IPCS INCHEM Home

    METHYLENE CHLORIDE

    Explanation

         The available biological data relating to both animal and human
    exposure to dichloromethane were evaluated by the Joint FAO/WHO Expert
    Committee on Food Additives in 1970. Since then the following data
    have been published.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         Male and female Sprague-Dawley rats (120-400 g/bw) were given
    single i.p. doses in corn oil, ranging from 412 to 930 mg/kg
    14C-labelled dichloromethane. Immediately following dosing the rats
    were placed in a metabolism chamber which enabled the collection of
    expired air, faeces and urine.

         Animals were killed at 2, 8 and 24 hours after the administration
    of the labelled dichloromethane. Analysis of excreta and body tissues
    indicated that at 24 h most of the dose (91.5%) was excreted unchanged
    in the expired air, 2% was eliminated as carbon monoxide and 3% as
    carbon dioxide. There was evidence that more than 75% of the dose was
    eliminated in the first 2 h after administration. There was no support
    for the theory that dichloromethane is metabolized to formaldehyde
    (DiVincenzo & Hamilton, 1975).

         Further evidence for the metabolism of dichloromethane to carbon
    monoxide and the subsequent formation of elevated carboxyhaemoglobin
    levels in the blood was obtained from a study in which male Sprague-
    Dawley rats were exposed to concentrations of 1935 mg/m3
    14C-labelled solvent in the air for 1 h. It was also shown in this
    experiment that the dichloromethane is distributed throughout the body
    tissues and its concentrations falls dramatically upon cessation of
    exposure (Carlsson & Hultengren, 1975).

         Roth et al. (1975) showed that exposure of rabbits of
    dichloromethane in the atmosphere resulted in an increase in the
    percentage of carboxyhaemoglobin (COHb) in blood. Extended exposure to
    high levels of dichloromethane resulted in COHb percentages which
    reached a plateau. This was thought to be the result of saturating the
    metabolic pathways of the solvent coupled with the elimination rate of
    carbon monoxide via the lungs.

         Exposure of male Wistar rats (80-100 g/bw) to 500 or 5000 ppm
    dichloromethane in air, 5 h/day for 10 days resulted in slight
    increases of cytochrome P450 at the 500 ppm level and both cytochrome
    P450 and aminopyrine demethylase activity at the 5000 ppm level
    (Norpoth et al., 1974).

    TOXICOLOGICAL STUDIES

    Teratology study

         Groups of 13 pregnant Swiss Webster mice and 19 pregnant Sprague-
    Dawley rats were exposed to 1250 ppm dichloromethane in the
    atmosphere, 7 h/day on days 6-15 of gestation. The young were removed
    by Caesarian section and examined for soft tissue and skeletal
    abnormalities. No significant material or foetal toxicity attributable
    to treatment was reported and there was no teratogenic potential in
    either species on the part of the solvent at this exposure level. The
    COHb content of blood was elevated in both mice and rats exposed to
    dichloromethane (Schwetz et al., 1975).

    Human data

         The concentration of dichloromethane was determined in the
    alveolar air and blood of 14 subjects exposed to 870 and 1740 mg/m3
    of the solvent in air during periods of rest and physical exercise.
    The uptake of the solvent was found to vary from 55% of the amount
    supplied at rest to 30% of the amount supplied during exercise. The
    percentage of COHb in the blood increased with increasing exposure and
    for a period after exposure. At the highest solvent exposure a level
    of 5.5% COHb was recorded (Astrand et al., 1975).

         Although exposure of human subjects to a level of 500 ppm
    CH2CL2 in the atmosphere for periods of up to three hours was
    reported to result in lapses of attention and decreased manual
    performance (Winneke & Fodor, 1976), in a similar experiment in which
    14 male subjects were exposed to levels of up to 1000 ppm
    dichloromethane in the air for two hours, no significant impairment of
    reaction time, short-term memory or numerical ability was reported
    (Gamberale et al., 1975).

         Studies of the COHb level were made of seven subjects who were
    exposed to solvent concentrations between 245 and 471 ppm in their
    working environment for eight hours every day. The results indicated
    that the % COHb rose from a mean of 4.5% immediately before exposure
    to a maximum of 9.0% after eight hours exposure then falling
    exponentially 4.5% by the start of work on the following day. The
    24-hours time-weighted average was found to be 7.3%.

    Comments

         There are no adequate short- or long-term oral toxicity studies
    with this solvent. However, the available data indicate that the
    metabolism and excretion pattern of methylene chloride are similar
    regardless of route of administration. In animals and man the majority
    of the dose is excreted unchanged in the expired air, a small
    percentage being converted to carbon monoxide which then binds with
    haemoglobin and results in an elevated COHb concentration in the
    blood.

         High dosage produces narcosis but a long history of industrial
    exposure indicates no major acute toxicity. The long-term inhalation
    data were available in summary form and there was no way of judging
    the precise solvent intake in the test animals. However, in short-term
    studies food extracted with the solvent appeared to be non-toxic.

         The use of this solvent should be restricted to that determined
    by good manufacturing practice, which is expected to result in minimal
    residues unlikely to have any significant toxicological effect.
    However, residues from each application should be judged individually.

    EVALUATION

    Estimate of temporary acceptable daily intake for man

    0-0.5 mg/kg bw (residues from each application should be judged
    individually).

    FURTHER WORK OR INFORMATION

    Required by 1983.

         Data from long-term oral studies in two rodent species.

    REFERENCES

    Astrand. I., Ovrum, P. & Carlsson, A. (1975) Exposure to methylene
         chloride. 1. Its concentration in alveolar air and blood during
         rest and exercise and its metabolism, Scand. J. Work. Environ.
         Hlth, 1, 78

    Carlsson, A. & Hultengren, M. (1975) Exposure to methylene chloride.
         III. Metabolism of 14C-labelled methylene chloride in rat,
         Scand. J. Work. Environ. Hlth, 1, 104

    DiVicenzo, G. D. & Hamilton, M. L. (1975) Fate and disposition of
         (14C) methylene chloride in the rat, Toxicol. Appl.
         Pharmacol., 32, 385

    Gamberale, F., Annwall, G. & Hultengren, M. (1975) Exposure to
         methylene chloride. II. Psychological functions, Scand. J. Work.
         Environ. Hlth, 1, 95

    Norpoth, K. et al. (1974) Induction of microsomal enzymes in the rat
         liver by inhalation of hydrocarbon solvents, Int. Arch.
         Arbeitsmed., 33, 315

    Ratney, R. S., Wegman, D. H. & Elkins, H. B. (1974) In vivo conversion
         of methylene chloride to carbon monoxide, Arch. Environ. Hlth,
         28, 223

    Roth, R. P. et al. (1975) Dichloromethane inhalation, carboxy-
         haemoglobin concentrations, and drug metabolizing enzymes in
         rabbits, Toxicol. Appl. Pharmacol., 33, 427

    Schwetz, B. A., Leong, B. K. J. & Gehring, P. J. (1975) The effect of
         maternally inhaled trichlorethylene, perchloroethylene, methyl
         chloroform, and methylene chloride on embryonal and foetal
         development in mice and rats, Toxicol. Appl. Pharmacol., 32,
         84

    Winneke G. & Fodor, G. G. (1976) Dichloromethane produces narcotic
         effect, Occ. Hlth Safety, 45, 34
    


    See Also:
       Toxicological Abbreviations
       Methyl chloride (ICSC)
       Methyl chloride (PIM 339)
       Methyl chloride (CICADS 28, 2001)
       Methyl Chloride (IARC Summary & Evaluation, Volume 71, 1999)