Organophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities. In 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17β-estradiol, and cortisol. We used general linear models to assess linear (β = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (β = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions. The organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (β = 5.88% [1.21%, 10.78%], β = 4.10% [-0.02%, 8.39%]), and cortisol (β = 6.06 [-0.23%, 12.75%]. nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (β = −0.17 (−0.33, −0.003), p = 0.04) and DHEA (β = −0.49 (−0.80, −0.19), p = 0.001) in boys. The neonicotinoid summary score (β = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (β = 3.90% [1.28%, 6.58%]) were positively associated with 17β-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and nitrophenol with DHEA. No associations were identified for AChE. We observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17β-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference.

中文翻译：

---

生活在厄瓜多尔农业社区的青少年中性激素和肾上腺激素与杀虫剂生物标志物的关系


有机磷、拟除虫菊酯和新烟碱类杀虫剂已导致动物和研究中的肾上腺和性腺激素紊乱；人类中存在有限的流行病学证据。我们评估了生活在厄瓜多尔农业社区的青少年尿中杀虫剂代谢物浓度与肾上腺和性腺激素的关系。 2016 年，我们对 522 名厄瓜多尔青少年（11-17 岁，50.7% 女性，22% 土著人；ESPINA 研究）进行了检查。我们测量了尿液杀虫剂代谢物、血液乙酰胆碱酯酶活性 (AChE) 和唾液睾酮、脱氢表雄酮 (DHEA)、17β-雌二醇和皮质醇。我们使用一般线性模型来评估 ln 代谢物或 AChE 与 ln 激素浓度之间的线性关系（β = 代谢物浓度每增加 50%，激素差异百分比）和曲线关系（β = ln 代谢物平方每增加单位激素差异） ，按性别分层，调整人体测量、人口统计和觉醒反应变量。贝叶斯核机器回归用于评估非线性关联和相互作用。有机磷代谢物马拉硫磷二羧酸 (MDA) 与睾酮（β = 5.88% [1.21%, 10.78%]、β = 4.10% [-0.02%, 8.39%]）和皮质醇（β = 6.06 [-0.23]）呈正相关。 %, 12.75%]。硝基苯酚（有机磷酸盐）与睾酮 (β = -0.17 (-0.33, -0.003), p = 0.04) 和 DHEA (β = -0.49 (-0.80, -0.19) 呈负趋势曲线关联。 ，p = 0.001）在男孩中新烟碱类药物总分（β = 5.60% [0.14%, 11.36%]）和新烟碱类啶虫脒-N-去甲基（β = 3.90% [1.28%, 6.58%]）与17β-雌二醇，仅在男孩中测量，未观察到拟除虫菊酯 3-苯氧基苯甲酸与激素之间的关联。 在女孩中，双变量反应关联确定了 MDA、硝基苯酚和 3,5,6-三氯-2-吡啶醇（有机磷酸酯）与睾酮和 DHEA 浓度的相互作用。在男孩中，我们观察到 MDA 和硝基苯酚与 DHEA 的相互作用。未发现与 AChE 存在关联。我们观察到青少年特定有机磷和新烟碱类代谢物暴露造成内分泌干扰的证据。尿液有机磷代谢物与睾酮和 DHEA 浓度相关，男孩的相关性强于女孩。尿中新烟碱类杀虫剂与 17β-雌二醇呈正相关。纵向重复测量分析将有利于因果推断。