Pyrethroid exposure biomarker 3-phenoxybenzoic acid (3-PBA) binds to transthyretin and is positively associated with free T3 in pregnant women

Pyrethroids constitute a large group of insecticides widely used in agriculture, indoor environments, and in vector control. Structurally, pyrethroids resemble thyroid hormones, and have been suggested to be thyroid hormone disruptors based on experimental studies. During pregnancy, even minor disturbances in maternal levels can affect fetal brain development. Therefore, we aimed to investigate whether three commonly used pyrethroids and their common metabolite, 3-PBA, were able to trigger thyroid disrupting effects on thyroid hormone production and transport, activation or deactivation of thyroid hormones, recycling of iodine, or on iodide uptake into the thyroid. Furthermore, we investigated associations between urinary 3-PBA concentrations (as biomarker of pyrethroid exposure) and serum concentrations of thyroid hormones in early pregnancy in the large prospective Odense Child Cohort (OCC). We found that the generic metabolite, 3-PBA, was capable of binding to transthyretin (TTR) at low concentrations, comparable to those reported in human cord blood. Among pregnant women in OCC, we found urinary 3-PBA concentrations to be positively associated with free triiodothyronine (fT3) serum levels. Displacement of thyroid hormones from TTR by pyrethroid exposure in early pregnancy may disturb the transplacental transport of thyroid hormones to the fetus during a very vulnerable window of development, including neural maturation. We did not find any evidence for thyroid disrupting effects in vitro for the three pyrethroids: Deltamethrin, α-cypermethrin, and etofenprox.