# Bis(morpholino)methan: MAK-Begründung, Nachtrag

## TL;DR

This paper re-evaluates the health risks of bismorpholinomethane, focusing on its classification as a carcinogen and mutagen, and its effects on the skin and respiratory system.

## Contribution

The paper provides a re-evaluation of bismorpholinomethane's health hazards and its classification based on new and existing data.

## Key findings

- Bismorpholinomethane is corrosive to rabbit skin and releases formaldehyde, which may cause local irritation.
- The substance shows mutagenic potential in vitro, likely due to formaldehyde release.
- Due to insufficient data, bismorpholinomethane is classified in Carcinogen Category 2 and Germ Cell Mutagen Category 3B.

## 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 Relevant studies were identified from a literature search and also unpublished study reports were used.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.