Trichloroethylene Implicated as Risk for Parkinsonism

By Judith Groch
LEXINGTON, Ky., Jan 8. -- Trichloroethylene is a probable risk factor for Parkinson's disease and parkinsonism, a study here found.
The finding came from a study of 31 workers at an industrial plant, including three workers with Parkinson's disease exposed to high levels of trichloroethylene, and from animal experiments, Don M. Gash, Ph.D., of the University of Kentucky, and colleagues reported online in the Annals of Neurology.
Trichloroethylene, a degreasing agent widely used in industry and the military, is also found in drinking water, surface water, and soil as a runoff from manufacturing sites. The chemical has been identified as an environmental contaminant by the Environmental Protection Agency.
One of the three workers with Parkinson's described 25 years of industrial exposure to trichloroethylene at a small industrial plant. He also said that two coworkers with long exposure to the chemical had also developed Parkinson's Disease.
Along with clinical evaluations of the index patient, who had no family history of the disease, and his two coworkers (one a woman) with Parkinson's, the researchers studied a cluster of 28 coworkers with Parkinson's and parkinsonism.
The workers had eight to 33 years of exposure to the chemical.
Exposure resulted from both inhalation and submerging unprotected arms and forearms in a chemical vat or touching parts that had been cleaned in it.
Neurological evaluations were conducted including a general physical and neurological exam and the Unified Parkinson's Disease Rating Scale. The investigators also measured fine motor speed and took an occupational history.
In addition, questionnaires about signs of Parkinson's Disease, such as slowness of voluntary movement, stooped posture, and trouble with balance, were mailed to 134 former workers.
Fourteen former workers who reported three or more parkinsonian signs worked close to the trichloroethylene source. They were significantly slower (up to 250%) in fine-motor hand movements than age-matched controls.
Thirteen workers reported no symptoms. Clinical exams revealed that they worked in the same area as the symptomatic workers or farther away from the chemical vat, thus respiratory exposure was their main contact.
However, their scores on the rating scale indicated some mild features of parkinsonism. As a group, their fine-motor hand movement times were significantly slower (P<0.0001) than age-matched controls, although they were faster than the group with symptoms.
While the clinical evaluations were underway, the researchers started rat studies 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, as this is a mechanism in other known environmental dopaminergic neurotoxins, they said.
Neurotoxic actions of trichloroethylene showed that oral administration of trichloroethylene for six weeks brought about selective Complex 1 mitochondrial impairment in the midbrain with concomitant striatonigral fiber degeneration and loss of dopamine neurons.
Converging evidence from a number of laboratories has implicated mitochondrial Complex 1 dysfunction as a central event in the degeneration of dopamine neurons in Parkinson's disease, the investigators said.
These results suggest that trichloroethylene joins other mitochondrial neurotoxins, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), and some pesticides as a risk factor for parkinsonism, Dr. Gash and colleagues said.
It is important, they said, to recognize that this study was not a large scale epidemiological investigation designed to address recall, case-findings, or other sources of bias. Nevertheless, these results demonstrate a strong potential link between chronic trichloroethylene exposure and parkinsonism.
Three coworkers with chronic dermal and inhalation exposure to trichloroethylene developed Parkinson's disease, and many coworkers with long exposure displayed features of parkinsonism, they said.
They pointed out that some trichloroethylene-exposed individuals developed frank Parkinson's, whereas others only had mild-to-moderate parkinsonism, suggesting the possible presence of comorbid factors.
"This would be consistent with the hypothesis that the progressive loss of dopamine neurons characterizing Parkinson's disease is due to multiple insults leading to the degeneration of the nigrostriatal dopamine system in the brain," they wrote. "We would broaden the hypothesis to include most manifestations of parkinsonism, including dyskinesia."
They added, "It will be important to follow the progression of movement disorders in this cohort over the next decade to more fully assess the long-term health risks from trichloroethylene exposure."
The authors declared to competing financial interests. The human studies were supported by endowment funds for Dr. Gash. The animal studies were supported in part through funding from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging (NIA). The neurochemical analysis was supported by the NIA.
Primary source: Annals of NeurologySource reference:Gash DM, et al "Trichloroethylene: parkinsonism and complex 1 mitochondrial neurotoxicity" Ann Neurol 2008: DOI: 10.1002/ana.21288.