Sex and Adrenal Hormones in Association with Insecticide Biomarkers among Adolescents Living in Ecuadorian Agricultural Communities

Background: Organophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro 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. Methods: 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), 1713-estradiol, and cortisol. We used general linear models to assess linear (13 = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (13 2 = 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. Results: The organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (13 boys = 5.88% [1.21%, 10.78%], 13 girls = 4.10% [-0.02%, 8.39%]), and cortisol (13 boys = 6.06 [-0.23%, 12.75%]. Paranitrophenol (organophosphate) had negatively -trending curvilinear associations, with testosterone (13 2 boys = -0.17 (-0.33, -0.003), p = 0.04) and DHEA (13 2 boys = -0.49 (-0.80, -0.19), p = 0.001) in boys. The neonicotinoid summary score (13 boys = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-Ndesmethyl (13 boys = 3.90% [1.28%, 6.58%]) were positively associated with 1713-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, Paranitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Paranitrophenol with DHEA. No associations were identified for AChE. Conclusions: 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 1713-estradiol. Longitudinal repeat -measures analyses would be beneficial for causal inference.