Background In-vitro and in-vivo studies have shown evidence for the immuno-modulatory properties of different pesticides. However, few epidemiological studies on inflammation and pesticide exposure exist, with none in children and adolescents. Associations between pesticide metabolites in urine and inflammatory biomarkers in serum were evaluated among children and adolescents (n=512) of rural Ecuador as part of the ESPINA study Methods Seventeen urinary biomarkers of insecticide, herbicide and N, N-diethyl-meta-toluamide (DEET) insect repellent exposure were measured. Among them, acetamiprid-N-desmethyl [AND], 3,5,6-Trichloro-2-pyridinol [TCPy], para-nitrophenol [PNP], malathion dicarboxylic acid [MDA], 3-phenoxybenzoic acid [3-PBA], 2,4-Dichlorophenoxyacetic acid [2,4-D], glyphosate and 3-(diethylcarbamoyl) benzoic acid [DCBA] were included in analyses as they were detected in >30% of participants. Serum analysis included c-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), serum amyloid A (SAA), and soluble CD14 (sCD14). Associations were evaluated by generalized estimating equations (GEE) and partial least squares (PLS) regression, adjusting for demographic, anthropometric and socioeconomic variables. Results Positive quadratic associations were found between 2,4-D and CRP (β2=0.13, [0.00, 0.27]), IL-6 (β2=0.10, [0.04, 0.15]), SAA (β2=0.13, [0.01, 0.30]), sICAM-1 (β2=53.25, [27.26, 79.24]) and sVCAM-1 (β2=61.11, [30.52, 91.70]). The pesticide metabolites PLS composite variable was positively associated with IL-6 (β=0.09, [0.01. 0.17]), SAA (β=0.43, [0.13, 0.17]), sICAM-1 (β=63.52, [9.92, 117.13]), sVCAM-1 (β=69.03, [8.29, 129.76]) and TNF-α (β=0.08, [0.00, 0.16]), and negatively associated with CRP (β=-0.28, [-0.49, -0.08], Figure 1). Conclusions Our findings demonstrate a novel pesticide/herbicide-inflammation link in adolescents, which may be an underlying mechanism of the health impacts of pesticides/herbicides.

The authors have declared no competing interest.

The 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, and U2CES026560.

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The 2016 examination of the ESPINA study was approved by the Institutional Review Boards of the University of California San Diego (UCSD), Universidad San Francisco de Quito and the Ministry of Public Health of Ecuador and endorsed by the Commonwealth of Rural 181 Parishes of Pedro Moncayo County. We obtained informed consent from adult participants (aged 18 years or older) and parents, as well as parental permission of participation and informed assent of child participants.

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