Paraquat and Parkinson's disease: A systematic review protocol according to the OHAT approach for hazard identification
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Background: Parkinson's disease (PD) is a progressive neurodegenerative condition that has genetic susceptibility, aging, and exposure to certain chemicals as risk factors. In recent decades, epidemiological and experimental studies have investigated the role of pesticides in the development of PD, in particular that of the herbicide paraquat. Here, we, therefore, aim to systematically review the association between paraquat exposure and PD. Methods: Observational studies (cohort, case-control, and cross-sectional) eligible for this systematic review will enroll any participant who was occupationally and/or environmentally exposed to paraquat. Experimental studies, including in vivo and in vitro assays designed to assess neurotoxicological endpoints or mechanisms of paraquat neurotoxicity, will also be eligible. Outcomes of interest include the following: PD diagnosis; neurobehavioral, biochemical, and/or morphological alterations; and cellular, biochemical, and/or molecular pathways to oxidative stress. Using terms to include all forms of paraquat combined with PD, the following electronic databases will be searched: PubMed, EMBASE, LILACS, Toxnet, and Web of Science, without restrictions as to language, year, or status of publication. A team of reviewers will independently select potential titles and abstracts, extract data, assess risk of bias, and determine the overall quality of evidence for each outcome using the Office of Health Assessment and Translation (OHAT) approach for systematic reviews and evidence integration. Dichotomous data will be summarized as odds ratios, and continuous data will be given as mean differences, both with their respective 95% confidence intervals. Discussion: This is the first time that the OHAT systematic review protocol will be applied to investigate a possible causal association between exposure to paraquat and PD. Results from this study could serve as basis for regulatory agencies to define paraquat levels of concern, supporting its risk assessment process. Systematic review registration: PROSPERO CRD42016050861.