Parkinson's Disease and Residential Exposure to Maneb and Paraquat From Agricultural Applications in the Central Valley of California

Department of Environmental Health Sciences, University of California, Berkeley, 94720-7360, USA.
American journal of epidemiology (Impact Factor: 5.23). 04/2009; 169(8):919-26. DOI: 10.1093/aje/kwp006
Source: PubMed

ABSTRACT Evidence from animal and cell models suggests that pesticides cause a neurodegenerative process leading to Parkinson's disease
(PD). Human data are insufficient to support this claim for any specific pesticide, largely because of challenges in exposure
assessment. The authors developed and validated an exposure assessment tool based on geographic information systems that integrated
information from California Pesticide Use Reports and land-use maps to estimate historical exposure to agricultural pesticides
in the residential environment. In 1998–2007, the authors enrolled 368 incident PD cases and 341 population controls from
the Central Valley of California in a case-control study. They generated estimates for maneb and paraquat exposures incurred
between 1974 and 1999. Exposure to both pesticides within 500 m of the home increased PD risk by 75% (95% confidence interval
(CI): 1.13, 2.73). Persons aged ≤60 years at the time of diagnosis were at much higher risk when exposed to either maneb or
paraquat alone (odds ratio = 2.27, 95% CI: 0.91, 5.70) or to both pesticides in combination (odds ratio = 4.17, 95% CI: 1.15,
15.16) in 1974–1989. This study provides evidence that exposure to a combination of maneb and paraquat increases PD risk,
particularly in younger subjects and/or when exposure occurs at younger ages.

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Available from: Sadie Costello, Sep 28, 2015
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    • "Evidence on the association of pesticides exposure and PD development is controversial [7] [8] [9] [10] [11]. In a series of studies , a group of researchers from California found positive associations of pesticides exposure and PD [12] [13] [14] [15]; Wang and colleagues, for instance, found higher risk for PD (OR 1.86, 95% CI 1.09; 3.18), associated with combined exposure to ziram, maneb, and paraquat [15]. Other studies found no evidence for pesticides as a risk factor of PD [8] [11]. "
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    ABSTRACT: The risk for developing Parkinson’s disease (PD) is a combination of multiple environmental and genetic factors. The Negev (Southern Israel) contains approximately 252.5 km 2 of agricultural cultivated fields (ACF). We aimed to estimate the prevalence and incidence of PD and to examine possible geographical clustering and associations with agricultural exposures. We screened all “Clalit” Health Services members in the Negev (70% of the population) between the years 2000 and 2012. Individual demographic, clinical, and medication prescription data were available. We used a refined medication tracer algorithm to identify PD patients. We used mixed Poisson models to calculate the smoothed standardized incidence rates (SIRs) for each locality. We identified ACF and calculate the size and distance of the fields from each locality. We identified 3,792 cases of PD. SIRs were higher than expected in Jewish rural localities (median SIR [95% CI]: 1.41 [1.28; 1.53] in 2001–2004, 1.62 [1.48; 1.76] in 2005–2008, and 1.57 [1.44; 1.80] in 2009–2012). Highest SIR was observed in localities located in proximity to large ACF (SIR 1.54, 95% CI 1.32; 1.79). In conclusion, in this population based study we found that PD SIRs were higher than expected in rural localities. Furthermore, it appears that proximity to ACF and the field size contribute to PD risk.
    Parkinson's Disease 09/2015; 2015(4):576564. DOI:10.1155/2015/576564 · 2.01 Impact Factor
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    • "Due to these observations, an environmental hypothesis of PD was derived stating that there are chemicals in the environment capable of selectively targeting the dopaminergic neurons of the substantia nigra (SNpc) [5]. In a recent paper, Costello et al. determined that geographical areas with high use of the pesticides maneb (MB) and paraquat (PQ) had a high prevalence of PD [1]. In addition, PQ in combination with the dithiocarbamates, ziram and MB, gives rise to an 80% "
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    ABSTRACT: Epidemiological studies indicate exposures to the herbicide paraquat (PQ) and fungicide maneb (MB) are associated with increased risk of Parkinson's disease (PD). Oxidative stress appears to be a premier mechanism that underlies damage to the nigrostriatal dopamine system in PD and pesticide exposure. Enhanced oxidative stress leads to lipid peroxidation and production of reactive aldehydes; therefore, we conducted proteomic analyses to identify carbonylated proteins in the striatum and cortex of pesticide-treated mice in order to elucidate possible mechanisms of toxicity. Male C57BL/6J mice were treated biweekly for 6 weeks with saline, PQ (10 mg/kg), MB (30 mg/kg), or the combination of PQ and MB (PQMB). Treatments resulted in significant behavioral alterations in all treated mice and depleted striatal dopamine in PQMB mice. Distinct differences in 4-hydroxynonenal-modified proteins were observed in the striatum and cortex. Proteomic analyses identified carbonylated proteins and peptides from the cortex and striatum, and pathway analyses revealed significant enrichment in a variety of KEGG pathways. Further analysis showed enrichment in proteins of the actin cytoskeleton in treated samples, but not in saline controls. These data indicate that treatment-related effects on cytoskeletal proteins could alter proper synaptic function, thereby resulting in impaired neuronal function and even neurodegeneration.
    Parkinson's Disease 09/2015; 2015:812532. DOI:10.1155/2015/812532 · 2.01 Impact Factor
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    • "Associations of paraquat and rotenone with PD have previously been reported in the parent Agricultural Health Study (Kamel et al., 2007) and in FAME (Tanner et al., 2011); our population is a subset of FAME, which is nested within the Agricultural Health Study. Paraquat has been associated with PD in other populations (Costello et al., 2009; Liou et al., 1997) and in a recent meta-analysis (Pezzoli and Cereda, 2013), although some studies have reported no effect (Engel et al., 2001; Hertzman et al., 1994). Relationships with trifluralin and permethrin have mainly been identified in experimental models. "
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    ABSTRACT: Pesticides have been associated with Parkinson's disease (PD), and protective gloves and workplace hygiene can reduce pesticide exposure. We assessed whether use of gloves and workplace hygiene modified associations between pesticides and PD. The Farming and Movement Evaluation (FAME) study is a nested case–control study within the Agricultural Health Study. Use of protective gloves, other PPE, and hygiene practices were determined by questionnaire (69 cases and 237 controls were included). We considered interactions of gloves and hygiene with ever-use of pesticides for all pesticides with ≥ 5 exposed and unexposed cases and controls in each glove-use stratum (paraquat, permethrin, rotenone, and trifluralin). 61% of respondents consistently used protective gloves and 87% consistently used ≥ 2 hygiene practices. Protective glove use modified the associations of paraquat and permethrin with PD: neither pesticide was associated with PD among protective glove users, while both pesticides were associated with PD among non-users (paraquat OR 3.9 [95% CI 1.3, 11.7], interaction p = 0.15; permethrin OR 4.3 [95% CI 1.2, 15.6] interaction p = 0.05). Rotenone was associated with PD regardless of glove use. Trifluralin was associated with PD among participants who used < 2 hygiene practices (OR 5.5 [95% CI 1.1, 27.1]) but was not associated with PD among participants who used 2 or more practices (interaction p = 0.02). Although sample size was limited in the FAME study, protective glove use and hygiene practices appeared to be important modifiers of the association between pesticides and PD and may reduce risk of PD associated with certain pesticides.
    Environment International 11/2014; 75. DOI:10.1016/j.envint.2014.11.002 · 5.56 Impact Factor
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