By Rivka Sachdev, MD
Assistant Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: Preliminary evidence suggests trichloroethylene is a potential environmental risk factor for Parkinson’s disease. Further research is needed to confirm this association.
SOURCE: Dorsey ER, Zafar M, Lettenberger SE, et al. Trichloroethylene: An invisible cause of Parkinson’s disease? J Parkinsons Dis 2023;13:203-218.
The authors of this article discuss exposure to trichloroethylene (TCE) as an important yet under-researched environmental cause of Parkinson’s disease (PD). TCE is a clear, colorless, volatile, nonflammable chemical solvent that first was synthesized in the laboratory in 1869. By the 1920s, its commercial production was underway, and TCE-containing solvents increasingly were used for a variety of industrial applications, including dry cleaning, automotive care, degreasing and cleaning of metal parts, paint removal, furniture care, and others.
Although its toxic effects were becoming more recognized (particularly as a carcinogen), production and use of the solvent continued to increase in the 1960s, with peak production in the United States occurring in the 1970s. It even was used as an inhaled anesthetic until the Food and Drug Administration banned its use in 1977. By 1978, the concern was not only about toxicity by direct inhalation or dermal contact, but also about more widespread exposure via “vapor intrusion.” It was found that TCE could evaporate from contaminated soil and ground water, ultimately making its way into workplace buildings and nearby homes. Although TCE now is banned in the European Union and in two U.S. states (Minnesota and New York), it still is permitted for some uses in the United States (for example, vapor degreasing and spot dry cleaning) and for authorized industrial uses in the European Union. Indeed, exposure to TCE remains quite widespread.
According to the United States Environmental Protection Agency and the World Health Organization, TCE is carcinogenic by all routes of exposure. A meta-analysis found occupational exposure to be associated with excess indices of various cancers, including liver cancer, kidney cancer, prostate cancer, brain cancer (as well as other central nervous system tumors), non-Hodgkin’s lymphoma, and multiple myeloma.
In terms of Parkinson’s disease, a link between exposure to TCE and PD was suspected at least as far back as 1969, based on case studies. In more recent years, evidence has grown about TCE exposure as a risk factor for PD, although the evidence is considered preliminary. The authors of this article discuss seven cases, supporting the hypothesis that TCE increases the risk for developing PD.
Case 1 involves a former professional basketball player who was diagnosed with PD at age 36 years, 30 years after living at Camp Lejeune, NC, for three years as a child. The water at that camp was contaminated with TCE.
Next is the case of a retired navy captain who also lived at Camp Lejeune for about three to four years. She was diagnosed with PD at the age of 57 years, 30 years after having used the water (contaminated with TCE) for bathing, swimming, cooking, and drinking. In 2017, the U.S. Department of Veterans Affairs established that PD had a “presumptive service connection” for those like her who served at Camp Lejeune from 1953-1987.
Case 3 involves an endocrinologist who was diagnosed with PD at age 38 years. He had grown up in an upstate New York community that was heavily contaminated with TCE. Interestingly, two years prior to his diagnosis, his mother was diagnosed with breast cancer and three years after his diagnosis, his father was diagnosed with prostate cancer (they had lived in the same household in upstate New York).
The next case is a physicist and industry executive who was diagnosed with PD at age 85 years. He was exposed to TCE as a child on a farm, as a graduate student, and while working at the National Aeronautics and Space Administration and a computer manufacturing company (where TCE contaminated the soil and ground water). Nineteen years after his PD diagnosis, he developed breast cancer. (The authors also pointed out that 78 men who had lived at Camp Lejeune later were diagnosed with breast cancer.)
Case 5 involves a retired teacher who was diagnosed with PD at the age of 68. He was exposed to TCE when working in a print shop in the 1970s and 1980s. He is a LRRK 2 carrier (neither of his parents had PD, but his paternal grandfather did). Later, he was diagnosed with monoclonal gammopathy of undetermined significance (MGUS), a pre-malignant state associated with multiple myeloma.
The sixth case describes a man who worked in construction and with automotives (using degreasing chemicals) who was diagnosed with PD at the young age of 33 years. He was exposed to TCE while working in the military and in the automotive industry. Later, at the age of 53 years, he was diagnosed with glioblastoma.
Finally, case 7 involves a U.S. senator diagnosed with PD at the age of 70 years. He was exposed to TCE while serving in the Georgia Air National Guard from 1966-1972 (a period when the military, including the Air Force, used TCE to degrease airplanes). Four years after his PD diagnosis, he developed renal cell carcinoma.
In terms of how TCE mediates toxicity, the authors suggested it may be through mitochondrial dysfunction, a theory supported by animal studies, including ones showing that mitochondrial complex I activity is dysregulated in the midbrain of rodents exposed to TCE. The authors suggested that genetic risk factors may play a role in TCE-induced neurodegeneration, citing a 2021 study revealing that chronic exposure to TCE elevated the kinase activity of LRRK 2 in the striatum and substantia nigra of rats after three weeks. Degeneration of dopaminergic neurons was evidenced by six weeks.
COMMENTARY
The link between TCE exposure and PD still is being investigated. The authors acknowledged that the evidence for TCE as a risk factor for PD still is preliminary and that more research is needed to confirm an association and determine the mechanism by which TCE exposure increases the risk for PD. They concluded by emphasizing the need to develop strategies to reduce TCE exposure worldwide to protect individuals from serious health risks associated with this ubiquitous chemical. Specifically, they called for conducting more research, more cleaning and containment of contaminated sites, monitoring of TCE levels and communicating its risks to the public, banning of TCE, and encouraging providers to listen to the occupational/environmental components of a patient’s history. Currently, most clinicians are unaware of the harmful effects of TCE. We need to pay more attention to the role TCE may be playing in the widespread prevalence of PD.
