Urinary Glyphosate, 2,4-D and DEET Biomarkers in Relation to Neurobehavioral Performance in Ecuadorian Adolescents in the ESPINA Cohort

• Type of Material: Article
• Authors: Briana N.C. Chronister, University of California, San Diego; Kun Yang, University of California, San Diego; Audrey R. Yang, University of California, San Diego; Tuo Lin, University of California, San Diego; Xin M. Tu, University of California, San Diego; Dolores Lopez-Paredes, Fundación Cimas del Ecuador; Harvey Checkoway, University of California, San Diego; Jose Suarez-Torres, Fundación Cimas del Ecuador; Sheila Gahagan, University of California, San Diego; Danilo Martinez, Fundación Cimas del Ecuador; Dana Boyd Barr, Emory University; Raeanne C. Moore, University of California, San Diego; Jose R. Suarez-Lopez, University of California, San Diego
• Language: English
• Date: 2023-10-11
• Publisher: EHP Publishing
• Publication Version: Final Published Version
• Copyright Statement: EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.
• Final Published Version (URL): https://doi.org/10.1289/EHP11383
• Title of Journal or Parent Work: Environmental Health Perspectives
• Volume: 131
• Issue: 10
• Start Page: 107007
• Grant/Funding Information: Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under award numbers R01ES025792, R01ES030378, R21ES026084, U2CES026560, and P30ES019776. B.N.C. Chronister was funded by the Institute of Mental Health (5T32MH122376).
• Keywords: glyphosate; Herbicides; pesticides; 2,4-dichlorophenoxyacetic acid; neurobehavior
• Research Categories: Health Sciences, Epidemiology; Biology, Neuroscience; Health Sciences, Toxicology; Health Sciences, Public Health; Environmental Sciences

Abstract

Background: Herbicides are the most used class of pesticides worldwide, and insect repellents are widely used globally. Yet, there is a dearth of studies characterizing the associations between these chemical groups and human neurobehavior. Experimental studies suggest that glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides can affect neurobehavior and the cholinergic and glutamatergic pathways in the brain. We aim to assess whether herbicides and insect repellents are associated with neurobehavioral performance in adolescents. Methods: We assessed 519 participants (11–17 years of age) living in agricultural communities in Ecuador. We quantified urinary concentrations of glyphosate, 2,4-D, and two N,N-diethyl-meta-toluamide (DEET) insect repellent metabolites [3-(diethylcarbamoyl)benzoic acid (DCBA) and 3-(ethylcarbamoyl)benzoic acid (ECBA)] using isotope-dilution mass spectrometry. We assessed neurobehavioral performance using 9 subtests across 5 domains (attention/inhibitory control, memory/learning, language, visuospatial processing, and social perception). We characterized the associations using generalized estimating equations and multiple imputation for metabolites below detection limits. Models were adjusted for demographic and anthropometric characteristics, urinary creatinine, and sexual maturation. Mediation by salivary cortisol, dehydroepiandrosterone, 17⁢β-estradiol, and testosterone was assessed using structural equation modeling. Results: The mean of each neurobehavioral domain score was between 7.0 and 8.7 [standard deviation (SD) range: 2.0–2.3]. Glyphosate was detected in 98.3% of participants, 2,4-D in 66.2%, DCBA in 63.3%, and ECBA in 33.4%. 2,4-D was negatively associated with all neurobehavioral domains, but statistically significant associations were observed with attention/inhibition [score difference per 50% higher metabolite concentration (β)=−0.19 95% confidence interval (CI): −0.31, −0.07], language [β=−0.12 (95% CI: −0.23, −0.01)], and memory/learning [β=−0.11 (95% CI: −0.22, 0.01)]. Glyphosate had a statistically significant negative association only with social perception [β=−0.08 (95% CI: −0.14, −0.01)]. DEET metabolites were not associated with neurobehavioral performance. Mediation by gender and adrenal hormones was not observed. Conclusion: This study describes worse neurobehavioral performance associated with herbicide exposures in adolescents, particularly with 2,4-D. Replication of these findings among other pediatric and adult populations is needed. https://doi.org/10.1289/EHP11383