Aromatic as well as aliphatic hydrocarbon solvent axonopathy

Authors: Spencer P.S.^{1, 2}; Kim M.S.¹; Sabri M.I.^{1, 2}

Source: International Journal of Hygiene and Environmental Health, Volume 205, Numbers 1-2, March 2002 , pp. 131-136(6)

Publisher: Urban & Fischer

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 (-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) -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.

Keywords: Superfund; neurotoxicity; organic solvents; biomarkers; neuropathy; testicular toxicity

Language: English

Document Type: Original article

DOI: http://dx.doi.org/10.1078/1438-4639-00138

Affiliations: 1: Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon, USA 2: Department of Neurology, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA

Publication date: 2002-03-01

• In this: publication
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• In this Subject: Microbiology ,  Ecology ,  Public Health ,  Toxicology
• By this author: Spencer P.S. ;  Kim M.S. ;  Sabri M.I.

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