Methenamin-3-chlorallylchlorid

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 Relevant studies were identified from a literature search and also unpublished study reports were used.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 there- fore attributed to the hydrolysis products formaldehyde and 3-chloroprop-2-en-1-amine. There are no studies available that investigated the carcinogenicity, toxicity and geno- toxic 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 con- centrations that exceed their detoxification capacity. As a formaldehyde releaser, the substance could be classified in Carcinogen Category 4. However, because it is not pos- sible 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. There- fore, 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 preg- nancy risk group. Current clinical findings confirm that frequent or regular contact with methenamine-3-chloroallyl chloride can lead to sensitization. Therefore, the “Sh” desig- nation has been retained. There are no data for respiratory sensitization. Skin contact is not expected to contribute significantly to systemic toxicity.