4-(2-Nitrobutyl)morpholin und 4,4′-(2-Ethyl-2-nitro-1,3-propandiyl)bismorpholin
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 4-(2-nitrobutyl)morpholine (70% w/w) and 4,4′-(2-ethyl-2-nitro-1,3-propanediyl)bismorpholine (20% w/w) [2224-44-4; 1854-23-5] (mixture) with regard to its carcinogenicity and germ cell mutagenicity classification, its ability to be absorbed through the skin, its sensitization potential and whether an occupational exposure limit value (maximum concentration at the workplace, MAK value) can be derived. Relevant studies were identified from a literature search. The mixture is a formaldehyde releaser and is expected to undergo rapid hydrolysis in aqueous solution. For this reason, the local irritation is attributed to the hydrolysis products formaldehyde, 1-nitropropane, and possibly 3-nitropentylmorpholine. Carcinogenicity, toxicity and genotoxicity of 4-(2-nitrobutyl)morpholine and 4,4′-(2-ethyl-2-nitro-1,3-propanediyl)bismorpholine in the upper respiratory tract or nose, the likely target organs, have not been investigated. The substance has 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, 4-(2-nitrobutyl)morpholine and 4,4′-(2-ethyl-2-nitro-1,3-propanediyl)bismorpholine could be classified in Carcinogen Category 4. However, because it is not possible to derive a MAK value, the mixture has been assigned to Carcinogen Category 2 and given 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 and the formaldehyde that is released by hydrolysis in tissues, there is no experimental evidence that the formaldehyde reaches the germ cells. Therefore, the mixture of 4-(2-nitrobutyl)morpholine and 4,4′-(2-ethyl-2-nitro-1,3-propanediyl)bismorpholine has been classified in Category 3 B for germ cell mutagens. The mixture is skin sensitizing. Skin contact is not expected to contribute significantly to systemic toxicity.
