Probing the Biological Plausibility of Fluoride as an Endocrine Disruptor

Fluoride has come under recent scrutiny regarding concerns over potential neurodevelopmental and endocrine-related toxicities, with recent reviews by the National Toxicology Program (NTP) and European Food Safety Authority (EFSA) concluding with moderate or reasonable confidence, respectively, that exposure to drinking water having greater than 1.5 mg fluoride/L is associated with lower IQ in children. A key outcome of these reviews is the uncertainty regarding the biological plausibility of these findings. However, it has been hypothesized that endocrine disruption could be a potential factor.

To determine if sodium fluoride exerts direct biological activity on molecular and cellular targets related to endocrine disruption, receptor binding and activity assays of thyroid and other hormone-related targets, H295R steroidogenesis, and sodium-iodide symporter (NIS) assays were carried out using exposures comparable to or in excess of those that have been reported to be associated with neurodevelopmental outcomes and other effects.

Sodium fluoride at up to 316 μM NaF did not affect synthesis of estrogen or testosterone. Sodium fluoride at up to 10 μM NaF did not interact with aromatase, steroid 5 alpha-reductase, estrogen receptors, androgen receptors, thyroid hormone receptors, nor did it inhibit thyroid peroxidase. Furthermore, there were no changes in iodide uptake via symporter transport (up to 300 μM NaF). Other endocrine targets were also evaluated at 10 μM NaF, including PR, PPARα, PPARγ, AhR, CAR, PXR, RARα, or GR, and no binding was observed either.

Together, the results from this series of experiments demonstrate an absence of effects of fluoride on endocrine disruption targets at concentrations comparable to or in excess of exposures reported in the literature to be associated with neurodevelopmental outcomes and other effects.