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

MAK Value Documentation, addendum – 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 summarized and re-evaluated the data for N,N′,N′′-tris(β-hydroxyethyl)hexahydro-1,3,5-triazine [4719-04-4] with regard to its carcinogenicity and germ cell mutagenicity classifications, its ability to be absorbed through the skin and in order to derive an occupational exposure limit value (maximum concentration at the workplace, MAK value). Relevant studies were identified from a literature search and also unpublished study reports were used. N,N′,N′′-Tris(β-hydroxyethyl)hexahydro-1,3,5-triazine rapidly releases formaldehyde in dilute aqueous solution. The substance is highly irritating to corrosive to the skin and eyes of rabbits and to the upper respiratory tract, which is attributed to the formation of the irritating formaldehyde and 2-aminoethanol. There are no studies that investigated the carcinogenic effects of N,N′,N′′-tris(β-hydroxyethyl)hexahydro-1,3,5-triazine and its genotoxic potential in the upper respiratory tract or nose. Formaldehyde was classified in Carcinogen Category 4 because it causes tumours in nasal tissues at concentrations that exceed their detoxification capacity. As formaldehyde is released from N,N′,N′′-tris(β-hydroxyethyl)hexahydro-1,3,5-triazine, the substance could likewise be classified in Carcinogen Category 4. In a 28-day inhalation study in rats with an aerosol of N,N′,N′′-tris(β-hydroxyethyl)hexahydro-1,3,5-triazine, multifocal squamous metaplasia of the larynx and nose as well as degeneration of the bronchial epithelium were observed at the lowest concentration tested of 3 mg/m³ and above. Due to the severity of these effects, it is not possible to derive a NOAEC or a MAK value from this study. Moreover, a MAK value cannot be established in analogy to the MAK value set for gaseous formaldehyde because aerosol impaction aggravates the effects. The substance has thus 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 on the systemic bioavailability of N,N′,N′′-tris(β-hydroxyethyl)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-hydroxyethyl)hexahydro-1,3,5-triazine has been classified in Category 3 B for germ cell mutagens. Skin contact is not expected to contribute significantly to systemic toxicity.

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