N,N′,N′′-Tris(β-hydroxypropyl)hexahydro-1,3,5-triazine

MAK Value Documentation – Translation of the German version from 2023

  Andrea Hartwig¹ (Chair of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft)
  MAK Commission<sup>2

1</sup> Institute of Applied Biosciences, Department of Food Chemistry and Toxicology, Karlsruhe Institute of Technology (KIT), Adenauerring 20a, Building 50.41, 76131 Karlsruhe, Germany
² Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft, Kennedyallee 40, 53175 Bonn, Germany

Abstract

The German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) has evaluated the data for N,N′,N′′-tris(β-hydroxypropyl)hexahydro-1,3,5-triazine [25254-50-6] 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 Relevant studies were identified from a literature search and also unpublished study reports were used. N,N′,N′′-Tris(β-hydroxypropyl)hexahydro-1,3,5-triazine is a formaldehyde releaser in aqueous solution. The substance is highly irritating to corrosive to the skin and eyes of rabbits. It is expected to undergo rapid hydrolysis in aqueous solution. For this reason, the observed local effects of irritation are attributed to the hydrolysis products formaldehyde and 1-aminopropan-2-ol. There are no studies that investigated the carcinogenic effects of N,N′,N′′-tris(β-hydroxypropyl)hexahydro-1,3,5-triazine and its toxicity and genotoxic potential in the upper respiratory tract or nose, which are assumed to be the likely target organs. The substance has low mutagenic and clastogenic potency in vitro, presumably due to the release of formaldehyde. Formaldehyde was classified in Carcinogen Category 4 because it causes tumours in nasal tissue at concentrations that exceed their detoxification capacity. As formaldehyde is released from N,N′,N′′-tris(β-hydroxypropyl)hexahydro-1,3,5-triazine, the substance could be classified in Carcinogen Category 4. However, because it is not possible to derive a MAK value for N,N′,N′′-tris(β-hydroxypropyl)hexahydro-1,3,5-triazine, the substance has been assigned to Carcinogen Category 2 and given 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 on the systemic bioavailability of N,N′,N′′-tris(β-hydroxypropyl)hexahydro-1,3,5-triazine and formaldehyde released by hydrolysis in tissues, there is no experimental evidence that the formaldehyde reaches the germ cells. Therefore, N,N′,N′′-tris(β-hydroxypropyl)hexahydro-1,3,5-triazine has been classified in Category 3 B for germ cell mutagens. The substance is a skin sensitizer in guinea pigs. Therefore, N,N′,N′′-tris(β-hydroxypropyl)hexahydro-1,3,5-triazine has been designated with “Sh” (for substances which cause sensitization of the skin). Skin contact is not expected to contribute significantly to systemic toxicity.

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