title: Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA. dongash@email.uky.edu
authors.forename: Don M
authors.initials: DM
authors.lastname: Gash
authors.forename: Kathryn
authors.initials: K
authors.lastname: Rutland
authors.forename: Naomi L
authors.initials: NL
authors.lastname: Hudson
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Sullivan
authors.forename: Guoying
authors.initials: G
authors.lastname: Bing
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Cass
authors.forename: Jignesh D
authors.initials: JD
authors.lastname: Pandya
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Dong-Yong
authors.initials: DY
authors.lastname: Choi
authors.forename: Randy L
authors.initials: RL
authors.lastname: Hunter
authors.forename: Greg A
authors.initials: GA
authors.lastname: Gerhardt
authors.forename: Charlie D
authors.initials: CD
authors.lastname: Smith
authors.forename: John T
authors.initials: JT
authors.lastname: Slevin
authors.forename: T Scott
authors.initials: TS
authors.lastname: Prince
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016000:Cluster Analysis; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D042967:Electron Transport Complex I / Q000187:drug effects* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D016273:Occupational Exposure / Q000706:statistics & numerical data*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D012720:Severity of Illness Index; D012997:Solvents / Q000506:poisoning / Q000633:toxicity; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D023382:Toxicity Tests, Acute; D014241:Trichloroethylene / Q000506:poisoning / Q000633:toxicity*
chemical_list: D012997:Solvents; D014241:Trichloroethylene; D042967:Electron Transport Complex I; D004298:Dopamine