Fungicides as a risk factor for the development of neurological diseases and disorders in humans: a systematic review

Abstract

Although studies show that pesticides, especially insecticides, may be toxic to humans, publications on the neurological effects of fungicides are scarce. As fungicides are used widely in Brazil, it is necessary to gather evidence to support actions aimed at safely using of these chemicals. We investigated through a systematic review of publications on the use of fungicides and consequences of exposure related to nervous system diseases or neurological disorders in humans. The protocol review was registered on PROSPERO and followed the guidelines of the PRISMA-Statement. As far as it is known, there is no apparent systematic review in the literature on this topic. The search was comprised of the following databases: PubMed; Web of Science; Scopus and EMBASE, using groups of Mesh terms and strategies specific to each database. Thirteen articles were selected for this review. Regarding the substances analyzed in the studies, some reported the use of fungicides in general, without separating them by type, while others summarized the categories of all pesticides by their function (insecticides, herbicides, fungicides, etc.) or chemical class (dithiocarbamate, dicarboximide, inorganic, etc.). However, most of the articles referred to fungicides that contain the metal manganese (Mn) in their composition. As for neurological disorders, articles addressed Parkinson’s disease (PD), neurodevelopmental outcomes, extrapyramidal syndrome resembling PD, cognitive disorders, depression, neural tube defects, motor neurone disease, and amyotrophic lateral sclerosis. Most investigations pointed to exposure to fungicides, mainly maneb and mancozeb, leading to the development of at least one neurological disease, which suggests the need for further multicentric clinical trials and prospective studies for greater clarity of the research problem.

Keywords:

• Fungicide exposure
• nervous system disease
• agriculture
• population
• systematic review

Acknowledgements

The authors are thankful to the Postgraduate Program in Biosciences and Pathophysiology and State University of Maringá. The authors would like to thank the external reviewers selected by the journal, who are anonymous to the authors, and whose comments and suggestions were of enormous value in reviewing and structuring the manuscript. The authors wish to thank the research group at the Toxicology Laboratory, the Poison Control Center at the Universidade Estadual de Maringá, the Pathology Laboratory and the Epidemiology research group at the Universidade Estadual de Maringá for the timely support and internal review process to submit the manuscript. All authors have agreed to the final version of the manuscript and are responsible for all aspects of the work related to the accuracy and integrity of each part of the work, which is appropriately investigated and resolved.

Author contributions

S.A.G.M., A.M.S.K., and R.S.L. generated the idea and design of the study. R.S.L., R.G.A., D.T.P.S., N.G.O., T.S.S., S.A.G.M., A.M.S.K., and J.J.V.T. searched the literature in databases. R.S.L., R.G.A., D.T.P.S., N.G.O., and T.S.S. searched for articles, extracted data and wrote the results and discussion section. S.A.G.M., A.M.S.K., and J.J.V.T. evaluated the selected articles, wrote some part of manuscript and supervised all parts of the revision part of the manuscript. R.S.L., R.G.A., D.T.P.S., N.G.O., T.S.S., S.A.G.M., A.M.S.K., and J.J.V.T. reviewed the manuscript. RSL acted as the corresponding author.

Declaration of interest

Five of the authors are from the Toxicology Laboratory at the State University of Maringá and participate in the study group at the Poison Control Center at the same university. Two of the authors belong to the Epidemiology study group at the State University of Maringá and one of the authors belongs to the study group at the Pathology Laboratory at the State University of Maringa. The authors’ affiliation is mentioned on the cover, and the manuscript is the result of the author’s individual experience on the current topic over many years. All authors were involved in the process of preparing and reviewing the article, and no individuals other than the cited authors were involved in any stage of work on this manuscript. The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this article. The authors have not participated and do not anticipate participating in any legal, regulatory or defense proceedings related to the content of the article.

Additional information

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001.