Diethylene glycol dimethyl ether
MAK Value Documentation, supplement – Translation of the German version from 2021
Andrea Hartwig1 (Chair of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft)MAK Commission2
1 Institute of Applied Biosciences, Department of Food Chemistry and Toxicology, Karlsruhe Institute of Technology (KIT), Adenauerring 20a, Building 50.41, 76131 Karlsruhe, Germany
2 Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft, Kennedyallee 40, 53175 Bonn, Germany
Abstract
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated the maximum concentration at the workplace (MAK value), the pregnancy risk group, sensitization, absorption through the skin and the germ cell mutagenicity of diethylene glycol dimethyl ether [111-96-6]. The critical effects of diethylene glycol dimethyl ether are its embryotoxic and fertility impairing effects, with the rat being the most sensitive species. The NOAEC for toxic effects on rat testes, derived from an inhalation study lasting only 2 weeks, is 30 ml/m3. It is likely that the metabolites 2-methoxyethanol and 2-methoxyacetic acid are responsible for the reproductive toxicity of diethylene glycol dimethyl ether. The MAK value of 2-methoxyethanol was calculated to be 1 ml/m3 on the basis of the BAT value of 2-methoxyacetic acid (15 mg 2-methoxyacetic acid/g creatinine). The MAK value of 2-methoxyacetic acid was established to be 1 ml/m3 in analogy to 2-methoxyethanol. Based on these data, the MAK value for diethylene glycol dimethyl ether is set at 1 ml/m3 (5.6 mg/m3). This value also takes the increased respiratory volume at the workplace into account (see List of MAK and BAT values, Section I b and I c). As the critical effect is systemic and the critical metabolite 2-methoxyacetic acid has a long half-life, Peak Limitation Category II with an excursion factor of 8 is retained. In rats, there is an elevated incidence of skeletal variations without maternal toxicity after nose-only inhalation at 25 ml/m3 and above. When the increased respiratory volume (1:2) is taken into account, the LOAEC of 25 ml/m3 corresponds to 13 ml/m3. The high (four-fold) foetal incidence of rudimentary lumbar ribs at this LOAEC indicates that the NAEC for developmental toxicity falls well below the required 10-fold margin to the MAK value. Therefore, the margin to the MAK value is not sufficient. The metabolite 2-methoxyethanol is teratogenic in rats, mice and rabbits and, at a MAK value of 1 ml/m3, assigned to Pregnancy Risk Group B. After inhalation, the potency of diethylene glycol dimethyl ether for inducing skeletal variations is just as strong as that of 2-methoxyethanol. In addition, the half-life of the toxic metabolite 2-methoxyacetic acid in blood is longer in humans than in rats. Therefore, diethylene glycol dimethyl ether remains assigned to Pregnancy Risk Group B. A carcinogenicity study has not been performed with diethylene glycol dimethyl ether. Diethylene glycol dimethyl ether is not genotoxic. As it is possible to absorb toxic amounts through the skin, diethylene glycol dimethyl ether remains designated with “H”. Available data show no sensitization.
