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

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.