dichloromethane; methylene chloride

Endpoint summary

Description of key information

Dichloromethane (DCM) is rapidly and extensively absorbed from the lungs into the systemic circulation (uptake in humans 70-75%) and is well absorbed from the gastrointestinal tract of animals (uptake 97%). Liquid DCM can be absorbed via the skin (absorption rate in mice 6.6 mg/cm2/h). However, due to its high volatility this route of exposure is of less significance than other routes of exposure under non-occlusive conditions. Dermal absorption of DCM vapour in rats is not significant. DCM is distributed to many organs, including liver, kidney, lungs, brain, muscle and adipose tissue, after respiratory and oral exposure. DCM is quite rapidly excreted after oral exposure, mostly via the lungs in the exhaled air. It can cross the blood-brain barrier and be transferred across the placenta, and small amounts can be excreted in urine or in milk. At high doses, most of the absorbed DCM is exhaled unchanged. The remainder is metabolized to carbon monoxide, carbon dioxide and inorganic chloride, whereby two routes of oxidative metabolism have been identified, one mediated by cytochrome P450 (predominantly in humans) and the other by glutathione-S-transferase (especially in mice).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

97

Absorption rate - dermal (%):

1

Absorption rate - inhalation (%):

70

Additional information

Information was taken from WHO (1996), IARC (1999), USEPA (2011), SCOEL (2009), IARC (2016), and MAK (2016). Dichloromethane is rapidly and extensively absorbed from the lungs into the systemic circulation (uptake in humans 70-75% following exposure to concentrations of 176-706 mg/m³(SCOEL, 2009)). There are currently no data available on absorption of dichloromethane following oral intake in humans, but on the basis of laboratory animal studies a rapid and nearly complete absorption in the gastrointestinal tract would be expected (97% of the label was detected in exhaled air within 24 hours) (US EPA, 2011). Three skin penetration studies were found where pure methylene chloride was applied to human or rat skin in vitro or to mouse skin in vivo. The three studies reported similar results, with transdermal fluxes ranging from 2.7 to 6.6 mg/cm2/h (SCOEL, 2009). According to SCOEL (2009), based on these data, a skin notation should be assigned because the amount of dichloromethane absorbed upon exposure of both hands and lower arms (2000 cm²) for one hour to liquid dichloromethane is expected to be 3- to 7-fold greater than that from an 8-h inhalation exposure at an OEL of 347 mg/m³, assuming 50% absorption. However, due to its high volatility this route of exposure is of less significance than other routes of exposure under non-occlusive conditions. The vapour absorption rate of DCM in rats during exposure at 30000, 60000 or 100000 ppm (106, 212 or 353 g/m3) was 0.031, 0.052 and 0.103 mg/cm2/h, respectively. The mean permeability constant was 0.28 cm/h.  

Dichloromethane is distributed to many organs, including liver, kidney, lungs, brain, muscle and adipose tissue, after respiratory and oral exposure. It is quite rapidly excreted after oral exposure, mostly via the lungs in the exhaled air. It can cross the blood-brain barrier and be transferred across the placenta, and small amounts can be excreted in urine or in milk. Exhalation of dichloromethane after inhalation exposure increases when exposed to higher concentrations. The remainder is metabolized to carbon monoxide, carbon dioxide and inorganic chloride (US EPA, 2011).

Metabolism occurs by either or both of two pathways, whose relative contribution to the total metabolism is markedly dependent on the dose and on the animal species concerned (see Figure 1). One pathway involves oxidative metabolism mediated by cytochrome P-450, and leads to both carbon monoxide and carbon dioxide. This pathway appears to operate similarly in rats, mice and man. Whilst this is the predominant metabolic route at lower doses, saturation occurs at a relatively low dose ( 1400-1800 mg/m³(400-500 ppm) in humans (US EPA, 2011)). Increasing the dose above the saturation level does not lead to extra metabolism by this route. The other pathway involves a glutathione transferase (GST), and leads via formaldehyde and formate, to carbon dioxide. This route seems only to become important at doses above the saturation level of the "preferred" oxidative pathway. In some species (e.g., the mouse) it becomes the major metabolic pathway at sufficiently high doses. In contrast, in other species (e.g., hamster, man) it seems to be used very little at any dose. Species differences in GST metabolism correlate well with the observed species differences in carcinogenicity (US EPA, 2011). The extent of metabolism by these pathways in relevant species has been used as the basis for a kinetic model to describe the metabolic behavior of dichloromethane in various species(WHO, 1996), including humans (David et al., 2006 cited by US EPA, 2011).

WHO (1996). Methylene Chloride - Second Edition. Environmental Health Criteria 164.

IARC (1999). IARC Monographs of the evaluation of carcinogenic risks to humans - Re-evaluation of some organic chemicals, hydrazine, and hydrogen peroxide. Vol. 71.

SCOEL (2009). Recommendation of the Scientific Committee on Occupational Exposure Limits for methylene chloride (dichloromethane). Report no: SCOEL/SUM/130.

US EPA (2011). Toxicological Review of Dichloromethane (Methylene Chloride) In Support of Summary Information on the Integrated Risk Information System (IRIS).EPA/635/R-10/003F. http://www.epa.gov/iris/toxreviews/0070tr.pdf.

IARC (2016). Dichloromethane - vol 110

MAK (2016). The MAK Collection for Occupational health and Safety - Dichloromethane, vol 1, no 3.