![]() ![]() The most comprehensive biomonitoring study for glyphosate is the Farm Family Exposure Study (FFES) (Mandel et al. The common assumption across all of these exposure metrics is that they provide a valid indication of glyphosate entering the body of persons classified as exposed.īiomonitoring for glyphosate sheds light on the validity of these various exposure definitions and provides an estimation of the potential range of corresponding doses (namely, the amount of chemical that is biologically internalized). Some studies use an ecological indirect exposure definition, such as total weight of a pesticide applied annually to certain crops within a state or county. Other studies classify exposure indirectly based on having a residential address within a specified distance from a reported pesticide application. ![]() For example, some studies classify indirect exposure based on having a household member who mixed or applied a pesticide, or working or living on a farm where a pesticide was applied, without necessarily having applied it oneself. In contrast, we refer to “indirect exposure metrics” as those that classify exposure to a pesticide based on possible routes other than personal use. Here, we refer to “direct exposure metrics” as those that classify exposure based on first-hand or personal application or mixing of a specific pesticide. In general, exposure to pesticides, including glyphosate, is variously defined in epidemiological studies. Data extraction was conducted by one investigator (ETC) and reviewed for accuracy and completeness by the two other investigators (NUO, JFA).Įxposure assessment is critically important in the epidemiology of glyphosate and is, therefore, introduced here in detail as background to inform the exposure assessment quality rating used in our systematic literature review (described in the next section). Studies were categorized according to whether they assessed neurodegenerative outcomes, neurobehavioral outcomes (e.g., depression, cognitive function), neurodevelopmental outcomes (e.g., autism spectrum disorder, neural tube defects), or other or mixed neurological outcomes. Where applicable, results with multivariable statistical adjustment were prioritized for reporting over unadjusted results, and results for multiple quantitative or semi-quantitative categories of glyphosate exposure were prioritized for reporting over those comparing ever vs. Study characteristics and results were extracted into a spreadsheet with separate fields for first author, publication year, study country, study design, study population (including size, setting, and participation rates), comparison population, exposure assessment method, exposure levels assessed, neurological outcomes assessed, outcome assessment method, confounders adjusted and considered, statistical approach, estimates of association (with interval estimates, e.g., 95% confidence intervals or credible intervals), and funding source. (neurotoxic* OR neurodevelopment* OR neurobehavior* OR neurobehaviour* OR neurologic* OR attention OR cognit* OR "developmental disability" OR social OR intelligence OR memory OR learning OR brain OR psychomotor OR behavior* OR behaviour* OR "Nervous System" OR parkinson* OR tremor OR “movement disorder” OR mental OR emotion* OR cognitive OR cognition OR dementia OR neuronal OR neuropathy OR motor OR sensory OR neurodegen* OR depression OR mood OR personality OR IQ OR autis* OR “amyotrophic lateral sclerosis” OR Alzheimer* OR “congenital anomaly” OR “congenital anomalies” OR “congenital disorder” OR “congenital disorders” OR “birth defect” or “birth defects” OR “neural tube defect” OR “neural tube defects” OR “spina bifida” OR “anencephaly” ) ![]() We also excluded case reports and case series, because they lack comparators, and thus cannot estimate exposure–outcome associations, and reviews, editorials, commentaries, letters, and other articles that did not report original data, although we examined the reference lists of these sources to identify additional potentially relevant studies. We excluded animal, in vitro, and mechanistic studies, because this review is limited to human epidemiology. Measures of association included relative risks (e.g., odds ratios, risk ratios, hazard ratios), risk differences, correlation coefficients, etc. Studies considered eligible for inclusion in our literature review were human epidemiological studies that reported a measure of association (or data sufficient to calculate a measure of association) between any chronic neurological condition, as described above, and glyphosate exposure, including direct exposure via personal use (i.e., spraying or mixing) of glyphosate, as well as possible indirect exposure via routes other than personal use. ![]()
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