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Review
. 2023;13(2):203-218.
doi: 10.3233/JPD-225047.

Trichloroethylene: An Invisible Cause of Parkinson's Disease?

E Ray Dorsey  1   2 , Maryam Zafar  1 , Samantha E Lettenberger  1 , Meghan E Pawlik  1 , Dan Kinel  1   2 , Myrthe Frissen  3 , Ruth B Schneider  1   2 , Karl Kieburtz  1   2 , Caroline M Tanner  4 , Briana R De Miranda  5 , Samuel M Goldman  6 , Bastiaan R Bloem  3
Affiliations
Review

Trichloroethylene: An Invisible Cause of Parkinson's Disease?

E Ray Dorsey et al. J Parkinsons Dis. 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 recognized 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. The colorless chemical was first linked to parkinsonism in 1969. Since then, 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.

Keywords: Air pollution; Parkinson’s disease; chemical water pollution; environment; indoor air pollution; solvents; tetrachloroethylene; trichloroethylene; water pollution.

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Conflict of interest statement

Dr. Dorsey has received honoraria for speaking at American Academy of Neurology, American Neurological Association, Excellus BlueCross BlueShield, International Parkinson’s and Movement Disorders Society, National Multiple Sclerosis Society, Northwestern University, Physicians Education Resource, LLC, PRIME Education, LLC, Stanford University, Texas Neurological Society, and Weill Cornell; received compensation for consulting services from Abbott, Abbvie, Acadia, Acorda, Bial-Biotech Investments, Inc., Biogen, Boehringer Ingelheim, California Pacific Medical Center, Caraway Therapeutics, Curasen Therapeutics, Denali Therapeutics, Eli Lilly, Genentech/Roche, Grand Rounds, Huntington Study Group, Informa Pharma Consulting, Karger Publications, LifeSciences Consultants, MCM Education, Mediflix, Medopad, MedRhythms, Merck, Michael J. Fox Foundation, NACCME, Neurocrine, NeuroDerm, NIH, Novartis, Origent Data Sciences, Otsuka, Physician’s Education Resource, Praxis, PRIME Education, Roach, Brown, McCarthy & Gruber, Sanofi, Seminal Healthcare, Spark, Springer Healthcare, Sunovion Pharma, Theravance, Voyager and WebMD; research support from Biogen, Biosensics, Burroughs Wellcome Fund, CuraSen, Greater Rochester Health Foundation, Huntington Study Group, Michael J. Fox Foundation, National Institutes of Health, Patient-Centered Outcomes Research Institute, Pfizer, PhotoPharmics, Safra Foundation, and Wave Life Sciences; editorial services for Karger Publications; stock in Included Health, stock in Mediflix and ownership interests in SemCap.

Dr. Schneider has received compensation for consulting services from Escape Bio and Parkinson’s Foundation; research support from Acadia Pharmaceuticals, Biohaven Pharmaceuticals, the Michael J. Fox Foundation for Parkinson’s Research, National Institutes of Health, Parkinson Study Group, and CHDI Foundation.

Dr. Kieburtz has research support from NIH (NINDS, NCATS) and the Michael J Fox Foundation. He is paid to serve on DSMBs of studies for Janssen, Lilly, and Roche/Genentech. He receives payments from Hoover Brown LLC and Clintrex Research Corp, and has equity interests in both. He also has equity interests in Biohaven, Inhibikase, Modality.AI and Safe Therapeutics LLC.

Dr. Tanner has received has received grant support from the NIH, the Michael J Fox Foundation, the Department of Defense, the Parkinson Foundation, the Marcus Program in Precision Medicine, Gateway LLC, Roche-Genentech, Biogen, Bioelectron Technology Corporation; personal compensation as a consultant/scientific advisory board /data & safety monitoring board member for CNS Ratings, Cadent, Adamas, Biogen, Neurocrine, Kyowa Kirin, Jazz/Cavion, Lundbeck and the Australian Parkinson’s Mission.

Dr. De Miranda is funded by the National Institutes for Environmental Health Sciences (R00ES029986).

Dr. Goldman has received research support from the Michael J. Fox Foundation, the National Institutes of Health, the Agency for Toxic Substances and Disease Registry (ATSDR), the Health Resources and Services Administration (HRSA), the US Department of Defense, and the Veterans Health Administration.

Prof. Bloem currently serves as co-Editor in Chief for the Journal of Parkinson’s Disease but was not involved in any way in the peer review process of this editorial. He serves on the editorial board of Practical Neurology and Digital Biomarkers, has received honoraria from serving on the scientific advisory board for Abbvie, Biogen and UCB, has received fees for speaking at conferences from AbbVie, Zambon, Roche, GE Healthcare and Bial, and has received research support from the Netherlands Organization for Scientific Research, the Michael J Fox Foundation, UCB, Not Impossible, the Hersenstichting Nederland, the Parkinson’s Foundation, Verily Life Sciences, Horizon 2020 and the Parkinson Vereniging (all paid to the institute).

Figures

Fig. 1a
Fig. 1a
Trichloroethylene (TCE) chemical structure [84].
Fig. 1b
Fig. 1b
The history of trichloroethylene (TCE) [15, 85]. EPA, Environmental Protection Agency; FDA, Food and Drug Administration.
Fig. 2a
Fig. 2a
Top ten exporters and importers of trichloroethylene, 2020 [33].
Fig. 2b
Fig. 2b
Countries with published studies of sites of groundwater TCE contamination [89].
Fig. 3a
Fig. 3a
U.S. cities that released the most TCE into the air, 1987 [35].
Fig. 3b
Fig. 3b
U.S. cities that released the most TCE into the air, 2020 [35].
Fig. 4
Fig. 4
Possible modes of exposure to trichloroethylene in the environment.
See this image and copyright information in PMC

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