Pesticides expenditures by farming type and incidence of Parkinson disease in farmers: A French nationwide study.

BACKGROUND: Professional pesticides exposure is associated with PD risk, but it remains unclear whether specific products, which strongly depend on farming type, are specifically involved. We performed a nationwide ecological study to examine the association of pesticides expenditures for the main farming types with PD incidence in French farmers. METHODS: We used the French National Health Insurance database to identify incident PD cases in farmers (2010-2015). We combined data on pesticides expenditures with the agricultural census to compute pesticides expenditures for nine farming types in 2000 in 3571 French cantons. The association between pesticides expenditures and PD age/sex standardized incidence was examined using multilevel Poisson regression, adjusted for smoking, neurologists' density, and deprivation index. RESULTS: 10,282 incident PD cases were identified. Cantons with the highest pesticides expenditures for vineyards without designation of origin were characterized by 16% (95% CI = 6-28%) higher PD incidence (p-trend corrected for multiple testing = 0.006). This association was significant in men and older farmers. There was no association with pesticides expenditures for other farming types, including vineyards with designation of origin. CONCLUSIONS: PD incidence increased significantly with pesticides expenditures in vineyards without designation of origin characterized by high fungicide use. This result suggests that agricultural practices and pesticides used in these vineyards may play a role in PD and that farmers in these farms should benefit from preventive measures aiming at reducing exposure. Our study highlights the importance of considering farming type in studies on pesticides and PD and the usefulness of pesticides expenditures for exposure assessment.

Agricultural activities and the incidence of Parkinson's disease in the general French population.

Most studies on pesticides and Parkinson's disease (PD) focused on occupational exposure in farmers. Whether non-occupational exposure is associated with PD has been little explored. We investigated the association between agricultural characteristics and PD incidence in a French nationwide ecologic study. We hypothesized that persons living in regions with agricultural activities involving more intensive pesticide use would be at higher risk. We identified incident PD cases from French National Health Insurance databases (2010-2012). The proportion of land dedicated to 18 types of agricultural activities was defined at the canton of residence level. We examined the association between agricultural activities and PD age/sex-standardized incidence ratios using multivariable multilevel Poisson regression adjusted for smoking, deprivation index, density of neurologists, and rurality (proportion of agricultural land); we used a false discovery rate approach to correct for multiple comparisons and compute q-values. We also compared incidence in clusters of cantons with similar agricultural characteristics (k-means algorithm). We identified 69,010 incident PD cases. Rurality was associated with higher PD incidence (p < 0.001). Cantons with higher density of vineyards displayed the strongest association (RRtop/bottom quartile = 1.102, 95% CI = 1.049-1.158; q-trend = 0.040). This association was similar in men, women, and non-farmers, stronger in older than younger persons, and present in all French regions. Persons living in the cluster with greatest vineyards density had 8.5% (4.4-12.6%) higher PD incidence (p < 0.001). In France, vineyards rank among the crops that require most intense pesticide use. Regions with greater presence of vineyards are characterized by higher PD risk; non-professional pesticides exposure is a possible explanation.

Combining crop-exposure matrices and land use data to estimate indices of environmental and occupational exposure to pesticides.

BACKGROUND: Exposure assessment represents a major challenge for studies on the relation between pesticides and health. OBJECTIVE: We developed a method combining information from crop-exposure matrices (CEMs) and land use data, in order to compute indices of environmental and occupational pesticide exposure. We illustrate our approach using French data (1979-2010). METHODS: We used CEMs for five crops (straw cereals, grain corn, corn fodder, potatoes, vineyards) that describe use (annual probability, frequency, intensity) of pesticide subgroups, chemical families, and active substances by region and time since 1960. We combined these data with land use data from agricultural censuses (1979, 1988, 2000, 2010) to compute indices of environmental and occupational pesticide exposure in cantons (small French administrative units). Indices of environmental exposure were calculated based on the area of each crop in the cantons, while indices of occupational exposure depended on combinations of crops in each farm from the cantons. To illustrate our approach, we selected a pesticide group (herbicides), chemical family of herbicides (phenoxyacetic acids), and active substance from the phenoxyacetic acids chemical family (2,4-D). RESULTS: The estimated proportion of the area of crops with CEMs and of farms sprayed with herbicides was close to 100% between 1979-2010, but the estimated average annual number of applications increased. There were decreasing time-trends for phenoxyacetic acids and 2,4-D over the same period for all indices of exposure. There was a high use of herbicides throughout France in 2010, except in the South coast. For phenoxyacetic acids and 2,4-D, the spatial distribution was heterogeneous for all indices of exposure, with the highest values in the Centre and North regions. IMPACT STATEMENT: Assessment of pesticide exposure is a key issue for epidemiological studies on their association with health outcomes. However, it presents some unique challenges, particularly for retrospective exposure and the investigation of chronic diseases. We present a method to compute indices of exposure by combining information from crop-exposure matrices for five crops and land use data. Specificities of environmental and occupational exposure are addressed using different methods. These methods are applied to pesticides used in agriculture in France for five crops (3 groups, 91 chemical families, 197 active substances) to produce indices at a small geographic scale from 1979 to 2010 for the whole metropolitan France. Besides using these indices in French epidemiological studies, our approach could be relevant for other countries.

Exposure of the general French population to herbicides, pyrethroids, organophosphates, organochlorines, and carbamate pesticides in 2014-2016: Results from the Esteban study.

Esteban is a nationwide cross-sectional study conducted in France in 2014-2016, including 2503 adults aged 18-74 years old and 1104 children aged 6-17 years old, as part of the French Human Biomonitoring programme. The present paper describes the biological levels of five families of pesticides analysed on random sub-samples of 900 adults and 500 children for urine concentrations, and 759 adults and 255 children for serum concentrations, and the determinants of exposure. Organophosphates, carbamates and herbicides were measured in urine by UPLC-MS/MS; chlorophenols and pyrethroids were measured in urine by GC-MS/MS; specific organochlorines were measured in serum by GC-HRMS. Multivariate analyses were performed to identify the determinants of exposure using a generalized linear model. Pyrethroid metabolites were quantified in 99% of adults and children, with the exeption of F-PBA, which was quantified in 31% of adults and 27% of children, respectively. Carbamates and some specific organophosphates were barely or not quantified. DMTP was quantified in 82% of adults and 93% of children, and γ-HCH (lindane) was quantified in almost 50% of adults and children. Concentration levels of pesticide biomarkers were consistent with comparable international studies, except for ß-HCH, DMTP, and the deltamethrin metabolite Br2CA, whose levels were sometimes higher in France. Household insecticide use and smoking were also associated with higher levels of pyrethroids. All pyrethroids concentration levels were below existing health-based HBM guidance values, HBM-GVsGenPop, except for 3-PBA, for which approximately 1% and 10% of children were above the lower and upper urine threshold values of 22 µg/L and 6.4 µg/L, respectively. Esteban provides a French nationwide description of 70 pesticide biomarkers for the first time in children. It also describes some pesticide biomarkers for the first time in adults, including glyphosate and AMPA. For the latter, urine concentration levels were overall higher in children than in adults. Our results highlight a possible beneficial impact of existing regulations on adult exposure to organochlorine and organophosphate pesticides between 2006 and 2016, as concentration levels decreased over this period.