Rate of neurotoxicant exposure determines morphologic manifestations of distal axonopathy

Richard M. LoPachin, E. J. Lehning, L. A. Opanashuk, B. S. Jortner

Research output: Contribution to journalArticle

34 Citations (Scopus)

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. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)75-86
Number of pages12
JournalToxicology and Applied Pharmacology
Volume167
Issue number2
DOIs
StatePublished - Sep 1 2000

Fingerprint

Axons
Swelling
Poisons
Biomarkers
Research
Risk assessment
Toxicity
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Rate of neurotoxicant exposure determines morphologic manifestations of distal axonopathy. / LoPachin, Richard M.; Lehning, E. J.; Opanashuk, L. A.; Jortner, B. S.

In: Toxicology and Applied Pharmacology, Vol. 167, No. 2, 01.09.2000, p. 75-86.

Research output: Contribution to journalArticle

LoPachin, Richard M. ; Lehning, E. J. ; Opanashuk, L. A. ; Jortner, B. S. / Rate of neurotoxicant exposure determines morphologic manifestations of distal axonopathy. In: Toxicology and Applied Pharmacology. 2000 ; Vol. 167, No. 2. pp. 75-86.
@article{570c12dacd3f4162afcaccd0d81f609c,
title = "Rate of neurotoxicant exposure determines morphologic manifestations of distal axonopathy",
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. (C) 2000 Academic Press.",
author = "LoPachin, {Richard M.} and Lehning, {E. J.} and Opanashuk, {L. A.} and Jortner, {B. S.}",
year = "2000",
month = "9",
day = "1",
doi = "10.1006/taap.2000.8984",
language = "English (US)",
volume = "167",
pages = "75--86",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Rate of neurotoxicant exposure determines morphologic manifestations of distal axonopathy

AU - LoPachin, Richard M.

AU - Lehning, E. J.

AU - Opanashuk, L. A.

AU - Jortner, B. S.

PY - 2000/9/1

Y1 - 2000/9/1

N2 - 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. (C) 2000 Academic Press.

AB - 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. (C) 2000 Academic Press.

UR - http://www.scopus.com/inward/record.url?scp=0034283043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034283043&partnerID=8YFLogxK

U2 - 10.1006/taap.2000.8984

DO - 10.1006/taap.2000.8984

M3 - Article

C2 - 10964758

AN - SCOPUS:0034283043

VL - 167

SP - 75

EP - 86

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 2

ER -