Fluoride in Tooth Dentin and Neurodevelopmental Outcome in a Canadian Cohort

加拿大队列中牙齿牙本质中的氟化物和神经发育结果

• 批准号: 10434821
• 负责人: BRUCE P LANPHEAR
• 金额: $ 23.23万
• 依托单位: YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10434821
• 关键词: Acquired Dental Fluorosis; Adult; Adverse effects; Archives; Attention; Attention deficit hyperactivity disorder; Behavior; Biological Markers; Birth; Brain; Canada; Child; Childhood; Chronic; Country; Data; Decision Making; Dental Enamel; Dental caries; Dentin; Development; Dose; Endocrine disruption; Exposure to; Fetal Development; Fetus; First Pregnancy Trimester; Fluorides; Funding; Goals; Grant; Growth; Health; Human; Hyperactivity; Infant; Infant formula; Ingestion; Iodine; Maps; Measurement; Measures; Mediating; Mediation; Methods; Modeling; National Research Council; North America; Outcome; Parents; Persons; Powder dose form; Predisposition; Pregnancy; Pregnant Women; Preschool Child; Problem behavior; Public Health Practice; Recommendation; Recording of previous events; Research; Resources; Risk; Risk Factors; Safety; Sample Size; Sampling; Sex Differences; Spottings; Structure; Testing; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Time; Tissues; Tooth Discoloration; Tooth structure; Toxic effect; United States; United States National Institutes of Health; Urine; Vulnerable Populations; Water Supply; Water fluoridation; analytical method; biobank; cohort; comparison group; cost; critical period; deciduous tooth; early childhood; early life exposure; environmental chemical; inattention; innovation; neurobehavioral; neurotoxic; neurotoxicity; novel marker; postnatal; prenatal; prenatal exposure; prevent; public drinking; public health relevance; safety testing; sex; thyroid disruption; toxic metal; urinary

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.

项目概要/摘要 水氟化是有争议的。在过去的十年中，人们对潜在毒性的担忧 氟化物有所增加，但仍然存在问题。大多数人类研究仅针对氟化物毒性 研究了接触高浓度氟化物的儿童，但只有少数研究进行了测量 发育关键时期的氟化物暴露。尿液，通常用于 量化一个人接触氟化物的情况，反映最近的接触情况，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——位于牙釉质下方的组织——用于测量氟化物的水平和时间 接触。牙齿牙本质是一种最佳的生物标志物，因为它提供了两者的历史记录 连续和累积接触摄入的氟化物。我们将测试以下具体目标： 目标 1. 使用棚屋量化产前、幼儿期和累积氟化物暴露水平 从 800 名儿童身上采集乳牙；目标 2. 测试牙本质氟化物浓度是否 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。 测试尿液和牙本质氟化物浓度是否影响甲状腺激素，以及 最终是智商分数和注意力问题。这项研究具有创新性，因为它将采用 最先进的分析方法来测量暴露水平和精确时间 牙齿牙本质中的氟化物和有毒金属。该研究利用了加拿大现有的 妊娠和出生队列，环境化学物质母婴研究。我们将 利用美国国立卫生研究院 (NIH) 资助的正在进行的研究中的现有数据来查明在 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 氟化物在怀孕期间可能会扰乱内分泌。我们的氟化物测量 牙齿牙本质和连续尿液样本中的暴露提供了前所未有的机会来检测 生命早期接触氟化物的神经毒性作用。大样本量会让我们知道是否 儿童性别、接触时间或接触婴儿配方奶粉都会影响氟化物的毒性。 主要贡献包括：1）胎儿发育过程中氟化物暴露的量化 和幼儿期使用牙本质； 2）将直接影响决策的结果 关于胎儿发育和幼儿时期氟化物暴露水平的安全性 与美国和加拿大相关。鉴于我们的存档资源，我们将能够完成 这项研究高效且具有成本效益。