Parkinson Disease: No Established Occupational Causes
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"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]
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"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]
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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."
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"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]
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". . . 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]
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"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]
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"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]
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"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"]
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"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]
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"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]
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"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]
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"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]
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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: 30 May, 2018
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