https://ntp.niehs.nih.gov/go/fluoride

Fluoride Exposure: Neurodevelopment and Cognition

The State of the Science Monograph is now available. The Meta-analysis Manuscript is now available.

Topic Overview

CASRN: 16984-48-8
Status: Evaluation completed

Background Information

Since 1945, the use of fluoride has been a successful public health initiative for reducing dental cavities and improving general oral health of adults and children. There is a concern, however, that some pregnant women and children may be getting more fluoride than they need because they now get fluoride from many sources including treated public water, water-added foods and beverages, teas, toothpaste, floss, and mouthwash, and the combined total intake of fluoride may exceed safe amounts.

Therefore, the National Toxicology Program (NTP) conducted a systematic review of the published scientific literature on the association between fluoride exposure and neurodevelopment and cognition. The NTP released their findings in a State of the Science Monograph (available below under Documents). A corresponding meta-analysis on children's IQ was published in JAMA Pediatrics on January 6, 2025 (see sidebar).

The NTP started this work in 2016. As with all research documents intended for publication, the NTP fluoride monograph and meta-analysis underwent rigorous scientific evaluation. The evaluation process has involved many steps. The draft fluoride monograph received critical feedback during peer-review by the National Academies of Science, Engineering and Medicine (NASEM), from other external experts, and from experts in several federal health agencies. After modifications were made, additional evaluation following a rigorous scientific framework was conducted by subject matter experts organized by the NTP Board of Scientific Counselors. This document is now complete and available for reference.

The monograph represents a thorough review of the data, and the various interpretations of the data, to accurately reflect what we know and where additional research is needed.

Findings

The NTP monograph concluded, with moderate confidence, that higher levels of fluoride exposure, such as drinking water containing more than 1.5 milligrams of fluoride per liter, are associated with lower IQ in children. The NTP review was designed to evaluate total fluoride exposure from all sources and was not designed to evaluate the health effects of fluoridated drinking water alone. It is important to note that there were insufficient data to determine if the low fluoride level of 0.7 mg/L currently recommended for U.S. community water supplies has a negative effect on children’s IQ. The NTP found no evidence that fluoride exposure had adverse effects on adult cognition.

The NTP uses 4 confidence levels - high, moderate, low, or very low - to characterize the strength of scientific evidence that associates a particular health outcome with an exposure. After evaluating studies published through October 2023, the NTP Monograph concluded there is moderate confidence in the scientific evidence that showed an association between higher levels of fluoride and lower IQ in children.

The determination about lower IQs in children was based primarily on epidemiology studies in non-U.S. countries such as Canada, China, India, Iran, Pakistan, and Mexico where some pregnant women, infants, and children received total fluoride exposure amounts higher than 1.5 mg fluoride/L of drinking water. The U.S. Public Health Service currently recommends 0.7 mg/L, and the World Health Organization has set a safe limit for fluoride in drinking water of 1.5 mg/L.

Application

An association indicates a connection between fluoride and lower IQ; it does not prove a cause and effect. Many substances are healthy and beneficial when taken in small doses but may cause harm at high doses. More research is needed to better understand if there are health risks associated with low fluoride exposures. This NTP monograph may provide important information to regulatory agencies that set standards for the safe use of fluoride. It does not, and was not intended to, assess the benefits of fluoride.

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Documents

Documents for Fluoride: Potential Developmental Neurotoxicity
Date Document
Oct 07, 2015 Federal Register notice requesting information on nominated substances
Nov 19, 2015 Proposed NTP Evaluation on Fluoride Concept
Dec 02, 2015 Presentation: NTP Evaluation of Fluoride Exposure and Potential for Developmental Neurobehavioral Effects
Jul 01, 2016 Completed Systematic Review (Abstract)
Preferred Citation: NTP (National Toxicology Program). 2016. Systematic literature review on the effects of fluoride on learning and memory in animal studies. NTP Research Report 1. Research Triangle Park, NC: National Toxicology Program. Research Report 1. https://doi.org/10.22427/NTP-RR-1
Jun 01, 2017 NTP Protocol for Systematic Review of Human, Animal, and Mechanistic Evidence
May 29, 2019 NTP Protocol for Systematic Review of Human, Animal, and Mechanistic Evidence - First Revision
Sept 16, 2020 NTP Protocol for Systematic Review of Human, Animal, and Mechanistic Evidence - Second Revision
Sept 16, 2020 Literature Search Results
Mar 15, 2023 Table of Contents
Documents Provided to the NTP Board of Scientific Counselors (BSC) and BSC Working Group
May 18, 2023 Transmittal Letter
Final Version of the NTP Board of Scientific Counselors Working Group Report
Aug 21, 2024 NTP Monograph - Final (Abstract)
Preferred Citation: National Toxicology Program (NTP). 2024. NTP monograph on the state of the science concerning fluoride exposure and neurodevelopment and cognition: a systematic review. Research Triangle Park, NC: National Toxicology Program. NTP Monograph 08. https://doi.org/10.22427/NTP-MGRAPH-8
Aug 21, 2024 Interactive Reference Flow Diagram for Updated Literature Search (NTP Monograph Addendum Figure 1)
Aug 21, 2024 Interactive Reference Flow Diagram (NTP Monograph Figure 2)
Jan 06, 2025 Meta-analysis Manuscript
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Meetings & Events

Listing of related events
Date Event Event Type Materials
May 04, 2023

Board of Scientific Counselors Meeting

Board of Scientific Counselors - BSC Meeting
  • Agenda
  • Meeting Materials

    Federal Register Notices
    May 4-5, 2023

    Board of Scientific Counselors Meeting Meeting Materials
    May 4-5, 2023

    Charge
    NTP Board of Scientific Counselors Working Group Report
    Table of Contents and Documents Provided to the NTP Board of Scientific Counselors (BSC) and BSC Working Group
    Fluoride: Assessment for Developmental Neurotoxicity web page on NTP website

     

    Public Comments

    Name, Affiliation, Sponsorship Technical and Scientific Public Comments
    J. William Hirzy, PhD, on behalf of the National Federation of Federal Employees, Local 2050 Public comment received April 27, 2023
    Rick North, Private Citizen Public comment received April 27, 2023
    Mark Moss, DDS, PhD, East Carolina University Public comment received April 27, 2023
    William Maas, DDS, MPH, MS, University of Maryland School of Dentistry Public comment received April 27, 2023
    George R. Shepley, DDS, and Raymond A. Cohlmia, DDS, on behalf of the American Dental Association Public comment received April 28, 2023
    Brian R. Berridge, DVM, PhD, B2 Pathology Solutions LLC Public comment received April 28, 2023
    Jack Kall, DMD, on behalf of the International Academy of Oral Medicine and Toxicology Public comment received April 28, 2023
    Bill Osmunson, DDS, MPH, on behalf of Washington Action for Safe Water, King County Citizens Against Fluoridation Public comment received April 28, 2023
    Public comment received May 10, 2023
    Christopher H. Fox, DMD, DMSc, and Alexandre Vieira, DDS, MS, PhD, on behalf of the American Association for Dental, Oral, and Craniofacial Research Public comment received April 28, 2023
    Paul Connett, PhD, on behalf of the Fluoride Action Network Public comment received April 28, 2023
    Chris Neurath, on behalf of the American Environmental Health Studies Project Public comment received April 29, 2023
    John F. Mueller Jr., Private Citizen Public comment received May 3, 2023
    Howard Pollick, MPH, on behalf of the American Dental Association Public comment received May 4, 2023
  • Members
  • Minutes
  • Presentations
  • Videos

    Board of Scientific Counselors Meeting Videos
    May 4-5, 2023

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    Videos and Closed Captioning

    May 4, 2023

    PM Part 1
     

     

    PM Part 2
     
Oct 19, 2020

Peer Review of the Revised NTP Monograph on Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects by the National Academies of Science, Engineering, and Medicine

Expert Panels - Other Panels
Nov 06, 2019

Peer Review of the Draft NTP Monograph on Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects by the National Academies of Science, Engineering, and Medicine

Expert Panels - Other Panels
    Dec 01, 2015

    NTP Board of Scientific Counselors Meeting

    Board of Scientific Counselors - BSC Meeting
    • Agenda
    • Meeting Materials

      NTP Board of Scientific Counselors Meeting Meeting Materials
      December 1-2, 2015

      Supplemental materials for some events, meetings, and workshops prior to 2021 have been archived. These archived materials frequently include presentations, background materials, and public comments. Email us or use our contact form to request a list or copy of archived materials.

    • Minutes
    May 16, 2023

    Board of Scientific Counselors Meeting

    Board of Scientific Counselors - BSC Meeting

    Supplemental materials for some events, meetings, and workshops prior to 2021 have been archived. These archived materials frequently include presentations, background materials, and public comments. Email us or use our contact form to request a list or copy of archived materials.
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    Meta-analysis

    The meta-analysis is an in-depth statistical analysis of 74 epidemiological studies specifically on children’s IQ and fluoride exposure from the recently published NTP Monograph: a Systematic Review of Fluoride Exposure and Neurodevelopment and Cognition, conducted by the same scientists.

    Of the 74 studies, 22 were rated as high quality (low risk of bias) and 52 were rated as low quality (high risk of bias). Studies were conducted in 10 countries, including Canada, China, Denmark, India, Iran, Mexico, Pakistan, New Zealand, Spain, and Taiwan. None of the studies were conducted in the United States. These studies measured fluoride in drinking water or in urine. The measurement of fluoride in urine is an estimate of total fluoride exposure.

    The meta-analysis found a statistically significant association between higher fluoride exposure and lower children's IQ scores, showing that the more fluoride a child is exposed to, the more likely that child's IQ will be lower than if they were not exposed.

    The meta-analysis found that for every 1 mg/L increase in urinary fluoride, there is a decrease of 1.63 IQ points in children.

    Using data from the high-quality studies, the analyses found that fluoride exposure was associated with lower IQ scores at levels below 1.5 mg/L fluoride measured in urine or drinking water. However, there were few studies, and therefore uncertainty, in the relationship below 1.5 mg/L when fluoride was measured only in drinking water. There were not enough data to determine if 0.7 mg/L of fluoride exposure in drinking water affected children’s IQ.