Exposure Assessment of Pesticides and the Effect of Combinations of Pesticides on Parkinson's Disease

Due to the heavy and expanding agricultural use of neurotoxic pesticides suspected to affect dopaminergic neurons, it is imperative to closely examine the role of pesticides in the development of Parkinson's disease (PD). We recruited 357 incident PD cases and 752 population-based controls from 2000-2010 in the Central Valley of California and collected demographic, covariate, as well as residential and occupational address information. We utilized a geographic information system (GIS)-based exposure assessment tool to estimate historical ambient exposure to agricultural pesticides at residential and occupational addresses.Combined exposure to ziram, maneb, and paraquat at workplaces increased risk of PD three-fold and combined exposure to ziram and paraquat, excluding maneb exposure, was associated with an 80% increase in risk. Risk estimates for ambient workplace exposure were greater than exposures at residences and were especially high for younger onset PD patients and when exposed in both locations. We estimated a greater than two-fold increase in risk of developing PD for participants exposed to organophosphates, organochlorines, dithiocarbamates, and paraquat individually after adjusting for covariates. However after adjusting for other pesticides, only ambient exposure to organophosphates remained strongly associated, suggesting that pesticides from other classes have a high degree of co-exposure and may require combined exposure to affect PD risk. Longer duration of exposure and co-exposure to a large number of pesticides within the same year were both associated with strong increases in PD risk.Ambient exposure to each organophosphate separately increased the risk of developing PD. However, it is difficult to estimate the risk associated with an individual pesticide due to the likelihood that participants were exposed to combinations of these pesticides rather than any one single pesticide. Combinations of organophosphates with mitochondrial disrupting properties exhibited larger risk increases and exposure-response patterns were observed with exposure to an increasing number of these chemicals.Taken together, our results provide support that ambient co-exposure to pesticides contributes to the etiology of PD