title: Aromatic as well as aliphatic hydrocarbon solvent axonopathy.
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 (gamma-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) gamma-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.
authors.affiliation: Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, 3181 S. W. Sam Jackson Park Road, Portland, Oregon 97201, USA. spencer@ohsu.edu
authors.forename: Peter S
authors.initials: PS
authors.lastname: Spencer
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Mohammad I
authors.initials: MI
authors.lastname: Sabri
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D006256:Hazardous Waste; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced*; D012997:Solvents / Q000009:adverse effects* / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D006256:Hazardous Waste; D012997:Solvents