Article

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: 4.98). 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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    • "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 · 5.66 Impact Factor
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    • "Similarly, rodent models of paraquat exposure are relatively acute, and generally conducted over the course of several weeks, a relatively small fraction of the rodent's lifetime (Liou et al., 1996; McCormack et al., 2002). Thus, neither current fly nor rodent models replicate the chronic time course of exposure seen in many patient populations (Costello et al., 2009). Moreover, most if not all Drosophila studies of acute paraquat exposure have utilized sucrose as a vehicle (Chaudhuri et al., 2007; Humphreys et al., 1993; Legan et al., 2008), which may increase "
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    ABSTRACT: The neurodegenerative effects of Parkinson's disease (PD) are marked by a selective loss of dopaminergic (DA) neurons. Epidemiological studies suggest that chronic exposure to the pesticide paraquat may increase the risk for PD and DA cell loss. However, combined exposure with additional fungicide(s) including maneb and/or ziram may be required for pathogenesis. To explore potential pathogenic mechanisms, we have developed a Drosophila model of chronic paraquat exposure. We find that while chronic paraquat exposure alone decreased organismal survival and motor function, combined chronic exposure to both paraquat and maneb was required for DA cell death in the fly. To initiate mechanistic studies of this interaction, we used additional genetic reagents to target the ubiquitin proteasome system, implicated in some rare familial forms of PD and the toxic effects of ziram. Genetic inhibition of E1 ubiquitin ligase, but not the proteasome itself, increased DA cell death in combination with maneb but not paraquat. These studies establish a model for long-term exposure to multiple pesticides, and support the idea that pesticide interactions relevant to PD may involve inhibition of protein ubiquitination.
    NeuroToxicology 09/2014; 44. DOI:10.1016/j.neuro.2014.08.005 · 3.05 Impact Factor
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    • "respectively. Two recent studies have identified specific long-lasting organochlorine pesticides (β- HCH, dieldrin) as increasing risk (Richardson et al., 2011; Weisskopf et al., 2010), while two others have identified paraquat and/or rotenone (Tanner et al., 2011; Costello et al., 2009). Recently the fungicide benomyl has been associated with PD (Fitzmaurice et al., 2013). "
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    ABSTRACT: Background: We previously screened 400 elderly Costa Ricans for neurodegenerative disease. Those reporting occupational pesticide exposure (18%) had an increased Parkinson's disease (PD) risk (OR 2.57, 95% CI 0.91-7.26), and worse cognition (Mini-Mental States Exam (MMSE) 24.5 versus 25.9 points, p=0.01). We subsequently measured long-lasting organochlorine pesticides (beta-HCH,DDE, DDT, and dieldrin) in a sub-sample (n=89). Dieldrin and beta-HCH have been linked to PD, and DDE to Alzheimer's disease. Methods: We ran regression models for MMSE and tremor-at-rest to assess associations with pesticides in 89 subjects. Results: The percent of beta-HCH, DDE, DDT (parent compound for DDE), and dieldrin above their limit of detection (LOD) were 100%, 93%, 75%, and 57%, respectively. Tremor-at-rest was found in 21 subjects, and the mean MMSE was 25. Those who reported occupational pesticide exposure (n=36) had more detectable dieldrin samples (p=0.005), and higher mean levels of dieldrin (p=0.01), than those not reporting exposure. Other pesticides did not differ between those with and without self-reported occupational exposure. There was a positive but non-significant trend of higher risk for tremor-at-rest with higher dieldrin (p=0.10 for linear trend). Neither DDE nor DDT showed a relationship with MMSE. However, after excluding two outliers with the lowest MMSE scores, higher DDT levels showed some modest association with lower MMSE (p=0.09 for linear trend). Conclusions: Our data are limited by small sample size. However, dieldrin was high in our population, has been previously linked to PD, and could be partly responsible for the excess PD risk seen in our population.
    Environmental Research 08/2014; 134C:205-209. DOI:10.1016/j.envres.2014.07.024 · 3.95 Impact Factor
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