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      Systematic literature review of the epidemiology of glyphosate and neurological outcomes

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          Abstract

          Purpose

          Human health risk assessments of glyphosate have focused on animal toxicology data for determining neurotoxic potential. Human epidemiological studies have not yet been systematically reviewed for glyphosate neurotoxicity hazard identification. The objective of this systematic literature review was to summarize the available epidemiology of glyphosate exposure and neurological outcomes in humans.

          Methods

          As of December 2021, 25 eligible epidemiological studies of glyphosate exposure and neurological endpoints were identified and assessed for five quality dimensions using guidance from the U.S. Environmental Protection Agency. Studies that assessed personal use of glyphosate were prioritized, whereas those assessing indirect exposure (other than personal use) were rated as low quality, since biomonitoring data indicate that indirect metrics of glyphosate exposure almost always equate to non-detectable glyphosate doses.

          Results

          Overall, the scientific evidence on glyphosate and neurotoxicity in humans is sparse and methodologically limited, based on nine included epidemiological studies of neurodegenerative outcomes (two high quality), five studies of neurobehavioral outcomes (two high quality), six studies of neurodevelopmental outcomes (none high quality), and five studies of other and mixed neurological outcomes (one high quality). The five high-quality studies showed no association between glyphosate use and risk of depression, Parkinson disease, or peripheral nerve conduction velocity. Results were mixed among the eight moderate-quality studies, which did not demonstrate consistent associations with any neurological endpoints or categories. Low-quality studies were considered uninformative about possible neurotoxic effects due primarily to questionable assessments of indirect exposure.

          Conclusions

          No association has been demonstrated between glyphosate and any neurological outcomes in humans. To move the state of science forward, epidemiological studies should focus on scenarios involving direct and frequent use of glyphosate while collecting information on validated health outcomes, concomitant agricultural exposures, and relevant personal characteristics.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00420-022-01878-0.

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          Most cited references40

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          The PRISMA 2020 statement: An updated guideline for reporting systematic reviews

          Matthew Page and co-authors describe PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.
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            THE ENVIRONMENT AND DISEASE: ASSOCIATION OR CAUSATION?

            A. B. Hill (1965)
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              Trends in glyphosate herbicide use in the United States and globally

              Background Accurate pesticide use data are essential when studying the environmental and public health impacts of pesticide use. Since the mid-1990s, significant changes have occurred in when and how glyphosate herbicides are applied, and there has been a dramatic increase in the total volume applied. Methods Data on glyphosate applications were collected from multiple sources and integrated into a dataset spanning agricultural, non-agricultural, and total glyphosate use from 1974–2014 in the United States, and from 1994–2014 globally. Results Since 1974 in the U.S., over 1.6 billion kilograms of glyphosate active ingredient have been applied, or 19 % of estimated global use of glyphosate (8.6 billion kilograms). Globally, glyphosate use has risen almost 15-fold since so-called “Roundup Ready,” genetically engineered glyphosate-tolerant crops were introduced in 1996. Two-thirds of the total volume of glyphosate applied in the U.S. from 1974 to 2014 has been sprayed in just the last 10 years. The corresponding share globally is 72 %. In 2014, farmers sprayed enough glyphosate to apply ~1.0 kg/ha (0.8 pound/acre) on every hectare of U.S.-cultivated cropland and nearly 0.53 kg/ha (0.47 pounds/acre) on all cropland worldwide. Conclusions Genetically engineered herbicide-tolerant crops now account for about 56 % of global glyphosate use. In the U.S., no pesticide has come remotely close to such intensive and widespread use. This is likely the case globally, but published global pesticide use data are sparse. Glyphosate will likely remain the most widely applied pesticide worldwide for years to come, and interest will grow in quantifying ecological and human health impacts. Accurate, accessible time-series data on glyphosate use will accelerate research progress. Electronic supplementary material The online version of this article (doi:10.1186/s12302-016-0070-0) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                echang@exponent.com
                Journal
                Int Arch Occup Environ Health
                Int Arch Occup Environ Health
                International Archives of Occupational and Environmental Health
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-0131
                1432-1246
                23 May 2022
                23 May 2022
                2023
                : 96
                : 1
                : 1-26
                Affiliations
                [1 ]GRID grid.418983.f, ISNI 0000 0000 9662 0001, Center for Health Sciences, , Exponent, Inc., ; 149 Commonwealth Dr, Menlo Park, CA 94025 USA
                [2 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, Department of Epidemiology and Biostatistics, , University of California, ; San Francisco, CA USA
                [3 ]GRID grid.418983.f, ISNI 0000 0000 9662 0001, Center for Health Sciences, , Exponent, Inc., ; Oakland, CA, USA
                [4 ]GRID grid.7048.b, ISNI 0000 0001 1956 2722, Department of Clinical Epidemiology, , University of Aarhus, ; Aarhus, Denmark
                Author information
                http://orcid.org/0000-0002-7169-157X
                Article
                1878
                10.1007/s00420-022-01878-0
                9823069
                35604441
                6e661d15-e295-4544-9cf2-42981cd2151c
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 January 2022
                : 26 April 2022
                Funding
                Funded by: Glyphosate Renewal Group
                Categories
                Review Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2023

                Occupational & Environmental medicine
                glyphosate,neurotoxicity,nervous system diseases,epidemiology,systematic review

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