Fluoride in Tooth Dentin and Neurodevelopmental Outcome in a Canadian Cohort

项目概要/摘要 水加氟是有争议的。在过去的十年里，对潜在毒性的担忧 氟化物的含量有所增加，但仍存在问题。大多数关于氟化物毒性的人体研究 研究了暴露于高水平氟化物的儿童，只有少数研究测量了 氟暴露在关键时期的发展。尿液，通常用于 量化一个人暴露于氟化物，反映最近的暴露，并需要连续采样， 测量不同发育时期的氟化物。我们提出的研究将分析牙齿 牙本质--位于牙釉质下面的组织--来测量氟化物的水平和时间 exposure.牙本质是最佳的生物标志物，因为它提供了两者的历史记录。 连续和累积暴露于摄入的氟化物。我们将测试以下具体目标： 目标1。使用shed量化产前、幼儿和累积氟暴露水平 从800名儿童收集的乳牙;目标2。为了测试牙本质中的氟化物浓度是否 乳牙与较低的智商分数（n=610）和注意力问题（n=898）有关;目标3。 测试尿氟和牙本质氟浓度是否影响甲状腺激素， 最终导致智商分数和注意力问题。这项研究是创新的，因为它将采用 最先进的分析方法，以衡量暴露的水平和精确的时间， 氟化物和有毒金属。这项研究利用了现有的加拿大 怀孕和出生队列，母婴环境化学品研究。我们将 利用我们正在进行的NIH资助的研究的现有数据， 早期的大脑发育会改变儿童的智商分数和行为问题。此外，我们将测试 怀孕期间氟化物的内分泌干扰潜力。我们对氟化物的测量 暴露在牙齿牙质和系列尿样提供了前所未有的机会，以测试 早期暴露于氟化物的神经毒性作用。大样本量将使我们能够确定是否 儿童性别、接触时间或接触婴儿配方奶粉会影响氟化物的毒性。 主要贡献包括：1）胎儿发育期间氟暴露的定量 和早期儿童使用牙本质;和2）将直接影响决策的结果 关于胎儿发育和幼儿期氟暴露的安全性， 与美国和加拿大有关。鉴于我们的存档资源，我们将能够实现 这项研究是有效和具有成本效益的。

Project Summary / Abstract Water fluoridation is controversial. Over the past decade, concern about the potential toxicity of fluoride has grown, but there are still questions. Most human studies of fluoride toxicity only studied children who were exposed to high levels of fluoride and only a few studies measured fluoride exposure during critical periods of development. Urine, which is commonly used to quantify a person’s exposure to fluoride, reflects recent exposure and requires serial sampling to measure fluoride during different periods of development. Our proposed study will analyze tooth dentin – the tissue that lies beneath enamel – to measure the level and timing of fluoride exposure. Tooth dentin is an optimal biomarker because it provides a historical record of both serial and cumulative exposure to ingested fluoride. We will test the following specific aims: Aim 1. To quantify prenatal, early childhood, and cumulative fluoride exposure levels using shed baby teeth collected from 800 children; Aim 2. To test whether dentin fluoride concentrations in baby teeth is associated with lower IQ scores (n=610) and attention problems (n=898); Aim 3. To test whether the urinary and dentin fluoride concentrations impact thyroid hormones, and ultimately IQ scores and attention problems. This study is innovative because it will employ state-of the-art analytical methods to measure the level and precise timing of exposures to fluoride and toxic metals in tooth dentin. The study capitalizes on an existing Canadian pregnancy and birth cohort, the Maternal-Infant Research on Environmental Chemicals. We will leverage existing data from our ongoing NIH-funded study to find out if fluoride exposure during early brain growth alters children’s IQ scores and behavioral problems. In addition, we will test the endocrine disrupting potential of fluoride during pregnancy. Our measurement of fluoride exposure in tooth dentin and serial urine samples offers an unprecedented opportunity to test for neurotoxic effects of early-life exposure to fluoride. The large sample size will let us find out if to child sex, timing of exposure, or exposure to powdered infant formula impact fluoride’s toxicity. Major contributions include: 1) quantification of exposure to fluoride during fetal development and early childhood using dentin; and 2) results that will directly impact decision making concerning the safety of fluoride exposure during fetal development and early childhood at levels relevant to the U.S. and Canada. Given our archived resources, we will be able to accomplish this study efficiently and cost-effectively.