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

J. A. Skare, N. J. Hewitt, E. Doyle, R. Powrie, C. Elcombe

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    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 beta-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.

    Original languageEnglish
    Pages (from-to)811-825
    Number of pages15
    JournalXenobiotica
    Volume39
    Issue number11
    DOIs
    Publication statusPublished - Nov 2009

    Keywords

    • Screening
    • hair dyes
    • oxidative metabolism
    • in vitro
    • BLADDER-CANCER RISK
    • CYTOCHROME-P-450 MONOOXYGENASES
    • HUMAN HEPATOCYTES
    • DOG BLADDER
    • RAT
    • 4-AMINOBIPHENYL
    • ARYLAMINES
    • ENZYMES
    • LIVER
    • MICE

    Cite this

    Skare, J. A., Hewitt, N. J., Doyle, E., Powrie, R., & Elcombe, C. (2009). Metabolite screening of aromatic amine hair dyes using in vitro hepatic models. Xenobiotica, 39(11), 811-825. https://doi.org/10.3109/00498250903134443
    Skare, J. A. ; Hewitt, N. J. ; Doyle, E. ; Powrie, R. ; Elcombe, C. / Metabolite screening of aromatic amine hair dyes using in vitro hepatic models. In: Xenobiotica. 2009 ; Vol. 39, No. 11. pp. 811-825.
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    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 beta-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.",
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    Skare, JA, Hewitt, NJ, Doyle, E, Powrie, R & Elcombe, C 2009, 'Metabolite screening of aromatic amine hair dyes using in vitro hepatic models', Xenobiotica, vol. 39, no. 11, pp. 811-825. https://doi.org/10.3109/00498250903134443

    Metabolite screening of aromatic amine hair dyes using in vitro hepatic models. / Skare, J. A.; Hewitt, N. J.; Doyle, E.; Powrie, R.; Elcombe, C.

    In: Xenobiotica, Vol. 39, No. 11, 11.2009, p. 811-825.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Metabolite screening of aromatic amine hair dyes using in vitro hepatic models

    AU - Skare, J. A.

    AU - Hewitt, N. J.

    AU - Doyle, E.

    AU - Powrie, R.

    AU - Elcombe, C.

    PY - 2009/11

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    N2 - 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 beta-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.

    AB - 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 beta-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.

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    KW - oxidative metabolism

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    KW - BLADDER-CANCER RISK

    KW - CYTOCHROME-P-450 MONOOXYGENASES

    KW - HUMAN HEPATOCYTES

    KW - DOG BLADDER

    KW - RAT

    KW - 4-AMINOBIPHENYL

    KW - ARYLAMINES

    KW - ENZYMES

    KW - LIVER

    KW - MICE

    U2 - 10.3109/00498250903134443

    DO - 10.3109/00498250903134443

    M3 - Article

    VL - 39

    SP - 811

    EP - 825

    JO - Xenobiotica

    JF - Xenobiotica

    SN - 0049-8254

    IS - 11

    ER -