5-Ethyl-3,7-dioxa-1-azabicyclo[3.3.0]octan (EDAO)
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 re-evaluated the data for 5-ethyl-3,7-dioxa-1-azabicyclo[3.3.0]octane (EDAO) [7747-35-5] to derive an occupational exposure limit value (maximum concentration at the workplace, MAK value) considering all toxicological end points. Relevant studies were identified from a literature search and also unpublished study reports were used. The substance is irritating to the skin and corrosive to the eyes of rabbits. EDAO is not expected to occur in aerosol form because of its vapour pressure. EDAO releases formaldehyde in aqueous solution. For this reason, the effects are attributed to the hydrolysis products formaldehyde and 2-amino-2-ethyl-1,3-propanediol. It is assumed that EDAO hydrolyses to formaldehyde in the respiratory tract. In the worst case, two formaldehyde molecules per molecule of EDAO could be released in the respiratory tract. Taking this into consideration, a MAK value of 0.15 ml/m3 has been derived for EDAO in analogy to the MAK value of 0.3 ml/m3 for formaldehyde. There are no studies that investigated the carcinogenicity, toxicity or genotoxic potential of EDAO in the upper respiratory tract or nose, the likely target organs. The substance has genotoxic potential in vitro, presumably due to the release of formaldehyde. Formaldehyde has been classified in Carcinogen Category 4 because it causes nasal tumours at concentrations that exceed the detoxification capacity of that tissue. Thus, in analogy to the classifications for formaldehyde, the substance has been assigned to Carcinogen Category 4 and Germ Cell Mutagenicity Category 5. In rats, the NOAELs for perinatal toxicity and teratogenicity of EDAO are 150 mg/kg and 250 mg/kg body weight, respectively. As the margins between the NOAELs and the MAK value are sufficiently large, EDAO has been assigned to Pregnancy Risk Group C. EDAO has skin sensitizing potential. Therefore, the “Sh” designation has been retained. There are no data for respiratory sensitization. Skin contact is not expected to contribute significantly to systemic toxicity.
