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1000
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Abstract/Summary
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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated dichloromethane to derive a maximum concentration at the work place (MAK value), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. Dichloromethane is a central nervous system depressant. A MAK value of 50 ml/m3 is derived based on acute behavioural effects indicative for CNS depression assessed by visual‐manual tasks in humans. Peak Limitation Category II is assigned due to the critical systemic effects and at an excursion factor of 2 the resulting concentration in blood is below the NOAEC. Dichloromethane is genotoxic in in vitro test systems in which the GSH‐dependent metabolic pathway is active. Genotoxicity studies in vivo indicated positive results only in somatic cells of mice in high concentrations. However, compared with humans, in mice the GSTT1 isoenzyme is of higher activity as well as the RNA‐adduct formation and the mRNA expression of GSTT1 in prostate, ovaries and placenta is higher. Due to lower sensitivity of humans compared with mice, dichloromethane is not expected to be mutagenic in germ cells of humans. Available epidemiological studies show no association between dichloromethane and cancer in humans. In mice adenomas and carcinomas are seen in the liver and the lung which can be explained by the rapid metabolism of dichloromethane via the GSH‐dependent pathways in this species and these organs. Using physiologically based pharmacokinetic models in mice and humans, unit risks for humans have been published. Linear extrapolation of the median unit risk by the Commission yields a median risk for liver and lung tumours of 2.5 x 10‐5 (0‐6.67 x 10‐5) for work place exposure to 50 ml dichloromethane/m3. Dichloromethane is classified in Carcinogen Category 5 because the genotoxicity is of prime importance for carcinogenicity of dichloromethane, the genotoxic mode of action is well‐understood and data to calculate the carcinogenic potency in man are available, showing a very slight contribution to human cancer risk, if the MAK value of 50 ml/m3 is observed. According to available information of CO‐Hb formation in blood, damage to the embryo or foetus cannot be excluded even if the MAK value is observed and dichloromethane is assigned to Pregnancy Group B. Dichloromethane is designated with an “H” notation since percutaneous absorption can contribute significantly to the systemic toxicity. Dichloromethane is not expected to be a sensitizer.
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