MONOGRAPH FOR UKPID
1,1,1-TRICHLOROETHANE
Maeve McParland
National Poisons Information Service (London Centre)
Medical Toxicology Unit
Guy's & St Thomas' Hospital Trust
Avonley Road
London
SE14 5ER
UK
This monograph has been produced by staff of a National Poisons
Information Service Centre in the United Kingdom. The work was
commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review group: Directors of the UK National Poisons Information
Service.
1 SUBSTANCE/PRODUCT NAME
1.1 Origin of substance
1,1,1-Trichloroethane is a synthetic chemical. There are no natural
sources, however it is a common environmental contaminant. It was
first prepared in 1840 by the action of chlorine on
1,1-dichloroethane, and first produced commercially in 1946. It is now
produced commercially by chlorination of ethane, or hydrochlorination
of 1,1-dichloroethylene or, more commonly, via hydrochlorination of
vinyl chloride (IARC Monograph, 1979; Durrans, 1971; ILO, 1983; Mark
et al, 1979).
1.2 Name
1.2.1 Brand/trade name
Tipp-ex, Tipp-ex Thinners (Tippex GmbH), Liquid Paper (Point GmbH).
1.2.2 Generic name
1,1,1-Trichloroethane
1.2.3 Synonyms
Methyl chloroform, alpha-trichloroethane, methyl trichloromethane,
1,1,1-Trichloroethan (German), 1,1,1-Trichloorethaan (Dutch),
1,1,1-Tricloroetano (Italian), 1,1,1-Trichloroethane (French).
1.2.4 Common names/street names
Genklene, Inhibisol, Chlorothene.
1.3 Chemical group/family
1,1,1-Trichloroethane is an organochlorine solvent belonging to the
family of chlorinated alkanes.
1.4 Substance identifier and/or classification by use
1.5 Reference numbers
CAS 71-55-6
RTECS KJ 2975000
EINECS 2007563
UN 831
EEC identity no 602-013-00-2
1.6 Manufacturer
Name Tipp-ex GmbH and Co. KG
Address Rossertstrasse 6, D-65835 Leiderbach.
Telephone 06196-6003-0
Fax Not known
Name Point GmbH
Address Vienna.
Telephone Not known
Fax Not known
1.7 Supplier/importer/agent/ licence holder
Name Tipp-ex Ltd
Address Camberley, Surrey GU15 3DT
Name Gillette UK Ltd (Liquid Paper)
Address London
1.8 Presentation
1.8.1 Form
Various.
1.8.2 Formulation details
Various.
1.8.3 Pack sizes available
Various. Tipp-ex and Tipp-ex thinnners are available in 30ml bottles.
Liquid Paper is available in 20ml bottles.
1.8.4 Packaging
Various. Tipp-ex and Liquid Paper are both available in white plastic
screw top bottles with black and red labelling.
1.9 Physico-chemical properties
Chemical structure
1,1,1-trichloroethane
Molecular Weight = 133.42
CH3CCL3
Physical state
Liquid (non-viscous)
Colour
Colourless
Odour
Sweetish odour similar to that of chloroform or carbon
tetrachloride. The odour of 1,1,1-trichloroethane is considered
distinctive or powerful enough to provide satisfactory warning of
exposure, however, it is usually noticeable at about 100ppm which
is below the level required to cause acute toxic effects (Clayton
and Clayton, 1981).
pH
No information available.
Solubility in water and organic solvents
It is slightly soluble in water, soluble in chloroform, ethanol,
ethyl ether, acetone, methanol, benzene, carbon disulphide, and
carbon tetrachloride. Solubility in water = 0.95g/L at 20°C.
Important chemical interactions
A mixture of 1,1,1-trichloroethane and potassium may explode on
light impact.
Violent decomposition with evolution of hydrogen chloride may
occur when 1,1,1-trichloroethane comes into contact with
aluminium, magnesium or their alloys (Bretherick, 1981).
It reacts violently with dinitrogen tetroxide, oxygen, liquid
oxygen, sodium, sodium hydroxide and sodium potassium alloy
(Sax, 1984).
Phosgene is produced when 1,1,1-trichloroethane comes into
contact with iron, copper, zinc or aluminium at high
temperatures (Carchman et al, 1984).
Analytical grade 1,1,1-trichloroethane has a purity of >99.0%
and contains no added stabilizers. Commercially available
technical and solvent grade 1,1,1-trichloroethane has a purity of
90-95% and usually contains 3-8% of stabilizers, mainly to
prevent the generation of hydrochloric acid and to avoid
corrosion of metal parts. The stabilizers (usually a mixture) are
nitromethane, N-methyl pyrole, 1,4-dioxane, butylene oxide,
1,3-dioxolane, nitroethane, toluene, di-isopropylamine, methyl
ethyl ketone, iso-butyl alcohol and 2-butanol (IARC Monograph
1979; Carchman et al, 1984; Fielder et al, 1984).
Major products of combustion/pyrolysis
A considerable amount of energy is required for ignition and it
will not sustain combustion (Clayton and Clayton, 1981).
Explosion limits
In air at 25°C = 8.0-10.5 vol %
Flammability
Nonflammable under normal conditions, vapour burns at high
temperatures (>360°C)
Boiling point
74.1° C
Density
1.3249 (26/4°C)
Vapour pressure
13.3 Kpa (100mmHg) at 20°C
Relative vapour density
4.6 (air =1)
Flash point
None
Reactivity
A mixture of 1,1,1-trichloroethane and potassium may explode on
light impact.
Violent decomposition with evolution of hydrogen chloride may
occur when 1,1,1-trichloroethane comes into contact with
aluminium, magnesium or their alloys (Bretherick, 1981).
It reacts violently with dinitrogen tetroxide, oxygen, liquid
oxygen, sodium, sodium hydroxide and sodium potassium alloy (Sax,
1984).
Phosgene is produced when 1,1,1-trichloroethane comes into
contact with iron, copper, zinc or aluminium at high temperatures
(Carchman et al, 1984).
1.10 Hazard/risk classification
1.11 Uses
1,1,1-Trichloroethane is used industrially and domestically as a
degreaser, dry cleaning agent, and solvent in paints, glues and
aerosol products. A common source is typewriter correction fluid, and
correction fluid thinners, in commercial products such as Tipp-ex(TM)
and Liquid paper(TM).
1,1,1-Trichloroethane has rapid anaesthetic action and was used for
this purpose medically but was abandoned with the advent of safer
agents.
It is an important chemical intermediate, and is used as an additive
to raise the flash point of many flammable solvents.
1.12 Toxicokinetics
1.12.1 Absorption
1,1,1-Trichloroethane is rapidly absorbed through the lungs and the
gastrointestinal tract. Absorption through skin also occurs (Stewart
and Dodd, 1964), but is of minor significance compared to uptake via
inhalation.
1,1,1-Trichloroethane has a relatively low blood/air partition
coefficient, therefore steady state tissue levels are attained slowly
and the vapour is eliminated relatively rapidly in expired air after
exposure.
Studies with human volunteers (males), exposed by inhalation to
1,1,1-trichloroethane at concentrations from around 35ppm to 350ppm
for 6 hours demonstrated that about 25-40 % of the trichloroethane
inhaled was absorbed by the lungs. The amount varied depending on the
1,1,1-trichloroethane concentration in the inhaled air, duration of
exposure, body weight and amount of adipose tissue, blood circulation
and other factors (Astrand et al, 1973; Monster et al, 1979; Nolan et
al, 1984). Uptake from inhalation increases with physical activity.
1.12.2 Distribution
1,1,1-Trichloroethane has a high lipid/blood partition coefficient and
is therefore expected to distribute widely into body tissues,
particularly into those with high lipid content such as the brain and
adipose tissue. It passes readily through the human blood-brain
barrier and is also believed to cross the placental barrier to the
foetus. In one postmortem examination following an acute lethal
exposure, 1,1,1-trichloroethane was detected in the blood, brain and
liver (D'Costa and Gunasekera, 1990).
1.12.3 Metabolism
1,1,1-Trichloroethane is mainly (90%) excreted unchanged through the
lungs (Nolan et al, 1984). 60%-80% of an absorbed dose is exhaled
within one week, however traces may be found in the post-exposure
expired breath for as long as one month (Baselt and Cravey, 1989).
Small amounts of 1,1,1-trichloroethane are slowly metabolized by
oxidation to trichloroethanol, which is conjugated with glucuronic
acid before excretion in the urine. This accounts for only about 2% of
an absorbed dose. Trichloroacetic acid is formed from trichloroethanol
as a further oxidation product and is also found in the urine to the
extent of about 1.5% of a dose (Monster et al, 1979). Simultaneous
exposure to other solvents tends to increase the retention and
decrease the metabolism of 1,1,1-trichloroethane (Savolainen et al,
1981).
1.12.4 Elimination
Regardless of the route of administration, the main excretary route
for 1,1,1-trichloroethane is exhalation via the lungs. Initial
excretion is fairly rapid (70% reduction of the level in expired air
within 2 hours (Monster et al, 1977), but this is followed by slower
elimination, with small amounts being detected in the breath for up to
several days post-exposure.
Studies with human volunteers show that over 90% of the absorbed
1,1,1-trichloroethane is excreted unchanged in the expired air. Only
minor quantities (5-6%) of the absorbed solvent are excreted in the
urine (as trichloroethanol glucuronide and trichloroacetic acid)
(Monster et al, 1979). Less than 1% of an absorbed dose remained in
the body after 9 days (Nolan et al, 1984).
1.12.5 Half-life
At or below TLV of 350 ppm elimination (in expired air) was reported
to be triexponential (Nolan et al, 1984):
Initial phase = 44 minutes,
Intermediate phase = 5-7 hours,
Terminal phase = 53 hours.
The half lives of the metabolites in urine were:
2,2,2-Trichloroethanol = 13 hours,
Trichloroacetic acid = 51 hours.
Urinary excretion rate of the two metabolites is very variable and
provides only a rough estimate of exposure (Nolan et al, 1984).
1.12.6 Special populations
Simultaneous exposure to other solvents tends to increase the
retention and decrease the metabolism of 1,1,1-trichloroethane
(Savolainen et al, 1981), so occupational exposure to mixed solvents
may put workers at greater risk of 1,1,1-trichloroethane toxicity.
2 SUMMARY
3 EPIDEMIOLOGY OF POISONING
Most cases of poisoning with 1,1,1-trichloroethane result from
accidental occupational exposure or intentional abuse, commonly
referred to as volatile solvent abuse (VSA). Accidents involving the
accumulation of high concentrations are rare, the highest risk group
are intentional abusers.
Occupational Exposure
A review of industrial accidents noted to the Factory Inspectorate in
the UK during the period 1961-1980, and involving certain halogenated
hydrocarbon solvents revealed 52 incidents due to
1,1,1-trichloroethane (McCarthy and Jones, 1983).
Volatile Substance abuse
Modes of abuse: Techniques vary depending on the product but all
involve deep breathing through the nose and mouth and not just
sniffing as the term 'glue sniffing' implies. Terms of abuse used are
'huffing' and 'bagging', and are methods used with the intention of
maximising the concentration of solvent in inhaled air:
Huffing:- The solvent (liquids - dry cleaning fluids and typewriter
correction fluids) is poured onto a piece of cloth and held to the
nose or mouth.
Bagging:- A small amount of the solvent (viscous products - usually
glue) is poured into a polythene bag and the open end placed over the
nose and mouth, the vapour released is rebreathed until the desired
effect is achieved.
The packaging and container size of typewriter correction fluids also
enables them to be inhaled directly from the bottle.
Products abused: The source for 1,1,1-Trichloroethane abuse is
commonly typewriter correction fluids (Tipp-ex(TM) and Liquid
Paper(TM)). Factors contributing to its popularity are: low cost,
availability and easy concealment.
Morbidity and Mortality: Bass (1970) first drew attention to the
increase in deaths attributable to VSA in the United States during the
1960s. In this review spot remover containing 1,1,1-trichloroethane
was identified as being responsible for 29 out of 110 (26%) cases of
sudden death. Death was from cardiac arrhythmias, leading to
fibrillation and cardiac arrest due to the combined effect of
hypercapnia (from repeated inhalation from a bag) and catecholamine
release (due to stress), on the myocardium that had been sensitized to
these agents by the volatile solvent.
Watson (1979) reported the first substantial study of VSA deaths in
Britain. She reported 45 cases of sudden death and showed a doubling
in the number of deaths between the time periods of 1970-1973 and
1974-1975. Anderson et al (1985), stated that deaths from VSA were
about 100 per annum, occurring most frequently in males under 20 years
of age.
In the United Kingdom between 3.5% and 10% of young people have at
least experimented with VSA and current users comprise 0.5-1% of the
secondary school population (Ramsey et al, 1989). There is a trend
towards the misuse of products containing gases, predominantly butane
(Esmail et al, 1992).
Prevention: In England and Wales the Intoxicating Substances
(Supply) Act (1985) makes it an offence to sell, or to offer for sale,
substances to children under the age of 18 years if the vendor has
grounds for believing that those substances are likely to be inhaled
to achieve intoxication.
In an attempt to address the problem of solvent abuse the German
company manufacturing Tipp-ex(TM) (Tipp-ex GmbH and Co) introduced a
water based correction fluid in addition to the older version
containing 1,1,1-trichloroethane. In 1984 the manufacturer of Liquid
Paper(TM) added mustard oil to the product in an attempt to discourage
abuse, and strengthened the wording of its product warning label.
4 MECHANISM OF ACTION/TOXICITY
1,1,1-Trichloroethane sensitizes the heart to catecholamines, is a
central nervous system and respiratory system depressant, and a skin
and mucous membrane irritant.
1,1,1-Trichloroethane is less toxic than other chlorinated
hydrocarbons which may be explained in part by its lesser degree of
metabolism, the majority of an inhaled dose being excreted via the
lungs. It is weakly anaesthetic when compared to other chlorinated
hydrocarbons (Kelafant et al, 1994).
Acute intoxication with 1,1,1-trichloroethane causes initial
excitement and euphoria followed by depression of the central nervous
system with dizziness, drowsiness, ataxia and headache, progressing to
coma and death from respiratory depression in severe cases. Death also
occurs from ventricular arrhythmias as at high concentrations the
solvent sensitizes the myocardium to adrenaline and other
catecholamines.
The vapour and liquid are irritating to the skin and mucous membranes.
Nausea, vomiting and diarrhoea have all been reported following
ingestion.
1,1,1-Trichloroethane causes minimal hepatic dysfunction, except in
high concentrations, and animal livers are relatively resistant to all
except lethal levels of 1,1,1-trichloroethane (Stewart,1971).
5 FEATURES OF POISONING
5.1 Acute
5.1.1 Ingestion
Ingestion of 1,1,1-trichloroethane causes irritation to the
gastrointestinal tract with subsequent nausea, vomiting, abdominal
pain and diarrhoea. Symptoms have been noted within 30 minutes of
ingestion (Gerace, 1981).
It is well absorbed by ingestion (Gerace, 1981) and causes central
nervous system depression with dizziness, drowsiness, headache and
ataxia, progressing to coma and death from respiratory depression in
severe cases (Stewart, 1968). Convulsions may occur.
Sensitization of the myocardium to adrenaline and other catecholamines
may occur causing potentially fatal arrhythmias (Hall and Hine, 1966;
Bass, 1970; Stewart, 1971; Reinhardt et al, 1973; Travers, 1974).
The irritant effect of 1,1,1-trichloroethane on the gastrointestinal
tract with concurrent decrease in conscious level presents the risk of
gastric aspiration.
In a report of accidental ingestion of 1 oz (approx. 28ml) of
1,1,1-trichloroethane, severe gastrointestinal irritation developed
shortly after ingestion requiring hospital admission, where a gastric
lavage was performed. No CNS disturbance or neurological abnormalities
were observed on investigation 4 hours post-exposure (Stewart and
Andrews, 1966).
5.1.2 Inhalation
1,1,1-Trichloroethane vapours are irritating to the eyes and mucous
membranes causing coughing and chest tightness as the concentration
increases (Environmental Health Criteria 136, 1992). It has a
depressant action on the central nervous system and is narcotic at
high concentrations.
With intentional abuse an initial excitatory phase occurs which may be
followed by depression and a hangover effect (similar although less
severe than that caused by alcohol) (Watson, 1982). This initial
euphoria may progress to confusion, disorientation, dizziness,
headache, incoordination, drowsiness, hallucinations and aggressive
behaviour while continued exposure will lead to coma, convulsions,
respiratory depression, cardiovascular collapse and death (Stewart,
1971).
Recovery from 1,1,1-trichloroethane induced narcosis is usually
complete with no serious sequelae (Torkelson et al, 1958; McCarthy and
Jones, 1983)
Vomiting can occur with the risk of aspiration of stomach contents
(Hall and Hine, 1966).
Sensitization of the myocardium to adrenaline and other catecholamines
may occur causing potentially fatal arrhythmias (Hall and Hine, 1966;
Bass, 1970; Stewart 1971; Reinhardt et al, 1973; Travers, 1974).
5.1.3 Dermal
Like many solvents 1,1,1-trichloroethane will defat the skin.
Absorption through the skin can occur but it is not a significant
route of exposure. Despite its widespread use only a few cases of skin
irritancy have been reported.
Skin vesication and erythema may occur with prolongued contact (Jones
and Winter, 1983).
In a volunteer study, immersion of a hand in liquid
1,1,1-trichloroethane for 30 minutes resulted in mild erythema, which
persisted for one hour (Stewart and Dodd, 1964).
Allergic contact dermatitis presenting as severe eczema has been
reported following exposure to 1,1,1-trichloroethane (Ingber, 1991).
5.1.4 Ocular
When 1,1,1-trichloroethane comes into contact with the eye only
superficial and transient eye irritation occurs. 1,1,1-Trichloroethane
tested by drop application to rabbit eyes caused slight conjunctival
irritation and no corneal damage (Grant and Schuman, 1993).
5.1.5 Other routes
Intraperitoneal
The intraperitoneal LD50 value has been reported to be 5.1g/kg in
the rat, and values in the range 2.6-4.9g/kg have been obtained in
mice. In all cases the compound was given as a solution in vegetable
oil. Much higher toxicity was reported when 1,1,1-trichloroethane was
given in dimethylsulphoxide (DMSO), the LD50 in this case being
84mg/kg in the mouse. This was presumably due to more rapid uptake
from the peritoneal cavity using this route. This study did not give
any indication of toxic effects other than lethality (Fielder et al,
1984).
In another intraperitoneal study using mice, liver damage was noted 24
hours after a dose of 3.7g/kg. The damage consisted of slight
necrosis, hepatocyte enlargement and vacuolation. A slight rise in
serum aminotransferase was also noted (Klassen and Plaa, 1966).
5.2 Chronic toxicity
5.2.1 Ingestion
There is no human data.
5.2.2 Inhalation
A Japanese study on women chronically exposed to levels of up to about
350ppm (established TLV) gave no evidence of any disturbances in the
central or peripheral nervous system (HSE Toxicity Review 9, 1984).
Kelafant et al (1994) studied 28 workers with long term repetitive
high exposures to 1,1,1-trichloroethane (exposure levels were not
known but thought to be very high as environmental controls were poor
and subjects frequently complained of mild neurological symptoms while
working). They were evaluated for complaints of short term memory
loss, moodiness, disequilibrium, irritability and decreased ability to
concentrate. As a group they had significant deficits on
neuropsychological testing and platform posturography demonstrated
deficits in vestibular, somatosensory and occular components of
balance. They concluded that the encephalopathic picture in these
subjects is similar to reported with other solvents.
House et al (1994), report a case of peripheral neuropathy occurring
possibly as a result of daily exposure to 1,1,1-trichloroethane.
5.2.3 Dermal
Prolonged or repeated skin contact with 1,1,1-trichloroethane may lead
to dermatitis, due to its defatting action. Despite its widespread use
only a few cases of skin irritancy have been reported. Skin vesication
and erythema may occur with prolonged contact (Jones and Winter,
1983).
Allergic contact dermatitis presenting as severe eczema has been
reported following exposure to 1,1,1-trichloroethane (Ingber, 1991).
Liss (1988), described two cases of peripheral neuropathy among
workers who immersed their hands in 1,1,1-trichloroethane while using
it as a degreaser.
Repeated topical application of 1,1,1-trichloroethane to abraded and
non-abraded rabbit skin for up to 90 days, resulted in slight
reversible irritation (Torkelson et al, 1957).
5.2.4 Ocular
Repeated daily application of about 50µl of 1,1,1-trichloroethane to
eyes of rabbits (5 days a week for 2 weeks) led to the development of
a mild inflammatory reaction. The reaction disappeared within 48 hours
of the last application (Fielder et al, 1984).
5.2.5 Other routes
No data.
5.3 Systematic description of clinical effects
5.3.1 Cardiovascular
Acute effects
Hypotension may be noted following acute exposure and cardiovascular
collapse has been reported after large, single exposures.
Sensitization of the myocardium to adrenaline and other catecholamines
may occur causing potentially fatal arrhythmias (Hall and Hine, 1966;
Bass, 1970; Stewart 1971; Reinhardt et al, 1973; Travers, 1974).
Chronic effects
Banathy and Chan (1983) described the postmortem findings in a 14 year
old Liquid Paper(TM) abuser who died suddenly which revealed
myocardial degenerative changes including interfibrillary oedema,
swollen and ruptured myofibrils (see case 12, section 7).
Wright and Strobl (1984) reported a case of prolonged cardiac
arrhythmias in a 45 year old man, after low level exposure to
1,1,1-trichloroethane. The patient was previously well with no history
of cardiovascular disease. He experienced almost continuous inhalation
and dermal exposure to 1,1,1-trichloroethane in his occupation. An
irregular heart beat was discovered on routine physical examination
and 24 hour monitoring revealed multiple ventricular ectopic beats,
episodes of ventricular bigeminy, trigeminy and ventricular
fibrillation. The arrhythmias continued for 2 weeks after cessation of
exposure and resolved completely after one month.
McCleod et al (1987) suggest an adverse interaction between
1,1,1-trichloroethane and halothane. The authors report on two
patients with repeated exposure to 1,1,1-trichloroethane who
experienced cardiac deterioration with halothane anaesthesia. They
proposed the possibility of chronic cardiac toxicity induced by
repeated exposure to 1,1,1-trichloroethane followed by a toxic
interaction with halothane.
5.3.2 Respiration
Respiratory system symptoms such as cough, breathlessness and chest
tightness are common in cases of acute poisoning (Boyer et al, 1987).
Respiratory depression may occur following acute exposure.
Woo et al (1983), reported a case of hypoxemia and chest pain
following inhalation of a 1,1,1-trichloroethane aerosol product. The
solvent was combined with a surface active agent in the product. The
combined formulation increased the water solubility of
1,1,1-trichloroethane and enhanced disposition in the upper airway
thus causing considerable respiratory distress. The authors concluded
that the symptoms could not be attributed to the propellant, surface
active agent or 1,1,1-trichloroethane alone.
5.3.3 Neurological
Acute effects
1,1,1-Trichloroethane causes central nervous system depression, the
severity of symptoms depending on the concentration and exposure time.
Initial mild effects: dizziness, headache, ataxia, incoordination,
fainting.
As concentration increases: collapse, coma.
A 15 year old boy suffered intense cerebral oedema with tonsillar
herniation following acute exposure (suspected abuse) to 1,1,1-
trichloroethane in typewriter correction fluid and subsequently died
(D'Costa and Gunaskera, 1990).
Chronic effects
A Japanese study on women chronically exposed to levels of up to about
350ppm (established TLV) gave no evidence of any disturbances in the
central or peripheral nervous system (HSE Toxicity Review 9, 1984).
Kelafant et al (1994) studied 28 workers with long term repetitive
high exposures to 1,1,1-trichloroethane (exposure levels were not
known but thought to be very high as environmental controls were poor
and subjects frequently complained of mild neurological symptoms while
working). They were evaluated for complaints of short term memory
loss, moodiness, disequilibrium, irritability and decreased ability to
concentrate. As a group they had significant deficits on
neuropsychological testing and platform posturography demonstrated
deficits in vestibular, somatosensory and occular components of
balance. They concluded that the encephalopathic picture in these
subjects is similar to reported with other solvents.
Liss (1988), described two cases of peripheral neuropathy among
workers who immersed their hands in 1,1,1-trichloroethane while using
it as a degreaser. House et al (1994) report a case of peripheral
neuropathy occurring possibly as a result of daily exposure to
1,1,1-trichloroethane.
5.3.4 Gastrointestinal
Nausea, vomiting and diarrhoea occur. Gastrointestinal symptoms may
predominate shortly after ingestion, with the later features
resembling those expected following inhalation exposure.
In a case of accidental ingestion of approximately 600mg of
1,1,1-trichloroethane/kg, signs of severe gastrointestional irritation
(vomiting, diarrhoea) were evident shortly after the ingestion
(Stewart and Andrews, 1966).
5.3.5 Hepatic
1,1,1-Trichloroethane causes minimal hepatic dysfunction, except in
high concentrations. In humans transient rises in liver enzymes have
been reported (Gerace, 1981).
Halevy et al (1980) report a case of liver damage following acute
occupational exposure to 1,1,1-trichloroethane, although this may have
been due to an individual hypersensitivity reaction (see case 6,
section 7).
In a study of long term occupationally exposed workers to
1,1,1-Trichloroethane for neurological deficits, hepatic function was
also monitored and was normal in all cases (Kelafant et al, 1994). In
a matched pair study under controlled conditions to 500ppm (7 hours a
day) for five days, volunteers showed evidence of mild CNS
disturbance, but there was no evidence of any liver or kidney
dysfunction from clinical chemistry studies at the end of the exposure
period (Stewart et al, 1969).
Thiele et al (1982) report a case of hepatic cirrhosis after several
years of heavy exposure to trichloroethylene followed by 3 months of
work that involved using an aerosolized degreaser containing
1,1,1-trichloroethane. They suggest that an individual suffering
hepatic injury from a chlorinated hydrocarbon may be at risk of
further progression of the disease upon subsequent exposure to even a
relatively non-toxic member of this family of organic solvents (in
this case 1,1,1-trichloroethane).
Animal livers are relatively resistant to all except lethal levels of
1,1,1-trichloroethane (Stewart, 1971).
5.3.6 Urinary
In a matched pair study under controlled conditions to 500ppm (7 hours
a day) for five days, volunteers showed evidence of mild CNS
disturbance. There was no evidence of any liver or kidney dysfunction
from clinical chemistry studies at the end of the exposure period
(Stewart et al, 1969).
5.3.7 Endocrine and reproductive system
No human data available.
5.3.8 Dermatological
Absorption through the skin can occur but is not a significant route
of exposure (ACGIH 1986). Skin vesication and erythema may occur with
prolongued contact (Jones and Winter, 1983).
Immersion of a hand in liquid 1,1,1-trichloroethane for 30 minutes
resulted in mild erythema, which persisted for one hour (Stewart and
Dodd, 1964).
Allergic contact dermatitis presenting as severe eczema has been
reported following chronic exposure to 1,1,1-trichloroethane (Ingber,
1991).
5.3.9 Eye, ears, nose and throat
1,1,1-Trichloroethane vapours are irritating to the eyes and mucous
membranes. Contact with the eyes will cause transient, superficial
irritation only.
No systemic toxic effects on the human eye occur from exposure to
1,1,1-Trichloroethane. 1,1,1-Trichloroethane tested by drop
application to rabbit eyes caused slight conjunctival irritation and
no corneal damage (Grant and Schuman, 1993).
5.3.10 Haematological
No abnormalities reported.
5.3.11 Immunological
No abnormalities reported.
5.3.12 Metabolic
5.3.12.1 Acid-base disturbances
No abnormalities reported.
5.3.12.2 Fluid and electrolyte distrurbances
No abnormalities reported.
5.3.12.3 Other
None.
5.3.13 Allergic reactions
Halevy et al (1980) report a case of liver damage following acute
occupational exposure to 1,1,1-trichloroethane, although this was
thought to have been due to an individual hypersensitivity reaction
(see case 6, section 7).
5.3.14 Other clinical effects
None.
5.4 At risk groups
5.4.1 Elderly
No data.
5.4.2 Pregnancy
No data.
5.4.3 Children
Gallagher (1990) recommends caution in the use of some adhesive tape
remover products in intensive care nurseries. 1,1,1-Trichloroethane is
a component of some commercially available tape remover pads that are
used in intensive care to lessen the skin trauma from removal of
adhesive tape. The simulated use of 2 different pads in an infant
incubator produced detectable levels of 1,1,1-trichloroethene for
several minutes. Since the risk to a neonate is unknown, the author
recommends that these pads should not be used on the skin of neonates
in incubators.
5.4.4 Enzyme deficiencies
No data.
5.4.5 Enzyme induced
No data.
5.4.6 Occupations
Mainly used as a metal degreaser therefore at risk occupations are:
heavy equipment mechanics and cleaners, automechanics, machine
operatives, assemblers, printers, garage workers, tool and dye makers.
Industrial chemists using it as an intermediate and dry cleaners are
also at risk.
Thiele et al (1982) suggested that pre-exposure to other chlorinated
hydrocarbons may increase the potential for hepatic damage from
1,1,1-trichloroethane.
5.4.7 Others
Adolescents are particularly susceptible to volatile substance abuse,
including the abuse of 1,1,1-trichloroethane.
Exposure to 1,1,1-trichloroethane may increase sensitivity to other
compounds, e.g. anaesthetics (McCleod et al, 1987).
6 MANAGEMENT
6.1 Decontamination
Following inhalation of 1,1,1-Trichloroethane patients should be
removed from the source of exposure. Maintain respiration and cardiac
output. Seek medical advice as soon as possible. First aiders should
wear protective clothing to prevent secondary contamination.
Contaminated clothing should be removed and exposed skin irrigated
immediately with copious amounts of water.
Eyes should be irrigated for at least 15 minutes with water or normal
saline. They should then be examined with fluorescein, referral to an
ophthalmologist may be necessary.
Although no evidence could be found to suggest that
1,1,1-trichloroethane is an aspiration hazard itself, the irritant
effect of 1,1,1-trichloroethane on the gastrointestinal tract with
concurrent CNS depression increases the risk of aspiration of stomach
contents. Thus emesis is contraindicated and gastric lavage with a
cuffed ET tube if necessary, is the preferred method of gastric
decontamination.
The use and efficacy of activated charcoal has not been studied, nor
the optimum timing for gastric lavage following ingestion, however a
abdominal x-ray (1,1,1-trichloroethane is radio-opaque) may aid the
decision.
6.2 Supportive care
Treatment is primarily symptomatic, with support of the cardiovascular
and respiratory systems. Use of adrenaline or related sympathomimetic
stimulants are contraindicated due to the risk of inducing ventricular
fibrillation.
6.3 Monitoring
Level of consciousness, ECG, respiratory rate function should all be
monitored, along with liver and kidney function in severe cases.
A chest x-ray is indicated in patients with respiratory symptoms and
in cases of suspected aspiration.
6.4 Antidotes
There is no specific antidote for 1,1,1-trichloroethane intoxication.
6.5 Elimination techniques
The efficacy of enhanced elimination techniques (e.g. haemodialysis,
haemoperfusion, etc) has not been established.
6.6 Investigations
1,1,1-Trichloroethane is radio-opaque and following acute
intoxications, abdominal x-ray examinations may be useful for
diagnosis. Furthermore, they may provide evidence for the
effectiveness of gastric lavage (Dally et al, 1986).
Typewriter correction fluid contains titanium dioxide and the presence
of white particulate matter in the nose and/or on hands maybe a clue
to diagnosis.
1,1,1-Trichloroethane is present in expired breath in significant
concentrations to allow specific identification if this technique is
available (Gerace, 1981).
Blood and urine toxicological analysis may be useful in confirming
exposure.
6.7 Management controversies
Although little evidence could be found to suggest that
1,1,1-trichloroethane is an aspiration hazard itself, the irritant
effect of 1,1,1-trichloroethane on the gastrointestinal tract with
concurrent CNS depression increases the risk of aspiration of stomach
contents. Thus emesis is contraindicated and gastric lavage with a
cuffed ET tube if required, is the preferred method of gastric
decontamination.
Dickerson and Biesemer (1982 - see section 9.10) from studies in rats,
concluded that 1,1,1-trichloroethane was capable of lung injury and
posed an aspiration risk from aspiration of the volatile hydrocarbon
itself. Travers (1974) references Hall and and Hine (1966) in claiming
one of the causes of death with 1,1,1-trichloroethane is aspiration of
the solvent.
Woo et al (1983), reported a case of hypoxemia and chest pain
following inhalation of a 1,1,1-trichloroethane aerosol product. The
solvent was combined with a surface active agent in the product. The
combined formulation increased the water solubility of
1,1,1-trichloroethane and enhanced deposition in the upper airway thus
causing considerable respiratory distress. The authors concluded that
the symptoms could not be attributed to the propellant, surface active
agent or 1,1,1-trichloroethane alone.
7 CASE DATA
CASES FROM THE LITERATURE
Case 1: Accidental in a child
Shortly after being put to bed by his parents, a previously well 4
year old boy was heard to be making unusual noises. He was found under
the bed clothes limp and apnoeic. While an ambulance was called his
father administered mouth to mouth resuscitation. En route to hospital
ventilatory support was continued. On arrival at hospital he was pale,
comatose and unresponsive to painful stimuli. An erythematous,
blistered area was noted on the right cheek. Vital signs were as
follows: pulse 120 beats/minute; blood pressure 100/70 mmHg;
respirations 24/minute. The child was monitored and oxygen by mask and
intravenous fluids were given. Twelve minutes after arrival in the
emergency department the patient started to move spontaneously and
then awoke and became alert and orientated. The stomach was emptied
and activated charcoal and magnesium sulphate administered.
Investigations revealed normal electrolytes, glucose, BUN, blood
count, and chest x-ray. A toxicology screen was also normal. Later in
the day however, alkaline phosphatase, LDH and SGOT were noted to be
raised. The child was discharged well 48 hours after admission and 6
month follow up revealed the child to being well with no long term
sequelae.
The child was thought to have attempted to play with a sibling's toy
flower making kit which contained a 30ml container of
1,1,1-trichloroethane. As this had been forbidden to him he had taken
it to play with under the covers. The fumes probably rendered him
unconscious at which time the 1,1,1-trichloroethane spilled onto the
bed. He fell with his cheek into the compound and continued to inhale
the fumes. The unusual noise heard may have been a seizure secondary
to hypoxia or airway compromise with a decreased level of
consciousness (Gerace, 1981).
Case 2: Fatal accidental occupational
A 15 year old male died 6 weeks after starting his first job. His
duties involved using 1,1,1-trichloroethane in a centrifuge to
degrease small metal parts. The process involved supporting the parts
on perforated trays, which rested across the top of a tank of cold
1,1,1-trichloroethane, and scooping up the solvent in cans and running
it over the parts. The open top of the tank measured approximately
0.9m by 0.6m and stood 0.75m above floor level by the doorway, it was
not fitted with extract ventilation.
The body of the deceased was found at about midday slumped over the
edge of the tank. It is thought he may have decided to wash his hands
in the solvent before going to lunch, and been over come by the vapour
while bending over the edge of the tank. Death was certified as being
due to cardiorespiratory failure due to 1,1,1-trichloroethane vapour
(Northfield, 1981).
Case 3: Fatal accidental occupational
A 20 year old apprentice electrician was found dead on the floor of a
fume filled room, where he had earlier been using
1,1,1-trichloroethane as a degreasing solvent from an open bowl. The
exact circumstances of the solvent's use leading to the incident are
not known, although an upright, half-full can of solvent was on the
workbench and there was evidence of some spillage on the floor. The
man had been seen 2 hours previously by a colleague and had appeared
well.
At postmortem the deceased had blistering and second degree burns on
his face and neck, the skin changes being in line with the folds of
his clothing, and consistent with prolonged contact of the solvent
with the body. There was oedema and congestion of the brain and lungs,
and small serous effusions in both pleural cavities. The stomach
showed mucosal congestion and a few scattered petechial haemorrhages.
The blood concentration of 1,1,1-trichloroethane was 4.2mg/100ml, and
the brain concentration was 123mg/100g and it was detected in the
liver. At inquest it was concluded that death resulted from
suppression of the respiratory centre secondary to severe central
nervous system depression (Jones and Winter, 1983).
Case 4: Fatal accidental occupational
A 27 year old radiator and metal tank repairman was dicovered by
colleagues in the tail portion of a 450-gallon aircraft tip with only
his legs protruding from the upper end of the tank. He was
unresponsive, cyanotic and apnoeic. Artificial resuscitation was begun
immediately upon removal and then continued with a respiration device
by an occupational nurse. An ambulance was summoned and artificial
respiration continued until the worker arrived at the industrial
dispensary where he was pronounced dead by the duty physician.
Environmental measurements obtained approximately one hour and twenty
minutes after the accident revealed a a 1,1,1-trichloroethane
concentration of 500 ppm within the tank. At autopsy the diagnoses
were coronary artery sclerosis and acute passive congestion of the
vicera and petechial haemorrhages in the lung and brain. Toxicological
analysis indicated a blood 1,1,1-trichloroethane concentration of
6mg/100ml (Hatfield and Maykoski, 1970).
Case 5: Fatal accidental occupational
An 18 year old male was found with his head submerged in a bath of
1,1,1-trichloroethane. There was respiratory and cardiac arrest with
fixed, dilated pupils. Artificial respiration and cardiac massage were
initiated about 15 minutes after his discovery and he was intubated
and ventilated. Spontaneous respiration was resumed but he did not
regain consciousness. Cerebral atrophy was evident on a CAT scan
carried out 2 months after the accident, and the protective eye reflex
was absent on both sides suggesting a lesion of the occipital cortex,
while the pupils remained dilated and inactive to light. There was
restlessness and jerking of the limbs and trunk and fixed flexion of
all four limbs developed. There were recurrent urinary infections and
the patient died 39 months after the accident.
At autopsy the brain showed symmetrical infarction of the lenticular
nuclei and of the occipital cortex, these changes possibly being the
cause of the neurological manifestations during life. The authors
noted that the pattern of cerebral hypoxia was similar, although not
identical to that found in carbon monoxide poisoning and suggested it
may be specific for 1,1,1-trichloroethane poisoning (Gresham and
Treip, 1983).
Case 6: Accidental occupational causing short term liver
damage (possibly individual hypersensitivity reaction)
A 55 year old male was spraying with 1,1,1-trichloroethane in a small
room with limited ventilation. Several hours after the exposure he
felt dizzy with headache, nausea, cramping abdominal pain and passed a
few watery stools. At 48 hours post-exposure his sclerae were noticed
to be yellow and he developed coughing and a temperature of 40°C.
Although the past medical history showed a previous episode of
hepatitis A during childhood, there had been no evidence of consequent
liver damage. On admission at 48 hours post-exposure, serum bilirubin
was 3.6mg/100ml of which 2.7mg/100ml was conjugated; SGOT 89iu; LDH
280iu; alkaline phosphatase 287 iu (normal 80). Creatinine in blood
was 1.55mg/100ml, and urinalysis showed a proteinuria with 2.9g in 24
hour urine collection. Liver function tests showed a continuing
deterioration until the 6th day post exposure, peak levels being
4.9mg/100ml total bilirubin (most of it conjugated), SGOT 287iu; LDH
328iu, and alkaline phosphatase 287iu. Liver function then began to
improve but not until 38 days post-exposure did it become normal. A
percutaneous liver biopsy taken 14 days after exposure to
1,1,1-trichloroethane, while the liver function was still grossly
deranged, showed preservation of the lobular structure with
infiltration of the portal spaces by lymphocytes, histocytes,
neutrophils, and eosinophils and cholestasis. At follow up at one year
after the intoxication there was no evidence of disturbed liver or
kidney function.
Other significant findings were an urticarial rash developing on day
9, eosinophilic infiltration was found in the liver, and a MIF
(migration inhibition factor) test following stimulation of the
patient's lymphocytes was positive for 1,1,1-trichloroethane. These
findings, along with the minimal neurological symptoms experienced,
suggest the possibility of an individual hypersensitivity reaction
(Halevy et al, 1980).
Case 7: Fatal intentional abuse
A 13 year old male was witnessed inhaling Tipp-ex(TM)
(1,1,1-trichloroethane) from a polythene bag in the early evening. He
returned home later and appeared well, and subsequently went to his
bedroom to inhale some more. Shortly after this he collapsed and died.
Resuscitation was attempted after rapid transfer to hospital but was
unsuccessful.
At autopsy, internal examination revealed mild venous congestion and
oedema of both lungs. The air passages contained blood stained fluid
along with sticky mucous and the mucosal lining was slightly reddened.
Toxicological analysis revealed a 1,1,1-trichloroethane blood
concentration of 0.003 µg/g (MacDougal et al, 1987).
Case 8: Fatal intentional abuse
A 15 year old boy became ataxic and disorientated after inhaling
Tipp-ex(TM) (1,1,1-trichloroethane) thinning fluid and was dead on
arrival at the casualty department less than 6 minutes later. The
deceased had been previously well and had never to his parents
knowledge abused solvents before.
Postmortem examination showed intense congestion and oedema of both
lungs, and frothy fluid in the main air passages. Toxicological
analysis revealed a blood 1,1,1-trichloroethane concentration of 0.2
µg/g (MacDougal et al, 1987).
Case 9: Fatal intentional abuse
A 18 year old apprentice seaman collapsed on the deck of his ship. A
bottle of 1,1,1-trichloroethane along with a rag soaked in the solvent
was found in his bunk. He received mouth to mouth resuscitation then
was moved to a dispensary where he was intubated and ventilated.
Ventricular fibrillation was observed and external cardiac massage was
started. Defibrillation was required numerous times and bicarbonate,
calcium, atropine, isoprenaline, lignocaine, noradrenaline, phenytoin
and intracardiac adrenaline were all administered. He was transferred
to a naval hospital, 6 hours after collapsing. At this stage he was
cyanotic, his blood pressure was 80/60, with a regular pulse of
160/minute, and he responded only to painful stimuli. A chest x-ray
showed bilateral pulmonary infiltrates and an ECG showed wide QRS
complexes along with ventricular tachycardia. Biochemistry was as
follows: serum sodium 154mEq/L; potassium 2.8mEq/L; chloride 87mEq/L;
CO2 32mEq/L; Blood urea nitrogen 18mg/100ml; glucose 410mg/100ml;
serum osmolality 344mOsm/L; haemoglobin 16.9 g/100ml; haematocrit 50.6
volumes per cent; white blood cell count 31,400mm3 . The SGOT was 160
IU, the alkaline phosphatase 27 IU, lactic dehydrogenase 1500 IU, with
a total bilirubin of 0.35mg/100ml. Arterial blood gas analysis while
the patient was breathing 5 litres of oxygen/minute via an
endotracheal tube revealed: pH 7.61; pO2 26mm Hg; haemoglobin
saturation 57%. There was adequate urine output but with gross
haematuria.
The patient was given steroids, antibiotics and potassium and
continued to be ventilated. Progressive hypotension and bradycardia,
unresponsive to isoprenaline and noradrenaline, and several episodes
of cardiac arrest eventuated in his death 24 hours after collapse.
Autopsy showed heavy and congested lungs but no evidence of pulmonary
oedema or aspiration pneumonitis. The heart showed right atrial
dilatation and circumferential left ventricular subendocardial
haemorrhage and microscopically there was widespread recent
infarction. This was probably due to a prolonged period of hypoxaemia
and hypotension followed by intensive resuscitation efforts. Except
for mild congestion of the vicera, cerebral oedema and Purkinje cell
chromatolysis, the remaining organs were grossly and microscopically
normal. The clinically described gross haematuria had no anatomic
counterpart in the kidneys and was probably due to traumatic insertion
of an indwelling catheter.
Postmortem tissue concentrations of 1,1,1-trichloroethane could not be
detected in the liver, kidney, blood or brain and the analyses for
other drugs (opiates, barbiturates, amphetamines) were negative with
only lignocaine present in tissues in detectable concentrations
(Travers, 1974).
Case 10: Fatal intentional abuse
A previously well 13 year old male was playing with a friend outdoors
when he suddenly got up and ran along a nearby path shouting and then
fell to the ground apparently lifeless. His friend said he thought he
had broken his neck on collapsing. An adult arrived on the scene and
as he could find no pulse attempted cardiopulmonary resuscitation
while an ambulance was called. The boy however was dead on arrival at
hospital. This was the only available clinical information prior to
autopsy.
Postmortem examination revealed no evidence of any significant bodily
injury, no evidence of head or neck injury and the brain appeared
normal. There was some congestion of the mucosa of the trachea and
major bronchi but no evidence of inhalation of any foreign material or
of gastric contents. The stomach contained partly digested food
material only, with no evidence of recent ingestion of tablets. The
heart appeared anatomically normal and showed no macroscopic
pathology. The remainder of the postmortem examination and subsequent
histological examination of body tissues showed no evidence of natural
disease, and in the absence of any significant macroscopic pathology
the cause of death was thought to be due to a cardiac arrhythmia.
During external examination of the body however, some white material
was noticed around the nail beds, and this along with venous blood and
lung tissue were taken for toxicological analysis. Results revealed
the presence of 1,1,1-trichloroethane in the blood and lung tissue and
the white material from the nails showed traces of titanium dioxide.
In view of the findings and subsequent police investigations the cause
of death was concluded to be acute ventricular dysrhythmia due to
inhalation of trichloroethane. The police investigations revealed that
the boy had started inhaling typewriter correction fluid vapour about
5 months prior to his death. He did this about three times a week and
during each of these occasions would use up to two bottles of fluid a
time. Numerous empty bottles of typwriter correction fluid were found
in his bedroom. The type of correction fluid used contained
1,1,1-trichloroethane as its solvent and the white particulate base
contained titanium dioxide (Ranson and Berry, 1986).
Case 11: Fatal intentional abuse
A previously healthy 15 year old boy retired to his bedroom early one
evening and 2 hours later appeared in the sitting room complaining of
double vision and hallucinations, he subsequently collapsed.
Resuscitation was commenced by ambulance men who arrived immediately
and was continued in hospital but was unsuccessful. A bottle of
Tipp-ex(TM) was later discovered in his room.
Postmortem examination showed a grossly oedematous brain and marked
tonsillar herniation and uncal grooving. Oedema was also present in
the lungs, liver and gut. The heart was normal. Toxicological analysis
revealed a blood 1,1,1-trichloroethane concentration of 1.7mg/L and
the solvent was also detected in the brain and liver. The rest of the
toxicology screen was negative and no alcohol was detected (D'Costa
and Gunaskera, 1990).
Case 12: Fatal Intentional abuse
A 14 year old boy had been sniffing Liquid Paper(TM) correction fluid
with friends and on leaving a house collapsed at the front gate and
died. Police enquiries revealed that he had been inhaling the
substance on an irregular basis for a few months.
Autopsy showed cerebral oedema with anoxic-hypoxic changes in the
cortex and medulla; yellowish to dark red areas in the septal and left
anterior regions of the myocardium; very congested lungs with
inhalation of gastric contents and intra-alveolar haemorrhages on
microscopy; and marked irritation of the airways with small
haemorrhagic areas. Microscopic examination of the myocardium revealed
degenerative changes including interfibrillary oedema, swollen and
ruptured myofibrils, and a wavy, fibrillar pattern.
Routine toxicological examinations performed on specimens of the
vicera, blood and urine, failed to detect the presence of any common
drugs or alcohols. Headspace gas chromatography with electron captive
detection was used to detect volatile substances. The presence of
1,1,1-trichloroethane was detected in each of the specimens although
concentrations were not measured (Banathy & Chan, 1983).
INTERNAL CASES NPIS (LONDON)
Accidental ingestion in children
Of 20 cases of accidental ingestion referred to the National Poisons
Information Service (London), 15 remained asymptomatic. In most cases
the amount ingested was given as either unknown (although very little)
or as a mouthful, although one 2 year old male was reported to have
taken 50ml. In the children showing clinical effects, these were
nausea and vomiting (2/5), drowsiness (3/5) and buccal irritation
(1/5). Of the twenty children, 5 were not admitted to hospital care,
14 were observed (3 of which were also given ipecac) and discharged
well within 24 hours of ingestion. The 2 year old male with a history
of ingestion of 50ml was x-rayed (1,1,1-trichloroethane is
radio-opaque, Dally et al, 1987) and although this was slightly more
opaque than usual it was not considered helpful in acertaining the
severity of exposure. He was discharged well after 3 days.
Fatal inhalation (intentional abuse)
A 15 year old boy suffered cardiorespiratory arrest at home after
inhaling Tipp-ex(TM). The amount of solvent or period of inhalation
was not known, but an episode of violent activity was reported prior
to his collapse. On arrival at hospital he was in asystole, and full
cardiopulmonary resuscitation was attempted but was unsuccessful (NPIS
(London) 84/22696).
Accidental ingestion (adult)
A 27 year old female accidentally ingested a small amount of
1,1,1-trichloroethane while syphoning. She developed dry mouth, mild
retrosternal burning, headache and slight drowsiness. She was observed
only and was discharged well after 3 hours (NPIS (London) 82/17087).
Skin exposure
A 19 year old male attended a burns unit having sustained a chemical
burn to the left forearm while at work. He had been working with a
cleaning fluid containing 1,1,1-trichloroethane. He was treated with
irrigation and dressings were applied and he attended regularly as an
out-patient for monitoring of the wound. The extent of necrosis
progressed and his forearm became swollen, inflamed and painful at 6
days. With arm elevation and co-fluampicil the swelling settled, and
the patient was discharged with arrangements for out-patient
dressings.
On day 30 the patient returned complaining that pain and swelling had
returned the previous day. Examination revealed minimal separation of
extensive eschar on the dorsum of the right forearm but moderate local
erythema and swelling. The wound was pus discharging and a swab of
this grew Staphylococcus aureus, which was treated with
flucloxacillin. At this stage surgical excision and a split skin graft
was carried out. There was good take of the graft and only minimal
scarring at 4 month follow up (NPIS (London) 87/8962).
The exposure was thought to be from 1,1,1-trichloroethane only,
however it is unlikely that 1,1,1-trichloroethane alone would have
caused such a severe reaction.
8 ANALYSIS
8.1 Agent/toxin/metabolite
1,1,1-Trichloroethane is stable in blood if sample precautions are
taken (see below). In fatal cases, analysis of tissues (particularly
brain) may show high concentrations of 1,1,1-trichloroethane even if
little is detectable in blood.
Analysis of expired air by direct mass spectrometry can detect many
solvents several days after an exposure but the technique is limited
to cooperative, conscious patients (Flanagan et al, 1990).
Urinary metabolites (trichloroethanol and trichloroacetic acid) serve
as a qualitative index of exposure only.
8.2 Sample containers to be used
A glass container with an anticoagulant (lithium heparin, ethylene
diamine tetra-acetic acid), preferably with a cap lined with metal
foil should be used. The tube should be as full as possible and should
only be opened when required for analysis and then only when cold
(4°C). If sample volume is limited, a container to match the available
volume should be selected to ensure minimal headspace (Flanagan et al,
1990).
8.3 Optimum storage conditions
Between -5°C and 4°C.
8.4 Transport of samples
Biological specimens should be packaged separately from any products
thought to have been abused to prevent chemical cross contamination.
8.5 Interpretation of data
Blood 1,1,1-trichloroethane concentrations were measured by headspace
chromatography in samples from 48 patients referred to the London
Poisons Unit during 1980-1986 and data from a further 18
1,1,1-trichloroethane related VSA (volatile substance abuse) deaths
were also obtained. Blood 1,1,1-trichloroethane concentrations ranged
from 0.1-60mg/L and although there was a broad relationship between
blood concentration and severity of poisoning, there were large
variations within each patient group. The absence of a good
correlation between blood concentration and clinical features was
thought to be due to rapid initial changes in tisssue distribution,
and in addition, in many non fatal cases, other compounds were
present, further complicating any interpretation of a dose response
relationship (Meredith et al, 1989).
8.6 Conversion factors
1mg/L = 183 ppm (approx.) at 25°C, 76mmHg
1ppm = 5.46 mg/m3 (approx.) at 25°C, 76mmHg
8.7 Other recommendations
None.
9 OTHER TOXICOLOGICAL DATA
9.1 Carcinogenicity
There are no adequate epidemiological studies available concerning
long term exposure to 1,1,1-trichloroethane and carcinogenicity. The
International Agency for Research on Cancer concluded that an
evaluation on human carcinogenicity of 1,1,1-trichloroethane could not
be made (IARC, 1979).
In a carcinogenicity study, rats and mice were orally administered
1,1,1-trichloroethane in two different dose levels, 5 days a week for
78 weeks. Both male and female test animals exhibited early mortality
compared with untreated controls, and a variety of neoplasms were
found in both treated animals and controls. Although rats of both
sexes demonstrated a positive dose-related trend, no relationship was
established between the dosage group and the species, sex, type of
neoplasm or sites of occurrence (National Cancer Institute, 1977).
9.2 Genotoxicity
No relevent data on human genotoxicity.
9.3 Mutagenicity
The mutagenicity of 1,1,1-trichloroethane has been studied extensively
in bacterial systems, however no data has been published on its
ability to produce mutations in mammalian cells in culture. There is
no evidence from the available data to indicate that the compound
itself has mutagenic potential but, in view of the limitations, no
conclusions can be drawn (Toxicity Review 9, HSE, 1984).
9.4 Reprotoxicity
No relevant data on human reprotoxicity.
9.5 Teratogenicity
No relevant data on human teratogenicity.
Suspicion of a cluster of spontaneous abortions and congenital heart
anomalies from pregnancies during a period of water contamination,
occurred in the US in 1981. A 1,1,1-trichloroethane level of 1.7mg/L
was detected in the well, along with other solvent contaminants
(dichloroethylene, isopropyl alcohol and freon - levels of these not
reported). Epidemiological studies indicated that a cluster did exist,
and that the odds ratio for spontaneous abortion was 2.3, and the
relative risk for congenital malformations was 3.1. A direct link
between the ingestion of the contaminated water and these effects,
however, could not be established (Goldberg et al, 1990).
Schwetz et al (1975), studied the teratogenicity of
1,1,1-trichloroethane in mice and rats, in which mean litter data only
was reported. At inhalation levels of 875ppm daily (7 hours/day on
days 6-15 of pregnancy), no evidence of embryolethality, fetotoxicity
or teratogenicity was found.
York et al (1982) reported no persistent detrimental effects in female
rats exposed to 1,1,1-trichloroethane before mating and or during
pregnancy. Levels of exposure were 2100 ± 200ppm.
9.6 ADI
9.7 MRL
9.8 AOEL
Long term exposure limit 350ppm (1900mg m-3).
Short term exposure limit 450ppm (2450 mg m-3).
9.9 TLV
Air: 350ppm (1900mg/m3)
9.10 Relevant animal data
In a study by Dickerson and Biesemeier (1982) forced aspiration of
1,1,1-trichloroethane resulted in death for 50% of the test animals
(male adult Sprague-Dawley albino rats) in less than 10 minutes. Death
appeared due to pulmonary haemorrhage and/or cardiac arrest. The
authors therefore concluded that use of a cuffed endotracheal tube
should be considered in cases of 1,1,1-trichloroethane ingestion.
Reinhardt et al (1973) reported that 1,1,1-trichloroethane caused
cardiac sensitation to adrenaline in dogs at and above the 0.5% v/v
level. The marked response was associated with ventricular
fibrillation following the challenge dose of adrenaline. At this level
the solvent was also associated with excitement and struggling in the
animals. Histopathological examination of samples from the dogs that
developed fatal arrhythmias did not show any gross or microscopic
abnormalities.
9.11 Relevant in vitro data
None.
10 ENVIRONMENTAL DATA
All the environmental data below was obtained from Environmental
Health Criteria 136 (WHO, 1992). The primary reference sources are
also listed in the reference section of this document.
10.1 Ecotoxicological data
Solubility in water
In water 1,1,1-trichloroethane is slowly dehydrochlorinated to
1,1-dichloroethane and hydrolysed to ethanoic acid, the former process
being favoured by alkalinity. McConnell et al (1975) reported rapid
transfer of 1,1,1-trichloroethane from water to air.
Volatilisation
In aquatic systems volatilization is the major route for
1,1,1-trichloroethane removal. Dilling et al (1975) found
1,1,1-trichloroethane to be rapidly evaporated from water. At 25°C,
90% evaporation occurred within 60-80 minutes from an aqueous solution
containing 1mg of 1,1,1-trichloroethane/litre, the half life being 20
minutes.
LC50
In rats after 4 hours = 18400ppm
In mice after 30 minutes = 22240ppm
In mice after 6 hours = 10300ppm
10.2 Behaviour
Adsorption onto soil
1,1,1-trichloroethane does not bind to soil particles. Urano (1985)
and Chiou et al (1979) presented data which show that adsorption by
soil organic matter occurs via a partitioning process rather than a
physical process.
Mobility/leaching data
1,1,1-Trichloroethane leaches readily into ground water.
10.3 Biodegradation
Environmental fate
1,1,1-trichloroethane enters the environment primarily via
evapouration to the atmosphere, although some is discharged in
industrial effluents. McConnell et al (1975) reported rapid transfer
of 1,1,1-trichloroethane from water to air and concluded that,
irrespective of whether 1,1,1-trichloroethane enters the environment
via water or air, a wide distribution of the chemical is likely.
In 1978, it was estimated that 97.3% of the 1,1,1-trichloroethane used
in the USA was released into the environment. Of this 86% was released
into the air, 1% to water, and about 10% was disposed of as waste
(Fischer et al, 1982). It was also estimated that only about 6% of the
1,1,1-trichloroethane produced is emitted to the air as waste or waste
water during production, the remainder being released during use.
1,1,1-Trichloroethane has a residence time of about 6 years in the
troposphere (Khalil & Ramussen, 1984; Prinn et al, 1987; Midgley,
1989) where it is oxidized to trichloroacetaldehyde and
trichloroacetic acid. It reaches the stratosphere in significant
amounts, which results in ozone depletion through the liberation of
reactive chlorine atoms. The ozone-depleting potential of
1,1,1-trichloroethane is ten times lower than that of trifluoromethane
(CFC-11), and the global warming potential is about 40 times lower.
1,1,1-Trichloroethane does not appear to bioaccumulate.
Abiotic transformation
Atmospheric:-
In the troposphere 1,1,1-trichloroethane is initially oxidized to
trichloroacetaldehyde and then further to trichloroacetic acid. In the
stratosphere it is degraded by photochemical processes and liberates
chlorine atoms.
In Water:-
In water degradation of 1,1,1-tricloroethane occurs by a)
dehydrochlorination to hydrochloric acid and 1,1-dichloroethene and b)
hydrolysis to hydrochloric and ethanoic acids.
Aerobic/anaerobic
Biodegradation to 1,1-dichloroethane and chloroethane has been
reported to occur under anaerobic conditions (Klecka et al, 1990).
Wilson et al (1983) found no aerobic degradation of trichloroethane,
at a concentration of 1mg/L, in soil samples collected from just above
and below the ground water table.
Microbial
Not known.
Photolysis
In the stratosphere, 1,1,1-trichloroethane is degraded by
photochemical processes, forming chlorine atoms, and therefore,
chlorine free radicals that have the potential to deplete
stratospheric ozone. In sunlight it forms 1,1,1,2-tetrachloroethane
with some penta- and hexachloroethane. Calculations indicate that 15%
of 1,1,1-trichloroethane is transferred to the stratosphere (McConnell
and Schiff, 1978; Singh et al, 1982). The ozone depleting effect of
1,1,1-trichloroethane is estimated to be 0.11 that of the
chlorofluorocarbon CFC-11 (UNEP, 1989).
Hydrolysis
Two parallel reactions result in the degradation of
1,1,1-trichloroethane in water;
a) degradation to hydrochloric acid and 1,1-dichloroethane,
b) hydrolysis to hydrochloric and ethanoic acids.
The reaction rates are influenced by temperature and alkalinity
(Gerkins and Franklin, 1989; CEFIC, 1986; Pearson, 1982).
Reduction and oxidation
1,1,1-Trichloroethane enters the troposphere and is oxidized (by free
hydroxyl radicals) to form trichloroacetaldehyde, which is further
oxidized to trichloroacetic acid. The half-life for oxidation is
estimated in the range of 2-5.5 years (Yung et al,1975; McConnell and
Schiff, 1978; Pearson, 1982).
Half-life in water, soil and vegetation
In water:-
In water containing 8.3ppm oxygen at 25°C = 6.9 months in natural
sunlight or in darkness.
In air:-
In air the half-life of oxidation ranges from 2-5.5 years.
In vegetation:-
Not known.
10.4 Environmentally important metabolites
1,1,1-Trichloroethane liberates reactive chlorine atoms in the
stratosphere, resulting in ozone depletion.
10.5 Hazard warnings
10.5.1 Aquatic life
10.5.2 Bees
10.5.3 Birds
10.5.4 Mammals
10.5.5 Plants
10.5.6 Protected species
10.6 Waste disposal data
Liquid spills can be treated in several ways:
a) If small, absorb on paper towels and evaporate in a fume cupboard
or remove outside for evaporation or subsequent disposal by another
method.
b) If large, absorb on sand or vermiculite, shovel into a covered
container and remove outside.
c) Any spillage up to about 2.5 litres can be treated by adding a
non-flammable dispersing agent and working it into an emulsion with
brush and water. About one volume dispersing agent is needed for every
two volumes of flammable water-insoluble liquid spilt (less with
non-flammable water-insoluble liquids) together with 10 volumes of
water. The emulsion can then be run to waste with large quantities of
water. With these proportions there is no danger of a flammable vapour
mixture developing in the drainage system. Advice should be obtained
from the water authority before this method of disposal is used.
Subsequent disposal of small amounts not run to waste can be dealt
with by evaporation in the open air. Larger amounts should be disposed
of by burial in a licenced site or by incineration in an approved
incinerator.
Following removal of the material from the site of the spillage, the
area should be ventilated to remove any residual vapour, and/or washed
with water and soap or detergent to remove any traces of material. Any
contaminated personal or protective clothing should be thoroughly
cleaned to remove all traces of contaminant. (Luxon, 1992).
Author
Maeve McParland
National Poisons Information Service (London Centre)
Medical Toxicology Unit
Guy's & St Thomas' Hospital Trust
Avonley Road
London
SE14 5ER
UK
This monograph was produced by the staff of the London Centre of the
National Poisons Information Service in the United Kingdom. The work
was commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review was undertaken by the Directors of the UK National Poisons
Information Service.
December 1995
REFERENCES
ACGIH 1986
Documentation of The Threshold Limit Values and Biological Exposures
Indices.
Am Conference of Govt Ind Hyg, Inc, Cincinnati, OH.
Anderson HR, McNair RS, Ramsey JD (1985)
Deaths from abuse of volatile substances: a national epidemiological
study.
Br Med J 290 pp304-307
Astrand I, Kilbom A, Wahlberg I and Ovrum P. 1973
Methyl chloroform exposure . I. Concentration in alveolar air and
blood at rest and during exercise.
Scand J Work Environ Health vol 10; pp69-81
Banathy LJ, Chan LTF (1983)
Fatality caused by inhalation of 'Liquid Paper' correction fluid.
Med J Aust 2 pp606
Baselt RC and Cravey RH 1989
Disposition of Toxic Drugs and Chemicals in Man. 3rd Edn.
Year Book Medical Publishers, Inc.
Bass M (1970)
Sudden sniffing death.
J Am Med Assoc 212 pp 2075-2079
Boyer JD, Ahlert RC, Kosson (1987)
Degradation of 1,1,1-Trichloroethane in Bench Scale Bioreactors.
Hazardous Waste, Hazardous Matter. 4 pp 241-260
Bretherick L. (Ed) 1981
Hazards in the Chemical Laboratory. 3rd. Ed.
The Royal Society of Chemistry
Carchman, R et al,. 1984
Health Assessment Document for 1,1,1-Trichloroethane (Methyl
Chloroform).
Report No. EPA-600/8-82-003F.
U.S. Environmental Protection Agency.
CEC (Commission of the European Communities) (1986)
Organochlorine Solvents: Health risks to workers, Cambridge.
Royal Society of Chemistry.
CEFIC (1986)
The occurance of chlorinated solvents in the environment.
Prepared by a workshop of the European Council of Chemical Industry
Federation (CEFIC).
Chem Ind pp861-869
Chiou CT, Peters LJ, Freed VH (1979)
A Physical Consept of Soil-Water Equilibria for Nonionic Organic
Compounds.
Science 206 pp831-832
Clayton GD and Clayton FE. 1981
Patty's Industrial Hygiene and Toxicology.
3rd. Rev. Ed. Vol. 2B. Toxicology.
John Wiley and Sons, Inc.
Dally S, Garnier R, Bismuth C (1987)
Diagnosis of chlorinated hydrocarbon poisoning by x-ray examination.
Brit J Ind Med Vol 44 pp424-425
D'Costa DF and Gunaskera NPR (1990)
Fatal cerebral oedema following trichloroethane abuse.
J R Soc Med Vol. 83 pp 533-534
Dickerson CL, Biesemeier JA (1982)
Aspiration of methyl chloroform.
Vet Hum Toxicol 24, 3 pp167-168
Durrans TH 1971
Solvents. 8th Rev.Ed.
Chapman and Hall Ltd
Environmental Health Criteria 136 (1992)
1,1,1-Trichloroethane.
IPCS
WHO
Esmail A, Anderson HR, Ramsey JD, Taylor J, Potter A. (1992)
Controlling deaths from volatile substance abuse in under 18s: The
effects of legislation.
Br Med J 305: 692.
Fielder FJ et al,. 1984
1,1,1-Trichloroethane. Toxicity Review 9.
Health and Safety Executive
Fischer M, Friesel P, Koch G, Milde G, Rosskamp E. (1982)
Evaluation of water pollution caused by chlorinated and brominated
ethanes.
(Unpublished report submitted to the Commission of the European
Comunities under Contract No. U71/516)
Flanagan RJ, Ruprah M, Meredith TJ, Ramsey JD 1990
An Introduction to the Clinical Toxicology of Volatile Substances.
Drug Safety 5 (5) pp 359-383
Gallagher JS, Kurt TL (1990)
Neonatal exposure to methyl chloroform in a tape remover.
Vet Hum Toxicol 32, no.1, pp43-45
Gerace RV 1981
Near fatal intoxication by 1,1,1-trichloroethane.
Ann Emerg Med 10:10 pp 533-534
Gerkens RR, Franklin JA (1989)
The rate of degradation of 1,1,1-trichloroethane in water by
hydrolysis and dehydrochlorination.
Chemosphere 19 pp1919-1937
Goldberg SJ, Lebowitz MD, Graver EJ, Hicks A (1990)
An association of human congenital cardiac malformations and drinking
water contaminants.
J Am Coll Cardiol 16 pp155-164
Grant WM and Schuman JS (1993)
Toxicology of the eye. 4th Ed.
Gresham GA, Treip CS (1983)
Fatal Poisoning By 1,1,1-Trichloroethane After Prolongued Survival.
Forensic Science International Vol 23 pp249-253
Halevy J, Pitlick S, Rosenfeld J (1980)
1,1,-Trichloroethane intoxication: A case report with transient liver
and renal damage. Review of the literature.
Clin Toxicol Vol 16, No.4 pp 467-472
Hall FB andHine CH (1966)
Trichloroethane Intoxication: A Report of Two Cases.
J Foren Sci Vol 2 No.3 pp404-413
Hatfield TR and Maykoski RT (1970)
A fatal methyl chloroform (trichloroethane) poisoning.
Arch Environ Health Vol 20 pp279-281
House RA, Liss GM, Wills MC (1994)
Peripheral sensory neuropathy associated with 1,1,1-trichloroethane.
Arch Environ Health 49 pp196-199
IARC (1979)
1,1,1-Trichloroethane. In: Some halogenated hydrocarbons, Lyon,
International Agency for Research on Cancer, pp. 515-532 (IARC
Monographs on the Evaluation of the Carcinogenic risk of Chemicals to
Humans, Vol. 20.)
IARC (1989)
Overall Evaluations of Carcinogenicity: An updating of IARC
Monographs.
Volumes 1-42, Lyon, International Agency For Research on Cancer.
(IARC Monographs on the Evaluations of Carcinogenic Risk to Humans,
Suppl. 7)
Imbriani M, Ghittori S, Pezzagno G, Huang J, Capodaglio E (1988)
1,1,1-Trichloroethane (Methyl chloroform) in urine as Biological Index
of exposure.
Am J Indust Med Vol. 13: pp 211-222
Ingber A (1991)
Occupational allergic contact dermatitis from methyl chloroform
(1,1,1-trichloroethane)
Contact Dermatitis. Vol. 25 pp193
International Labour Office (ILO) 1983
Encyclopaedia of Occupational Health and Safety. 3rd. Ed.
Jones RD and Winter DP (1983)
Two case reports of death on industrial premises attributed to
1,1,1-trichloroethane.
Arch Environ Health Vol. 38 pp59-61
Kelafant GA, Berg RA, Schleenbaker R (1994)
Toxic Encephalopathy Due to 1,1,1-Trichloroethane Exposure.
Am J Ind Med 25 pp439-446
Khalil MA, Ramussen RA (1984)
Methyl chloroform: Global distribution, seasonal cycles and
anthropogenic chlorine.
Chemosphere 13 pp789-800
Klaassen CD, Plaa GL (1966)
Relative effects of variuos chlorinated hydrocabons on liver and
kidney function in mice.
Toxicol Appl Pharmacol Vol 9 pp139-151
Klecka GM, Gonsior SJ, Markham DA (1990)
Biological Transformations of 1,1,1-Trichloroethane in Subsurface
Soils and Ground Water.
Environ. Toxicol. Chem. 9 pp1437-1451
Liss GM (1988)
Peripheral neuropathy in two workers exposedto 1,1,1-trichloroethane.
J Am Med Assoc 260, pp2217
Luxon SG. Ed. (1992)
Hazards in the Chemical Laboratory. 5th Edition.
The Royal Society of Chemistry.
McCarthy TB, Jones RD (1983)
Industrial gassing poisonings due to trichloroethylene,
perchloroethylene and 1,1,1 trichloroethylene 1961-1980.
Brit J Ind Med Vol 40 pp450-455
McConnell G, Ferguson DM, Pearson CR (1975)
Chlorinated Hydrocarbons and the Environment.
Endeavour 34 pp13-18
McConnell JC, Schiff HI (1978)
Methyl Chloroform: Impact on Stratospheric Ozone.
Science 199 pp174-177
Mark HF et al,. Eds (1979)
Kirk-Othmer Encyclopaedia of Chemical Technology. 3rd Ed. Vol. 5.
John Wiley and Sons Inc.
Meredith TJ, Ruprah M, Liddle A, Flanagan RJ (1989)
Diagnosis and Treatment of Acute Poisoning with Volatile Substances.
Hum Toxicol Vol 8 pp 277-286
Midgley PM (1989)
The production and release to the atmosphere of 1,1,1-trichloroethane
(methyl chloroform).
Atmos Environ 23 pp2663-2665
Monster AC, Boersma G, Steenweg H. (1979)
Kinetics of 1,1,1-trichloroethane in volunteers: influence of exposure
concentration and workload.
Int Arch Occup Environ Health Vol 42; pp 293-301
Nolan RJ, Freshour NL, Rich DL, McCarty DL, Saunders JH (1984)
Kinetics and metabolism of inhaled methyl chloroform
(1,1,1-trichloroethane) in male volunteers.
Fundam Appl Toxicol Vol 4. pp 654-662
Northfield 1981
Avoidable deaths due to acute exposure to 1,1,1,trichloroethane
J Soc Occup Med 31, pp 164-166
Pearson CR (1982)
C1 and C2 Halocarbons.
In; Hutzinger O., ed. The Handbook of Environmental Chemistry. Vol 3,
part B pp69-88
Springer-Verlag.
Prinn R, Cunnold D, Ramussen R, Simmonds P, Alyea F, Crawford A,
Fraser P, Rosen R. (1987)
Atmospheric trends in methylchloroform and the global average for the
hydroxyl radical.
Science 238 pp945-950
Ranson DL, Berry PJ (1986)
Death Associated with the Abuse of Typewriter Correction Fluid.
Med Sci Law Vol 26, No.4 pp308-310
Ramsey J, Anderson HR, Bloor K, Flanagan RJ (1989)
An Introduction to the Practice, Prevalence and Chemical Toxicology of
Volatile Substance Abuse.
HumToxicol 8 pp261-269
Reinhardt RA, Mullen LS, Maxfield ME (1973)
Epinephrine-induced Cardiac Arrhythmia Potential of Some Common
Industrial Solvents.
J Occup Med Vol 15 pp 953-955
Russell J (1993)
Fuel of the Forgotten Deaths.
New Scientist, 6th February pp21-23
Savolainen K, Riihimaki V, Laine A, Kekoni J (1981)
Short term Exposure of Human Subjects to m-Xylene and
1,1,1-Trichloroethane.
Int Arch Occup Environ Health 49 pp89-98
Sax NI 1984
Dangerous Properties of Industrial Materials. 6th. Ed.
Van Nostrand Reinhold Co.
Singh HB, Salas LJ, Stiles RE (1982)
Distribution of selected gaseous organic mutagens and suspect
carcinogens in ambient air.
Environ Sci Technol 16 pp872-880
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.
Toxoicol App Pharmacol 32 pp84-96
Stewart RD (1971)
Trichloroethane intoxication; Diagnosis and Treatment.
J Am Med Assoc 215 pp1789-1792
Stewart RD, Andrews JT (1966)
Acute intoxication with methyl chloroform.
J Am Med Assoc Vol 195. pp904-906
Stewart RD and Dodd HC 1964
Absorption of Carbon tetrachloride, trichloroethylene,
tetrachloroethylene, methylene chloride and 1,1,1-trichloroethane
through the human skin.
Am Ind Hyg Assoc J Vol 25: pp 439-446
Stewart RD, Gay HH, Schaffer AW, Erley DS, Rowe VK (1969)
Experimental Human Exposure to Methyl Chloroform Vapour.
Arch Environ Health 19; pp467-472
Thiele DL, Eigenbrodt EH, Ware AJ (1982)
Cirrhosis after Repeated Trichloroethylene and 1,1,1-Trichloroethane
exposure.
Gastroenterology 83 pp926-929
Torkelson TR, Oyen F, McCollister DD, Rowe VK (1958)
Toxicity of 1,1,1-Trichloroethane as Determined on Laboratory Animals
and Human Subjects.
Am Ind Hyg Assoc J Vol 19 pp 353-362
Toxicity Review 9 (1984)
1,1,1-Trichloroethane
Health and Safety Executive.
HMSO
Travers H 1974
Death From 1,1,1-Trichloroethane Abuse: Case Report.
Milit Med Vol 139 pp889-890
UNEP (1989)
Technical Progress on Protecting the Ozone Layer. Report of the
Technology Review Panel.
United Nations Environment Programme, Nairobi.
Urano K (1985)
Usage and Pollution Control of Chlorinated Organic Compounds.
Jpn J Water Pollut Res 8 pp269-273
Watson JM (1979)
Mortality and morbidity statistics on solvent abuse.
Med Sci Law 19 pp246-252
Watson JM (1981)
Solvent Abuse: prevention and clinical diagnosis.
HumToxicol Vol 1 pp249-256
Wilson JT, McNabb JF, Wilson BH, Noonan MJ (1983)
Biotransformation of Selected Organic Pollutants in Ground Water.
Dev Ind Miocrbiol 24 pp125-223
Wright MF, Strobl DJ (1984)
1,1,1-Trichloroethane cardiac toxicity: Report of a case.
J Am Osteopath Assoc Vol 84 No. 3 pp285-288
Woo OF, Healey KM, Sheppard D, Tong TD (1983)
Chest Pain and Hypoxemia from Inhalation of a Trichloroethane Aerosol
Product.
J Toxicol Clin Toxicol 20 (4) pp331-341
York GY, Sowry BM, Hastings L, Mason JM (1982)
Evaluation of Teratogenicity and Neurotoxicity with Maternal
Inhalation to Methyl Chloroform.
J Toxicol Environ Health 9 pp251-266
Yung YL, McElroy MB, Wofsy SC (1975)
Atmospheric Halocarbons: A Discussion with the Emphasis on Chloroform.
Geophys Res Lett 2 pp397-399