# 1,3-Bis(hydroxymethyl)harnstoff: MAK-Begründung, Nachtrag

## TL;DR

This paper evaluates the health risks of 1,3-bis(hydroxymethyl)urea, focusing on its potential to cause cancer and genetic mutations.

## Contribution

The paper provides a new classification of 1,3-bis(hydroxymethyl)urea based on updated toxicological data and formaldehyde release.

## Key findings

- 1,3-bis(hydroxymethyl)urea is classified as a skin and eye irritant due to its hydrolysis products.
- The substance is classified in Carcinogen Category 2 due to insufficient data for a MAK value.
- No significant sensitizing effects were observed in mice.

## Abstract

The German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) has re-evaluated 1,3-bis(hydroxymethyl)urea [140-95-4] 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. 1,3-Bis(hydroxymethyl)urea is a skin and eye irritant after prolonged exposure. The substance 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 and urea. Carcinogenicity, toxicity and genotoxicity of 1,3-bis(hydroxymethyl)urea in the upper respiratory tract or nose, the likely target organs, have not been investigated. The substance has 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, 1,3-bis(hydroxymethyl)urea could likewise be classified in Carcinogen Category 4. However, because it is not possible to derive a MAK value for 1,3-bis(hydroxymethyl)urea, 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 1,3-bis(hydroxymethyl)urea and the formaldehyde that is released by hydrolysis in tissues, there is no experimental evidence that the formaldehyde reaches the germ cells. Therefore, 1,3-bis(hydroxymethyl)urea has been classified in Category 3 B for germ cell mutagens. There are no data investigating sensitizing effects in humans. A local lymph node assay in mice yielded negative results. Skin contact is not expected to contribute significantly to systemic toxicity.