Solvent exposures and Parkinson disease risk in twins.

OBJECTIVE: Several case reports have linked solvent exposure to Parkinson disease (PD), but few studies have assessed associations with specific agents using an analytic epidemiologic design. We tested the hypothesis that exposure to specific solvents is associated with PD risk using a discordant twin pair design. METHODS: Ninety-nine twin pairs discordant for PD ascertained from the National Academy of Sciences/National Research Council World War II Veteran Twins Cohort were interviewed regarding lifetime occupations and hobbies using detailed job task-specific questionnaires. Exposures to 6 specific solvents selected a priori were estimated by expert raters unaware of case status. RESULTS: Ever exposure to trichloroethylene (TCE) was associated with significantly increased risk of PD (odds ratio [OR], 6.1; 95% confidence interval [CI] 1.2-33; p = 0.034), and exposure to perchloroethylene (PERC) and carbon tetrachloride (CCl(4) ) tended toward significance (respectively: OR, 10.5; 95% CI, 0.97-113; p = 0.053; OR, 2.3; 95% CI, 0.9-6.1; p = 0.088). Results were similar for estimates of exposure duration and cumulative lifetime exposure. INTERPRETATION: Exposure to specific solvents may increase risk of PD. TCE is the most common organic contaminant in groundwater, and PERC and CCl(4) are also ubiquitous in the environment. Our findings require replication in other populations with well-characterized exposures, but the potential public health implications are substantial.

Rotenone, paraquat, and Parkinson's disease.

BACKGROUND: Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson's disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans. OBJECTIVES: Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans. METHODS: We assessed lifetime use of pesticides selected by mechanism in a case-control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controls:one case. RESULTS: In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR)=1.7; 95% confidence interval (CI), 1.0-2.8] including rotenone (OR=2.5; 95% CI, 1.3-4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2-3.6), including paraquat (OR=2.5; 95% CI, 1.4-4.7). CONCLUSIONS: PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally-those that impair mitochondrial function and those that increase oxidative stress-supporting a role for these mechanisms in PD pathophysiology.