Metabolite screening of aromatic amine hair dyes usingin vitrohepatic models
Autor: | N. J. Hewitt, Robert Powrie, Julie A. Skare, Clifford R. Elcombe, Edward Doyle |
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Rok vydání: | 2009 |
Předmět: |
Stereochemistry
Health Toxicology and Mutagenesis Metabolite Hair Dyes Pyrazolone Oxidative phosphorylation Toxicology Biochemistry Mass Spectrometry Mice chemistry.chemical_compound medicine Animals Humans Amines Chromatography High Pressure Liquid Pharmacology chemistry.chemical_classification Aromatic amine General Medicine Metabolism Rats 4-Aminobiphenyl chemistry Hepatocytes Microsomes Liver Microsome Female Oxidation-Reduction NADP Drug metabolism medicine.drug |
Zdroj: | Xenobiotica. 39:811-825 |
ISSN: | 1366-5928 0049-8254 |
Popis: | 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. 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. 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 beta-nicotinamide adenine dinucleotide phosphate (NADPH)-dependent covalent binding to microsomal protein, suggesting that these are not reactive metabolites. Metabolism of AHT, MHEAP, PMP, and TDA was further studied in human hepatocytes. All these compounds underwent conjugation, but no oxidative metabolites were found. The results suggest that none of the hair dye ingredients tested showed evidence of hepatic metabolism to potentially biologically reactive oxidized metabolites. |
Databáze: | OpenAIRE |
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