Evidence for competitive inhibition of iodide uptake by perchlorate and translocation of perchlorate into the thyroid.
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.
Clewell
Rebecca A
RA
Geo-Centers, Inc., Wright-Patterson AFB, Ohio, USA. rclewell@ciit.org
Merrill
Elaine A
EA
Narayanan
Latha
L
Gearhart
Jeffery M
JM
Robinson
Peter J
PJ
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001711:Biotransformation; D006801:Humans; D007454:Iodides / Q000378:metabolism*; D010472:Perchlorates / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding; D027981:Symporters / Q000378:metabolism; D013961:Thyroid Gland / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
D007454:Iodides; D010472:Perchlorates; D027981:Symporters; D000099209:Sodium-Iodide Symporters