# Methenamin-3-chlorallylchlorid: MAK-Begründung, Nachtrag

## TL;DR

This paper evaluates the health risks of methenamine 3-chloroallylchloride and classifies its carcinogenic and mutagenic potential based on available data.

## Contribution

The paper provides a re-evaluation of methenamine 3-chloroallylchloride's toxicological profile and its classification for occupational exposure.

## Key findings

- Methenamine 3-chloroallylchloride releases formaldehyde, which contributes to its toxic effects.
- The substance is classified in Carcinogen Category 2 due to insufficient data for a MAK value.
- No MAK value was derived due to lack of data on systemic bioavailability and target organ toxicity.

## Abstract

The German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) summarized and re-evaluated the data for methenamine 3-chloroallylchloride [4080-31-3 (
cis
/trans), 51229-78-8 (cis)] to derive an occupational exposure limit value (maximum concentration at the workplace, MAK value) considering all toxicological end points. Relevant studies were identified from a literature search and also unpublished study reports were used. Methenamine 3-chloroallylchloride releases formaldehyde in aqueous solution. The effects are therefore attributed to the hydrolysis products formaldehyde and 3-chloroprop-2-en-1-amine. There are no studies available that investigated the carcinogenicity, toxicity and genotoxic potential of methenamine 3-chloroallylchloride in the upper respiratory tract or nose, which are the likely target organs. 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, the substance could be classified in Carcinogen Category 4. However, because it is not possible to derive a MAK value for methenamine 3-chloroallylchloride, 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 no data are available for the systemic bioavailability of methenamine 3-chloroallylchloride and the formaldehyde that is released in tissues by hydrolysis, there is no experimental evidence that the formaldehyde reaches the germ cells. Therefore, methenamine 3-chloroallylchloride has been classified in Category 3 B for germ cell mutagens. A new developmental toxicity study that was carried out according to OECD Test Guideline 414 does not confirm the foetal eye defects found by an earlier study. As no MAK value has been derived, the substance is no longer assigned to a pregnancy risk group. Current clinical findings confirm that frequent or regular contact with methenamine-3-chloroallyl chloride can lead to sensitization. Therefore, the “Sh” designation has been retained. There are no data for respiratory sensitization. Skin contact is not expected to contribute significantly to systemic toxicity.