N‐Methylaniline

MAK Value Documentation, addendum – Translation of the German version from 2017

  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 Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) of N‐methylaniline [100‐61‐8] considering all toxicity endpoints. Available publications and unpublished study reports are described in detail. Critical effect is the formation of methaemoglobin (MetHb). Adequate data in humans to derive a MAK value are not available; thus, data with rats are used. In rats, N‐methylaniline forms MetHb 2.7 times more efficiently than aniline. Based on the MAK value for aniline of 2 ml/m³, the MAK value for N‐methylaniline of 0.5 ml/m³ is confirmed. As the critical effect is systemic, Peak Limitation Category II is retained; as the half‐life in blood is unknown, the default excursion factor of 2 is also retained. N‐Methylaniline remains in Pregnancy Risk Group D because developmental toxicity studies are lacking. The substance does not induce mutations in bacteria, but is clastogenic in mammalian cells. Studies on genotoxicity in vivo have not been performed. Adequate data to assess the carcinogenic potential of N‐methylaniline are not available. Data for the metabolite aniline are used to assess the carcinogenic potential of N‐methylaniline. Aniline induces spleen tumours in rats, but not in mice. The putative mode of action is an indirect tumour development by induction of MetHb and haemolytic effects which result in erythrocyte toxicity and its consequences, perturbations in iron metabolism in the spleen. The metabolites phenylhydroxylamine and nitrosobenzene are mainly responsible for the erythrocyte toxicity of aniline. As nitrosobenzene is also a metabolite of N‐methylaniline, a similar mode of action has to be assumed for N‐methylaniline. Therefore, a non‐genotoxic mode of action is of prime importance and genotoxic effects play at most a minor part provided the MAK and BAT values are observed. Thus, N‐methylaniline is classified as a suspected carcinogen in Carcinogen Category 3B. Skin contact may contribute significantly to systemic toxicity and the “H” notation is retained. There are no clinical data concerning the sensitizing activity of the substance. Results of a local lymph node assay in mice were negative.

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