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 focus our investigation on pesticide use in
California’s heavily agricultural central valley by utilizing a unique pesticide use
reporting system. From 2001 to 2007, we enrolled 362 incident PD cases and 341 controls living in
the Central Valley of California. Employing our geographic information system model, we estimated
ambient exposures to the pesticides ziram, maneb, and paraquat at work places and residences from
1974 to 1999. At workplaces, combined exposure to ziram, maneb, and paraquat increased risk of PD
three-fold (OR: 3.09; 95% CI: 1.69, 5.64) and combined exposure to ziram and paraquat, excluding
maneb exposure, was associated with a 80% increase in risk (OR:1.82; 95% CI: 1.03, 3.21). Risk
estimates for ambient workplace exposure were greater than for exposures at residences and were
especially high for younger onset PD patients and when exposed in both locations. Our study is the
first to implicate ziram in PD etiology. Combined ambient exposure to ziram and paraquat as well as
combined ambient exposure to maneb and paraquat at both workplaces and residences increased PD risk
substantially. Those exposed to ziram, maneb, and paraquat together experienced the greatest
increase in PD risk. Our results suggest that pesticides affecting different mechanisms that
contribute to dopaminergic neuron death may act together to increase the risk of PD
considerably.