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Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity

Authors

  • Don M. Gash PhD,

    Corresponding author
    1. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY
    2. The Morris K. Udall Parkinson's Disease Research Center of Excellence, College of Medicine, University of Kentucky, Lexington, KY
    • 317 Whitney-Hendrickson (MRISC) Department of Anatomy and Neurobiology, College of Medicine, University of Kentucky, 800 Rose Street, Lexington, KY 40536
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  • Kathryn Rutland MPH, MD,

    1. College of Public Health, University of Kentucky, Lexington, KY
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  • Naomi L. Hudson MPH,

    1. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY
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  • Patrick G. Sullivan PhD,

    1. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY
    2. The Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY
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  • Guoying Bing MD, PhD,

    1. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY
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  • Wayne A. Cass PhD,

    1. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY
    2. The Morris K. Udall Parkinson's Disease Research Center of Excellence, College of Medicine, University of Kentucky, Lexington, KY
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  • Jignesh D. Pandya PhD,

    1. The Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY
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  • Mei Liu MD,

    1. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY
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  • Dong-Yong Choi MS,

    1. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY
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  • Randy L. Hunter MS,

    1. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY
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  • Greg A. Gerhardt PhD,

    1. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY
    2. The Morris K. Udall Parkinson's Disease Research Center of Excellence, College of Medicine, University of Kentucky, Lexington, KY
    3. Department of Neurology, College of Medicine, University of Kentucky, Lexington, KY
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  • Charlie D. Smith MD,

    1. Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY
    2. Department of Neurology, College of Medicine, University of Kentucky, Lexington, KY
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  • John T. Slevin MD,

    1. The Morris K. Udall Parkinson's Disease Research Center of Excellence, College of Medicine, University of Kentucky, Lexington, KY
    2. Department of Neurology, College of Medicine, University of Kentucky, Lexington, KY
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  • T. Scott Prince MD

    1. College of Public Health, University of Kentucky, Lexington, KY
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Abstract

Objective

To analyze a cluster of 30 industrial coworkers with Parkinson's disease and parkinsonism subjected to long-term (8–33 years) chronic exposure to trichloroethylene.

Methods

Neurological evaluations were conducted on the 30 coworkers, including a general physical and neurological examination and the Unified Parkinson's Disease Rating Scale. In addition, fine motor speed was quantified and an occupational history survey was administered. Next, animal studies were conducted to determine whether trichloroethylene exposure is neurotoxic to the nigrostriatal dopamine system that degenerates in Parkinson's disease. The experiments specifically analyzed complex 1 mitochondrial neurotoxicity because this is a mechanism of action of other known environmental dopaminergic neurotoxins.

Results

The three workers with workstations adjacent to the trichloroethylene source and subjected to chronic inhalation and dermal exposure from handling trichloroethylene-soaked metal parts had Parkinson's disease. Coworkers more distant from the trichloroethylene source, receiving chronic respiratory exposure, displayed many features of parkinsonism, including significant motor slowing. Neurotoxic actions of trichloroethylene were demonstrated in accompanying animal studies showing that oral administration of trichloroethylene for 6 weeks instigated selective complex 1 mitochondrial impairment in the midbrain with concomitant striatonigral fiber degeneration and loss of dopamine neurons.

Interpretation

Trichloroethylene, used extensively in industry and the military and a common environmental contaminant, joins other mitochondrial neurotoxins, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and some pesticides, as a risk factor for parkinsonism. Ann Neurol 2007

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