N-Phenyl-2-naphthylamine

MAK Value Documentation, addendum – Translation of the German version from 2021

  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) summarized and re-evaluated the data for the carcinogenicity and germ cell mutagenicity of N-phenyl-2-naphthylamine [135-88-6]. Relevant studies were identified from a literature search. N-Phenyl-2-naphthylamine is used as antioxidant e.g. in rubber and lubricants. N-Phenyl-2-naphthylamine is metabolized to 2-naphthylamine, a well-known human bladder carcinogen. 2-Naphthylamine exerts its carcinogenic potential after enzymatic conversion to reactive metabolites able to form adducts with macromolecules such as DNA or haemoglobin. As 2-naphthylamine-haemoglobin adducts were found after oral administration of N-phenyl-2-naphthylamine to rats, this shows that N-phenyl-2-naphthylamine is activated to carcinogenic metabolites. The study concluded that approximately 1% (absolute) of the 2-naphthylamine that originates from N-phenyl-2-naphthylamine can be further metabolized. As occupational exposure to N-phenyl-2-naphthylamine may lead to the formation of 2-naphthylamine, and this in turn may induce the development of bladder tumours, N-phenyl-2-naphthylamine has been classified in Carcinogen Category 1. Exposure-risk relationships for the induction of bladder tumours by N-phenyl-2-naphthylamine and 2-naphthylamine are established. In analogy to 2-naphthylamine, N-phenyl-2-naphthylamine is regarded as a germ cell mutagen and has been classified in Category 3 A for germ cell mutagens. N-Phenyl-2-naphthylamine is absorbed via the skin in small amounts. As subsequent metabolic activation to the carcinogen 2-naphthylamine is likely, N-phenyl-2-naphthylamine has been designated with “H”. The data for skin sensitizing effects confirm the “Sh” designation. There is no data on a potential sensitization of the airways.

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