The health effects of methylene chloride (dichloromethane) have been studied extensively. Laboratory studies have shown an increased incidence of lung and liver cancer in mice, but not in rats or hamsters.  Results of extensive pharmacokinetic and mechanistic research indicate that rats, hamsters, and humans metabolize methylene chloride to a far lesser extent by the metabolic pathway associated with tumor formation than do mice.  Further, the tissue effects associated with tumor formation in mice are not likely to occur to a significant degree in humans. In addition, epidemiology studies of five separate worker cohorts exposed to the chemical over extended periods of time have, overall, shown no increased risk of cancer.

Methylene chloride is a widely used chemical solvent with a diverse number of applications.  It was introduced as a replacement for more flammable solvents over 60 years ago.  Methylene chloride is commonly used in paint removers and in various chemical processing operations.  It also is employed in the production of flexible urethane foams, aerosol and adhesive formulations, as a cleaning agent for fabricated metal parts, and as an extraction solvent.

Methylene chloride is a member of a family of saturated aliphatic halogenated compounds. It is a colorless, volatile liquid, completely miscible with a variety of other solvents.  Total U.S. demand for the chemical in 2006 was estimated at about 185 million pounds (83,900 metric tons) of which about 19 million pounds (8,600 metric tons) were imported.  About 150 million pounds (68,000 metric tons) were exported.

Methylene chloride is a highly desirable chemical for many applications because of the following characteristics:

For 2006, the use of methylene chloride in its various applications is estimated to be:

Methylene chloride is the active ingredient in many formulations of paint removers including industrial paint and commercial furniture strippers, home paint removers, and products used for aircraft maintenance. The chemical has a unique ability to penetrate, blister, and lift a wide variety of paint coatings. Formulations of the chemical are used extensively in both flow-over and immersion (dip) tanks in furniture refinishing operations. For the maintenance of military and commercial aircraft, a methylene chloride­based product has commonly been used to inspect the surface for damage.

Methylene chloride is used in aerosols as a strong solvent, a flammability suppressant, vapor pressure depressant, and viscosity thinner.  Current aerosol uses of methylene chloride include specialized spray paints and lubricants.

Pharmaceutical Manufacture

Methylene chloride is used as an effective reaction and recrystallization solvent in the extraction of several pharmaceutical compounds and in the production of many antibiotics and vitamins.  The chemical also has been used as a carrier for pharmaceutical tablet coatings. In these applications, essentially no methylene chloride is left in the coating of the tablet.  Residue tolerances have been established by the Food and Drug Administration (FDA) for this particular use.

Methylene chloride is employed in the manufacture of polycarbonate resin used for the production of thermoplastics.  It is used as a solvent in the production of cellulose triacetate which serves as a base for photographic film.  Other applications include its use in the solvent welding of plastic parts, and as a releasing agent to prevent the manufactured part from permanently bonding to the mold.

It is often necessary to remove grease, oil, or similar substances used as lubricants or temporary protective coatings during metal fabrication. Methylene chloride is used extensively for this purpose, both for cold (room temperature) cleaning and vapor degreasing of metal parts.

Foam Manufacture

Methylene chloride is used as an auxiliary blowing agent in the production of softer grades of slabstock flexible polyurethane foams for the furniture and bedding industries.  Evaporation of the solvent during production of the urethane polymer expands the cells of the foam, reducing its density without making it stiff or rigid.  The solvent also helps to control the reaction temperature, which otherwise could get sufficiently high to burn or scorch the foam interior.

Methylene chloride also is used as an extractant in the recovery and purification of a wide variety of materials including oils, fats, and waxes. The chemical is used to decaffeinate coffee and tea, extract oleoresins from a variety of spices, and for the extraction of hops.  As with tablet coatings, little or none of the chemical remains in the finished product.  Methylene chloride also is used as a chemical intermediate in the production of hydrofluorocarbon (HFC) 32 which is used in refrigerant blends developed to replace substances with higher global warming potential.

Methylene chloride is painful and irritating if splashed into the eyes or held in contact with the skin.  Overexposure to methylene chloride vapor may cause central nervous system depression (anesthesia) and irritation to the skin, eyes, mucous membranes, and respiratory tract.  These effects become more pronounced as the vapor concentration increases, but generally are not observed below 200 parts per million (ppm).  Visible symptoms of anesthesia have been reported in several animal species during exposure to methylene chloride concentrations of approximately 4,000 ppm and greater.

Carbon monoxide is an end product of metabolism of methylene chloride.  Studies in humans have demonstrated that 8­hour exposures to concentrations of 100 to 200 ppm of methylene chloride vapor produce carboxyhemoglobin (COHb) concentrations of 3 to 7 percent, approximating those produced by CO at 50 ppm and well below COHb levels generally required to produce symptoms.  The metabolic pathway becomes saturated in man at concentrations from 300 to 500 ppm, thus limiting the production of CO and preventing excessive buildup of COHb.

A potential concern linked with elevated COHb levels is that they may exacerbate heart disease.  An epidemiology study of Eastman Kodak workers occupationally exposed to methylene chloride (discussed below) showed no increase in deaths due to cardiovascular disease, suggesting that COHb­induced cardiac effects have not been, and are unlikely to be, a problem at occupational exposure levels.  Methylene chloride produces cardiac sensitization at very high exposure levels (24,000 ppm) in dogs, but this effect is unlikely to lead to human problems when methylene chloride is correctly used.

Liver effects have not been reported in humans, but liver changes have been observed in several long-term studies with laboratory animals.  Inhalation of 500 to 3,500 ppm methylene chloride for two years produced only minimal, nonproliferative changes in the liver of Sprague­Dawley rats (the no-observed­effect level was equal to 200 ppm) and no liver effects in hamsters.  Nonproliferative changes were noted in rats in another study after exposure to 1,000 to 4,000 ppm.  Liver enlargement has been observed in mice exposed to 2,000 and 4,000 ppm of methylene chloride for 11 days.  The slight liver toxicity observed in laboratory rodents after exposure to high concentrations of methylene chloride is not particularly striking.  The human experience indicates the liver is not adversely affected by methylene chloride, particularly when used in accordance with current exposure guidelines and label instructions.

In a wide variety of tests for genotoxicity, only one - the Ames bacterial mutagenicity test - has given consistently positive results across laboratories.  In tests using mammalian systems (cells in culture or whole animals), the observed responses have generally been negative or, in a few instances, equivocal.  Research sponsored by HSIA has shown, both in vivo and in vitro, that metabolites of the primary pathway by which methylene chloride is metabolized (see below) interact with DNA in mouse liver and lung tissue.  This effect, responsible for the tumors observed in mice, is not detectable in human cells in vitro even under extreme conditions.

In 2000, HSIA completed a study of methylene chloride’s potential to harm the immune system of laboratory animals and, thereby, reduce their ability to combat disease.  The study, designed in conjunction with the ATSDR and following guidelines developed by the US Environmental Protection Agency (EPA), exposed male and female Sprague-Dawley rats to a high level of methylene chloride (5,000 ppm) for five days per week for a period of four weeks.  Measuring a variety of end points for immunological function, the researchers found no evidence of adverse effects related to exposure to the solvent.

HSIA has sponsored extensive testing in rats of methylene chloride for potential neurotoxic effects. The results indicate no significant neurotoxic effects after exposure to concentrations up to 2,000 ppm for 90 days.  No neurotoxic effects have been observed in humans at typical occupational exposures.

Administration of methylene chloride in the drinking water of mice and rats at concentrations up to 250 milligrams per kilogram body weight per day by Serota and others did not induce tumors.  Similarly, administration of the solvent to hamsters via inhalation at concentrations up to 3,500 ppm for two years was not tumorigenic in a study conducted by The Dow Chemical Company.

In inhalation studies conducted on rats by Burek and others, an increase in the number of benign mammary gland tumors was found upon exposure to concentrations of 500 to 3,500 ppm methylene chloride.  At lower concentrations of 50 to 200 ppm, no significant increase in these tumors was observed. Importantly, no progression toward malignancy was observed in these studies.  A small increase in ventral neck region tumors in and around the salivary glands also was observed among male (but not female) rats exposed to 1,500 to 3,500 ppm of methylene chloride in the study by Burek and others.  This increase was not seen in subsequent studies and was not thought by EPA’s Science Advisory Board to have relevant human health implications.

In 1986 the National Toxicology Program (NTP) reported the results of inhalation bioassays in mice (2,000 and 4,000 ppm) and rats (1,000 to 4,000 ppm). There was an increase in the incidence of benign mammary gland tumors in male and female Fischer 344 rats (no progression towards malignancy), and increased incidence of malignant liver and lung tumors in B6C3Fl mice.  NTP concluded that these data demonstrated “clear evidence” of carcinogenicity in mice and female rats and “some evidence” of carcinogenicity in male rats.

The conclusions regarding inter-species differences are supported by the available epidemiology studies that show no association between increased cancer risk and exposure to relatively high concentrations of methylene chloride.  Studies of five occupational cohorts are available for the assessment of mortality effects in exposed populations.  These studies include two cohorts of photographic film base manufacturing workers at an Eastman Kodak facility in New York, two cohorts of fiber production employees at plants in Maryland and South Carolina owned by Hoechst Celanese, and a cohort of fiber production workers in the United Kingdom.

The epidemiology studies have many features that make them useful for evaluating potential health effects associated with methylene chloride, including:  (1) relatively large study groups with significant numbers of long-term employees; (2) large numbers of workers with career mean & hourly exposures above the currently recommended levels; and (3) lengthy intervals between first exposure and the end of follow-up.  In addition, the Eastman Kodak studies contain a detailed exposure characterization allowing dose-response analyses.

Considered as a whole, the available epidemiological evidence does not indicate a carcinogenic risk associated with occupational exposures to methylene chloride.  The studies consistently demonstrate no excess mortality for all causes of death, total cancer, and the cancers that were observed in the NTP mouse bioassay (lung and liver cancers).  In addition, no positive dose-response relationships have been observed.  The small number of excess deaths from biliary tract tumors observed in the first Celanese study has not been replicated in the other investigations.  Similarly, findings of excess prostate and cervical cancer in the second Celanese study were not replicated in the other studies.

The epidemiology studies also do not support an association between methylene chloride exposure and astrocytic brain cancer.  Such an association was suggested in a statistical treatment by Heineman and others using job codes to estimate whether, and to what extent, solvent exposure had occurred.  Among several methodological concerns, the job codes selected for this analysis do not relate well to methylene chloride use.

Methylene chloride is one of nearly 200 substances designated as hazardous air pollutants (HAPs) under Section 112 of the Clean Air Act, as amended.  Section 112 requires EPA to develop national emission standards based on maximum achievable control technology (MACT) for major sources, or generally available control technology (GACT) for small (area) sources, of HAPs.  Section 112 also requires EPA to review the need for additional control of regulated sources within eight years of the implementation of the technology standard.  Methylene chloride also is regulated as a toxic air pollutant by some states.

A MACT standard for halogenated solvent cleaning (degreasing) with methylene chloride and other chlorinated solvents became effective for existing sources in December 1997. As a result, degreasing sources are required to install one of several control options to reduce emissions.  The standard was amended in May 2007 to require that, in addition to the MACT control requirements, facilities emit no more than 40,000 kilograms (88,000 pounds) of methylene chloride annually from their degreasing operations.  The facility-wide limit becomes effective in April 2009 for most existing facilities.  Degreasing sources generally are required to obtain an operating permit from their state regulatory agency.

EPA also has developed MACT standards that apply to methylene chloride use in aircraft depainting, pharmaceutical manufacture, wood furniture manufacturing, polyurethane foam production, and foam fabrication.  A detailed discussion of the requirements of these standards, which generally apply to major sources that emit at least 20,000 pounds of methylene chloride per year, is beyond the scope of this paper.  In 2007, EPA promulgated requirements for use of methylene chloride in foam production and fabrication at area sources, including a prohibition on its use in foam adhesives.  In early 2008, EPA promulgated a GACT standard for emissions of methylene chloride from area source paint stripping operations requiring the implementation of management practices at all facilities to reduce evaporative losses of the solvent and the development of a written management plan at sources that use more than 2,000 pounds of methylene chloride annually.

Because methylene chloride does not contribute appreciably to smog formation, EPA has indicated that it is exempt from regulation as a volatile organic compound (VOC) under state regulations implementing the national ambient air quality standard for ozone.  Methylene chloride is exempt in almost all of the states with VOC regulations, in accordance with federal guidelines.  A few states have prohibited its use in certain consumer and commercial products based on its HAP designation.

EPA has established national drinking water regulations setting a maximum contaminant level of 5 micrograms per liter (µg/l), equal to 5 parts per billion (ppb), for methylene chloride.  The maximum contaminant level goal (MCLG) for methylene chloride is zero.  EPA has indicated that the establishment of an MCLG at zero is “an aspirational goal which includes a margin of safety.”  States also may have drinking water regulations that apply to methylene chloride.  For various industry categories, EPA has established effluent limitation guidelines, which may contain limits for methylene chloride.  EPA also has published ambient water quality criteria for the halomethane class, including methylene chloride, for use by states in developing water quality standards.

Methylene chloride waste is considered hazardous under the federal Resource Conservation and Recovery Act (RCRA) and many state laws.  The waste must be stored, transported, and disposed of in accordance with applicable RCRA and state requirements.

The reportable quantity (RQ) for releases of methylene chloride under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA or Superfund) is 1,000 pounds.  Methylene chloride is one of several hundred chemicals subject to the material safety data sheet (MSDS), inventory, and release reporting requirements of the Emergency Planning and Community Right-to-Know Act (Title III of the Superfund Amendments and Reauthorization Act of 1986).

OSHA’s permissible exposure limits (PELs) for methylene chloride are 25 ppm as an 8-hour, time-weighted average (TWA) and 125 ppm as a short-term exposure limit (STEL).  OSHA’s comprehensive standard for the solvent also requires medical surveillance and contains a number of other ancillary provisions.

The Consumer Product Safety Commission has issued a Statement of Interpretation and Enforcement Policy for household products containing methylene chloride that establishes labeling guidance for these products under the Federal Hazardous Substances Act.  In addition, the use of methylene chloride in cosmetic products and as a decaffeinating agent is restricted by the Food and Drug Administration.

HSIA does not recommend the use of methylene chloride in any application, including cold cleaning, unless all applicable workplace and disposal and other environmental regulatory requirements are met.  In addition to complying with these various regulatory requirements, many prudent operators of cleaning and other equipment have elected to adopt practices and standards for the use, management, and disposal of methylene chloride and waste containing methylene chloride that go beyond strict legal requirements.  These operators recognize that environmental protection is their responsibility.  They also understand that they are potentially liable for environmental contamination that can be traced to their solvent waste, whether at their own plant or elsewhere, regardless of the fact that they may have complied with the letter of the law.  These operators recognize that additional measures that go "beyond compliance" make good business sense because they minimize the risks of liability that arise when methylene chloride is released to the environment.