Characterisation of the toxic metabolite(s) of naphthalene

Andrew S. Wilson, Carl D. Davis, Dominic P. Williams, Alan R Buckpitt, Munir Pirmohamed, B. Kevin Park

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


The toxicity of naphthalene and its metabolites has been investigated in vitro. Both naphthalene and its metabolite 1-naphthol were bioactivated by human hepatic microsomes to metabolite(s) which were toxic to mononuclear leucocytes (MNL). However, 1-naphthol was more cytotoxic than naphthalene (49.8 ± 13.9% vs. 19.0 ± 10.0% cell death; P < 0.01), indicating that the toxicity of naphthalene is dependent on the bioactivation of 1-naphthol. CYP2E1-induced rat liver microsomes increased metabolism of naphthalene by 13% compared to control microsomes with a concomitant increase in both 1-naphthol and dihydrodiol formation. The cytotoxicity of naphthalene but not of 1-naphthol was increased by CYP2E1 induction, indicating that separate enzymes are involved in the bioactivation of 1-naphthol. The metabolites of 1-naphthol, 1,2-naphthoquinone (51.4 ± 6.6% cell death) and 1,4-naphthoquinone (49.1 ± 3.4% cell death) were directly toxic to MNL and depleted glutathione to 1.0% of the control levels. Both quinones were also and enotoxic to human lymphocytes. In contrast, the primary metabolite of naphthalene, the 1,2-epoxide (0-100 μM) was neither cytotoxic nor genotoxic, and did not deplete glutathione. In conclusion, our data suggests that the cytotoxicity and genotoxicity of naphthalene is associated with the formation of quinones from 1-naphthol rather than naphthalene-1,2-epoxide.

Original languageEnglish (US)
Pages (from-to)233-242
Number of pages10
Issue number3
StatePublished - Dec 18 1996


  • 1-Naphthol
  • CYP2E1
  • Naphthalene
  • Naphthalene 1,2-epoxide
  • Naphthoquinones
  • Toxicity

ASJC Scopus subject areas

  • Toxicology


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