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Journal of Parkinson's Disease 2023The 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... (Review)
Review
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.
Topics: Animals; Trichloroethylene; Parkinson Disease; Solvents; Risk Factors
PubMed: 36938742
DOI: 10.3233/JPD-225047 -
IARC Monographs on the Evaluation of... 1976
Review
Topics: Animals; Carcinogens; Cats; Dogs; Drug Evaluation, Preclinical; Environmental Exposure; Female; Haplorhini; Humans; Kidney; Lethal Dose 50; Liver; Male; Maximum Allowable Concentration; Mice; Organ Specificity; Rats; Species Specificity; Trichloroethylene; Water Pollutants, Chemical
PubMed: 825436
DOI: No ID Found -
Journal of Occupational Medicine. :... Mar 1974
Review
Topics: Accident Prevention; Animals; Breath Tests; Chromatography; Drug Synergism; Environmental Exposure; Ethanol; Eye Diseases; Humans; Male; Maximum Allowable Concentration; Medical Records; Memory; Perception; Psychomotor Disorders; Psychophysiologic Disorders; Reaction Time; Solvents; Spectrophotometry, Infrared; Trichloroethylene
PubMed: 4593984
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1995
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Humans; Solvents; Trichloroethylene
PubMed: 9139130
DOI: No ID Found -
Reviews of Environmental Contamination... 1988
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IARC Monographs on the Evaluation of... Oct 1979
Review
Topics: Air Pollutants; Anesthesia; Animals; Carcinogens; Embryo, Mammalian; Embryo, Nonmammalian; Female; Fishes; Humans; Male; Mice; Neoplasms, Experimental; Pregnancy; Rats; Risk; Teratogens; Trichloroethylene; Water Pollutants, Chemical
PubMed: 397178
DOI: No ID Found -
Environmental Health Perspectives May 2000A major focus in the study of metabolism and disposition of trichloroethylene (TCE) is to identify metabolites that can be used reliably to assess flux through the... (Review)
Review
A major focus in the study of metabolism and disposition of trichloroethylene (TCE) is to identify metabolites that can be used reliably to assess flux through the various pathways of TCE metabolism and to identify those metabolites that are causally associated with toxic responses. Another important issue involves delineation of sex- and species-dependent differences in biotransformation pathways. Defining these differences can play an important role in the utility of laboratory animal data for understanding the pharmacokinetics and pharmacodynamics of TCE in humans. Sex-, species-, and strain-dependent differences in absorption and distribution of TCE may play some role in explaining differences in metabolism and susceptibility to toxicity from TCE exposure. The majority of differences in susceptibility, however, are likely due to sex-, species-, and strain-dependent differences in activities of the various enzymes that can metabolize TCE and its subsequent metabolites. An additional factor that plays a role in human health risk assessment for TCE is the high degree of variability in the activity of certain enzymes. TCE undergoes metabolism by two major pathways, cytochrome P450 (P450)-dependent oxidation and conjugation with glutathione (GSH). Key P450-derived metabolites of TCE that have been associated with specific target organs, such as the liver and lungs, include chloral hydrate, trichloroacetate, and dichloroacetate. Metabolites derived from the GSH conjugate of TCE, in contrast, have been associated with the kidney as a target organ. Specifically, metabolism of the cysteine conjugate of TCE by the cysteine conjugate ss-lyase generates a reactive metabolite that is nephrotoxic and may be nephrocarcinogenic. Although the P450 pathway is a higher activity and higher affinity pathway than the GSH conjugation pathway, one should not automatically conclude that the latter pathway is only important at very high doses. A synthesis of this information is then presented to assess how experimental data, from either animals or from (italic)in vitro (/italic)studies, can be extrapolated to humans for risk assessment. (italic)Key words(/italic): conjugate beta-lyase, cysteine glutathione, cytochrome P450, glutathione (italic)S(/italic)-transferases, metabolism, sex dependence, species dependence, tissue dependence, trichloroethylene.
Topics: Absorption; Animals; Cytochrome P-450 Enzyme System; Glutathione; Hazardous Substances; Health; Humans; Oxidation-Reduction; Risk Factors; Solvents; Tissue Distribution; Trichloroethylene
PubMed: 10807551
DOI: 10.1289/ehp.00108s2177 -
Journal of Toxicology and Environmental... Jan 1977Trichloroethylene (TCE) has been an industrial chemical of some importance for the past 50 years. First synthesized by Fischer in 1864, TCE has enjoyed considerable... (Review)
Review
Trichloroethylene (TCE) has been an industrial chemical of some importance for the past 50 years. First synthesized by Fischer in 1864, TCE has enjoyed considerable industrial usage as a degreaser and limited medical use as an inhalation anesthetic and analgesic. This TCE overview provides a narrative survey of the reference literature. Highlights include history, nomenclature, physical and chemical properties, manufacture, analysis, uses, metabolism, toxicology, carcinogenic potential, exposure routes, recommended standards, and conclusions. Chemically, TCE is a colorless, highly volatile liquid of molecular formula C2HCl3. Autoxidation of the unstable compound yields acidic products. Stabilizers are added to retard decomposition. TCE's multitude of industrial uses center around its highly effective fat-solvent properties. Metabolically, TCE is transformed in the liver to trichloroacetic acid, trichloroethanol, and trichloroethanol glucuronide; these breakdown products are excreted through the kidneys. Most toxic responses occur as a result of industrial exposures. TCE affects principally the central nervous system (CNS). Short exposures result in subjective symptoms such as headache, nausea, and incoordination. Longer exposures may result in CNS depression, hepatorenal failure, and increased cardiac output. Cases of sudden death following TCE exposure are generally attributed to ventricular fibrillation. Current interest in TCE has focused on recent experimental data that implicate TCE as a cause of hepatocellular carcinoma in mice. No epidemiological data are available that demonstrate a similar action in humans. The overall population may be exposed to TCE through household cleaning fluids, decaffeinated coffee, and some spice extracts. The NIOSH recommended standard for TCE is 100 ppm as a time-weighted average for an 8-hr day, with a maximum allowable peak concentration of 150 ppm for 10 min.
Topics: Anesthetics; Animals; Biotransformation; Carcinogens; Cats; Chemistry; Dogs; Drug Interactions; Drug Stability; Ethanol; Food; Haplorhini; History, 20th Century; Humans; Intestinal Absorption; Mice; Rabbits; Rats; Glycine max; Substance-Related Disorders; Trichloroethylene
PubMed: 403297
DOI: 10.1080/15287397709529469 -
Giornale Italiano Di Medicina Del Lavoro 1991Trichloroethylene (TCE), a synthetic compound widely used in many occupational and non-occupational settings, is one of the leading environmental contaminants. In this... (Review)
Review
Trichloroethylene (TCE), a synthetic compound widely used in many occupational and non-occupational settings, is one of the leading environmental contaminants. In this paper, current information on sources, human exposure, metabolism, toxicology and health impact of TCE is reviewed. The central nervous system is the major target for TCE toxicity. This compound, however, can also exert toxic effects on other tissues and organs, for example the myocardium, the kidney and the liver. Several rodent bioassays indicate that TCE is a carcinogen for laboratory animals. Human carcinogenicity, however, is still controversial as there are limited epidemiological studies available for assessment and important species differences in metabolism that make extrapolation from animal studies more challenging. Current regulatory standards are discussed in connection with the analysis of technical and medical prevention.
Topics: Animals; Humans; Lethal Dose 50; Mutagens; Neoplasms; Neoplasms, Experimental; Occupational Diseases; Occupational Exposure; Trichloroethylene
PubMed: 1845454
DOI: No ID Found -
International Journal of Dermatology Mar 1977
Topics: Dermatitis, Exfoliative; Dermatitis, Occupational; Humans; Intestinal Absorption; Skin Absorption; Trichloroethylene
PubMed: 139379
DOI: 10.1111/j.1365-4362.1977.tb01837.x