Paraquat and Parkinson’s disease: a systematic review and meta-analysis of observational studies

ABSTRACT

This investigation aimed to conduct a systematic review of the literature and meta-analysis to determine whether exposure to the herbicide paraquat was associated with the development of Parkinson’s disease (PD). Observational studies that enrolled adults exposed to paraquat with PD as the outcome of interest were searched in the PubMed, Embase, LILACS, TOXNET, and Web of Science databases up to May 2019. Two authors independently selected relevant studies, extracted data, and assessed methodological quality. The evidence certainty was assessed by the GRADE approach, which served as basis for a tentative causality assessment, supplemented by the Bradford Hill criteria when necessary. Results from nine case–control studies indicated that PD occurrence was 25% higher in participants exposed to paraquat. The only cohort investigation included demonstrated a non-significant OR of 1.08. Results from subgroup analyses also indicated higher PD frequency in participants that were exposed to paraquat for longer periods or individuals co-exposed with paraquat and any other dithiocarbamate. Data indicate apositive association between exposure to paraquat and PD occurrence, but the weight-of-evidence does not enable one to assume an indisputable cause–effect relationship between these two conditions. Better designed studies are needed to increase confidence in results.

Systematic Review Registration: PROSPERO CRD42017069994.

KEYWORDS:

• Paraquat
• Parkinson’s disease
• systematic review
• meta-analysis
• GRADE

Acknowledgments

We would like to thank Arthur Oscar Shelp and Cristiane Murta Ramalho Nascimento for their help during the development of the risk of bias criteria. We would also like to thank Marluci Betini for her help during the search strategy and Marcus Tolentino Silva for his help with Egger’s test. Carolina Vaccari and Regina El Dib have received a Brazilian Research Council (CNPq) scholarship (No. 134411/2015-3 and No. 310953/2015-4, respectively).

Competing Interests

All of the authors were associated with academic institutions when the paper was prepared. After the study had been finalized, the main author – Carolina Vaccari –became an employee at the FERST Consulting Company, which provides services in the toxicology field for private firms involved with the manufacturing and marketing of agrochemicals. None of the authors have appeared before regulatory agencies or participated in legal proceedings concerning paraquat safety.

Supplementary Material

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Additional information

Funding

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico [134411/2015-3,310953/2015-4].