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Methyl chloride

1. NAME
   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. SUMMARY
   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. KINETICS
   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. TOXICOLOGY
   7.1 Mode of Action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 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
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 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
         9.4.3.1 CNS
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 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
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
   9.6 Summary
10. MANAGEMENT
   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
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES
    1. NAME
     1.1 Substance
       Chloromethane (IUPAC)
     1.2 Group
       Alkyl chloride, alkyl halide, halo alkane
     1.3 Synonyms
       Chloor-methaan
       Chlor-methan
       Chlorure de methyle
       Clorometano
       Cloruro di metile
       Methyl chloride
       Methylchlorid
       Metylu chlorek
       Monochloromethane
     1.4 Identification numbers
       1.4.1 CAS number
             74-87-3
       1.4.2 Other numbers
             RTECS PA6300000
             UN 1063
     1.5 Brand names, Trade names
       Cumitox
       Artic
     1.6 Manufacturers, Importers
       MURPHY-PHOENIX Co
       9505 Cassius Ave,
       Cleveland, Ohio 44105
       216-341-2211
     2. SUMMARY
     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 
       cause frostbite.
       
       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.
     2.3 Diagnosis
       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 
       chromatographic analysis.
       
       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.
       
       First-aid summary
       
       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 
       attention immediately.
       
       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
       Chloromethane
       
       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 
       flame.
       
       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
     4.1 Uses
       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
     5.1 Oral
       Not applicable (at room temperature methyl chloride is a gas).
     5.2 Inhalation
       This is the most significant and frequent source of exposure.
     5.3 Dermal
       Contact with liquid form may result in cryogenic injury, rash 
       and blistering; skin absorption may be significant.

     5.4 Eye
       Accidental spraying with the liquid or concentrated vapour may 
       cause burns from freezing and systemic absorption may be 
       possible.
     5.5 Parenteral
       An unlikely but possible route of entry.
     5.6 Others
       No data available.
    6. KINETICS
     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 
       al, 1985).
     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.
     6.4 Metabolism
       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 
       inhibited.
       
       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 
       amounts.
     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. TOXICOLOGY
     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 Toxicity
       7.2.1 Human data
             7.2.1.1 Adults
                     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.
             7.2.1.2 Children
                     No data available.
       7.2.2 Relevant animal data
             Acute toxicity.
             
             Oral:
             LD50 (rat)                1 800  mg/kg
             
             Inhalation:
             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
             
             (RTECS, 1987)
             
             The effects of methyl chloride depend partly on the 
             duration of exposure and the concentration:
             
             Single exposure                         Methyl chloride
                                                     concentration (ppm)
             
             Kills most animals in a                 150 000 - 300 000
             short time
             
             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
             serious effect
             
             Repko & Lasley (1979)
             
             Chronic toxicity
             
             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 
             the monograph
       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 
             three-hour period.
             
             TLV ACGIH (Threshold limit value; American Conference of 
             Governmental and Industrial Hygienists): 50 ppm (105 
             mg/m3).
             
             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.
     7.3 Carcinogenicity
       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 
       carcinogen.
     7.4 Teratogenicity
       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, 
       1986b).
     7.5 Mutagenicity
       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).
     7.6 Interactions
       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
             8.1.1.1 Toxicological analyses
             8.1.1.2 Biomedical analyses
             8.1.1.3 Arterial blood gas analysis
             8.1.1.4 Haematological analyses
             8.1.1.5 Other (unspecified) analyses
       8.1.2 Storage of laboratory samples and specimens
             8.1.2.1 Toxicological analyses
             8.1.2.2 Biomedical analyses
             8.1.2.3 Arterial blood gas analysis
             8.1.2.4 Haematological analyses
             8.1.2.5 Other (unspecified) analyses
       8.1.3 Transport of laboratory samples and specimens
             8.1.3.1 Toxicological analyses
             8.1.3.2 Biomedical analyses
             8.1.3.3 Arterial blood gas analysis
             8.1.3.4 Haematological analyses
             8.1.3.5 Other (unspecified) analyses
     8.2 Toxicological Analyses and Their Interpretation
       8.2.1 Tests on toxic ingredient(s) of material
             8.2.1.1 Simple Qualitative Test(s)
             8.2.1.2 Advanced Qualitative Confirmation Test(s)
             8.2.1.3 Simple Quantitative Method(s)
             8.2.1.4 Advanced Quantitative Method(s)
       8.2.2 Tests for biological specimens
             8.2.2.1 Simple Qualitative Test(s)
             8.2.2.2 Advanced Qualitative Confirmation Test(s)
             8.2.2.3 Simple Quantitative Method(s)
             8.2.2.4 Advanced Quantitative Method(s)
             8.2.2.5 Other Dedicated Method(s)
       8.2.3 Interpretation of toxicological analyses
     8.3 Biomedical investigations and their interpretation
       8.3.1 Biochemical analysis
             8.3.1.1 Blood, plasma or serum
                     Elevated serum bilirubin, blood urea, uric acid 
                     and elevated serum creatinine have been reported 
                     (Jones, 1942; Spevak et al, 1976).
             8.3.1.2 Urine
                     Urine may contain casts and protein, red cells, 
                     elevated carbonates and porphyrins (Dreisbach & 
                     Robertson, 1987; Jones, 1942).
             8.3.1.3 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 
       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
             Not applicable (methyl chloride is a gas at room 
             temperature).
       9.1.2 Inhalation
             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, 
             1987).
       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 
             data).
       9.1.6 Other
             No data available.
     9.2 Chronic poisoning
       9.2.1 Ingestion
             Not applicable (at room temperature methyl chloride is a 
             gas).
       9.2.2 Inhalation
             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, 
             1974) 
       9.2.3 Skin exposure
             Systemic absorption may occur through the skin and 
             mucous membranes.
       9.2.4 Eye contact
             Non-irritating even at levels that produce systemic 
             toxicity.
       9.2.5 Parenteral exposure
             No data available in man (see section 6.2 for animal 
             data).

       9.2.6 Other
             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 
       for months.
     9.4 Systematic description of clinical effects
       9.4.1 Cardiovascular
             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, 
             1976).
       9.4.2 Respiratory
             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).
       9.4.3 Neurological
             9.4.3.1 CNS
                     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 
                     gait.
             9.4.3.2 Peripheral nervous system
                     Chronic poisoning may cause numbness of the 
                     extremities (Dreisbach & Robertson, 1987).
             9.4.3.3 Autonomic nervous system
             9.4.3.4 Skeletal and smooth muscle
       9.4.4 Gastrointestinal
             Both chronic and acute exposures may be asociated with 
             nausea and vomiting (MacDonald, 1964).
       9.4.5 Hepatic
             Liver congestion with degenerative cellular changes may 
             occur (Dreisbach &
             Robertson, 1987).
             
             After acute exposure, jaundice with elevated bilirubin 
             has been reported; liver biopsy revealed centrilobular 
             degenerative and necrotic changes (Spevak, 1976; Jones, 
             1942).
       9.4.6 Urinary
             9.4.6.1 Renal
                     Proteinuria, elevated serum creatinine and 
                     degenerative changes similar to acute 
                     glomerulonephritis may occur (Spevak, 1976).
             9.4.6.2 Others
                     Loss of libido has been reported as a long term 
                     consequence of acute methyl chloride exposure 
                     (Gudmundson, 1977).
                     
       9.4.7 Endocrine and reproductive systems
       9.4.8 Dermatological
             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 
             toxicity.
       9.4.10 Haematological
              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).
       9.4.11 Immunological
              No data available.
       9.4.12 Metabolic
              9.4.12.1 Acid-base disturbances
                       No data available.
              9.4.12.2 Fluid and electrolyte disturbances
                       No data available.
              9.4.12.3 Others
                       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 
              (Kucera, 1968).
     9.5 Others
       No data available.
     9.6 Summary
     10. MANAGEMENT
      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 
         indicated.
         
         Convulsions should be controlled by cautious use of 
         diazepam.
         
         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 
         alkali.
         
         Renal failure should be treated appropriately.
      10.4 Decontamination
         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, 
         cardiopulmonary resuscitation.
         
         Ingestion - not relevant.
      10.5 Elimination
         Measures to enhance elimination have no role.

      10.6 Antidote treatment
         10.6.1 Adults
                There is no specific antidote (see Section 10.7).
         10.6.2 Children
                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 
         synthesis
         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
         occlusion.
         
         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 
         two.
      11.2 Internally extracted data on cases
         None available.
      11.3 Internal cases
    12. ADDITIONAL INFORMATION
      12.1 Availability of antidotes
         Not relevant.
      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.

      12.3 Other
         No data available.
    13. REFERENCES
    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, 
    85:367-379.
    
    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 
    Pharmacology. 65:135-143.
    
    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-
    355.
    
    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. 
    16(2):112-113.
    
    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 
    ADDRESSES
    Author(s): Darren A. Saunders
               Nerida A. Smith
               Wayne A. Temple
               National Toxicology Group
               University of Otago Medical School
               P.O. Box 913
               Dunedin
               New Zealand
    
               Tel: 64-3-4797244
               Fax: 64-3-4770509
    
    Date:      20th December 1991
    
    Peer Review:  Newcastle-upon-Tyne, United Kingdom, February 1992




    See Also:
       Toxicological Abbreviations
       Methyl chloride (ICSC)
       Methyl chloride (WHO Food Additives Series 14)
       Methyl chloride (CICADS 28, 2001)
       Methyl Chloride (IARC Summary & Evaluation, Volume 71, 1999)