Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity

Don M. Gash, Kathryn Rutland, Naomi L. Hudson, Patrick G. Sullivan, Guoying Bing, Wayne A. Cass, Jignesh D. Pandya, Mei Liu, Dong Yong Choi, Randy L. Hunter, Greg A. Gerhardt, Charlie D. Smith, John T. Slevin, T. Scott Prince

Research output: Contribution to journalArticlepeer-review

153 Scopus citations

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.

Original languageEnglish
Pages (from-to)184-192
Number of pages9
JournalAnnals of Neurology
Volume63
Issue number2
DOIs
StatePublished - Feb 2008

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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