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Parkinson’s disease linked to common chemical – global study

Investigators are calling for a complete ban on the chemical trichloroethylene (TCE), saying exposure has long been associated with an increased risk of Parkinson’s Disease (PD), cases of which have more than doubled in the past 30 years.

Without change, they will double again by 2040, experts warn.

TCE was once used widely in everything from producing decaf coffee to typewriter correction fluids and is also commonly used in dry cleaning, but has been highlighted in a recent study as potentially being a significant cause of many cases of Parkinson’s.

Having already been linked with increased risks of cancer and miscarriages, reports Science Alert, the chemical isn’t used as commonly as it once was, but the researchers, led by the University of Rochester, New York, suggest that its role in PD has been largely overlooked.

They pulled together evidence of the extent to which TCE has been used in industrial processes, reviewed previous studies linking the chemical with PD, and investigated several cases where TCE and the disease could well be linked.

“TCE is a simple, six-atom molecule that can decaffeinate coffee, degrease metal parts and dry clean clothes,” write the researchers, adding that the colourless chemical was first linked to Parkinsonism in 1969.

Its use peaked in the 1970s, when around 10m people in the US would have had contact with the chemical or something similar every day. It was being used to do everything from clean engines to anaesthetise patients.

While TCE use is now much more restricted in the EU and certain US states, globally it continues to be in demand, particularly from China. Even in areas where the chemical is banned, the researchers argue, people are still being exposed to it, due to the ongoing contamination of water and soil.

The hypothesis paper used seven individual case studies to make the connection between TCE exposure and PD, even if contact was decades earlier, and findings showed people in the military, as well as dozens of other professions – including mechanics, sewage workers, and painters – were at the greatest risk for exposure to the chemical.

The disease has numerous genetic risk factors, but most people diagnosed with it don’t carry any of these mutations.

Lead investigator Dr Ray Dorsey, professor of neurology at the University of Rochester, called PD “the world’s fastest-growing brain disease”, and told Medscape Medical News that it “may be largely preventable”.

“Countless people have died over generations from cancer and other disease linked to TCE (and) Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”

In the paper, which was published online in the Journal of Parkinson’s Disease, the authors said they see TCE as an “invisible force” associated with a 500% increased risk of this progressive and debilitating neurological condition.

The liquid is still used extensively in industrial processes and a multitude of everyday household products. It’s been banned in Europe, but is still legal in 48 US states. Only New York and Minnesota have outright prohibited its use, but the government has not, despite findings by the Environmental Protection Agency (EPA) as recently as 2022 that the chemical poses “an unreasonable risk to human health”.

TCE was first synthesised in the early 20th century. Concerns about its potential harm began to emerge almost immediately, when reports surfaced of people developing neurological symptoms after working with the chemical.

Since then, numerous studies have established its negative health effects including cancer, immune system disorders, and other neurological disorders besides Parkinson’s.

Circumstantial blame 

The evidence suggests that TCE damages brain cells that produce the neurotransmitter dopamine, which is responsible for muscle function and movement. It has also been shown to increase oxidative stress which leads to inflammation in the brain.

And additionally, reports the journal Psychiatrist.com, it may increase the formation of alpha-synuclein aggregates in the brain, a protein found in high levels in the grey matter of people with Parkinson’s.

TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the US and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected”, the researchers note.

“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dorsey said.

He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by ageing alone. “Certain pesticides…are possible causes but would not explain the high prevalence of PD in urban areas, as is the case in the US.”

Rather, he added, “other factors” are involved, and “TCE likely to be one such factor”.

Yet, despite widespread contamination and increasing industrial, commercial and military use, clinical investigations of TCE and PD have been limited.

To fill this knowledge gap, Dorsey and his co-authors of the book Ending Parkinson's Disease: A Prescription for Action, scrutinised studies focusing on the potential association of TCE and PD.

“Like many genetic mutations (e.g. Parkin) and other environmental toxicants…TCE damages the energy-producing parts of cells, i.e. the mitochondria,” said Dorsey.
TCE and PCE “likely mediate their toxicity through a common metabolite”. Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses”, the researchers hypothesise.

Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might partially explain the link to PD.

People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution”, they said.

They note that TCE contaminates up to one-third of US drinking water, has polluted the groundwater in more than 20 countries on five continents and is found in half of the 1 300 most toxic “Superfund” sites that are "part of a federal clean-up programme, including 15 in California’s Silicon Valley, where TCE was used to clean electronics”.

But there have been challenges with pinning the blame on TCE, the researchers said. The lag time between exposure and first symptoms can be up to 40 years. Many people don’t know, or don’t recall, how they may have come into contact with it.

That doesn’t make the threat any less urgent, they cautioned, calling for, among other measures, a complete ban on the substance as well as more concerted efforts to clean up and contain contaminated sites.

Commenting for Medscape Medical News, Dr Rebecca Gilbert, chief scientific officer, American Parkinson Disease Association (APDA), said the authors “are very frank about the limitations of this approach (illustrative cases) as proof of causation between PD and TCE exposure”.

Another limitation is that TCE exposure is very common, “as argued in the paper”. “But most people with exposure do not develop PD,” Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”

Gilbert, an associate professor of neurology at NYU Langone Medical Centre who was not involved with the study, acknowledges that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD”.

In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers”, she said. Therefore, the authors’ goals appear to be educating the public about known health risks; working to clean up known sites of contamination; and advocating to ban future use of TCE.

“These goals do not need to wait for (proof of) firm causation between TCE and PD,” she said.

Study details

Trichloroethylene: An Invisible Cause of Parkinson’s Disease?

Dorsey, E. Raya;   Zafar, Maryama; Lettenberger, Samantha;  Pawlik, Meghan;  Kinel, Dana; Frissen, Myrthec;  Schneider, Ruth; Kieburtz, Karla; Tanner, Caroline; De Miranda, Briana; Goldman, Samuel; Bloem, Bastiaan.

Published in the Journal of Parkinson's Disease on 14 March 2023

Abstract
The etiologies of Parkinson’s disease (PD) remain unclear. Some, such as certain genetic mutations and head trauma, are widely known or easily identified. However, these causes or risk factors do not account for the majority of cases. Other, less visible factors must be at play. Among these is a widely used industrial solvent and common environmental contaminant little recognised for its likely role in PD: trichloroethylene (TCE). TCE is a simple, six-atom molecule that can decaffeinate coffee, degrease metal parts, and dry clean clothes. Since it was first linked to Parkinsonism in 1969, four case studies involving eight individuals have linked occupational exposure to TCE to PD. In addition, a small epidemiological study found that occupational or hobby exposure to the solvent was associated with a 500% increased risk of developing PD. In multiple animal studies, the chemical reproduces the pathological features of PD.
Exposure is not confined to those who work with the chemical. TCE pollutes outdoor air, taints groundwater, and contaminates indoor air. The molecule, like radon, evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected. Despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited. Here, through a literature review and seven illustrative cases, we postulate that this ubiquitous chemical is contributing to the global rise of PD and that TCE is one of its invisible and highly preventable causes. Further research is now necessary to examine this hypothesis.

 

Journal of Parkinson’s Disease article – Trichloroethylene: An Invisible Cause of Parkinson’s Disease? (Open access)

 

Medscape article – What's Driving the 'World's Fastest-Growing' Brain Disease'? (Open access)

 

Psychiatrist.com article – 500% Rise in Parkinson’s Linked to a Common Dry Cleaning Chemical (Open access)

 

Science Alert article – Dry Cleaning Chemical Could Be Major Cause of Parkinson's, Scientists Warn (Open access)

 

See more from MedicalBrief archives:

 

Environmental factors worsen neurologic health – US review of 30 years’ research

 

Prostate drug associated with lower risk of Parkinson’s — large international analysis

 

Parkinson’s breakthrough: New disease-causing mechanism found

 

Evidence grows of air pollution link to neurodegenerative disease

 

 

 

 

 

 

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