Bis(morpholino)methan
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) has re-evaluated bismorpholinomethane [5625-90-1] with regard to its carcinogenicity and germ cell mutagenicity classification, its ability to be absorbed through the skin, its sensitization potential and the derivation of an occupational exposure limit value (maximum concentration at the workplace, MAK value) can be derived. Relevant studies were identified from a literature search and also unpublished study reports were used. Bismorpholinomethane is corrosive to the skin of rabbits. The substance is a formaldehyde releaser and is expected to undergo rapid hydrolysis in aqueous solution. The local irritation is therefore attributed to the hydrolysis products formaldehyde and morpholine. The carcinogenicity, toxicity and genotoxicity induced by bismorpholinomethane in the upper respiratory tract or nose, the likely target organs, have not been investigated. The substance exhibited mutagenic and clastogenic potential in vitro, presumably due to the release of formaldehyde. Formaldehyde was classified in Carcinogen Category 4 because it induces tumours in nasal tissues at concentrations that exceed their detoxification capacity. As a formaldehyde releaser, bismorpholinomethane could likewise be classified in Carcinogen Category 4. However, because it is not possible to derive a MAK value for bismorpholinomethane, the substance has been assigned to Carcinogen Category 2 with the footnote “Prerequisite for Category 4 in principle fulfilled, but insufficient data available for the establishment of a MAK or BAT value”. As there are no data for the systemic bioavailability of bismorpholinomethane and the formaldehyde that is released in tissues by hydrolysis, there is no experimental evidence that the formaldehyde reaches the germ cells. Therefore, bismorpholinomethane has been classified in Category 3 B for germ cell mutagens. Clinical data in humans reveal a skin sensitizing potential that is also caused by the release of formaldehyde. Bismorpholinomethane has been designated with the “Sh” notation. Skin contact is not expected to contribute significantly to systemic toxicity.
