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.

项目总结/摘要 水氟化是有争议的。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只研究了 暴露于高水平氟化物的儿童，只有少数研究测量了氟化物暴露 在发展的关键时期。尿液，通常用于量化一个人的暴露 反映了最近的暴露，并需要连续采样，以测量不同时期的氟化物。 发展时期。我们提出的研究将分析牙齿的牙本质-位于下面的组织 釉质-测量氟化物暴露的水平和时间。牙本质是一种理想的生物标志物 因为它提供了连续和累积摄入氟化物的历史记录。 我们将测试以下具体目标：目标1。为了量化产前，幼儿，和累积 氟暴露水平使用脱落的婴儿牙齿收集360名儿童;目标2。审查 婴儿牙齿（牙本质）中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）。 这项研究是创新的，因为它将采用最先进的分析方法来衡量水平， 以及暴露于牙本质中的氟化物和有毒金属的精确时间。这项研究利用了一个 加拿大现有的怀孕和出生队列，母婴环境研究 化学品我们将利用我们正在进行的NIH资助的研究的现有数据， 在早期大脑发育期间暴露于辐射会改变儿童的智商分数和行为问题。我们 测量牙齿牙本质和连续尿样中的氟化物暴露量提供了前所未有的 有机会测试早期暴露于氟化物的神经毒性效应。 主要贡献包括：1）胎儿发育期间氟暴露的量化， 儿童早期使用牙本质;和2）结果将直接影响决策， 在胎儿发育期间和幼儿期暴露于氟的安全性 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 有效和经济地完成这项研究。

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 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

Sex-specific neurotoxic effects of early-life exposure to fluoride: A review of the epidemiologic and animal literature.

• DOI: 10.1007/s40471-020-00246-1
• 发表时间: 2020-12
• 期刊: Current epidemiology reports
• 影响因子: 3.3
• 作者: Green R;Rubenstein J;Popoli R;Capulong R;Till C
• 通讯作者: Till C