Trade names|
| 1.6 Manufacturers, Importers|
| 2.1 Main risks and target organs|
| 2.2 Summary of clinical effects|
| 2.3 Diagnosis|
| 2.4 First-aid measures and management principles|
|3. PHYSICO-CHEMICAL PROPERTIES|
| 3.1 Origin of the substance|
| 3.2 Chemical structure|
| 3.3 Physical properties|
| 3.4 Other characteristics|
|4. USES/CIRCUMSTANCES OF POISONING|
| 4.1 Uses|
| 4.2 High risk circumstance of poisoning|
| 4.3 Occupationally exposed populations|
|5. ROUTES OF ENTRY|
| 5.1 Oral|
| 5.2 Inhalation|
| 5.3 Dermal|
| 5.4 Eye|
| 5.5 Parenteral|
| 5.6 Others|
| 6.1 Absorption by route of exposure|
| 6.2 Distribution by route of exposure|
| 6.3 Biological half-life by route of exposure|
| 6.4 Metabolism|
| 6.5 Elimination by route of exposure|
| 7.1 Mode of Action|
| 7.2 Toxicity|
| 7.2.1 Human data|
| 22.214.171.124 Adults|
| 126.96.36.199 Children|
| 7.2.2 Relevant animal data|
| 7.2.3 Relevant in vitro data|
| 7.2.4 Workplace standards|
| 7.2.5 Acceptable daily intake (ADI) and other guideline levels|
| 7.3 Carcinogenicity|
| 7.4 Teratogenicity|
| 7.5 Mutagenicity|
| 7.6 Interactions|
|8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS|
| 8.1 Material sampling plan|
| 8.1.1 Sampling and specimen collection|
| 188.8.131.52 Toxicological analyses|
| 184.108.40.206 Biomedical analyses|
| 220.127.116.11 Arterial blood gas analysis|
| 18.104.22.168 Haematological analyses|
| 22.214.171.124 Other (unspecified) analyses|
| 8.1.2 Storage of laboratory samples and specimens|
| 126.96.36.199 Toxicological analyses|
| 188.8.131.52 Biomedical analyses|
| 184.108.40.206 Arterial blood gas analysis|
| 220.127.116.11 Haematological analyses|
| 18.104.22.168 Other (unspecified) analyses|
| 8.1.3 Transport of laboratory samples and specimens|
| 22.214.171.124 Toxicological analyses|
| 126.96.36.199 Biomedical analyses|
| 188.8.131.52 Arterial blood gas analysis|
| 184.108.40.206 Haematological analyses|
| 220.127.116.11 Other (unspecified) analyses|
| 8.2 Toxicological Analyses and Their Interpretation|
| 8.2.1 Tests on toxic ingredient(s) of material|
| 18.104.22.168 Simple Qualitative Test(s)|
| 22.214.171.124 Advanced Qualitative Confirmation Test(s)|
| 126.96.36.199 Simple Quantitative Method(s)|
| 188.8.131.52 Advanced Quantitative Method(s)|
| 8.2.2 Tests for biological specimens|
| 184.108.40.206 Simple Qualitative Test(s)|
| 220.127.116.11 Advanced Qualitative Confirmation Test(s)|
| 18.104.22.168 Simple Quantitative Method(s)|
| 22.214.171.124 Advanced Quantitative Method(s)|
| 126.96.36.199 Other Dedicated Method(s)|
| 8.2.3 Interpretation of toxicological analyses|
| 8.3 Biomedical investigations and their interpretation|
| 8.3.1 Biochemical analysis|
| 188.8.131.52 Blood, plasma or serum|
| 184.108.40.206 Urine|
| 220.127.116.11 Other fluids|
| 8.3.2 Arterial blood gas analyses|
| 8.3.3 Haematological analyses|
| 8.3.4 Interpretation of biomedical investigations|
| 8.4 Other biomedical (diagnostic) investigations and their interpretation|
| 8.5 Overall Interpretation of all toxicological analyses and toxicological investigations|
| 8.6 References|
|9. CLINICAL EFFECTS|
| 9.1 Acute poisoning|
| 9.1.1 Ingestion|
| 9.1.2 Inhalation|
| 9.1.3 Skin exposure|
| 9.1.4 Eye contact|
| 9.1.5 Parenteral exposure|
| 9.1.6 Other|
| 9.2 Chronic poisoning|
| 9.2.1 Ingestion|
| 9.2.2 Inhalation|
| 9.2.3 Skin exposure|
| 9.2.4 Eye contact|
| 9.2.5 Parenteral exposure|
| 9.2.6 Other|
| 9.3 Course, prognosis, cause of death|
| 9.4 Systematic description of clinical effects|
| 9.4.1 Cardiovascular|
| 9.4.2 Respiratory|
| 9.4.3 Neurological|
| 18.104.22.168 CNS|
| 22.214.171.124 Peripheral nervous system|
| 126.96.36.199 Autonomic nervous system|
| 188.8.131.52 Skeletal and smooth muscle|
| 9.4.4 Gastrointestinal|
| 9.4.5 Hepatic|
| 9.4.6 Urinary|
| 184.108.40.206 Renal|
| 220.127.116.11 Others|
| 9.4.7 Endocrine and reproductive systems|
| 9.4.8 Dermatological|
| 9.4.9 Eye, ears, nose, throat: local effects|
| 9.4.10 Haematological|
| 9.4.11 Immunological|
| 9.4.12 Metabolic|
| 18.104.22.168 Acid-base disturbances|
| 22.214.171.124 Fluid and electrolyte disturbances|
| 126.96.36.199 Others|
| 9.4.13 Allergic reactions|
| 9.4.14 Other clinical effects|
| 9.4.15 Special risks|
| 9.5 Others|
| 9.6 Summary|
| 10.1 General principles|
| 10.2 Relevant laboratory analyses and other investigations|
| 10.2.1 Sample collection|
| 10.2.2 Biomedical analysis|
| 10.2.3 Toxicological analysis|
| 10.2.4 Other investigations|
| 10.3 Life supportive procedures and symptomatic treatment|
| 10.4 Decontamination|
| 10.5 Elimination|
| 10.6 Antidote treatment|
| 10.6.1 Adults|
| 10.6.2 Children|
| 10.7 Management discussion|
|11. ILLUSTRATIVE CASES|
| 11.1 Case reports from literature|
| 11.2 Internally extracted data on cases|
| 11.3 Internal cases|
|12. ADDITIONAL INFORMATION|
| 12.1 Availability of antidotes|
| 12.2 Specific preventive measures|
| 12.3 Other|
|14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES|
Chlorinated aliphatic hydrocarbon
1.4 Identification numbers
1.4.1 CAS number
1.4.2 Other numbers
RTECS KJ 2975000
1.5 Brand names, Trade names
Tergo Electrosol TCE
Products containing TCE as a major component include:
CRC Belt Grip
CRC CDT Cutting Oil
Gamlen Drum Cleaner Solvent
Kodak Movie Film Cleaner with Lubricant
Liquid Paper Correction Fluid
Superglo Plastic Cement
Synthetic Lubricating Fluid No. 610
Textile No. 1
Yukoff Bumper and Tyre Sheen
1.6 Manufacturers, Importers
Robert Bryce and Company
2.1 Main risks and target organs
The major danger is respiratory depression with a risk of
cerebral and cardiac anoxia; and depression of the CNS with
coma and respiratory insufficiency. Primary effects are most
marked on the nervous system; at levels in excess of 10,000
ppm, anaesthesia gradually develops, associated with
respiratory depression. Unprotected, unsupervised exposure in
confined and/or unventilated areas is a significant risk.
While this solvent is less toxic than some other chlorinated
hydrocarbons, care is still warranted during its use.
Inhalation abuse is associated with serious risk and has
resulted in fatalities. In these cases cardiac sensitisation,
perhaps exacerbated by relative hypoxia, may be responsible
for cardiac arrhythmias. Cardiovascular effects including
myocardial depression and arrhythmias are the crucial factors
in some deaths (see 9.4), especially in those cases related to
2.2 Summary of clinical effects
Systemic effects: most symptoms and signs reflect the
depressant effect on the central nervous system, which include
disturbances in equilibrium and coordination, followed by
headache and general lassitude. With increasing
concentrations there may be progressive drowsiness and
disorientation, progressing finally to coma and respiratory
arrest. With heavy exposures myocardial depression and
hypotension can occur. Cardiac arrhythmia and deaths have
occurred. Serious hepatotoxicity is uncommon even with
moderately high levels.
Following inhalation, mild mucous membrane and upper
respiratory tract irritation can occur.
Severe irritant effects on the gastrointestinal tract mucosa
have been observed following ingestion.
Contact dermatitis has been described.
It is based on history of exposure and CNS depression.
Environmental monitoring of ambient air can be accomplished
most simply with samples taken by Drager tube, charcoal tube
Breath analysis is the most useful form of biological
monitoring, due to the small renal excretion and low blood
levels commonly found. The best approximation to alveolar air
is that obtainable immediately after normal expiration
(expiratory reserve volume).
Samples should be collected in glass containers or tubes which
can be sealed with a suitable closure for subsequent gas
2.4 First-aid measures and management principles
Treatment is basically symptomatic.
The first aid priority is to make a proper assessment of
airway, breathing, circulation and neurological status of
patient. If respiration is markedly depressed, maintain a
clear airway and support ventilation. With heavy exposures
and/or evidence of significant nervous system effects, monitor
blood pressure, and ECG. Mild to moderate hypotension may
occur, with ST segment changes on the ECG.
After oxygenation, intravenous fluids may be helpful.
Sympathomimetic pressor agents, including dopamine, should be
used only as a last resort, and adrenaline is specifically
contraindicated, due to the probable increased risk of cardiac
sensitisation to these agents.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Manufactured by the action of chlorine on 1,1-dichloroethane
or the catalytic addition of HCl to 1,1-dichloroethylene.
3.2 Chemical structure
Molecular Weight: 133.4 daltons
Structural Formula: CH3CCl3
3.3 Physical properties
Boiling point: 74°C
Melting point: -30°C to -39°C
Flash point: none by standard ASTM
Autoignition temperature: 537°C
Relative vapour density: 4.6
Vapour pressure (20°C): 130 mbar = 13KPa
Solubility: insoluble in water; soluble in
acetone, benzene, carbon tetrachloride, methanol and
ether (Windholz, 1983) Explosive limits:
lower limit 7.5% in air (at 25°C)
upper limit 15.0% in air
Relative molecular mass: 133.41
3.4 Other characteristics
Colourless liquid at room temperature, with a sweet odour.
Vapour hazards: Reacts violently with potassium and sodium.
Incompatible with strong oxidising agents, strong bases,
magnesium, zinc, aluminium and its alloys, (Bretherick, 1985).
At temperatures above 500°C, hydrogen chloride and small
amounts of phosgene are formed. Other combustion/decomposition
products include carbon monoxide and carbon dioxide.
Limits of flammability: 7.5%-15% in air. Will not readily
sustain or support combustion; will not ignite from sparking
sources such as static electricity or friction grinders.
Fire extinguishing media: water spray or carbon dioxide, dry
chemical powder, alcohol or polymer foam.
Management of spills: Cover with dry lime or soda ash, deposit
in closed container and burn in appropriate incinerator.
Ventilate area and wash spill site. Use rubber gloves, boots
and self-contained breathing apparatus.
Water pollution: effect of low concentrations on aquatic life
is not well known. Aquatic toxicity rating: TLM 75-150
ppm/pinfish saltwater (time period not specified) (Weiss,
Commercial products normally contain 3%-7% stabilisers such as
dioxane, isobutyl alcohol, butylene oxide and nitromethane.
4. USES/CIRCUMSTANCES OF POISONING
TCE is often used in household aerosol products, such as
oven cleaners, stain removers, furniture polish,
degreasers, water repellant, suede waterproofer, and
also in hairspray, cosmetics, and typewriter correction
fluids (Kings et al., 1985; Pointer, 1982), and in
crafts. Thus the potential for misuse of these products
must be considered. In one study, 28% of 110 sudden
deaths in glue sniffers were associated with
trichloroethane (Bass, 1970).
TCE is also used as a solvent for natural and synthetic
resins, oils, waxes, tar and alkaloids; for adhesives,
coatings and for textile dyeing operations; and as a dry
cleaning extraction solvent; a coolant and lubricant in
metal-cutting oils; and a chemical intermediate in
4.2 High risk circumstance of poisoning
Work in small, enclosed and/or poorly ventilated spaces,
particularly if unsupervised. Use of excessively large
volumes of solvent for cleaning, e.g. pouring directly onto
floor or other surfaces to be cleaned.
4.3 Occupationally exposed populations
Workers in a range of chemical industries may be exposed to
TCE due to its use as a solvent for natural and synthetic
resins, oils, waxes, tar, alkaloids, and in adhesives,
coatings and textile dyeing. Chemical plant workers may be
involved due to its use as a chemical intermediate in some
synthetic processes or as an extraction solvent. Workers in
the engineering industry may also be exposed; for example
those involved in metal degreasing or cutting or removal of
oils and waxes. The dry-cleaning industry has also used this
5. ROUTES OF ENTRY
Ingestion is possible but infrequently encountered.
This is the most frequent and significant route of entry.
Most commonly occupationally-related but may also be involved
in inhalational abuse.
Exposure can be considerable but while absorption can occur,
it is rarely likely to be significant.
Unlikely to be a significant route given the small amounts and
transient nature of inadvertent eye contact.
Cases involving injection are not well documented.
No human data.
6.1 Absorption by route of exposure
Rapid absorption through gastrointestinal tract.
Expired air concentrations after topical application of TCE or
continuous immersion of the hand for 30 minutes were 0.5 ppm
and 10 ppm respectively at 30 minutes post-exposure. In
contrast, respiratory exposure for a similar time to levels
sufficient to cause only mild symptoms, i.e. 910 ppm, was
associated with expired air concentrations of around 35 ppm at
30 minutes post-exposure (Stewart et al, 1961). The skin is
therefore a considerably less significant route of absorption
than the lung. Stewart and Dodd (1964) estimated peak alveolar
levels of 45 ppm after immersion of both hands in TCE for 30
minutes, similar to peak levels observed after respiratory
exposure of the same duration to 100-500 ppm in air.
Penetration is less with topical application than after total
immersion by a factor of about 20. They concluded that
provided the solvent is not confined beneath an impermeable
barrier there is little likelihood that toxic amounts will be
absorbed during normal industrial use.
The vapour itself is not absorbed in significant amounts
through the skin (Riihimaki and Pfaffli, 1978).
Monster (1978) exposed 6 volunteers for 4 hours at 70 ppm and
145 ppm with and without exercise periods. At rest, lung
clearance (reflecting absorption rate) decreased significantly
over time, from 6 l/min initially to 3.7 l/min at 10 min and
1.9 l/min at 4 hours. Alveolar retention at 4 hours was
calculated at 30%. These findings are consistent with those
of Astrand et al. (1973) and Humbert et al. (1977), whose
respective findings included a lung clearance of 3.25 l/min
after 30 minutes and an alveolar retention of 28% after 4
hours at 72 ppm. Exercise of 100 watts increased lung
clearance and the rate of absorption, but a similar decrease
in retention and lung clearance over time occurs with exposure
under workload. The relatively low uptake of TCE in contrast
to trichloroethylene, and its tendency to decline further
during the course of exposure, can be explained by both its
much less extensive metabolism (3.5% v. 75%) and its
significantly lower partition coefficient between blood and
air (5 v. 15), (Monster, 1978).
6.2 Distribution by route of exposure
Monster (1978) estimated a partition coefficient of 6 between
venous blood and alveolar air, similar to that of 5 estimated
by Astrand et al. (1973).
6.3 Biological half-life by route of exposure
Monster (1978) found that concentrations in exhaled air
following exposure paralleled the decline in blood levels.
Due to differences in distribution and elimination
characteristics of the various tissues, the elimination half-
life is not constant; in the above study the half-life was
estimated at 9, 20 and 26 hours at 20, 50 and 100 hours
respectively post-exposure. (The blood concentration was
about 8.2 times that in mixed exhaled air, which is, however,
about 70% that of alveolar air.)
About 10% is metabolized to trichloroethanol and to a lesser
extent to trichloroacetic acid, which are excreted in the
urine (Ikeda et al., 1972), the latter as a glucuronide
Monster (1978) estimated that maximum concentrations of
trichloroethanol in blood occurred within two hours of the end
of exposure and thereafter declined rapidly, with a half-life
of approximately 10-12 hours. In contrast, blood
trichloroacetic acid continues to rise until about 40 hours
post-exposure, and from about 60 hours declines exponentially
with a half-life of 70-85 hours.
6.5 Elimination by route of exposure
The greater part of absorbed trichloroethane is excreted
unchanged in exhaled air. The remainder is largely
metabolised to trichloroethanol and trichloroacetic acid.
Thus Monster found that after 162 hours (about 1 week) the
total amount exhaled was estimated to represent 80% of the
uptake after exposure to 70 ppm at rest, and a little less
with higher exposure levels, with or without workload. The
relatively rapid alveolar elimination of TCE of 75% at 50 hr
(in comparison with perchloroethylene, for example), can be
explained by its lower blood gas partition coefficient (5 v.
15). In contrast, total urinary excretion of trichloroethanol
and trichloroacetic acid were estimated at only 2% and 0.5%
respectively of the uptake after 3 days. (This latter figure
rose to 1.5% after 7 days). Trichloroethanol is also excreted
in exhaled air but at a level much lower than that in urine.
While the major portion of the trichloroethanol is eliminated
in the urine within one day, only about 30% of the total
trichloroacetic acid is excreted in urine in the first 3 days
after exposure. Thus this compound can accumulate with
7.1 Mode of Action
The specific mode of action is not well known but is presumed
to include effects on cell membranes, due to its lipophilic
properties. In consequence, trans-membrane ion transport
systems are affected; resulting effects include impairment of
neuronal impulse coordination.
7.2.1 Human data
Inhalation - no physiological effects were
observed below 350 ppm (Stewart, 1968). There
is variation in human response, as evidenced by
particularly susceptible individuals exhibiting
impairment on the modified Romberg Test of
balance at 400 ppm while in another experiment
30 healthy volunteers exposed to 500 ppm for
variable time periods performed this test
normally (Stewart et al, 1961). At 800-1000 ppm
some subjects showed minor CNS impairment
(Stewart et al, 1961; Torkelson et al, 1958).
Other investigators (Salvini et al, 1971) have
found similar results. Exposure at 900-1000 ppm
causes mild eye and nasal discomfort, with
slight loss of equilibrium at one hour. At
2000 ppm loss of equilibrium may occur at 15-30
minutes and loss of coordination after one hour
(American Industrial Hygiene Association, 1964).
Above 1700 ppm disturbances of equilibrium
become more obvious and lassitude and headache
may occur (Stewart et al, 1961).
Over 30 deaths and accidental intoxications have
been reported following over-exposure but it is
difficult to assess the levels involved in
fatalities. In one case, the concentration at
the time of an accident was "well in excess of
5000 ppm" (Kleinfeld and Feiner, 1966), and
circumstantial evidence suggests that this is
applicable to other fatalities.
The minimal anaesthetic concentrations are
considered to lie within the range 10,000 to 26,
000 ppm (Dornette & Jones, 1960). A
concentration of 30,000 ppm has been used for
induction of anaesthesia, which was maintained
at levels of 20,000-30,000 ppm. A five-minute
exposure to 5000 ppm can be expected to produce
marked incoordination, and anaesthesia occurs at
20,000 ppm (Stewart, 1968). Recovery from light
plane anaesthesia occurs in 3-5 minutes. With
chronic exposure, significant effects are most
unlikely at levels below the TLV of 350 ppm.
In an exercise reconstructing the circumstances
of a fatal incident, the concentration reached
levels of 62,000 ppm (Hatfield and Maykoski,
Ingestion - Stewart and Andrews (1966) report a
case of an adult male accidentally ingesting
about 28 g of inhibited TCE, an estimated dose
of 0.6 g/kg (Gosselin et al, 1984). The most
notable symptoms were nausea and severe vomiting
and diarrhoea; the physical examination was
normal. A slight elevation in serum total
bilirubin (48 IU) was the only other abnormality
noted. This suggests that, based on a specific
gravity of 1.33, doses of up to about 0.5 ml/kg
may not produce marked systemic effects,
although gastrointestinal irritation may be
considerable. Reversible central nervous
depression has been reported after accidental
ingestion of approximately 0.1 ml/kg of a 95%
trichloromethane solution, (Dornette & Jones,
Skin exposure - cutaneous absorption is probably
too slow to produce significant toxicity
(Stewart & Dodd, 1964).
No data available.
7.2.2 Relevant animal data
Inhalation - Adams et al (1950) reported the following
maximum non-lethal and no observed effect levels (NOEL)
in rats. These values will approximate the LClo and
TClo respectively and have been labelled as such.
LClo 6 min at 30,000 ppm
18 min at 18,000 ppm (various species)
90 min at 15,000 ppm
7 hr at 8,000 ppm
TClo 518 min at 18,000 ppm
5 hr at 8,000 ppm
Thus the maximum NOEL is close to the maximum exposure
level survived, indicating relatively low acute toxicity
for most organs. This has been supported by other
studies (Klaasen and Plaa, 1966, 1967; Plaa and Larson,
Gehring (1968) also showed that with exposure at 13,500
ppm for the median lethal time of 593 minutes
(approximately 10 hours), liver function was virtually
unaffected unless exposures approached those causing
At anaesthetic concentrations (>10,000 ppm),
idioventricular rhythms may be induced with adrenaline
in animals (Rennick, et al, 1949).
Oral - Torkelson et al (1958) reported the following
Male rats 12.3 g/kg
Female rats 10.3 g/kg
Female mice 11.24 g/kg
Female rabbits 5.66 g/kg
Male guinea pigs 9.47 g/kg
Carpenter et al (1949) reported the oral LD50s in four
species of laboratory animal of 8.6 - 14.3 g/kg.
After application to the skin in the rabbit, all animals
survived 3.9 g/kg applied for 24 hrs under occlusion.
Eyes (rabbit) - minor, transient irritation.
Inhalation - Adams et al (1950) also studied long-term
exposures in rats:
10,000 ppm: 10 mins - staggering gait and weakness 3
hrs - irregular perspiration, semiconsciousness
5,000 ppm: 1 hr - mild but definite narcotic effect
with reduced activity. No apparent injury with repeated
exposures. Slight growth retardation.
3,000 ppm: No response in rabbits and monkeys over 2
Prendergast et al (1967) exposed rabbits and dogs to 2,
200 ppm for 8 hours per day for 6 weeks. Although
weight loss occurred there were no visible signs of
7.2.3 Relevant in vitro data
In vitro evaluation of mutagenicity suggests, at most, a
weak action (Dow Chemical Company, unpublished data,
1981). The data indicate that TCE itself is not likely
to be positive in mutagenic tests. Weakly positive Ames
test have been reported sporadically (Simmon et al,
1977) but may be due to various stabilisers used, some
of which are electrophilic in nature.
7.2.4 Workplace standards
ACGIH (1986) TLV-TWA 350 ppm (1900 mg/m3)
TLV-STEL 450 ppm (2450 mg/m3).
CEC (1986) has recommended corresponding values of 200
ppm and 350 ppm respectively. No BEI or BLV appears to
have been set for TCE, unlike trichloroethylene.
Recommendations have been made, (Stewart 1961, Lauwerys
7.2.5 Acceptable daily intake (ADI) and other guideline levels
Value not found. Probably not relevant.
No evidence of carcinogenic properties exists. In one U.S.
National Cancer Institute bioassay study (NCI,1977) large
doses given by gavage were associated with significantly
increased mortality in rats and mice. However, while
assessment was difficult, no statistically significant
increase in tumours was observed. In a second study, 3 of 49
animals in the high dose group (4-6 g/kg/day) developed liver
cell adenomas and one an hepatocellular carcinoma.
Quast et al (1975) exposed rats to 875 ppm and 1750 ppm by
inhalation for 6 hours per day for 1 year and then observed
them throughout their lifetimes. There was no apparent
increase in tumours, nor any other adverse effects.
A CEC Committee (1986) considered that the carcinogenic
potential of TCE has not been fully evaluated and that
stabilisers may contribute to the toxicity in as yet uncertain
TCE did not produce teratogenic effects in pregnant rats or
mice exposed for 7 hours per day to 875 ppm during the period
of organogenesis, ie days 6-15 of gestation, (Schwetz et al,
1975). No effects were observed on the average number of
implantation sites per litter, litter size, incidence of
foetal resorptions, foetal sex ratios or foetal body
measurements. No treatment-related increase in the incidence
of skeletal or visceral malformations was observed. No dose-
dependent effects on fertility, gestation, viability or
lactation indices were observed in a multigeneration
reproductive study; nor any teratogenic effects (Torkelson &
Rowe, 1981). Dosage levels tested were 99.4, 2640 and 8520
Simmon et al (1977) reported mutagenicity in Salmonella
typhimurium strain TA100, with or without a microsomal
activation system. They considered that stabilisers or
inhibitors may have been responsible. In a review of
organochlorine solvents (CEC, 1986) the authors comment that
although the liquid does not produce point mutations in Ames-
developed strains of S. typhimurium, the vapour gave a
positive result in two studies. However, they suggest that
one of these results may have been due to an epoxide
stabiliser in the preparation, and the full range of
constituents in the other was not detailed.
This group concluded that there is no strong evidence that TCE
itself is a potential mutagen but that available data do not
allow final conclusions to be made. They state that no
studies have been published on the mutagenicity of TCE in
mammalian cells in culture, but there is no evidence from
other tests to suggest chromosomal damage; thus negative
results were found with a micronucleus and dominant lethal
assay in mice, and no indication of sister chromatid exchange
in Chinese hamster ovary cells.
Some case reports involve concurrent exposure to other
compounds, as is commonly the case with solvents. It is not
clear however, whether the effects are anything other than
simply additive. Some liquid paper products contain both TCE
and trichloroethylene (Pointer 1982, King et al, 1985).
Deliberate abuse of this product has resulted in death from a
combination of nervous system depression and cardiotoxicity,
but either of these compounds is capable of such effects at
the concentrations encountered with solvent abuse. It may be
that trichloroethylene is the more toxic.
There may be some potentiation of effect by ethanol but this
is described more with trichloroethylene than 1,1,1-
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
188.8.131.52 Toxicological analyses
No data available.
184.108.40.206 Biomedical analyses
Environmental monitoring is most simply
accomplished by the use of Draeger tubes or
similar grab sampling.
Biological monitoring involves collection of
expired air samples and subsequent analysis.
Urinalysis is not helpful, due to the small
amount of urinary excretion of TCE and its
metabolites estimated at 2% of uptake as
trichloroethanol and 0.5% of uptake as
trichloroacetic acid (Monster, 1978).
220.127.116.11 Arterial blood gas analysis
May be useful in the presence of respiratory
18.104.22.168 Haematological analyses
22.214.171.124 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
126.96.36.199 Toxicological analyses
188.8.131.52 Biomedical analyses
184.108.40.206 Arterial blood gas analysis
220.127.116.11 Haematological analyses
18.104.22.168 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
22.214.171.124 Toxicological analyses
126.96.36.199 Biomedical analyses
188.8.131.52 Arterial blood gas analysis
184.108.40.206 Haematological analyses
220.127.116.11 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
18.104.22.168 Simple Qualitative Test(s)
22.214.171.124 Advanced Qualitative Confirmation Test(s)
126.96.36.199 Simple Quantitative Method(s)
188.8.131.52 Advanced Quantitative Method(s)
Infra-red spectrometry of expired breath.
8.2.2 Tests for biological specimens
184.108.40.206 Simple Qualitative Test(s)
220.127.116.11 Advanced Qualitative Confirmation Test(s)
18.104.22.168 Simple Quantitative Method(s)
22.214.171.124 Advanced Quantitative Method(s)
126.96.36.199 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
While Hall and Hine (1966) reported blood levels of 72
mg% and 13 mg% in two fatal cases, others have reported
lower levels. Stahl et al (1969) reported levels of 6.0,
6.2 and 12.0 mg% in three of six fatal cases, very
similar to the 6 mg% reported by Hatfield and Maykoski
(1970). Exposure to essentially non-toxic levels of 500
ppm for 78 minutes resulted in blood levels of just
0.15mg% - 0.65 mg% (Stewart et al, 1961). Jones and
Winter (1983) reported two fatalities in whom post-
mortem blood levels were 4.2 mg% and 1.8 mg%.
In two of the above cases, the brain concentrations were
123 mg% and 8 mg% respectively; in the second case,
inhalation of vomitus was thought a contributing factor
in the death (Jones and Winter, 1983).
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
188.8.131.52 Blood, plasma or serum
Abnormal serum bilirubin, SGOT, alkaline
phosphatase and prolonged prothrombin time have
been reported in sniffers of spot remover
containing trichloroethane and trichloroethylene
(Litt & Cohen, 1969).
Elevated urinary urobilinogen has been reported
in one volunteer seven days after exposure to
900 ppm for 20 minutes to trichloroethane at a
concentration increasing continually from 0-2650
184.108.40.206 Other fluids
8.3.2 Arterial blood gas analyses
Respiratory acidosis in respiratory insufficiency.
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
In blood samples from 66 patients concentrations ranged
from 0.1 to 60 mg/l. A broad relationship between blood
concentration and the severity of poisoning was observed
but there were large variations. There was no strong
correlation between blood concentration and clinical
features (Meredith et al, 1989).
Using infrared spectrometric analysis of expired breath
(Section 8), serial measurements following exposure
allow the construction of an excretion curve which can
then be compared to the excretion curves of subjects
previously exposed to known amounts of solvents. This
gives some indication of the level of exposure. If a
level obtained very soon after exposure is extremely
high, serial measurements are unnecessary to establish
that exposure was severe.
8.4 Other biomedical (diagnostic) investigations and their
8.5 Overall Interpretation of all toxicological analyses and
9. CLINICAL EFFECTS
9.1 Acute poisoning
Mouth and upper gastrointestinal discomfort followed by
nausea, vomiting and severe diarrhoea have been observed
following one case where the dose was estimated at 0.6
g/kg (Stewart and Andrews, 1966). A slight elevation
in serum total bilirubin at 48 hours in absence of
clinical hepatotoxicity was observed. No significant
drowsiness or incoordination was described. Reversible
nervous system depression was described after accidental
ingestion of about 0.1 ml/kg of a 95% solution (Dornette
and Jones, 1960).
Some individual variation in susceptibility appears
likely at least at lower exposure levels. Early
symptoms may include mild eye and nasal discomfort and
impairment of equilibrium and coordination.
Increased lassitude and headache occur with heavier
exposures and in severe poisoning progressive CNS
depression occurs. Hepatotoxicity may not become
manifest until near-anaesthetic levels are reached.
Nausea is apparently not common. Several deaths have
occurred following industrial exposure in confined
spaces and also in the context of solvent abuse. The
evidence suggests, particularly in cases of abuse, that
the arrhythmogenic and cardiodepressive effects become
crucial factors at very high levels.
9.1.3 Skin exposure
Stewart and Dodd (1964) tested skin absorption in
volunteers by total immersion of the hands. A mild
burning sensation was noted after 10 minutes. Mild
erythema and scaling were noted on removal which settled
within 30 to 60 minutes. This fairly mild skin
irritation contrasted with that of some other
chlorinated hydrocarbon solvents. They established
that skin absorption is not high.
9.1.4 Eye contact
Severe eye irritation has not been reported in man; this
is consistent with animal studies where only slight
conjunctival irritation without corneal damage has been
9.1.5 Parenteral exposure
No data available.
No data available.
9.2 Chronic poisoning
Chronic effects are considered to be of little
consequence with the most usual industrial exposure
situations below TLV levels (Kramer et al, 1978). Thus
in one controlled study of 151 subjects, no adverse
effects and no evidence of hepatotoxic or cardiotoxic
effects were found.
9.2.3 Skin exposure
Contact dermatitis of the simple irritant type can occur
with repetitive exposure.
9.2.4 Eye contact
Mild conjunctivitis with chronic vapour exposure.
9.2.5 Parenteral exposure
9.3 Course, prognosis, cause of death
In mild poisonings subjects may exhibit eye and nasal
discomfort, with slight loss of equilibrium and coordination.
In moderate cases, increasing headache, lassitude and nausea
may occur. With severe and prolonged exposure, progressive
central nervous system and respiratory depression will
develop; however considerable evidence indicates that
cardiovascular effects including myocardial depression and
arrhythmias are the crucial factors in some deaths.
9.4 Systematic description of clinical effects
Effects on human cardiac function have been observed
when TCE was used as an anaesthetic agent.
Dornette and Jones (1960) reviewed experience with 50
anaesthetic administrations. With concentrations
sufficient to produce light anaesthesia (in combination
with nitrous oxide), a decrease in systolic blood
pressure of 5-10 mm Hg was noted in about half the
patients, with greater depression in 6%. Three of 32
monitored patients exhibited premature ventricular
contractions of varying degree and/or depressed ST-
segments in the electrocardiograph. However, the
former occurred only in association with respiratory
obstruction and reversion occurred when this was
corrected. Thus relative hypoxia contributes to the
One of the patients with depressed ST-segments developed
cardiac arrest following a steady decline in blood
It is likely that cardiac arrhythmias could have played
a role in some industrial deaths and certainly those
involving inhalational abuse, given the rapidity of
onset and other features of the cases. Bass (1970)
discussed this possibility in a review of 110 cases of
sudden death in solvent sniffers, 29 involving TCE. The
threshold for cardiac conduction defects is probably
high since no ECG abnormalities developed after exposure
of volunteers to up to 1,000 ppm (Torkelson et al,
The vapour is not a serious respiratory tract irritant
and few signs of such irritation occur, even at
concentrations presenting risks from respiratory
depression. TEC has been used as an anaesthetic. The
pulmonary congestion and oedema found in fatal cases is
likely to be a secondary manifestation. In survivors of
severe exposure, recovery is generally prompt with
little residual respiratory function deficit.
Kramer el al. (1978) conclude that chronic exposure to
levels typical in industry are not a hazard to the
respiratory tract. However, Woo et al. (1983) describe a
case of cough, dyspnoea and chest pain associated with
hypoxia in a man using an aerosolised product containing
TCE, and other cases have been reported. They suggest
that aerosol inhalation may result in higher local
mucosal concentrations of liquid TCE whose contact with
epithelium could have been enhanced by the particular
surface active agent included in the product.
Impairment of central nervous system functions
is the most characteristic feature of TCE. The
earliest symptoms are usually slight impairment
of equilibrium and coordination, followed by
lassitude and headache. One study by Salvini et
al (1971) involving just 6 subjects found no
statistically significant impairment of
psychophysiological function at levels of 450
ppm, indicating that the TLV is an appropriate
level. Thus assessment of memory, complex
reaction time, manual dexterity and perception
showed no difference from controls. On the
other hand Gamberale and Hultengren (1973) did
obtain significant differences from controls in
measures of reaction time, perceptual speed and
manual dexterity at 350 ppm. In a series of
volunteer studies by Stewart et al (1961) it was
found that exposure at 900 ppm for one hour
could cause slightly impaired balance. At 2650
ppm, following gradually increasing exposure
over 15 minutes, two of seven subjects could not
stand and three others became lightheaded, only
one still performing a Romberg test normally.
Progressive CNS depression occurs with
increasing concentrations of TCE. Anaesthesia
can be induced at concentrations between 10,000
ppm and 26,000 ppm (Dornette & Jones 1960) and
light anaesthesia is maintained at
concentrations between 6000 and 22,500 ppm.
(They considered that in this series of patients
at least one quarter of the narcotic effect was
attributable to nitrous oxide). Recovery from
light anaesthesia usually occurred within three
to five minutes.
220.127.116.11 Peripheral nervous system
Peripheral neuropathies have not been directly
associated with TCE exposure.
18.104.22.168 Autonomic nervous system
Effects on the autonomic nervous system may be
possible but have not been clearly described.
Secondary responses may be anticipated to the
apparently negative isotropic and vasodilator
effects of TCE (Herd et al., 1974).
22.214.171.124 Skeletal and smooth muscle
Effects on smooth muscle have been little
researched. The possibility has been raised by
Herd et al (1974) that the reduced myocardial
contractility observed may be mediated by
changes in distribution in calcium,
administration of which restored function
towards normal. It is possible that skeletal
muscle function could be affected by similar
Gastrointestinal symptoms with inhalational exposures
are not marked although, as with solvent abuse, nausea
and in severe cases vomiting can occur. In one ingestion
episode, oropharyngeal and gastrointestinal discomfort
were followed by nausea, vomiting and severe diarrhoea
(Stewart & Andrews, 1966). In another (Gerace, 1981)
burns of the oesophagus were noted.
Rare episodes involving ingestion suggest a severe
irritant effect on alimentary tract mucosa.
TCE has been used in controlled high doses as an
anaesthetic agent. Experience, including a series of 51
cases reported by Dornette & Jones (1960), suggests it
is not frequently or significantly hepatotoxic, even at
such high levels. This is consistent with a number of
animal studies (Adams et al, 1950). Plaa et al (1958),
and Klaasen & Plaa (1966) suggest that it is less
hepatotoxic than most other chlorinated hydrocarbons.
Stewart et al. (1961) reported one volunteer with
elevated urinary urobilinogen seven days after exposure
to 900 ppm for 20 minutes. This finding was also noted
in two of seven subjects exposed for 15 minutes to TCE
at a concentration increased continuously from 0 to 2650
Litt and Cohen (1969) reported abnormal serum bilirubin,
SGOT, alkaline phosphatase and prolonged prothrombin
time in five teenage males who had sniffed a spot
remover containing both TCE and trichloroethylene. Some
had been previous solvent abusers.
Halevy et al (1980) describe an episode where hepatic
and renal effects predominated, with little acute CNS
symptoms, suggesting exposure levels were not high (see
section 11.1, Illustrative cases). Liver function tests
remained elevated for 38 days and biopsy showed
cholestasis, eosinophilia and inflammatory cell
infiltrate. A hypersensitivity reaction was suggested
as the underlying mechanism.
Effects on the urinary system appear uncommon
and have not been reported in some volunteer
studies (Stewart et al., 1969) and reviews of
workforce populations (Kramer et al., 1978).
However renal effects have been described
following both acute and long-term exposure, and
in one ingestion episode: in this case,
microscopic haematuria and mild proteinuria (1+)
were observed on admission but were resolved
(Stewart & Andrews 1966).
Halevy et al (1980) reported a patient with
proteinuria and abnormal renal function indices
(creatinine clearance 70 ml/minute, serum
creatinine 1.55 mg%). All were reversible
within ten days.
Some case-control studies have associated
glomerulonephritis with chronic solvent exposure
(Zimmerman et al., 1975; Lagrue et al., 1977)
although it is difficult to identify the
relevant solvent(s) in sometimes complex
exposures, and negative associations have also
been claimed (Van der Laan, 1980). Nathan and
Toseland (1979) discussed a patient with
GoodPasture's syndrome attributed to prolonged
glue sniffing in whom TCE abuse exacerbated the
clinical picture; it may also have been one of
the solvents initially involved.
Solvent abuse has been implicated in some cases
of renal tubular lesions, and biochemical
markers of tubular effects e.g. urinary ß-
glucuronidase were elevated in drycleaning
workers exposed to one chlorinated hydrocarbon
(Franchini et al., 1983). However TCE does not
appear to have been directly implicated with
No data available.
9.4.7 Endocrine and reproductive systems
There appears to be no evidence of significant adverse
effects in humans, although this issue has not been
studied in depth. In one study in mice (Lane et al.,
1982), 1 g/kg daily via drinking water had no effect on
In volunteer studies involving hand immersion (Stewart &
Dodd, 1964), a burning sensation was produced within ten
minutes, followed by erythema and scaling on removal;
this resolved within 60 minutes. Chronic exposure can
result in irritant contact dermatitis. Excessive
contact can result in blistering and second degree
chemical burns (Jones & Winter, 1983).
9.4.9 Eye, ears, nose, throat: local effects
Direct eye contact with the liquid can produce mild
conjunctivitis, subsiding within a few days (Dow
Chemical Company, Medical Records). Eye irritation may
occur with vapour exposure.
Case histories (Stewart, 1971; Halevy et al., 1980) and
workforce population studies (Kramer et al., 1978)
suggest that significant haematological toxicity rarely,
if ever, occurs.
Parameters of immunological disturbance do not appear
to have been well studied. However glomerular basement
membrane antibodies have been isolated in some cases of
glomerulonephritis attributed to chronic exposure to
solvents which have included TCE in some cases.
126.96.36.199 Acid-base disturbances
188.8.131.52 Fluid and electrolyte disturbances
9.4.13 Allergic reactions
9.4.14 Other clinical effects
9.4.15 Special risks
Pregnancy - There is little information by which to
assess the risk to man. While York et al. (1982) found
some foetal developmental delay in rats when dams were
exposed to 2100 ppm, postnatal development was normal;
there is no evidence of teratogenicity (Schwetz et al.,
1975; York et al., 1982). Lane et al. (1982) showed no
adverse reproductive or fertility effects in mice.
No data available.
10.1 General principles
TCE is primarily a central nervous system depressant and at
high levels can cause severe respiratory depression with
life-threatening hypoxia, and/or serious cardiac arrhythmia
which is exacerbated by endogenous catecholamines. The most
critical aspect of management is immediate support of vital
functions; toxicity to other organs is relatively low and
there is no specific antidote.
The first priority is to make a proper assessment of the
airways, breathing, circulation and neurological status of
the patient and to monitor blood pressure and ECG.
Sympathomimetic agents, in particular adrenaline, should not
be used even in the face of such apparent indications as
severe hypotension, as these agents may potentiate the
arrhythmogenic effects of TCE, particularly under conditions
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
Breath analysis is the most appropriate biological
monitoring method. Expired air can be collected in a
container which can be sealed. Any other specimens
collected should be placed in containers which can be
sealed to prevent loss of vapour.
10.2.2 Biomedical analysis
In severe cases with depressed respiration, arterial
blood gas analysis may be a useful monitoring aid.
10.2.3 Toxicological analysis
Using analysis of expired breath (Section 8), serial
measurements following exposure allow the
construction of an excretion curve which can then be
compared to the excretion curves of subjects
previously exposed to known amounts of solvents.
This gives some indication of the level of exposure:
if a level obtained very soon after exposure is
extremely high, serial measurements are unnecessary
to establish that exposure was severe.
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic treatment
Make a proper assessment of the airways, breathing,
circulation and neurological status of the patient. Maintain
a clear airway.
If spontaneous respiration is inadequate, perform mouth-to-
mouth resuscitation or endotracheal intubation and support
ventilation using an appropriate mechanical device.
Monitor vital signs. Hypotension may respond to adequate
oxygenation and IV fluid replacement. There appears to be
little experience with pharmacological treatment of
hypotension or arrhythmia, but ventricular fibrillation has
been reversed successfully with defibrillation in at least
one case. Measure arterial blood gases and monitor fluid
electrolytes, including calcium.
Inhalation - Move patient to fresh air. In severe cases
administer oxygen by mask or nasal cannula. If spontaneous
respiration is inadequate perform endotracheal intubation
and support ventilation using an appropriate mechanical
device. There is no evidence that the co-administration of
carbon dioxide to act as a respiratory centre stimulant
achieves greater clinical improvement or increased
elimination, but this has not been well studied. While the
primary purpose of ventilation is to correct hypoxia, it
will also result in increased elimination of TCE because the
vapour is largely eliminated through the breath.
Ingestion - The minimum systemically toxic oral dose in
humans is uncertain but is probably greater than 0.5 g/kg
and may be higher. Decontamination need be considered only
above this level.
Ingestion episodes are fortunately very rare and management
experience is slight. In the two most commonly cited cases
(Stewart & Andrews, 1966; Gerace, 1981) both vomiting and
diarrhoea occurred, within thirty minutes in the latter case
(report not yet obtained) which was also associated with
oesophageal burns. Inducing emesis (e.g. with syrup of
ipecac) may not be warranted in some cases and may even be
contraindicated if there is evidence of severe
It may be preferable to administer activated charcoal but
large volumes may be necessary and will obscure the mucosa
from direct visualisation. Administer a cathartic unless
already given with activated charcoal or diarrhoea is
evident. Emesis is contraindicated in coma, with
convulsions or evidence of ulceration of the
gastrointestinal mucosa. A third alternative for large
ingestions is to perform gastric lavage in the absence of
severe corrosive injury and with protected airway in
comatose or convulsing patients. Emesis and particularly
lavage will be relatively ineffective after one hour.
Skin - wash skin with soap and copious amounts of water.
Eye - Exposed eyes should be irrigated with copious amounts
of water at room temperature for at least 15 minutes.
Established measures to enhance elimination have no role.
10.6 Antidote treatment
There are no specific antidotes.
There are no specific antidotes.
10.7 Management discussion
In the great majority of severe TCE poisonings, subjects
have either been found dead or dying before adequate
resuscitation can be instituted, or they recover fairly
rapidly with minimal requirement for active intervention.
In only a minority have emergency resuscitative and
treatment measures been both immediately indicated and
available and their relative efficacy is not well
established. This applies to pharmacological agents for the
treatment of hypotension and arrhythmia. However adrenaline
and probably similar agents should be avoided in the
treatment of hypotension or bradycardia; electroconversion
may be useful in the treatment of ventricular fibrillation,
given the success of Wodka and Jeong (1989). Adequate
oxygenation is the mainstay of treatment; in patients with
spontaneous respiration, oxygen can be given successfully
via a nasal cannula (Pointer, 1982). The patient should be
disturbed or stressed as little as possible. Follow up
should include monitoring of hepatic, renal and neurological
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
One of the first fatalities reported was that by Kleinfeld
and Feiner (1966). Four public utility workers entered an
underground vault (14 x 7 x 7 feet) to remove grease from
conduits using rags soaked in TCE. They experienced
giddiness and light headedness so retired to fresh air. One
then returned with a circulating fan, but before
successfully connecting it he decided once again to leave
the vault and shortly thereafter had a respiratory arrest.
Blood and tissue analyses were made but levels were not
reported. It was estimated that his time in the vault was
about 10 minutes and concentrations of TCE were well above
Hatfield and Maykoski (1970) describe the fatal case of a
worker found in the lower portion of a 450 gallon aircraft
tip tank. The blood concentration of TCE was 6 mg% and
there was acute passive congestion of pulmonary and cerebral
tissues with minimal alveolar oedema. With the usually
employed technique of reaching through the end opening or
access port to clean the interior, peak concentrations of
800 ppm occurred inside the tank, with breathing zone levels
of just 200 ppm. However a reconstruction of this worker's
cleaning habits was made by an individual wearing an airline
respirator. This involved climbing into the tank itself
having first poured some solvent into the tank and
saturating a cleaning pad. After a few minutes the solvent
in air had reached a concentration of 62,000 ppm.
The above blood level is similar to that of three of the
four levels reported from the six fatal cases reported by
Stahl et al (1969). Their fourth case was the exception in
that blood and brain levels were just 0.15 and 0.32 mg/100
ml respectively. This youth had been cleaning an air vent
in a room of 6 x 8 x 10 feet. He had been observed to
appear quite well over an initial four hour period but was
found dead just before a further four hours had elapsed.
Because of elevated lactic acid levels in brain tissue, it
was considered that in this case oxygen deprivation must
have been a critical factor.
Caplan et al. (1976) describes the death of a 40-year-old
woman redecorating a small unventilated bathroom. She was
found in the early morning with paint and paint thinner
spilled on the floor and mixed with mats and towels. Tissue
levels of TCE included blood 2 mg%, brain 36 mg%, liver 5
mg% and lung 1 mg%. There was acute pulmonary congestion
and oedema. While the recorded blood level was lower than
that in most other reported fatalities (with the exception
of one of the Stahl et al. series discussed above), it is
consistent with the estimate of Stewart et al. (1961) that
incapacitating nervous system depression may occur at blood
levels of 1.0 to 1.5 mg/100 ml. A consistent theme with
these fatalities is unprotected exposure in relatively small
poorly ventilated areas.
Northfield (1981) describes two fatalities in young newly-
employed workers in the UK. In the first case, air levels
ranged from 65 ppm with normal working conditions to 735 ppm
in the absence of usual ventilatory measures, the previous
employee had been unaffected over a period of several years.
Analysis revealed 27 mg% in blood and 118 mg% in lung
tissue and there was good circumstantial evidence suggesting
solvent sniffing. The second person worked at a degreasing
tank using cans to scoop up cold solvent present at a few
inches in depth at the bottom of the tank, and then pour it
over metal parts on a perforated tray across the top. When
found he was slumped over the edge of the tank.
Environmental monitoring of the undisturbed tank revealed
just 200 ppm 15cm from the tank. However, it was 6000 ppm
at 8 to 15 cm below the rim and over 70,000 ppm nearer the
base, 8 to 15 cm above the solvent surface. Measurements
were repeated during normal operations, when liquid was
disturbed and carried to the tray at the top.
Concentrations were 73,000 ppm at 8 cm and 94,000 ppm at 15
cm respectively below the tank rim. It was suggested the
worker had either been bending down to wash his hands in
solvent or had otherwise lost his balance, in either case he
was exposed to rapidly fatal concentrations near the base of
the tank. This underlines the need for properly designed
degreasing operations not requiring the worker to bend down
into the tank. TCE has a heavy vapour (relative vapour
density 4.6) and levels may be very much higher below than
above the rim.
Jones and Winter (1983) describe two fatal episodes with
associated levels of 4.2 mg% and 1.8 mg% respectively in
blood and 123 mg% and 8 mg% in brain tissue. The latter
case involved spraying and wiping motor vehicle upholstery.
The worker was found slumped on the floor with his head
behind the driver's door, which had been pushed forward.
Inhalation of vomitus was a significant factor in the death.
An estimated volume of 100 to 200 ml of solvent had been
used and a simulation exercise involving deliberate spillage
of 100 ml onto a cloth demonstrated just 515 ppm, 15 cm
above the floor but rising sharply to 6410 ppm, 2.5 cm above
There have been several reports of abuse of typewriter
correction fluid containing TCE. Whilst there has been a
fatal outcome in some cases, recovery from severe effects
has occurred in others.
Wodka and Jeong (1989) described a 15-year-old boy found in
cardiopulmonary arrest with coarse ventricular fibrillation
evident on electrocardiography. Cardiac defibrillation was
attempted twice, with restoration of sinus rhythm and a
complication-free recovery. Echocardiogram showed distal
septal wall motion abnormality while electrocardiograms
suggested anteroseptal myocardial injury but not persistent
ischaemia. They postulated a mechanism of temporary
coronary artery spasm which has been suggested as the cause
of infarction and fibrillation in one case of toluene
inhalation (Cunningham et al., 1987).
Pointer (1982) discussed the case of a 14-year-old girl
found slumped in a city park with partially dried TCF on her
hands, face and clothing. Initially she responded only to
deep painful stimuli, but was just mildly drowsy on arrival
at hospital. Low flow oxygen was administered per nasal
cannulae and the patient became completely alert within ten
further minutes of observation.
Halevy et al. (1980) describe an episode where hepatic and
neural effects predominated. No monitoring was undertaken
so that the severity of exposure was uncertain. However, the
relatively mild CNS manifestations suggested that exposure
had not been great. The major symptoms were dizziness,
headache, nausea, abdominal pain and diarrhoea occurring
several hours later with fever, jaundice and cough after 48
hours. Investigations included elevated (mainly conjugated)
bilirubin, SGOT, LDH and alkaline phosphatase with increased
serum creatinine (1.5%), reduced creatinine clearance (70
ml/minute), and considerable proteinuria (2.9 gm in 24
hours). Renal function parameters returned to normal with
ten days. Liver function tests reversed only after 38 days
and biopsy showed inflammatory cell infiltrate plus
eosinophils and cholestasis. This degree of hepatorenal
dysfunction is unusual in the absence of more severe CNS
injury and the authors postulated an individual
hypersensitivity reaction in this patient. The time delay
between exposure and the initial symptoms is unusual however,
and perhaps the most convincing evidence of causality was
that tests for lymphocyte migration inhibition factor were
positive for TCE but negative for ajmalin, a prescribed anti-
11.2 Internally extracted data on cases
No data available.
11.3 Internal cases
To be completed by the centre.
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes
12.2 Specific preventive measures
Adequate ventilation conditions are essential, but may need
to be supplemented with approved respiratory protective
equipment. Use in confined, enclosed spaces should be
avoided unless supplied air respirators are available.
Unprotected and unsupervised exposure to high concentrations,
such as may occur in confined and/or poorly ventilated
areas, is the major concern. Unawareness of this risk,
coupled with just gradually increasing unsteadiness and
drowsiness, may result in the worker not instituting
suitable evasive measures until finding great difficultly in
Major signs of severe intoxication are reduced level of
consciousness, coma and depressed respiration.
In circumstances of sudden high concentrations, as in
inhalation abuse, increased adrenergic activity may be a
significant factor and resulting cardiac arrhythmias due to
sensitisation to adrenalin can occur.
Essential first aid measures are the assessment and
establishment of airway and ventilation. To maintain a clear
airway the mouth should be cleared of debris, the tongue
pulled forward and an oropharyngeal airway inserted. If
spontaneous respirations are inadequate, perform an
endotracheal intubation and support ventilation using
appropriate mechanical device.
ACGIH (1986) Documentation of TLV's, methyl chloroform.
American Conference Of Governmental Hygienists, Cincinatti, pp
Adams EM, Spencer HC, Rowe VK, & Irish DD (1950) Vapor toxicity
of 1,1,1-trichloroethane (methylchloroform) determined by
experiments on laboratory animals. Arch Industr Hyg Occup Med,
American Industrial Hygiene Association, Toxicology Committee
(1964) Emergency exposure limits. Am Indust Hyg J, 25: 578-586.
Astrand I, Kilbom A, Wahlberg I & Ovrum P (1973)
Methylchloroform exposure. I. Concentration in alveolar air and
blood at rest and during exercise. Work Environ Health, 10: 69-
Bass M (1970) Sudden sniffing death. JAMA, 212: 2075-2079.
Bretherick L ed. (1985) Hazards in the chemical laboratory, 4th
ed. London, The Royal Society of Chemistry.
Caplan YH, Backer RC, & Whitaker JQ (1976) 1,1,1-
trichloroethane: report of a fatal intoxication. Clin Toxicol 9:
Carpenter CP, Smyth HF & Pozzani UC (1949) The assay of acute
vapor toxicity, and the grading and interpretation of results on
96 chemical compounds. J Ind Hyg Toxicol 31: 343-349.
CEC (1986) 1,1,1-trichloroethane. In: Organo-chlorine solvents,
Commission of the European Communities, Royal Society of
Cunningham SR, Dalzell GWN, McGirr P, Khan MM (1987) Myocardial
infarction and primary ventricular fibrillation after glue
sniffing. Br Med J 294: 739-740.
Dornette WHL & Jones JP (1960) Clinical experiences with 1,1,1-
trichloroethane: a preliminary report of 50 anaesthetic
administrations. Anaesthesia and Analgesia, 39: 249-263
Franchini I, Cavatorta A, Falzoi M, Lucertini S & Mutti A (1983)
Early indicators of renal damage in workers exposed to organic
solvents. Int Arch Occup Environ Health, 52: 1-9.
Gamberale F & Hultengren M (1973) Methylchloroform exposure II.
Psychophysiological functions. Work Environ Health, 10: 82-92.
Gehring PJ (1968) Hepatotoxic potency of various chlorinated
hydrocarbon vapors relative to their narcotic and lethal
potencies in mice. Toxicol Appl Pharmacol, 13: 287-298.
Gerace RV (1981) Near-fatal intoxication by 1,1,1-
trichloroethane. Ann Emerg Med, 10: 533-534.
Gosselin RE, Smith RP & Hodge HC eds. (1984) 1,1,1-
trichloroethane. In: Clinical Toxicology of Commercial Products,
5th ed. Baltimore, Williams & Wilkins, pp II-166.
Halevy J, Pitlik S, Rosenfeld J & Eitan BD (1980) 1,1,1,-
trichloroethane intoxication: a case report with transient liver
and renal damage. Review of the literature. Clin Toxicol, 16:
Hall FB & Hine CH (1966) Trichloroethane intoxication: a report
of two cases. J Foren Sci, 11: 404-413.
Hatfield TR & Maykoski RT (1970) A fatal methyl chloroform
(trichloroethane) poisoning. Arch Environ Health, 20: 279-281.
Herd PA, Lipsky M & Martin HF (1974) Cardiovascular effects of 1,
1,1-trichloroethane. Arch Environ Health, 28: 227-233.
Humbert BE & Fernandez JG (1977) Exposition au 1,1,1-
trichloroethane contribution a l'etude de l'absorption de
l'ecretion du metabolisme sur des subjets humains. Arch Mal prof,
Ikeda M, Hatsue O, Imamura T & Komike Y (1972) Urinary excretion
of total trichloroethanol, and trichloroacetic acid as a measure
of exposure to trichloroethylene and tetrachloroethylene. Br J
Ind Med, 29: 328-333.
Jones RD & Winter DP (1983) Two case reports of deaths on
industrial premises attributed to 1,1,1-trichloroethane. Arch
Environ Health, 38: 59-61.
King GS, Smialek JE, Troutman WG (1985) Sudden death in
adolescents resulting from the inhalation of typewriter
correction fluid. JAMA, 253: 1604.
Klaasen CD & Plaa GL (1966) Relative effects of various
chlorinated hydrocarbons on liver and kidney function in mice.
Toxicol Appl Pharmacol, 9: 139-151.
Klaasen CD & Plaa GL (1967) Relative effects of various
chlorinated hydrocarbons on liver and kidney function in dogs.
Toxicol Appl Pharmacol, 10: 119-131.
Kleinfeld M & Feiner B (1966) Health hazards associated with
work in confined spaces. J Occup Med, 8: 358-364.
Kramer CG, Gerald Ott M, Fulkerson JE, Hicks N & Imbus HR (1978)
health of workers exposed to 1,1,1,-trichloroethane: a matched-
pair study. Arch Environ Health, 33: 331-342.
Lagrue G, Kalamodine T, Hirbec G, Bernaudin JF, Guerrero J &
Zhepova F (1977) Role de l'inhalation de substances toxiques dans
la genese des glomerulonephrites. Nouv Presse Med, 6: 3609-3613.
Lane RW, Riddle BL, Borzelleca JF (1982) Effects of 1,2-
dichloroethane and 1,1,1-trichloroethane in drinking water on
reproduction and development in mice. Toxicol Appl Pharmacol,
Lauwerys RR (1986) Occupational toxicology. In: Klaassen CD,
Amdur MO & Doull J eds. Casarett & Doull's Toxicology. New York,
Litt IF & Cohen MI (1969) "Danger--vapour harmful": spot-remover
sniffing. N. Eng. J. Med., 281: 543-544.
Meredith TJ, Ruprah M, Liddle A & Flanagan RJ (1989) Diagnosis
and treatment of acute poisoning with volatile substances. Hum
Toxicol, 8: 277-286
Monster AC (1978) Kinetics of chlorinated hydrocarbon solvents.
Organisation for Health Research. TNO.
National Cancer Institute (1977). Bioassay of 1,1,1-
trichloroethane for possible carcinogenicity. NCI-CG-TR-3.
NIOSH (1975) Occupational exposure to 1,1,1-trichloroethane -
criteria for a recommended standard. U.S. Department of Health
Education and Welfare.
Northfield RR (1981) Avoidable deaths due to acute exposure to 1,
1,1-trichloroethane. J Soc Occup Med, 31: 164-166.
Plaa GL & Larson RE (1965) Relative nephrotoxic properties of
chlorinated methane, ethane, and ethylene derivatives in mice.
Toxicol Appl Pharmacol, 7: 37-44.
Plaa GL, Evans EA & Hine CH (1958) Relative hepatotoxicity of
seven halogenated hydrocarbons. J Pharmacol Exp Ther, 123: 224-
Pointer J (1982) Typewriter correction fluid inhalation: a new
substance of abuse. J Toxicol - Clin Toxicol, 19: 493-499.
Prendergast JA, Jones RA, Jenkins LJ & Siegel J (1967) Effects
on experimental animals of long-term inhalation of
trichloroethylene, carbon tetrachloride, 1,1,1-trichloroethane,
dichlorodifluoromethane, and 1,1-dichloroethylene. Toxicol Appl
Pharmacol 10: 270-289
Quast JF, Leong BKJ, Rampy LW & Gehring PJ (1975) Toxicologic
and carcinogenic evaluation of a methylchloroform (1,1,1-
trichloroethane) formulation by chronic inhalation in rats -
interim report after 24 months. Midland, Michigan, The Dow
Rennick BR, Balton SD, Moe GS & Seevers MH (1949) Induction of
idioventricular rhythms by 1,1,1-trichloroethane and epinephrine.
J Pharmacol Exp Therap, 8: 327.
Riihimaki V & Pfaffli P (1978) Percutaneous absorption of
solvent vapors in man. Scand J Work Environ Health, 4: 73-85.
Salvini M, Binaschi S & Riva M (1971) Evaluation of the
psychophysiological functions in humans exposed to the 'threshold
limit value' of 1,1,1-trichloroethane. Br J Ind Med, 28: 286-
Schwetz BA, Leong BKJ & Gehring PJ (1975) The effect of
maternally inhaled trichloroethylene, perchloroethylene, methyl
chloroform, and methylene chloride on embryonal and fetal
development in mice and rats. Toxicol Appl Pharmacol, 32: 84-96.
Simmon VF, Kauhanen K & Tardiff RG (1977) Progress in genetic
toxicology. Scott D, Bridges BA, & Sobel FH eds. Elsevier,
North Holland Biomedical Press, pp 249 - 58.
Stahl CJ, Fatteh AV & Dominguez AM (1969) Trichloroethane
poisoning: observations on the pathology and toxicology in six
fatal cases. J Forensic Sci, 14: 393-397.
Stewart RD (1968) The toxicology of 1,1,1-trichloroethane.
Annals Occup Hyg, 11: 71-79.
Stewart RD (1971) Methyl chloroform intoxication. Diagnosis and
treatment. JAMA, 215: 1789-1792.
Stewart RD & Andrews JT (1966) Acute intoxication with
methylchloroform. JAMA, 195: 120-122.
Stewart RD & Dodd HC (1964) Absorption of carbon tetrachloride,
trichloroethylene, tetrachloroethylene, methylene chloride, and 1,
1,1-trichloroethane through the human skin. Ind Hyg J, 25: 439-
Stewart RD, Gay HH, Erley DS, Hake CL & Schaffer AW (1961) Human
exposure to 1,1,1-trichloroethane vapor: relationship of expired
air and blood concentrations to exposure and toxicity. Ind Hyg J,
Stewart RD, Gay HH, Schaffer AW, Erley DS & Rowe VK (1969)
Experimental human exposure to methyl chloroform vapour. Arch
Environ Health, 19: 467-472.
Torkelson TR and Rowe VK (1981) Halogenated aliphatic
hydrocarbons. In: Clayton GD & FE eds Patty's Industrial
Hygiene and Toxicology, Vol IIB. New York, John Wiley & Sons, pp
Torkelson TR, Oyen F, McCollister DD & Rowe VK (1958) Toxicity
of 1,1,1-trichloroethane as determined on laboratory animals and
human subjects. Ind Hyg J, 19: 353-362.
Van Der Laan (1980) Chronic glomerulonephritis and organic
solvents: a case control study. Int Arch Occup Environ Health,
Weiss G (1980) (Ed.) Hazardous Chemicals Data Book. Noyes Data
Corporation, Park Ridge, New Jersey, USA, p. 875.
Windholz M ed. (1983) The Merck Index: an encyclopedia of
chemicals, drugs, and biologicals, 10th ed. Rahway, New Jersey,
Merck and Co., Inc.
Wodka RM & Jeong WS (1989) Cardiac effects of inhaled typewriter
correction fluid. Annals Int Med, 110: 91-92.
Woo OF, Healy KM, Sheppard D, & Tong TG (1983) Chest pain and
hypoxemia from inhalation of a TCE aerosol product. J Toxicol
Clin Toxicol, 20: 333-341.
York RG, Sowry BM, Hastings L & Manson JM (1982) Evaluation of
teratogenicity and neurotoxicity with material inhalation
exposure to methyl chloroform. J Toxicol Environ Health, 9: 251-
Zimmerman SW, Groehler K & Beirne GJ (1975) Hydrocarbon exposure
and chronic glomerulonephritis. Lancet, 2: 199-201.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
Author: Dr D M G Beasley
National Poisons and Hazardous Chemicals Information
Otago University Medical School
P.O. Box 913
Date: February 1991
Reviewer: Professor ANP van Heijst
3735 MJ Bosch en Duin
Date: March 1991
Peer review: Adelaide, Australia, April 1991