Aromatic as well as aliphatic hydrocarbon solvent axonopathy.
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.
Spencer
Peter S
PS
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
Kim
Min Sun
MS
Sabri
Mohammad I
MI
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*
D015415:Biomarkers; D006256:Hazardous Waste; D012997:Solvents