Gash DM, Rutland K, Hudson NL, et al. Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity. Ann Neurol. 2008;63:184-92. [PubMed]

In addition to genetic influences, environmental factors play a role in the pathogenesis of idiopathic Parkinson’s disease. Historically this has been most clearly demonstrated by exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This compound causes mitochondrial damage in dopaminergic neurons of the substantia nigra; people exposed to it go on to develop PD.

Another compound, trichloroethylene (TCE), is a degreasing solvent most commonly used in tool and automobile production. It is also used in correction fluid, paint remover, and anesthetics. Exposure has been widespread due to its volatility; workers in industrial degreasing operations have the highest risk of exposure. But many people have been exposed either from air pollution near factories that use TCE or as a result of ground and surface water contamination from industrial discharges or improper disposal of industrial wastes in landfills. TCE has been described in a limited number of previous reports as a potential cause of PD. In the present report, TCE was initially implicated by an industrial worker as the cause of his development of PD-like symptoms. A cluster of 30 of his coworkers who had long-term chronic exposure to TCE, and who developed PD and parkinsonism, were subsequently analyzed for neurologic function, fine motor speed, and occupational history.

In a parallel study the researchers administered TCE to rats to directly determine if it caused damage to dopaminergic neurons in the substantia nigra, and if mitochondrial function in those cells was impaired. Diagnosis of PD in the workers was based on the presence of at least two of three signs: tremor at rest, rigidity, and bradykinesia, as well as a positive response to levodopa or dopamine. The index case and three coworkers who worked in the vicinity of the same work site were all chronically exposed to TCE through dermal or inhalation routes. Other workers in the same factory were surveyed for symptoms of parkinsonism. They all demonstrated signs of parkinsonism and had significantly slower hand movement than age-matched controls. Self-reporting symptomatic workers were mapped to work locations near the source of TCE, whereas survey respondents who denied symptoms worked at increasing distances from the TCE source. Nevertheless, these latter workers demonstrated slower hand movements than normal controls, although these movements were not as slow as in the symptomatic workers.

The TCE-exposed rats had significantly inhibited mitochondrial function in the substantia nigra, with lower complex 1 function than in vehicle-treated controls. Bioenergetic changes were seen only in mitochondria from the substantia nigra. Dopamine neurons in this region showed degenerative changes and reduced levels of tyrosine hydroxylase activity and reduced numbers of tyrosine hydroxylase–positive neurons. Increased levels of inclusions were present in the substantia nigra and dorsal motor nucleus but other neural systems appeared unaffected. Reduced levels of dopamine were also limited to cells of the substantia nigra.

Although possible comorbid factors remain to be identified for the factory workers, the clustering of greatest symptom severity near the source of TCE, together with the experimental results in rats, strongly link TCE exposure to development of PD and parkinsonism.