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, 17β-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.

中文翻译：

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尿草甘膦、2,4-D 和避蚊胺生物标志物与 ESPINA 队列中厄瓜多尔青少年神经行为表现的关系。

背景技术除草剂是全世界最常用的一类农药，并且驱虫剂在全球广泛使用。然而，缺乏表征这些化学基团与人类神经行为之间关联的研究。实验研究表明，草甘膦和 2,4-二氯苯氧基乙酸 (2,4-D) 除草剂可以影响神经行为以及大脑中的胆碱能和谷氨酸能通路。我们的目的是评估除草剂和驱虫剂是否与青少年的神经行为表现有关。方法 我们对生活在厄瓜多尔农业社区的 519 名参与者（11-17 岁）进行了评估。我们定量了草甘膦、2,4-D 和两种 N,N-二乙基间甲苯酰胺 (DEET) 驱虫代谢物 [3-(二乙基氨基甲酰基)苯甲酸 (DCBA) 和 3-(乙基氨基甲酰基)苯甲酸 ( ECBA)]使用同位素稀释质谱法。我们使用跨 5 个领域（注意力/抑制控制、记忆/学习、语言、视觉空间处理和社会感知）的 9 个子测试来评估神经行为表现。我们使用广义估计方程和低于检测限的代谢物的多重插补来表征关联性。模型根据人口统计和人体测量特征、尿肌酐和性成熟进行了调整。使用结构方程模型评估唾液皮质醇、脱氢表雄酮、17β-雌二醇和睾酮的调节作用。结果 每个神经行为领域评分的平均值在 7.0 至 8.7 之间[标准差 (SD) 范围：2.0-2.3]。98.3% 的参与者检测到草甘膦，66.2% 的参与者检测到 2,4-D，63.3% 的参与者检测到 DCBA，33.4% 的参与者检测到 ECBA。2,4-D 与所有神经行为领域呈负相关，但与注意/抑制存在统计显着相关性 [每升高 50% 代谢物浓度 (β) 的分数差异 = -0.19 95% 置信区间 (CI)：-0.31，- 0.07]、语言 [β=-0.12 (95% CI: -0.23, -0.01)] 和记忆/学习 [β=-0.11 (95% CI: -0.22, 0.01)]。草甘膦仅与社会认知呈统计学显着负相关[β=-0.08 (95% CI: -0.14, -0.01)]。避蚊胺代谢物与神经行为表现无关。没有观察到性别和肾上腺激素的调节。结论 这项研究描述了与青少年接触除草剂（尤其是 2,4-D）相关的更差的神经行为表现。需要在其他儿童和成人人群中复制这些发现。https://doi.org/10.1289/EHP11383。