Chronic Trichloroethylene Exposure Increases Risk for Parkinsonism

Susan Jeffrey

January 15, 2008

January 15, 2008 — A study involving a group of coworkers who were chronically exposed to trichloroethylene (TCE), a chemical used in industry, suggests such exposure is a strong risk factor for the development of parkinsonism.

Don M. Gash, PhD, John T. Sleven, MD, and colleagues from the University of Kentucky, in Lexington, followed up a patient with Parkinson's disease (PD) participating in a clinical trial at their institution who suspected his PD might be related to long-term exposure to the chemical in his job. They found a cluster of other employees of the same company who had symptoms of parkinsonism, some of whom were not aware of their subtle symptoms, and 2 other cases of Parkinson's disease in workers who had workstations adjacent to the index case. Subsequent animal work confirmed the neurotoxicity of TCE, particularly to neurons in the substantia nigra.

TCE, they write, "joins other mitochondrial neurotoxins, MPTP, and some pesticides as a risk factor for parkinsonism."

Their paper is published online December 21, 2007 in the Annals of Neurology.

A Growing Concern

A large proportion of the population has been exposed to TCE through its use as a degreasing agent in industrial or military applications, the use of products containing it, or consuming drinking water contaminated with the organic compound from the "numerous sites where it has been used or disposed," the authors write. In Europe, it was used for a time as an inhaled anesthetic, Dr. Gash noted.

TCE has been identified as an environmental contaminant in 852 of 1430 Superfund sites listed by the US Environmental Protection Agency as priority for cleanup and has also been widely found in drinking water as a result of leaching from these disposal sites. "A recent assessment of . . . health risks . . . by the National Academy of Sciences noted an association between chronic exposure to trichloroethylene and nervous system toxicity that is not well understood," the authors write.

The current study arose out of a clinical trial in Parkinson's disease carried out at the University of Kentucky. An in-depth medical history of these patients turned up 1 patient who felt his PD might be related to prior industrial exposure. The researchers then analyzed a cluster of 31 coworkers from the same company and found that 3 of them, including the index patient, fulfilled standard criteria for a diagnosis of Parkinson's disease. All those with PD worked directly with TCE, with chronic inhalation as well as dermal exposure from handling TCE-soaked metal parts, and all had workstations adjacent to each other.

Respiratory Exposure

They also examined 27 other coworkers, 14 of whom felt they had symptoms of parkinsonism and 13 of whom, by their own self-report, did not have such symptoms. These workers did not work directly with TCE and had workstations more distant from the material but had chronic respiratory exposure.

The 14 workers who felt they had symptoms did not meet Unified Parkinson's Disease Rating Scale criteria for PD but did have features of parkinsonism, including significant motor slowing in fine motor movements assessed using the Movement Analysis Panel.

"But what was surprising is that the 13 asymptomatic workers were also significantly slower, indicating that in working in the same factory, exposed to trichloroethylene, there may be some subtle to significant effects of long-term exposure on the nervous system," Dr. Gash said.

In addition to the clinical studies, they also conducted animal experiments to try to establish if TCE exposure could be neurotoxic to the nigrostriatal dopamine system that is affected in PD. The experiments looked specifically at complex 1 mitochondrial neurotoxicity, which is the purported mechanism of action of other known environmental dopaminergic neurotoxins such as pesticides and MPTP.

In young adult rats, they showed that oral administration of TCE for 6 weeks caused selective complex 1 mitochondrial impairment in the midbrain, along with striatonigral fiber degeneration and the loss of dopamine neurons.

Mitochondrial Damage the Common Factor?

Their work adds to converging evidence that injury to the mitochondria in dopaminergic neurons may be a common mechanism linking environmental exposures like pesticides and TCE with the development of PD, Dr. Gash said. Their group is currently exploring ways to upregulate mitochondrial function to see whether they might have some clinical potential in PD.

They also have made arrangements to follow these factory workers over time to see whether those with parkinsonism progress to Parkinson's disease. The factory is now closed, but the workers still live in the same community. "The median age at onset for PD is 55 years, and the median age of these workers is about 55 years, so we'll follow them to see if their symptoms continue to progress or not," he said.

The authors declare they have no financial conflict of interest.

Ann Neurol. Published online December 21, 2007. Abstract


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