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.

项目概要/摘要 在过去的十年中，人们对水氟化的潜在毒性存在争议。 氟化物的含量有所增加，但大多数人类研究仅研究氟化物的毒性。 接触高浓度氟化物的儿童，只有少数研究测量了氟化物接触情况 在发育的关键时期，尿液通常用于量化一个人的暴露程度。 氟化物，反映了最近的暴露情况，需要连续取样以测量不同时期的氟化物 我们提出的研究将分析牙齿牙本质——位于牙本质下方的组织。 牙釉质——测量氟化物暴露的水平和时间，是最佳的生物标志物。 因为它提供了连续和累积接触氟化物的历史记录。 我们将测试以下具体目标： 目标 1. 量化产前、幼儿期和累积 使用从 360 名儿童身上收集的脱落乳牙来确定氟化物暴露水平； 乳牙（牙本质）产前和产后氟化物水平与神经发育之间的关系 婴儿和儿童的心理结果（n=300，有牙齿和行为数据）。 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水平 该研究利用了牙齿牙本质中氟化物和有毒金属暴露的精确时间。 现有的加拿大怀孕和出生队列，母婴环境研究 我们将利用 NIH 资助的正在进行的研究的现有数据来查明氟化物是否存在。 早期大脑发育过程中的暴露会改变儿童的智商分数和行为问题。 牙齿牙本质和连续尿液样本中氟化物暴露的测量提供了前所未有的 有机会测试生命早期接触氟化物的神经毒性作用。 主要贡献包括：1）胎儿发育过程中氟化物暴露的量化和 幼儿期使用牙齿牙本质的结果；以及 2) 将直接影响相关决策的结果 胎儿发育和幼儿期氟化物暴露水平的安全性与 鉴于我们在怀孕期间收集的存档样本，我们将能够 有效且经济高效地完成这项研究。

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

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

Iodine Status Modifies the Association between Fluoride Exposure in Pregnancy and Preschool Boys' Intelligence.

• DOI: 10.3390/nu14142920
• 发表时间: 2022-07-16
• 期刊: Nutrients
• 影响因子: 5.9