Evidence for Competitive Inhibition of Iodide Uptake by Perchlorate and Translocation of Perchlorate into the Thyroid

Abstract

Various published data sets that investigate the potential effect of exogenous perchlorate (ClO4-) on the uptake of iodide in the thyroid and subsequent changes in thyroid hormone levels are available. In order to best use the data towards the prediction of human health effects resulting from ClO4- exposure, the available literature data must be integrated into a self-consistent, coherent, and parsimonious quantitative model based on the most likely mode of action of perchlorate effect on thyroid function. We submit that the simplest mode of action for ClO4- in the thyroid that remains consistent with all available data involves competitive inhibition of iodide transport into the thyroid follicle, transport of perchlorate into the thyroid follicle against a concentration gradient, further transport into the thyroid lumen (where it may again interfere with iodide transport), and, finally, passive diffusion back into the blood. We believe this description of perchlorate's kinetic behavior should serve as the foundation for predictive physiologically based pharmacokinetic (PBPK) models and as a working hypothesis for further experimental exploration.

Urinary Perchlorate and Thyroid Hormone Levels in Adolescent and Adult Men and Women Living in the United States

“…The mechanism of perchlorate’s effect is competitive inhibition of iodide uptake by the thyroid (Clewell et al 2004; Wolff 1998). Based on this mechanism, individuals with less iodide available to compete with perchlorate may be more vulnerable to impaired iodide uptake.…”

Endocrine disruptors and thyroid hormone physiology

“…They have also been detected in U.S. drinking water supplies at levels ranging from 4 to 200 microg/liter [26]. Perchlorates are competitive inhibitors of iodide transport into thyroid follicular cells, and are established inhibitors of TH synthesis [27]. This property is the basis of its use in the diagnosis of TH synthesis dysfunction and the treatment of hyperthyroidism.…”

Radiolabeling and biodistribution studies of polymeric nanoparticles as adjuvants for ocular vaccination against brucellosis

“…Se establecieron cinco grupos de 6 ratones cada uno ( 99m Tc-NP, 99m Tc-Man-NP, 99m Tc-NP-HS, 99m TcMan-NP-HS y 99m TcO 4 -libre). Una hora antes de la administración de las distintas formulaciones se inyectó a los ratones una dosis intravenosa de perclorato potásico de 3 mg/Kg para bloquear la captación en estómago y evitar así errores en los resultados debidos a la captación en estómago y tiroides de la pequeña proporción de 99m TcO 4 -libre que pudiera haber en la formulación 22 . Una única dosis de 8 µl de cada formulación se depositó en cada ojo de los ratones de cada grupo.…”