Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity

Ann Neurol. 2008 Feb;63(2):184-92. doi: 10.1002/ana.21288.

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Cluster Analysis
  • Corpus Striatum / drug effects
  • Corpus Striatum / pathology
  • Corpus Striatum / physiopathology
  • Dopamine / metabolism
  • Electron Transport Complex I / drug effects*
  • Electron Transport Complex I / metabolism
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Occupational Exposure / statistics & numerical data*
  • Parkinson Disease, Secondary / chemically induced*
  • Parkinson Disease, Secondary / diagnosis
  • Parkinson Disease, Secondary / physiopathology
  • Rats
  • Rats, Inbred F344
  • Severity of Illness Index
  • Solvents / poisoning
  • Solvents / toxicity
  • Substantia Nigra / drug effects
  • Substantia Nigra / pathology
  • Substantia Nigra / physiopathology
  • Toxicity Tests, Acute
  • Trichloroethylene / poisoning
  • Trichloroethylene / toxicity*

Substances

  • Solvents
  • Trichloroethylene
  • Electron Transport Complex I
  • Dopamine