1,1-Dichlorethen
MAK-Begründung, Nachtrag
Andrea Hartwig1 (Vorsitz der Ständigen Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Deutsche Forschungsgemeinschaft)MAK Commission2
1 Institut für Angewandte Biowissenschaften, Abteilung Lebensmittelchemie und Toxikologie, Karlsruher Institut für Technologie (KIT), Adenauerring 20a, Geb. 50.41, 76131 Karlsruhe, Deutschland
2 Ständige Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Deutsche Forschungsgemeinschaft, Kennedyallee 40, 53175 Bonn, Deutschland
Abstract
The German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) summarized and evaluated the data for 1,1-dichloroethene [75-35-4] considering all toxicological end points. Relevant studies were identified from a literature search. In two-year carcinogenicity studies, 1,1-dichloroethene increased the incidences of adenomas of the nasal respiratory epithelium in rats and of rare renal tubular carcinomas in male rats. In female rats, the incidences of C-cell adenomas and carcinomas of the thyroid gland were increased with statistical significance at the lowest concentration tested of 25 ml/m3 and above. In male mice, the incidences of renal adenomas and carcinomas were increased with statistical significance at the lowest concentration tested of 6.25 ml/m3 and above; rare hepatocholangiocarcinomas developed in animals of all exposure groups. The incidences of hepatocellular carcinomas were increased with statistical significance in female mice at 12.5 ml/m3 and above. After exposure to 25 ml/m3, bronchiolar-alveolar carcinomas, haemangiosarcomas of the liver and the sum of haemangiomas and sarcomas in all organs in female mice were increased with statistical significance. On the basis of these effects, 1,1-dichloroethene has been classified in Carcinogen Category 2. 1,1-Dichloroethene is mutagenic and clastogenic in vitro after metabolic activation. Genotoxicity was observed in vivo in indicator tests in metabolically competent tissues (lungs, liver, kidneys). However, no clastogenicity was induced in the bone marrow or germ cells, even at high concentrations. Thus, 1,1-dichloroethene has not been classified in a germ cell mutagenicity category. However, a genotoxic mechanism of action for the carcinogenic effects cannot be ruled out. Developmental toxicity in rats and rabbits such as variations, delayed ossification (rats) and increased resorptions (rabbits) occurred only with concomitant maternal toxicity in the form of reduced body weight gains. In vitro studies found that 1,1-dichloroethene is absorbed via the skin. The substance has been designated with “H” because of the systemic carcinogenic effects. A sensitizing potential is not expected based on the data available.
