Associations Between Urinary Pesticide Metabolites and Serum Inflammatory Biomarkers in Adolescents Living in an Agricultural Region

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. 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-alpha (TNF-alpha), 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. Positive quadratic associations were found between 2,4-D and CRP (beta(2) = 0.13, [0.00, 0.27]), IL-6 (beta(2) = 0.10, [0.04, 0.15]), SAA (beta(2) = 0.13, [0.01, 0.30]), sICAM-1 (beta(2) = 53.25, [27.26, 79.24]) and sVCAM-1 (beta(2) = 61.11, [30.52, 91.70]). The pesticide metabolites PLS composite variable was positively associated with IL-6 (beta = 0.09, [0.01. 0.17]), SAA (beta = 0.43, [0.13, 0.17]), sICAM-1 (beta = 63.52, [9.92, 117.13]), sVCAM-1 (beta = 69.03, [8.29, 129.76]), and TNF-alpha (beta = 0.08, [0.00, 0.16]), and negatively associated with CRP (beta = - 0.28, [- 0.49, - 0.08]). Our findings demonstrate a novel pesticide/herbicide-inflammation link in adolescents, which may be an underlying mechanism of the health impacts of pesticides/herbicides.