Elsevier

Environment International

Volume 107, October 2017, Pages 100-110
Environment International

Environmental exposure to pesticides and the risk of Parkinson's disease in the Netherlands

https://doi.org/10.1016/j.envint.2017.07.001Get rights and content

Highlights

  • Environmental exposure to four a priori selected pesticides was not significantly associated with PD.

  • A broad screen revealed increased PD risk for a group of 21 (related) pesticides.

  • Results were suggestive for an association between bulb cultivation and PD risk.

  • Findings should be seen a hypothesis generating and as leads for future research.

Abstract

Background

Exposure to pesticides has been linked to Parkinson's disease (PD), although associations between specific pesticides and PD have not been well studied. Residents of rural areas can be exposed through environmental drift and volatilization of agricultural pesticides.

Objectives

Our aim was to investigate the association between lifetime environmental exposure to individual pesticides and the risk of PD, in a national case-control study.

Methods

Environmental exposure to pesticides was estimated using a spatio-temporal model, based on agricultural crops around the residential address. Distance up to 100 m from the residence was considered most relevant, considering pesticide drift potential of application methods used in the Netherlands. Exposure estimates were generated for 157 pesticides, used during the study period, of which four (i.e. paraquat, maneb, lindane, benomyl) were considered a priori relevant for PD.

Results

A total of 352 PD cases and 607 hospital-based controls were included. No significant associations with PD were found for the a priori pesticides. In a hypothesis generating analysis, including 153 pesticides, increased risk of PD was found for 21 pesticides, mainly used on cereals and potatoes. Results were suggestive for an association between bulb cultivation and PD.

Conclusions

For paraquat, risk estimates for the highest cumulative exposure tertile were in line with previously reported elevated risks. Increased risk of PD was observed for exposure to (a cluster of) pesticides used on rotating crops. High correlations limited our ability to identify individual pesticides responsible for this association. This study provides some evidence for an association between environmental exposure to specific pesticides and the risk of PD, and generates new leads for further epidemiological and mechanistic research.

Introduction

Parkinson disease (PD) is an idiopathic neurodegenerative disease, which is second most prevalent worldwide after Alzheimer's Disease. Decreased motor function is one of the main symptoms, caused by the progressive degeneration of dopaminergic neurons in the substantia nigra, resulting in dopamine deficiency (Wirdefeldt et al., 2011). Motor symptoms become apparent when roughly 30% of dopaminergic neurons are lost, but several non-motor symptoms have been reported to precede motor symptoms and PD diagnosis by several years to decades (Tolosa and Pont-Sunyer, 2011, Pont-Sunyer et al., 2015). Research indicates that PD is associated with aging and gender, and familial aggregation studies support the role of genetics. However, these genetic factors appear to be mainly associated with early-onset PD (Martin et al., 2011). Environmental factors have been suggested as potentially involved in the etiology of PD, especially for older-onset PD cases (Wirdefeldt et al., 2011).

Pesticides are one of the exposures frequently linked to PD. Occupational exposure to pesticides has rather consistently been associated with an increased risk of PD, and a meta-analysis found a 60% increased risk for being ever exposed (van der Mark et al., 2012). Besides occupational exposure to pesticides, several studies also investigated environmental residential exposure to pesticides, utilizing spatial data on agricultural land-use in geographic information systems (GIS) and data on pesticide use (Nuckols et al., 2007, Brody et al., 2002). Although environmental exposure to pesticides is expected to be lower than exposure in occupational settings, the number of potentially exposed individuals will be higher, including possibly more susceptible subgroups (e.g. children, elderly, subjects with preexisting conditions and poor health). Positive associations between environmental exposure to pesticides and PD risk have been reported, although these studies are mainly limited to the USA (California) (Wang et al., 2014, Costello et al., 2009). Only few epidemiological studies have investigated the association between exposure to individual pesticides and PD.

The Netherlands is unique in terms of dense agriculture and a high population density and a substantial part of the general population therefore may be exposed to (low) concentrations of pesticides in the environment originating from agricultural applications. We have previously developed a spatio-temporal model for the Netherlands to estimate environmental pesticide exposure at the residential addresses, going back to 1961 (Brouwer et al., 2017).

In the current study, we extend on previous work by studying the association between PD risk and residential exposure to pesticides in a European setting, focusing both on pesticides previously suggested to be potentially associated with PD, and a broad screen of pesticides used in the Dutch agricultural sector from 1961 to 2010. This work is part of a large hospital-based case-control study on PD in the Netherlands (van der Mark et al., 2014a).

Section snippets

Cases and controls

Details of the case-control study have been described previously (van der Mark et al., 2014a). In brief, cases and controls were recruited in five hospitals, covering four regions of the Netherlands, between 2010 and 2012 (Fig. 1). Patients with a first PD diagnosis between January 2006 and December 2011 were considered and their medical files were reviewed by a neurologist to confirm case diagnosis. Controls were selected from patients attending the same neurology departments between January

Results

In accordance with the known higher prevalence of PD among men, we observed a higher percentage of male PD cases (63%). The median age at diagnosis was 67 years (Table 1). As previously described, cases were more often never-smokers, and those who did smoke smoked less and quitted earlier (van der Mark et al., 2014a). Furthermore, cases more often had white-collar jobs and lived in neighborhoods with a smaller percentage of low income inhabitants than controls. A family history of PD occurred

Discussion

In our primary analysis we observed no significant associations between lifetime environmental exposure to four a priori selected pesticides (i.e. paraquat, maneb, lindane and benomyl) within 100 m from the residence and the risk of PD. The elevated ORs in the highest cumulative exposure tertiles can be seen as suggestive, however, as well as the significant associations found between cumulative exposure to paraquat and lindane and PD, when considering specific time windows of exposure. In a

Conclusions

In summary, we investigated the association between lifetime environmental exposure to individual pesticides and PD, in a hospital based case-control study in the Netherlands. Environmental exposure to four a priori selected pesticides was not significantly associated with PD risk, but for paraquat, risk estimates were in line with previously reported elevated risks. This study found increased risk of PD with exposure to (a cluster of) 21 pesticides mainly used on two rotating crops. High

Competition of financial interests

None declared.

Conflict of interest

The authors declare no conflict of interest.

Acknowledgements

This work was supported by Stichting Internationaal Parkinson Fonds, The Netherlands [2007-18].

References (31)

  • J.A. Firestone et al.

    Occupational factors and risk of Parkinson's disease: a population-based case-control study

    Am. J. Ind. Med.

    (2010)
  • A.G. Fitzmaurice et al.

    Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease

    Proc. Natl. Acad. Sci. U. S. A.

    (2013)
  • FOCUS

    Working group on pesticides in air

  • H.J. Heusinkveld et al.

    Azole fungicides disturb intracellular Ca2 + in an additive manner in dopaminergic PC12 cells

    Toxicol. Sci.

    (2013)
  • Kadaster

    Key-Registry of Addresses and Buildings (BAG) of the Netherlands

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