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: 10813234
• 负责人: BRUCE P LANPHEAR
• 金额: $ 50.49万
• 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/10813234
• 关键词: Administrative Supplement; Behavioral; Biological Markers; Birth; Brain; Canada; Child; Chronic; Data; Decision Making; Dental Enamel; Dentin; Development; Exposure to; Fetal Development; Fluorides; Funding; Human; Infant; Ingestion; Measurement; Measures; Outcome; Persons; Predisposition; Pregnancy; Problem behavior; Recommendation; Research; Safety; Sampling; Testing; Tissues; Tooth structure; Toxic effect; United States National Academy of Sciences; United States National Institutes of Health; Urine; Vulnerable Populations; Water fluoridation; analytical method; biological specimen archives; cohort; cost; critical period; early childhood; early life exposure; environmental chemical; innovation; neurotoxic; novel marker; postnatal; prenatal; safety testing; toxic metal

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 360 children; Aim 2. To examine the association between prenatal and postnatal fluoride levels in baby teeth (dentin) and neurodevelop- mental outcomes in infants and children (n=300 with tooth and behavioral data). 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 development alters children’s IQ scores and behavioral problems. 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. Major contributions include: 1) quantification of exposure to fluoride during fetal development and early childhood using tooth 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 specimens collected during pregnancy, we will be able to accomplish this study efficiently and cost-effectively.

项目摘要 /摘要 氟化是有争议的。在过去的十年中，人们对潜在毒性的关注 氟化物已经成长，但仍然有问题。大多数人类氟化物毒性的研究仅研究 暴露于高水平氟化物的儿童，只有少数研究测量了氟化物的暴露 在关键时期。尿液，通常用于量化一个人的暴露 到氟化物，反映了最近的暴露，需要在不同的情况下进行串行采样以测量氟化物 发展时期。我们提出的研究将分析牙齿牙本质 - 位于下面的组织 搪瓷 - 测量氟化物暴露的水平和时间。牙齿牙本质是最佳的生物标志物 因为它提供了摄入的氟化物的连续和累积暴露的历史记录。 我们将测试以下特定目标：目标1。量化产前，幼儿和累积 使用360名儿童收集的乳牙的露天牙齿暴露水平；目标2。检查 乳牙（牙本质）和神经发育的产前和产后氟化物水平之间的关联 - 婴儿和儿童的心理结果（n = 300牙齿和行为数据）。 这项研究具有创新性，因为它将采用最新的分析方法来测量水平 和牙齿牙本质中氟化物和有毒金属的曝光的精确时机。该研究大写了 现有的加拿大怀孕和出生队列，《环境中的孕产妇研究》 化学物质。我们将利用正在进行的NIH资助的研究中的现有数据来找出氟化物是否存在 早期大脑发育期间的暴露会改变儿童的智商分数和行为问题。我们的 牙齿牙本质和连续尿液样品中氟化物暴露的测量提供了前所未有的 测试早期暴露于氟化物的神经毒性作用的机会。 主要贡献包括：1）在胎儿发育过程中接触氟化物的数量和 幼儿时期使用牙齿牙本质； 2）结果将直接影响有关的决策 胎儿发育期间氟化物暴露的安全性和幼儿期在与 美国和加拿大。鉴于我们在怀孕期间收集的存档标本，我们将能够 有效，成本效益地完成这项研究。

项目成果

Critical windows of fluoride neurotoxicity in Canadian children.

• DOI: 10.1016/j.envres.2021.111315
• 发表时间: 2021-09
• 期刊: ENVIRONMENTAL RESEARCH
• 影响因子: 8.3
• 作者: Farmus, Linda;Till, Christine;Green, Rivka;Hornung, Richard;Mier, E. Angeles Martinez;Ayotte, Pierre;Muckle, Gina;Lanphear, Bruce P.;Flora, David B.
• 通讯作者: Flora, David B.

Association of water fluoride and urinary fluoride concentrations with attention deficit hyperactivity disorder in Canadian youth.

• DOI: 10.1016/j.envint.2019.105190
• 发表时间: 2019-12
• 期刊: Environment international
• 影响因子: 11.8
• 作者: Riddell JK;Malin AJ;Flora D;McCague H;Till C
• 通讯作者: Till C

Fluoride exposure and hypothyroidism in a Canadian pregnancy cohort.

• DOI: 10.1016/j.scitotenv.2022.161149
• 发表时间: 2023-04-15
• 期刊: SCIENCE OF THE TOTAL ENVIRONMENT
• 影响因子: 9.8
• 作者: Hall, Meaghan;Lanphear, Bruce;Chevrier, Jonathan;Hornung, Rick;Green, Rivka;Goodman, Carly;Ayotte, Pierre;Martinez-Mier, Esperanza Angeles;Zoeller, R. Thomas;Till, Christine
• 通讯作者: Till, Christine

Iodine status in a large Canadian pregnancy cohort.

• DOI: 10.1016/j.ajogmf.2022.100784
• 发表时间: 2023-01
• 期刊: American journal of obstetrics & gynecology MFM
• 影响因子: 6.3

Maternal fluoride exposure, fertility and birth outcomes: The MIREC cohort.

母亲氟化物暴露、生育力和出生结果：MIREC 队列。

• DOI: 10.1016/j.envadv.2021.100135
• 发表时间: 2022
• 期刊: Environmental advances
• 作者: Goodman,Carly;Hall,Meaghan;Green,Rivka;Hornung,Richard;Martinez-Mier,EsperanzaAngeles;Lanphear,Bruce;Till,Christine
• 通讯作者: Till,Christine