alexa Rate of neurotoxicant exposure determines morphologic manifestations of distal axonopathy.
General Science

General Science

Journal of Forensic Research

Author(s): LoPachin RM, Lehning EJ, Opanashuk LA, Jortner BS, LoPachin RM, Lehning EJ, Opanashuk LA, Jortner BS

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Abstract Exposure to a variety of agricultural, industrial, and pharmaceutical chemicals produces nerve damage classified as a central-peripheral distal axonopathy. Morphologically, this axonopathy is characterized by distal axon swellings and secondary degeneration. Over the past 25 years substantial research efforts have been devoted toward deciphering the molecular mechanisms of these presumed hallmark neuropathic features. However, recent studies suggest that axon swelling and degeneration are related to subchronic low-dose neurotoxicant exposure rates (i.e., mg toxicant/kg/day) and not to the development of neurophysiological deficits or behavioral toxicity. This suggests these phenomena are nonspecific and of uncertain pathophysiologic relevance. This possibility has significant implications for research investigating mechanisms of neurotoxicity, development of exposure biomarkers, design of risk assessment models, neurotoxicant classification schemes, and clinical diagnosis and treatment of toxic neuropathies. In this commentary we will review the evidence for the dose-related dependency of distal axonopathies and discuss how this concept might influence our current understanding of chemical-induced neurotoxicities. Copyright 2000 Academic Press. This article was published in Toxicol Appl Pharmacol and referenced in Journal of Forensic Research

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