Parkinson Disease: No Established Occupational Causes

  1. "Parkinson's disease (PD) is a debilitating degenerative disorder that affects up to 2% of persons over age 65. PD is a disease involving multiple systems and brain regions; but most clinically appreciable features are related to motor symptoms, including rest tremor, bradykinesia, postural instability, and gait disturbance. PD is the predominant form of parkinsonism, which also includes motor disorders secondary to stroke affecting basal ganglia, medications, and a few toxicants, e.g. solvents and carbon monoxide poisoning. The underlying cause of motor symptoms associated with PD is dopamine (DA) deficiency due to loss of dopaminergic neurons, primarily in the substantia nigra pars compacta (SNpc). Proteinaceous inclusions, known as Lewy bodies and neurites, in surviving neurons are the pathologic hallmarks of PD." [Solvents and Parkinson disease: a systematic review of toxicological and epidemiological evidence]

  2. "Parkinson disease (PD) is a debilitating neurodegenerative motor disorder, with its motor symptoms largely attributable to loss of dopaminergic neurons in the substantia nigra. The causes of PD remain poorly understood, although environmental toxicants may play etiologic roles. Solvents are widespread neurotoxicants present in the workplace and ambient environment. Case reports of parkinsonism, including PD, have been associated with exposures to various solvents, most notably trichloroethylene (TCE). Animal toxicology studies have been conducted on various organic solvents, with some, including TCE, demonstrating potential for inducing nigral system damage. However, a confirmed animal model of solvent-induced PD has not been developed. Numerous epidemiologic studies have investigated potential links between solvents and PD, yielding mostly null or weak associations. An exception is a recent study of twins indicating possible etiologic relations with TCE and other chlorinated solvents, although findings were based on small numbers, and dose-response gradients were not observed. At present, there is no consistent evidence from either the toxicological or epidemiologic perspective that any specific solvent or class of solvents is a cause of PD. Future toxicological research that addresses mechanisms of nigral damage from TCE and its metabolites, with exposure routes and doses relevant to human exposures, is recommended. Improvements in epidemiologic research, especially with regard to quantitative characterization of long-term exposures to specific solvents, are needed to advance scientific knowledge on this topic." [Solvents and Parkinson disease: a systematic review of toxicological and epidemiological evidence]

  3. The authors of this 2013 paper, Edward A. Lock, Jing Zhang, and Harvey Checkoway, also state, "Thus far, as the toxicology findings in rats with TCE have all come from one group in the same institution (Gash et al., 2008; Liu et al. 2010; Sauerbeck et al., 2012); thus, confirmation by other research groups is needed."

  4. "The focus on pesticides was initially prompted by recognition that the active metabolite of MPTP (MPP+) is structurally similar to the herbicide paraquat. Epidemiological findings are suggestive of associations with insecticides and herbicides, although consistent evidence implicating any specific pesticides is lacking." [Solvents and Parkinson disease: a systematic review of toxicological and epidemiological evidence]

  5. ". . . the clinical features of manganism and PD have considerable overlap, whereas deposition of manganese as well as associated brain damage occurs preferentially in brain regions other than the SNpc, at least in the cases exposed to high concentrations of manganese." [Solvents and Parkinson disease: a systematic review of toxicological and epidemiological evidence]

  6. "The available evidence from human and nonhuman primate studies using behavioral, neuroimaging, neurochemical, and neuropathological end points provides strong support to the hypothesis that, although excess levels of Mn accumulation in the brain results in an atypical form of parkisonism, this clinical outcome is not associated with the degeneration of nigrostriatal dopaminergic neurons as is the case in PD." [Manganese and Parkinson's disease: a critical review and new findings]

  7. "In fact, chronic occupational exposures by inhalation may lead to injury to the central nervous system (CNS), with the most serious effect being manganism, an occupational disease previously mistaken for Parkinson’s disease." [Synthesis of scientific knowledge on the health risks following occupational exposure to manganese]

  8. "Because manganese is a paramagnetic element, magnetic resonance imaging (MRI) can identify where manganese accumulates in the brain. In humans, manganese preferentially accumulates in the globus pallidus, followed by the substantia nigra pars reticularis, the corpus striatum, pineal gland, olfactory bulb, and substantia nigra pars compacta. This contrasts with PD, where the substantia nigra pars compacta is the first site to degenerate. Also, manganism involves impairment in GABA-related pathways, whereas PD does not. Manganism may be associated with some effect on dopamine pathways but does not respond to treatment with L-dopa, whereas PD shows severe impairment of dopamine metabolism and improves with administration of L-dopa." [ACGIH 2013 Update of "Manganese, Elemental and Inorganic Compounds"]

  9. "Welding and manganese exposure are not associated with increased PD risk. Possible explanations for the inverse association between welding and PD include confounding by smoking, healthy worker effect, and hormesis." [Associations of welding and manganese exposure with Parkinson disease: review and meta-analysis]

  10. "The present study examines welding occupation and mortality from neurodegenerative diseases among men in the United States using the National Cause of Death databases 1985 to 1999. Information was abstracted from death certificates for states that collected data on occupation. Of 4,252,490 men who died during the study period, 107,773 had welding-related occupations. Multivariable logistic regression models were used to calculate mortality odds ratios (MOR) and 95% confidence intervals (CI) for odds of dying from Parkinson's disease or other neurodegenerative diseases among men who were welders as compared with men of other occupations, adjusting for attained age, race, region of residence, and year of death. During the study period, 49,174 deaths were attributed to Parkinson's disease, 54,892 to Alzheimer's disease, and 19,018 to presenile dementia. There was no evidence of an increased odds of Parkinson's disease mortality among welders as compared with men with other occupations (MOR = 0.83, 95% CI 0.78-0.88)." [Welding occupations and mortality from Parkinson's disease and other neurodegenerative diseases among United States men, 1985-1999]

  11. "Among a Danish population, there was no increased odds of hospitalizations related to Parkinson's disease among 6000 welders compared with the general population. In a nationwide study of more than 49,000 welders and cutters in Sweden there was no evidence of an increased rate of Parkinslon's disease (RR - 0.89, 95% CD 0.79-0.99) or any disorder of the basal ganglia (RR = 0.91, 95% CI 0.81-1.01) compared with the general population." [Welding occupations and mortality from Parkinson's disease and other neurodegenerative diseases among United States men, 1985-1999]

  12. "Epidemiological studies suggest that some pesticides might constitute a risk factor for Parkinson's disease (PD). However, risk assessment cannot be performed in the current experimental animal models because they use non-natural pathways of pesticide exposure, such as intraperitoneal or intravenous injection, that might bypass body defences. A new model based on daily inoculation of neurotoxins in the nasal cavity of C57BL/6 mice for 30 days was used to evaluate risk of three complex I inhibitors, 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP), rotenone and paraquat. These compounds displayed very different effects on motor activity, striatal dopamine and dihydroxyphenylacetic acid (DOPAC) levels and loss of dopaminergic neurons. MPTP-treated mice developed motor deficits that correlated with a severe depletion of striatal dopamine levels, and loss of tyrosine hydroxylase staining in substantia nigra and striatum. By contrast, rotenone-treated mice or rats were asymptomatic. Paraquat induced severe hypokinesia and vestibular damage but did not alter the nigrostriatal system. The new animal model described here, based on chronic intranasal inoculation of neurotoxicants, provides a new tool to assess the potential danger of environmental toxins as risk factors for development of PD." [Chronic inhalation of rotenone or paraquat does not induce Parkinson's disease symptoms in mice or rats]

  13. Concerning the difference between Idiopathic Parkinson Disease (IPD) and parkinsonism, see this web page. "Although an interaction between genetic and environmental factors has been reported, the etiology of IPD remains unknown. In contrast, the association between parkinsonism and chemical exposure, including manganese, has been well established." [APHA] For people living past the age of 80, 10% have IPD. [Merck Manual] See the Haz-Map page on Manganism.

See Arc Welding, Manganese, and Manganism.

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Last Editied: 15 March, 2015  

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