Redefining toxic distal axonopathies

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