Redefining toxic distal axonopathies

Nerve damage classified as a central-peripheral distal axonopathy is produc ed by a variety of chemicals (e.g. acrylamide, n-hexane). Historically, axo n swelling and secondary degeneration have been considered the morphologic hallmarks of toxic axonopathies and substantial research has been devoted t oward deciphering corresponding molecular mechanisms. However, recent studi es from the author's laboratory investigating rate (mg toxicant/kg/day) and route (i.p. vs gavage) of intoxication have shown that swelling and degene ration were related to neurotoxicant dosing conditions (i.e. low-dose, subc hronic exposure) and not to development of neurophysiological deficits or c lassic behavioral toxicity. This suggests the presumed hallmarks of distal axonopathy are epiphenomena of uncertain pathophysiologic significance. The refore, the current definition of and chemical classification scheme for to xic distal axonopathies requires re-evaluation. (C) 2000 Elsevier Science I reland Ltd. All rights reserved.