Probing the Biological Plausibility of Fluoride as an Endocrine Disruptor.

IF 2 4区医学 Q4 DEVELOPMENTAL BIOLOGY

Birth Defects Research Pub Date : 2026-05-01 DOI:10.1002/bdr2.70046

Ashley M Mudd, Bladimir J Ovando, George P Daston

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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探讨氟化物作为内分泌干扰物的生物学合理性。

背景：氟化物因潜在的神经发育和内分泌相关毒性而受到最近的审查，国家毒理学计划（NTP）和欧洲食品安全局（EFSA）最近的审查分别以中等或合理的信心得出结论，暴露于氟化物含量超过1.5毫克/升的饮用水与儿童智商较低有关。这些综述的一个关键结果是这些发现的生物学合理性的不确定性。然而，据推测，内分泌紊乱可能是一个潜在的因素。方法：为了确定氟化钠是否对与内分泌干扰相关的分子和细胞靶点产生直接的生物活性，对甲状腺和其他激素相关靶点、H295R甾体生成和碘化钠同体（NIS）进行了受体结合和活性测定，暴露量与已报道的与神经发育结果和其他影响相关的暴露量相当或超过这些暴露量。结果：316 μM NaF下氟化钠对雌激素和睾酮的合成无影响。在10 μM NaF下，氟化钠不与芳香化酶、类固醇5 α -还原酶、雌激素受体、雄激素受体、甲状腺激素受体相互作用，也不抑制甲状腺过氧化物酶。此外，通过同向转运体（高达300 μM NaF）的碘吸收没有变化。其他内分泌靶点包括PR、PPARα、PPARγ、AhR、CAR、PXR、RARα、GR，均在10 μM NaF下未观察到结合。结论：综上所述，这一系列实验的结果表明，氟化物对内分泌干扰目标的影响与文献中报道的与神经发育结果和其他影响相关的暴露浓度相当或超过该浓度时并不存在。

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来源期刊

Birth Defects Research Medicine-Embryology

CiteScore

3.60

自引率

9.50%

发文量

153

期刊介绍： The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks. Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.