Metabolite screening of aromatic amine hair dyes using in vitro hepatic models

Abstract

1. Aromatic amines and heterocyclic amines are widely used ingredients in permanent hair dyes. However, little has been published on their potential for oxidation via hepatic cytochrome P450s. Therefore, the authors screened nine such compounds for their potential to undergo oxidative metabolism in human liver microsomes.

2. Toluene-2,5-diamine (TDA), p-aminophenol, m-aminophenol, p-methylaminophenol, N,N′-bis(2-hydroxyethyl)-p-phenylenediamine, and 1-hydroxyethyl-4,5-diaminopyrazole showed no evidence of oxidative metabolism.

3. Oxidized metabolites of 4-amino-2-hydroxytoluene (AHT), 2-methyl-5- hydroxyethylaminophenol (MHEAP), and phenyl methyl pyrazolone (PMP) were detected, but there was no evidence of β-nicotinamide adenine dinucleotide phosphate (NADPH)-dependent covalent binding to microsomal protein, suggesting that these are not reactive metabolites.

4. Metabolism of AHT, MHEAP, PMP, and TDA was further studied in human hepatocytes. All these compounds underwent conjugation, but no oxidative metabolites were found.

5. The results suggest that none of the hair dye ingredients tested showed evidence of hepatic metabolism to potentially biologically reactive oxidized metabolites.

Keywords::

• Screening
• hair dyes
• oxidative metabolism
• in vitro

Acknowledgements

The authors would like to thank Dr Robert Strife, The Procter & Gamble Company, for technical assistance in the interpretation of the mass spectrometry results for 4-amino-2-hydroxytoluene (AHT) and for providing the hydroxymethyl-AHT standard. They also thank Dr Carsten Goebel, The Procter & Gamble Company, and Dr David Hein, University of Louisville, for a critical review of the manuscript.

Declaration of interest: The author J. A. Skare is an employee of the Procter & Gamble Company. The Procter & Gamble Company funded the studies described in the paper, and the author N. J. Hewitt participated in the preparation of the paper as a paid consultant to the Procter & Gamble Company. The hair dye ingredients studies in this paper are currently used in commercial products marketed by the Procter & Gamble Company. The authors alone are responsible for the content and writing of the paper.