| 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|
| 126.96.36.199 Adults|
| 188.8.131.52 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|
| 184.108.40.206 Toxicological analyses|
| 220.127.116.11 Biomedical analyses|
| 18.104.22.168 Arterial blood gas analysis|
| 22.214.171.124 Haematological analyses|
| 126.96.36.199 Other (unspecified) analyses|
| 8.1.2 Storage of laboratory samples and specimens|
| 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|
| 8.1.3 Transport 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|
| 8.2 Toxicological Analyses and Their Interpretation|
| 8.2.1 Tests on toxic ingredient(s) of material|
| 22.214.171.124 Simple Qualitative Test(s)|
| 126.96.36.199 Advanced Qualitative Confirmation Test(s)|
| 188.8.131.52 Simple Quantitative Method(s)|
| 184.108.40.206 Advanced Quantitative Method(s)|
| 8.2.2 Tests for biological specimens|
| 220.127.116.11 Simple Qualitative Test(s)|
| 18.104.22.168 Advanced Qualitative Confirmation Test(s)|
| 22.214.171.124 Simple Quantitative Method(s)|
| 126.96.36.199 Advanced Quantitative Method(s)|
| 188.8.131.52 Other Dedicated Method(s)|
| 8.2.3 Interpretation of toxicological analyses|
| 8.3 Biomedical investigations and their interpretation|
| 8.3.1 Biochemical analysis|
| 184.108.40.206 Blood, plasma or serum|
| 220.127.116.11 Urine|
| 18.104.22.168 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|
| 22.214.171.124 CNS|
| 126.96.36.199 Peripheral nervous system|
| 188.8.131.52 Autonomic nervous system|
| 184.108.40.206 Skeletal and smooth muscle|
| 9.4.4 Gastrointestinal|
| 9.4.5 Hepatic|
| 9.4.6 Urinary|
| 220.127.116.11 Renal|
| 18.104.22.168 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|
| 22.214.171.124 Acid-base disturbances|
| 126.96.36.199 Fluid and electrolyte disturbances|
| 188.8.131.52 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|
Alkyl chloride, alkyl halide, halo alkane
Chlorure de methyle
Cloruro di metile
1.4 Identification numbers
1.4.1 CAS number
1.4.2 Other numbers
1.5 Brand names, Trade names
1.6 Manufacturers, Importers
9505 Cassius Ave,
Cleveland, Ohio 44105
2.1 Main risks and target organs
At normal temperature and pressure, chloromethane is a gas.
Heavy exposures may depress the central nervous system and
cause coma and death.
Cardiovascular effects include pulmonary edema and
hypotension. Pulmonary edema and bronchial pneumonia are the
commonest cause of death.
Autopsies in man have revealed damage to the lungs, liver,
kidneys, brain, gastrointestinal tract, cardiovascular system
and respiratory tract.
2.2 Summary of clinical effects
Symptoms of acute poisoning may include nausea, vomiting and
convulsions progressing over 4 to 6 hours. After a latent
period of 1 to 4 hours, the original episode may be followed
by apparent recovery then recurrence of symptoms.
Gastrointestinal disturbances may include nausea, vomiting,
abdominal pain and diarrhea. Skin contact causes irritation,
erythema and vesiculation, exposure to the liquid form can
Heavy acute exposure will result in central nervous system
depression, headache, dizziness, weakness or paralysis,
oliguria, anuria, drowsiness, pulmonary edema, convulsions and
finally coma and death. Chronic effects after an almost
lethal acute dose have been reported to last for as long as 5
to 13 years.
Following exposure to low concentrations symptoms may not
appear for 12 to 24 hours. Chronic poisoning (from inhalation
or skin absorption) may cause blurred vision, numbness of the
extremities, confusion, hallucination, somnolence,
bronchospasm, inebriation, ataxia and tremors. Symptoms may
persist for several months following severe chronic exposure.
The diagnosis is made according to the patient's history and
the clinical presentation.
Environmental sampling and analysis may be performed by
collection of methyl chloride on activated carbon, in a glass
collection tube, followed by desorption thermally or with
methanol, dichloromethane or carbon disulphide and gas
Exposure testing in humans is usually undertaken in the
occupational setting, and involves analyzing for methyl
chloride in expired air or excess S-methylcysteine in urine.
Biochemical analyses should include plasma electrolytes, CO2
and chloride to detect and measure metabolic acidosis. The
urine may contain albumin, cells and casts.
2.4 First-aid measures and management principles
Remove victim from further exposure and observe carefully for
the first 48 hours.
In acute cases, because of CNS depression with coma and
respiratory paralysis, artificial ventilation may become
necessary, and administration of positive pressure oxygen may
also be indicated. Convulsions should be controlled with
cautious use of diazepam. Bronchospasm is treated with
bronchodilators. Pulmonary edema or bronchial pneumonia may
be treated by corticosteroids and antibiotics if needed.
Marked acidosis should be corrected cautiously. Renal failure
should be treated appropriately.
Inhalation: Take proper precautions to ensure personal safety
before attempting rescue (i.e., wear appropriate protective
equipment). Remove victim to fresh air. Administer
artificial respiration or cardiopulmonary resuscitation as
required. Obtain medical attention immediately.
Eye contact: If irritation occurs, remove any contact lenses
then flush contaminated eyes with water for 10 to 15 minutes
holding eyelids open. Obtain medical advice immediately.
Skin contact: Avoid direct contact with the liquid form of
this chemical; wear impervious gloves if necessary. Remove
contaminated clothing, shoes and leather goods (i.e., watch
bands, belts). As quickly as possible flush the contaminated
area gently with water for 10 to 15 minutes. Obtain medical
Ingestion: Not applicable.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Manufactured principally by the reaction of methanol and
hydrogen chloride in the presence of a catalyst, either in the
vapour or the liquid phase. The chlorination of methane is
also used, but to a lesser extent (Finar, 1967).
3.2 Chemical structure
Molecular weight 50.49 daltons
Structural formula CH3-Cl
3.3 Physical properties
Boiling point 24.22 °C
Melting point 97.7 °C
Flash point below 58 °C
Autoignition temperature 634 °C
Relative vapour density 1.8
(air = 1 at boiling point
of methyl chloride)
Vapour pressure 4.8 atm at 20 °C
1.0 atm at -24 °C
Solubility 0.9 g/100 ml water at 20 °C
7.8 g/100 ml ethanol at 20 °C
soluble in ethylether, chloroform,
acetone and glacial acetic acid
Explosive limits in air 8.1 to 17.2% v/v
Specific gravity 0.9159 g/ml (-10 °C)
Refractive index 1.3389
Conversion factors 1 mg/litre (= 484 ppm)
2.09 mg/m3 (= 1 ppm)
(Clayton & Clayton, 1981)
3.4 Other characteristics
Colourless gas at normal temperature and pressure with a
pleasant ethereal odour; compresses to a colourless liquid
which has a sweet taste and burns with a smokey greenish
Reacts violently with Al, Mg, K, Na, NaK alloy (alkali metals),
aluminium trichloride, and ethylene. Explodes on contact
with magnesium and reacts with NaK alloy to become impact
sensitive; forms spontaneously flammable trimethylaluminium
with aluminium trichloride (Bretherick, 1985).
At temperatures above 400 °C or in strong ultraviolet light in
the presence of air and moisture it decomposes with the
emission of HCl, CO2, CO, phosgene and chlorine.
Very dangerous fire hazard when exposed to heat, flame or
powerful oxidizers. Fire extinguishing: stop the flow of gas,
use CO2, dry chemical, or spray.
Management of spills: Remove all ignition sources, ventilate
leak area and stop gas flow. Methyl chloride may be disposed
of by burning in a suitable combustion chamber equipped with
an appropriate effluent gas cleaning device.
4. USES/CIRCUMSTANCES OF POISONING
Methyl chloride is used in the manufacture of silicone
resins; tetramethyl lead; as a methylating agent and a
dewaxing agent in petroleum refining; and as a catalyst
solvent in the production of butyl rubber.
Methyl chloride is also used in the synthesis of a
variety of compounds, and as an extractant for greases,
oils and resins.
It is utilized as a foaming agent in the production of
plastics (Lanham, 1982), in the manufacture and
application of pesticides, pharmaceuticals and perfumes.
It has been used as a propellant in aerosols and as a
refrigerant (Spevak et al., 1976).
Methyl chloride also finds use in the illicit
manufacture of drugs of abuse.
4.2 High risk circumstance of poisoning
Working in small, enclosed and/or poorly ventilated spaces,
and using improper handling techniques.
4.3 Occupationally exposed populations
Workers in a range of chemical industries may be exposed to
methyl chloride due to its widespread use as a solvent in the
butyl rubber industry, in petroleum refining, and as an
extractant for oils and fats.
5. ROUTES OF ENTRY
Not applicable (at room temperature methyl chloride is a gas).
This is the most significant and frequent source of exposure.
Contact with liquid form may result in cryogenic injury, rash
and blistering; skin absorption may be significant.
Accidental spraying with the liquid or concentrated vapour may
cause burns from freezing and systemic absorption may be
An unlikely but possible route of entry.
No data available.
6.1 Absorption by route of exposure
Six male volunteers exposed for a 6-hour period to 50 ppm
methyl chloride absorbed 1.4 to 3.7 microgram/min/kg (Nolan et
6.2 Distribution by route of exposure
Blood-air partition coefficients (BAP) in 6 male volunteers
(Nolan et al, 1985):
50 ppm/6 hours BAP = 1.71 to 1.83
10 ppm/6 hours BAP = 2.12 to 2.49
In dogs administered methyl chloride intravenously (Sperling
et al, 1950):
Concentration methyl chloride in tissue at sacrifice
Animal Survival Weight Dose Blood Brain Liver Kidney
Time (min) (kg) (mg) mcg/ml mcg/g mcg/g mcg/g
1 60 12.2 2120 35 3 0 10
2 60 9.2 2100 39 4 0 9
3 60 10.9 1680 41 4 7 17
4 0 18.8 3360 122 4 8 11
5 0 15.4 2780 135 3 - 8
6 0 10.2 2100 119 11 4 0
7 0 9.7 1680 123 9 9 12
6.3 Biological half-life by route of exposure
Nolan et al. (1985) found that blood concentrations increased
rapidly and reached an apparent plateau (proportional to
exposure concentration) during the first hour of exposure to
50 or 10 ppm in 6 male volunteers.
When exposure was terminated, methyl chloride was rapidly
cleared from the blood of all volunteers in a biexponential
manner. The terminal elimination phase half-life for rapid
human metabolisers was t´ = 50 min and for the slow human
metabolisers t´ = 90 min.
Methyl chloride undergoes variable metabolism to S-
methylcysteine, which is excreted in the urine in most exposed
people. Approximately 60% of people also convert methyl
chloride to S-methylglutathione (van Doorn et al, 1980; Peters
et al, 1989).
Kornburst & Bus (1982) found that formate appeared in the
blood and urine of rats exposed to methyl chloride but did not
accumulate to significant levels unless formate metabolism was
Landry (1983) determined that rats exposed to 100, 375 or 1500
ppm [14C] methyl chloride for 6 hours excreted CO2 in expired
air amounting to 51.5 to 41.4% of radioactivity accumulated
during the 6-hour exposure. Twenty to thirty per cent of the
radioactivity was excreted in the urine.
Methyl chloride selectively binds to sulfur cysteine residues
on plasma albumin and glutathione residues in erythrocytes.
(Redford-Ellis and Gowenlock, 1971)
Douglas et al. (1982) exposed rats to 14C methyl chloride (0,
50, 25, 600, 1000 ppm) for 6 hours; in a sub group exposed to
14C methyl chloride, urine was collected and 14C metabolites
were determined. They found N-acetyl-S-methylcysteine and
methylthioacetic acid sulfoxide in the urine in significant
6.5 Elimination by route of exposure
In the rat, methyl chloride is rapidly excreted from the
blood. Only 5% appeared in expired air after 1 hour and only
small amounts in bile and urine (Sperling, 1950).
Bus (1978) reported that 63.9, 32.2, and 3.9% of inhaled [14C]
methyl chloride was excreted in rats in exhaled air, urine and
faeces respectively and that very little radioactivity
remained in the body after 24 hours.
7.1 Mode of Action
Methyl chloride is a central nervous system depressant,
possibly due to methylation of SH groups essential to cellular
oxidation (Klaassen et al., 1986).
7.2.1 Human data
In exposed industrial workers, average levels of
inhaled methyl chloride of 33.6 ppm produced no
neurological effects (Repko et al, 1976) .
Severe exposures from massive releases have
proved immediately fatal.
However, case studies (Lanham, 1982; Scharnweber,
1974) have reported symptoms of methyl chloride
intoxication in patients exposed to 200 ppm for
extended periods. Also, in such subjects levels
as low as 100 ppm may be sufficient to cause
symptoms of poisoning.
Short-term exposure to levels of 1000 ppm can
cause CNS depression, and exposure to 20 000 ppm
for 2 hours has resulted in death.
No data available.
7.2.2 Relevant animal data
LD50 (rat) 1 800 mg/kg
LD50 (rat) 15 200 mg/m3/30 min
LD50 (mouse) 3 146 ppm/7 h
LCLo (dog) 14 661 ppm/6 h
LCLo (cat) 128 700 mg/m3/4 h
LCLo (guinea-pig) 20 000 ppm/2 h
The effects of methyl chloride depend partly on the
duration of exposure and the concentration:
Single exposure Methyl chloride
Kills most animals in a 150 000 - 300 000
Dangerous to life in 20 000 - 40 000
30 - 60 mins
Maximum concentration for 7 000
60 mins without serious effect
Maximum for 8 hours without 500 - 1 000
Repko & Lasley (1979)
Of ten species exposed to methyl chloride 6 hours/day
for 6 days, the most evident neurotoxicity occurred in
monkeys and adult animals. This suggests that methyl
chloride may be more toxic to humans than animals (Repko
& Lasley, 1979).
7.2.3 Relevant in vitro data
No relevant information at the time of preparation of
7.2.4 Workplace standards
The current OSHA standard for methyl chloride is 100 ppm
averaged over an eight-hour work shift, with a ceiling
level of 200 ppm and a 5-minute peak of 300 ppm in any
TLV ACGIH (Threshold limit value; American Conference of
Governmental and Industrial Hygienists): 50 ppm (105
STEL ACGIH (Short-term exposure limit): 100 ppm (205
mg/m3) - skin.
7.2.5 Acceptable daily intake (ADI) and other guideline levels
No data available.
The International Agency for Research on Cancer concludes that
there is insufficient information to evaluate the
carcinogenicity risk of exposure to methyl chloride.
NIOSH classifies methyl chloride as a potential occupational
No controlled studies of adverse effects in humans have been
published. In a single case report, a 23 year old woman
occupationally exposed to methyl chloride vapours during
pregnancy gave birth to a child with multiple skeletal
Malformations who died shortly after birth (Kucera, 1968).
In animals, inhalation of methyl chloride is associated with a
statistically significant increased incidence of skeletal
abnormalities in the offspring, except in those animals
exposed to the lowest concentrations (Wolkowski et al, 1983).
Exposure of male rats to methyl chloride results in bilateral
testicular degeneration, epididymal inflammation and sperm
granuloma formation. Females bred to these males in a
dominant lethal assay exhibited elevated rates of
postimplantation embryonic death during the first two weeks
after treatment and increased preimplantation embryonic loss
during weeks 2 to 8 post exposure.
Methyl chloride-induced preimplantation loss was a result of
cytotoxic effects on sperm, with a significant decrease in the
count of motile sperm of normal morphology (Chellman et al,
Methyl chloride is mutagenic in bacterial mutagenicity tests
(Andrews et al., 1976).
Methyl chloride induces a dose-related increase in mutated
fraction in an established human lymphoblast line; it may
therefore be a weak-acting mutagen in bacteria and human cells
(Fostel et al, 1985).
In one human study there was limited evidence that diazepam
may have an additive effect with methyl chloride in causing
neurologic damage (Clayton & Clayton, 1981).
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
184.108.40.206 Toxicological analyses
220.127.116.11 Biomedical analyses
18.104.22.168 Arterial blood gas analysis
22.214.171.124 Haematological analyses
126.96.36.199 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
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
8.1.3 Transport 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
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
22.214.171.124 Simple Qualitative Test(s)
126.96.36.199 Advanced Qualitative Confirmation Test(s)
188.8.131.52 Simple Quantitative Method(s)
184.108.40.206 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
220.127.116.11 Simple Qualitative Test(s)
18.104.22.168 Advanced Qualitative Confirmation Test(s)
22.214.171.124 Simple Quantitative Method(s)
126.96.36.199 Advanced Quantitative Method(s)
188.8.131.52 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
184.108.40.206 Blood, plasma or serum
Elevated serum bilirubin, blood urea, uric acid
and elevated serum creatinine have been reported
(Jones, 1942; Spevak et al, 1976).
Urine may contain casts and protein, red cells,
elevated carbonates and porphyrins (Dreisbach &
Robertson, 1987; Jones, 1942).
220.127.116.11 Other fluids
8.3.2 Arterial blood gas analyses
Acidosis may be associated with respiratory depression.
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
8.5 Overall Interpretation of all toxicological analyses and
9. CLINICAL EFFECTS
9.1 Acute poisoning
Not applicable (methyl chloride is a gas at room
Exposure to 20 000 ppm for 2 hours can be fatal to
humans (Deuichmann et al., 1969). Symptoms of acute
exposure consist of headache, nausea, vomiting,
drowsiness, dizziness, diarrhoea, confusion, ataxia,
paralysis, convulsions, delerium, coma, and death.
9.1.3 Skin exposure
Skin contact causes irritation and vesiculation;
spraying with liquid or concentrated vapour may cause
cryogenic injury from freezing (Dreisbach & Robertson,
9.1.4 Eye contact
Eye irritation does not occur after exposure to methyl
chloride vapour even at concentrations which cause
toxicity. However, contact with the liquid form may
cause cryogenic injury.
9.1.5 Parenteral exposure
No data available in man (see section 6.2 for animal
No data available.
9.2 Chronic poisoning
Not applicable (at room temperature methyl chloride is a
The effects of long-term low-level exposure are confined
to the CNS.
In six workers exposed occupationally to 200 to 400 ppm
TWA 8 hours for 2 to 3 weeks, symptoms included
hypertension, confusion, blurred vision and
headache. These symptoms were still apparent after 3
months though somewhat improved (Scharnweber et al,
9.2.3 Skin exposure
Systemic absorption may occur through the skin and
9.2.4 Eye contact
Non-irritating even at levels that produce systemic
9.2.5 Parenteral exposure
No data available in man (see section 6.2 for animal
Rapid metabolisers may be more susceptible to the toxic
effects of methyl chloride.
9.3 Course, prognosis, cause of death
Acute poisoning - nausea, vomiting, abdominal pain, diarrhoea,
anorexia, dizziness, headache, weakness, blurred vision,
euphoria, mental confusion, slurred speech, ataxia,
convulsions. These symptoms progress to renal and hepatic
dysfunction, metabolic acidosis, convulsions and coma. Death
is usually due to pulmonary oedema and bronchial pneumonia.
Patients who survive for 48 to 72 hours after an acute dose
usually recover completely, but neurotoxic effects may persist
9.4 Systematic description of clinical effects
Mild hypertension has been reported in patients
chronically and acutely exposed (Scharnweber et al.,
1974; Spevak et al., 1976). Examples of long-term,
disturbed cardiac function (abnormal ECG) as a result of
acute exposure have also been reported (Repko et al,
Acute poisoning can result in pneumonia; chronic
poisoning in bronchospasm (Dreisbach & Robertson, 1987).
Methyl chloride can cause pathological changes of the
respiratory tract (Repko, 1981).
CNS depression is the most prominent effect of
methyl chloride poisoning.
Mild intoxication is characterised by headache,
blurred vision and mental confusion. More
severe intoxication can produce diffuse toxic
damage to the CNS, with ataxic gait, nervousness,
emotional instability, insomnia, anorexia,
dimness of vision, reading difficulty, attacks
of vertigo, tremor, muscle spasms, convulsions,
weakness and incoordination of the limbs, and
coma (Ellenhorn & Barceloux, 1988).
No neurological effects were found in workers
exposed to a mean ambient air concentration of
33.6 ppm (Repko et al, 1976). However,
Scharnweber et al. (1974) reported 6 case
studies in which time weighted average exposures
as low as 265 ppm (calculated as 8 hour TWA)
after two weeks working for 12 to 16 hours a day
produced tiredness, blurred vision, dizziness
and other neurological problems.
Lanham (1982) reported the case of a husband and
wife exposed to levels of 200 ppm from leaking
polystyrene foam who experienced blurred vision,
fatigue, vertigo, nausea, and unsteadiness of
18.104.22.168 Peripheral nervous system
Chronic poisoning may cause numbness of the
extremities (Dreisbach & Robertson, 1987).
22.214.171.124 Autonomic nervous system
126.96.36.199 Skeletal and smooth muscle
Both chronic and acute exposures may be asociated with
nausea and vomiting (MacDonald, 1964).
Liver congestion with degenerative cellular changes may
occur (Dreisbach &
After acute exposure, jaundice with elevated bilirubin
has been reported; liver biopsy revealed centrilobular
degenerative and necrotic changes (Spevak, 1976; Jones,
Proteinuria, elevated serum creatinine and
degenerative changes similar to acute
glomerulonephritis may occur (Spevak, 1976).
Loss of libido has been reported as a long term
consequence of acute methyl chloride exposure
9.4.7 Endocrine and reproductive systems
Cryogenic injury occurs with the liquid form (Dreisbach
& Robertson, 1987).
9.4.9 Eye, ears, nose, throat: local effects
Non-irritant even at levels that produce systemic
Haematological investigations after acute and chronic
exposure have not revealed signs of toxicity (Spevak,
1976; MacDonald, 1964; Jones, 1942). A slight increase
in red cell count and haemoglobin percentage has been
noted following exposure to methyl chloride but may not
be significant (Jones, 1942).
No data available.
188.8.131.52 Acid-base disturbances
No data available.
184.108.40.206 Fluid and electrolyte disturbances
No data available.
No data available.
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
No controlled studies of adverse effects in humans have
been published. In a single case report, a 23 year old
woman occupationally exposed to methyl chloride vapours
during pregnancy gave birth to a child with multiple
skeletal malformations who died shortly after birth
No data available.
10.1 General principles
Methyl chloride is primarily a central nervous system
depressant. Death is due to pulmonary oedema and bronchial
pneumonia. Exposed individuals should be removed from
further exposure immediately and observed carefully for 48
hours. Treatment is supportive.
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
10.2.2 Biomedical analysis
Liver function tests should be undertaken to assess
hepatic impairment. Urine may contain casts, red
blood cells and protein.
10.2.3 Toxicological analysis
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic treatment
In acute cases, because of CNS depression with coma and
respiratory paralysis, artificial ventilation may be
necessary and positive pressure oxygen may also be
Convulsions should be controlled by cautious use of
Bronchospasm, is treated by bronchodilators. Pulmonary
oedema or bronchial pneumonia may be treated by
corticosteroids and organism specific antibiotics.
Correct marked acidosis by the cautious administration of
Renal failure should be treated appropriately.
Inhalation - Remove the source of contamination and move
victim to fresh air. If breathing has stopped, begin
artificial respiration or, if the heart has stopped,
Ingestion - not relevant.
Measures to enhance elimination have no role.
10.6 Antidote treatment
There is no specific antidote (see Section 10.7).
There is no specific antidote (see Section 10.7).
10.7 Management discussion
Although there is no specific antidote, the lethal effects
of acute exposure to 2500 ppm of methyl chloride for 6 hours
in mice were completely prevented by glutathione depletion
by pretreatment with the glutathione synthesis inhibitor, L-
buthionine-S, R-sulfoximine (Chellman et al, 1986a).
The adverse effects of methyl chloride toxicity on the
epididymis of the rat is inhibited by a potent anti-
inflammatory agent (3-amino-1-[m-(trifluoromethyl)phenyl]-2-
pyrazoline. This inhibits cyclooxygenase and lipoxygenase
enzymes, preventing both prostaglandin and leukotriene
and reducing the cytotoxic and genotoxic effects on sperm
caused by methyl chloride-induced epididymal inflammation
(Chellman et al., 1986b).
Although methanol poisoning has been attributed to methyl
chloride intoxication (Dreisbach & Robertson, 1987) this
claim is disputed (Gosselin et al., 1984).
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Although some medical or manufacturing uses were known
before the turn of the century, cases of poisoning were not
reported until methyl chloride became a common component of
refigeration units (Repko et al., 1976).
Case 1. Two adults, inhalation
Lanham (1982) described the case of a husband and wife who
purchased boards of polystyrene foam which they stored in
their basement. Over the next several days they experienced
blurred vision, fatigue, vertigo, nausea, vomiting, tremor
and unsteadiness of gait.
The association between symptoms and methyl chloride was
established, and air levels of methyl chloride were
determined in their home by three different methods and
found to be in excess of 200 ppm.
They recovered fully.
Case 2. Four persons, inhalation
Spevak et al. (1976) described loss of consciousness due to
methyl chloride poisoning in four family members due to a
leaking refrigerator. They exhibited drunken behaviour on
admission to hospital, as well as confusion, ataxia and
dysarthia. Later, all showed disturbances involving cranial
nerves (optic, oculomotor and facial). They also exhibited
tremors, tachycardia and elevated blood pressure. Recovery
followed fairly rapidly after treatment with isotonic
glucose, B-complex vitamins and oxygen.
Case 3. Industrial workers, inhalation
Scharnweber et al. (1974) reported six cases of intoxication
in industrial workers exposed to between 200 and 400 ppm on
an eight hour time-weighted average for prolonged periods.
Symptoms included confusion, blurred vision, headache,
memory loss, tiredness, nervousness, stuttering, staggering
gait and in some cases elevated blood pressure. All six
recovered within three months.
Case 4. Industrial workers, inhalation
MacDonald (1964) described eight case reports of methyl
chloride intoxication. Following acute exposure to
concentrations as high as 10 000 ppm, in some cases patients
who then returned to work exhibited enhanced sensitivity to
the presence of methyl chloride. They would complain of
symptoms even though the levels did not exceed 100 ppm
during the entire time they were working.
Case 5. Fishing trawler workers, inhalation
Gudmundson (1977) described the long term results of an
accident on a fishing trawler involving a leaking
refrigeration unit. Fifteen people developed methyl
chloride poisoning. One person died within 24 hours of the
episode; 2 developed severe depression and committed suicide
11 and 18 months later respectively; and one other died 10
years later from a fresh coronary
Thirteen years after the accident signs of neurological
injury were observed in the 10 people who could be traced.
Symptoms included fine tremor in the hands and peripheral
neuropathy. Some complained of reduced tolerance to alcohol,
fatigue and decreased stamina. Six patients exhibited
marked neurotic and depressive symptoms. Decreased libido
was a complaint in two cases and severe headaches in another
11.2 Internally extracted data on cases
11.3 Internal cases
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes
12.2 Specific preventive measures
Adequate ventilation is essential. Use in confined,
enclosed spaces should be avoided unless appropriate
respiratory and dermal protective equipment is available.
No data available.
Andrews AW, Zawistowski ES and Valentine CR (1976) A comparison
of the mutagenic properties of vinyl chloride and methyl
chloride. Mutation Research 40:273-276.
Bretherick L (1985) Handbook of reactive chemical hazards.
Butterworths, London, 1852 pp.
Bus JS (1978) The Pharmacologist. 20: 214. Cited in: Clayton
GD & Clayton FE (1981) Patty's Industrial Hygiene and
Toxicology. Vol.IIB. John Wiley & Sons, New York. 3816 pp.
Chellman, Gary J, White, Russell D, Norton, Ronald M, & Bus,
James S (1986a) Inhibition of the acute toxicity of methyl
chloride in male B6C3F1 mice by glutathione depletion.
Toxicology and Applied Pharmacology, 86:93-104.
Chellman GJ, Morgan KT, Bus JS & Working PK (1986b) Inhibition of
methyl chloride toxicity in male F-133 rats by the anti-
inflammatory agent BW755C. Toxicology and Applied Pharmacology,
Clayton GD & Clayton FE (1981) Patty's Industrial Hygiene and
Toxicology. Vol. IIB. John Wiley & Sons, New York. 3816 pp.
Deuichmann WB & Gerarde HW (1969) Toxicology of Drugs and
Chemicals. Academic Press Inc., New York & London.
Douglas J, Kornburst & James S, Bus (1982). Metabolism of methyl
chloride to formate in rats. Toxicology and Applied
Dreisbach RH & Robertson WO (1987) Handbook of Poisoning:
Prevention, diagnosis and treatment. 12th edition. Appleton &
Lange, Norwalk, Connecticut/Los Altos, California, 589 pp.
Ellenhorn MJ & Barceloux DG (1988) Medical Toxicology. Diagnosis
and treatment of human poisoning. Elsevier Science Publishing
Company, Inc: New York, New York.
Finar IL (1967). Organic Chemistry. 5th Edition. Longmans,
Green and Co Ltd: London, 906 pp.
Fostel J, Allen PF, Bermudez E, Kligerman AD, Wilmer JL, & Skopek
TR (1985) Assessment of the genotoxic effects of methyl chloride
in human lymphoblasts. Mutation Research. 155:75-81.
Gosselin RE, Smith RP & Hodge HC (1984) Clinical Toxicology of
commercial products. Williams & Wilkins, Baltimore.
Gudmundson G (1977) Methyl chloride poisoning 13 years later.
Archives of Environmental Health, 18:236-237.
Hahne RMA (1990) Evaluation of the GMD systems, Inc., thermally-
desorbable diffusional dosimeter for monitoring methyl chloride.
Am. Ind. Hyg. Assoc. J. 51(2):96-101.
Jones AM (1942) Methyl chloride poisoning. Q.J. Med. 1:29-43.
Klaassen CD, Amdur MO, & Doull J (Eds). Toxicology. The basic
science of toxicology. 3rd Edition, 1986. MacMillan Pubishing
Company, New York, New York, 974 pp.
Kucera J (1968) Exposure to fat solvents. A possible cause of
sacrolagenesis in man. J. Pediatr. 72:857-859.
Landry TD, Gushow TS, Langvardt PW, Wall JM & McKenna MJ (1983)
Pharmacokinetics and metabolism of inhaled methyl chloride in the
rat and dog. Toxicology and Applied Pharmacology 68:473-486.
Lanham JM (1982) Methyl chloride an unusual incident of
intoxication [letter], Can. Med. Assoc. J. 26(6):593.
MacDonald JDC (1964) Methyl chloride intoxication. Report of 8
cases. Journal of Occupational Medicine. 6(2):81-84.
NIOSH (1984) Current Intelligence Bulletin 43. September 27,
1984. Monohalomethanes. Methyl chloride, methyl bromide, methyl
iodide. U.S. department of health and human services, Public
health service, Centres for disease control, National institute
for occupational safety and health.
Nolan RJ, Rick DL, Landry TD, McCarty LP, Agin GL & Saunders JH
(1985) Pharmacokinetics of inhaled methyl chloride (CH3Cl) in
male volunteers. Fundamental and Applied Toxicology. 5:361-369.
Peter H, Deutschmann S, Reichal C & Hallier E (1989). Metabolism
of methyl chloride by human erythrocytes. Arch. Toxicol. 63:351-
Redford-Ellis M & Gowenlock AH (1971) Studies on the reaction of
chloromethane with preparations of liver, brain, and kidney.
Acta. Pharmacol. Toxicol. 30:49-58.
Repko JD (1981). Neurotoxicity of methyl chloride. Neurobehav.
Toxicol. Teratol. 3(4):425-429.
Repko JD, Jones PD, Garcia LS, Schneider EJ, Roseman E & Corum CP
(1976) Behavioural and neurological effects of methyl chloride.
U.S. HEW (NIOSH) Publ. No. 77-125.
Repko JD & Lasley SM (1979). Behavioural, neurological and toxic
effects of methyl chloride: a review of the literature. CRC
Crit. Rev. Toxicol. 6(4):283-302.
RTECS (1987) Registry of Toxic Effects of Chemical Substances.
1985-1986 Edition. US Department of Health and Human Services,
Public Health Services, Centers for Disease Control, National
Institute for Occupational Safety and Health, 5147 pp.
Scharnweber HC, Spears GN & Cowles SR (1974) Chronic methyl
chloride intoxication in six industrial workers. J. Occup. Med.
Sperling F, Macri FJ & von Ottengen WF (1950) Distribution and
excretion on intravenously administered methyl chloride. Archives
of Industrial Hygiene and Occupational Safety 1:215-222.
Spevak L, Nadj V & Felle D (1976). Methyl chloride poisoning in
four members of a family. Br. J. Industr. Med. 33(4):272-4.
van Doorn R, Borm PJA, Leijdekkers Ch-M, Henderson PTh, Reuvers J
& van Bergen TJ (1980) Detection and identification of S-
methylcysteine in urine of workers exposed to methyl chloride.
Int. Arch. Occup. Environ. Health. 46:99-109.
Wolkowski-Tyl R, Lawton AD, Phelps M, & Hamm TE (1983)
Evaluation of heart malformations in B6C3F1 mouse fetuses induced
by in utero exposure to methyl chloride. Teratol. 27:197-206.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
Author(s): Darren A. Saunders
Nerida A. Smith
Wayne A. Temple
National Toxicology Group
University of Otago Medical School
P.O. Box 913
Date: 20th December 1991
Peer Review: Newcastle-upon-Tyne, United Kingdom, February 1992