Fluoride in Tooth Dentin and Neurodevelopmental Outcome in a Canadian Cohort

项目摘要/摘要 水的氟化是有争议的。在过去的十年里，对潜在毒性的担忧 氟化物有所增加，但仍然存在问题。大多数关于氟化物毒性的人体研究仅限于 研究了接触高氟化物的儿童，只有几项研究测量了 在发育的关键时期暴露于氟。尿液，通常用来 量化一个人的氟化物暴露，反映最近的暴露，并要求连续采样以 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-牙釉质下面的组织-测量氟化物的水平和时间 曝光。牙本质是一种最理想的生物标志物，因为它提供了这两种情况的历史记录 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： 目的1.使用SHEAD量化产前、儿童早期和累积的氟暴露水平 从800名儿童中收集乳牙；目标2。测试牙本质氟浓度是否在 乳牙与低智商(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，以及 归根结底，智商得分和注意力问题。这项研究具有创新性，因为它将采用 最先进的分析方法，以测量暴露于 牙齿牙本质中的氟和有毒金属。这项研究利用了一位现有的加拿大人 怀孕和出生队列，母婴环境化学品研究。我们会 利用我们正在进行的NIH资助的研究中的现有数据，找出在 早期大脑发育会改变儿童的智商分数和行为问题。此外，我们还将测试 孕期氟化物的内分泌干扰潜能。我们对氟化物的测量 暴露在牙齿、牙本质和连续尿样中提供了前所未有的机会来检测 早期接触氟化物的神经毒性效应。大的样本量将让我们知道是否 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)量化胎儿发育期间的氟暴露 和儿童早期使用牙本质；2)将直接影响决策的结果 关于在胎儿发育和儿童早期水平暴露氟的安全性 与美国和加拿大相关。考虑到我们存档的资源，我们将能够完成 这项研究效率高，成本效益高。

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.