Bis(morpholino)methan

The German Senate Commission for the Investigation of Health Hazards of Chemi- cal Compounds in the Work Area (MAK Commission) has re-evaluated bismor- pholinomethane 5625-90-1 with regard to its carcinogenicity and germ cell muta- genicity classification, its ability to be absorbed through the skin, its sensitization poten- tial and the derivation of an occupational exposure limit value (maximum concentra- tion at the workplace, MAK value) can be derived. Relevant studies were identified from a literature search and also unpublished study reports were used. Bismorpholi- nomethane 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 car- cinogenicity, toxicity and genotoxicity induced by bismorpholinomethane in the upper respiratory tract or nose, the likely target organs, have not been investigated. The sub- stance 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 classi- fied 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 reach- es 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 desig- nated with the “Sh” notation. Skin contact is not expected to contribute significantly to systemic toxicity.