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 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只研究了 暴露在高水平氟中的儿童，只有几项研究测量了氟暴露 在发展的关键时期。尿液，通常用来量化一个人的暴露 对于氟化物，反映了最近的暴露，并需要连续采样来测量不同时期的氟化物 发展阶段。我们提出的研究将分析牙牙本质--其下面的组织 牙釉质-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.量化产前、幼儿和累积 使用从360名儿童采集的脱落乳牙的氟化物暴露水平；目标2。检查 乳牙(牙本质)出生前后氟化物水平与神经发育的关系 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，因为它将使用最先进的分析方法来衡量水平 以及暴露于牙本质中氟化物和有毒金属的准确时间。这项研究利用了一个 现有的加拿大妊娠和出生队列、母婴环境研究 化学品。我们将利用我们正在进行的NIH资助的研究中的现有数据来找出氟化物 大脑发育早期的暴露会改变儿童的智商分数和行为问题。我们的 测量牙齿、牙本质和系列尿样中的氟化物暴露提供了前所未有的 测试早期接触氟化物的神经毒性效应的机会。 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)将直接影响有关决策的结果 胎儿发育和儿童早期接触氟化物的安全性与 美国和加拿大。考虑到我们在怀孕期间收集的存档标本，我们将能够 高效、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