1,2-Diacetylbenzene, the neurotoxic metabolite of a chromogenic aromatic solvent, induces proximal axonopathy

Min Sun Kim, Mohammad I. Sabri, Victor H. Miller, Robert J. Kayton, David A. Dixon, Peter S. Spencer

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Several widely used aromatic hydrocarbon solvents reportedly induce blue-green discoloration of tissues and urine in animals and humans. The chomophore has been proposed to result from a ninhydrin-like reaction with amino groups in proteins. The present study examines the neurotoxic property of 1,2-diacetylbenzene (1,2-DAB), the active metabolite of the chromogenic and neurotoxic aromatic solvent 1,2-diethylbenzene. Rats treated with 1,2-DAB, but not with the nonchromogenic isomer 1,3-DAB or with ninhydrin developed blue discoloration of internal organs, including the brain and spinal cord. Only 1,2-DAB induced limb weakness associated with nerve fiber changes, which were most prominent in spinal cord and spinal roots. Changes began with the formation of proximal, neurofilament-filled axonal swellings of the type seen after treatment with 3,4-dimethyl-2,5-hexanedione, a potent derivative of the active metabolite of the neurotoxic aliphatic hydrocarbon solvents n-hexane and methyl n-butyl ketone. These compounds are metabolized to a γ-diketone that forms pyrroles with target proteins, such as neurofilament proteins. A comparable mechanism is considered for 1,2-DAB, an aromatic γ-diketone.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalToxicology and Applied Pharmacology
Volume177
Issue number2
DOIs
StatePublished - Dec 1 2001

Keywords

  • Aromatic solvent
  • Axonopathy
  • Chromophore
  • Diacetylbenzene
  • Diethylbenzene
  • Green urine
  • Neuropathy
  • Ninhydrin
  • Tetralin

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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