Aromatic as well as aliphatic hydrocarbon solvent axonopathy

Peter Spencer, Min Sun Kim, Mohammad I. Sabri

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Superfund sites that contain mixtures of aromatic and aliphatic solvents represent an undefined health hazard. After prolonged exposure to relatively high levels of certain aliphatic solvents (e.g. n-hexane, 2-hexanone), humans and animals develop a dose-dependent neurodegeneration that occurs clinically as a symmetrical peripheral neuropathy. This is triggered by the action of 2,5-hexanedione (1,2-diacetylethane), a 1,4-diketone (γ-diketone) metabolite that targets proteins required for the maintenance of neuronal (and testicular Sertoli cell) integrity. Certain aromatic solvents (1,2-diethylbenzene, 1,2,4-triethylbenzene) cause electrophysiological changes consistent with sensorimotor neuropathy in rodents, but the underlying mechanisms and pathogenesis are unclear. Our recent studies show that the o-diacetyl derivative and likely metabolite of 1,2-diethylbenzene, 1,2-diacetylbenzene, behaves as a neurotoxic (aromatic) γ-diketone of high neurotoxic potency. Rats treated with 1,2-diacetylbenzene develop limb weakness associated with proximal, neurofilament-filled giant axonal swellings comparable to those seen in animals treated with the potent 3,4-dimethyl derivative of 2,5-hexanedione. The blue chromogen induced by treatment with 1,2-diacetylbenzene is under study as a possible urinary biomarker of exposure to aromatic solvents (e.g. 1,2-diethylbenzene, tetralin) with neurotoxic potential. Development and validation of sensitive new biomarkers, especially for non-cancer endpoints, will aid in assessing the health risk associated with exposure to hazardous substances at Superfund sites.

Original languageEnglish (US)
Pages (from-to)131-136
Number of pages6
JournalInternational Journal of Hygiene and Environmental Health
Volume205
Issue number1-2
StatePublished - 2002

Fingerprint

Hydrocarbons
Methyl n-Butyl Ketone
Biomarkers
Hazardous Substances
Diacetyl
Intermediate Filaments
Sertoli Cells
Health
Peripheral Nervous System Diseases
Rodentia
Extremities
Maintenance
1,2-diacetylbenzene
1,2-diethylbenzene
Proteins

Keywords

  • Biomarkers
  • Neuropathy
  • Neurotoxicity
  • Organic solvents
  • Superfund
  • Testicular toxicity

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Aromatic as well as aliphatic hydrocarbon solvent axonopathy. / Spencer, Peter; Kim, Min Sun; Sabri, Mohammad I.

In: International Journal of Hygiene and Environmental Health, Vol. 205, No. 1-2, 2002, p. 131-136.

Research output: Contribution to journalArticle

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