Water fluoridation has long been hailed as an effective method of reducing dental caries (tooth decay). Over the years, however, people have raised concerns about adverse health effects of fluoride exposure. Of particular concern are results of epidemiologic studies—typically conducted in regions that have high naturally occurring fluoride—that have reported neurodevelopmental and cognitive effects in humans. That concern and a nomination from the Fluoride Action Network (FAN) prompted the National Toxicology Program (NTP) Office of Health Assessment and Translation to undertake a systematic review to evaluate the evidence of adverse neurodevelopmental and cognitive effects of fluoride exposure in humans. To ensure the integrity of its evaluation, NTP asked the National Academies of Sciences, Engineering, and Medicine (the National Academies) to review its monograph Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects (NTP 2019).1 As a result of that request, the National Academies convened the present committee, which prepared this report.
Water fluoridation in the United States began in 1945 as a public-health practice to prevent dental caries. In 1962, the US Public Health Service recommended optimal fluoride concentrations of 0.7–1.2 mg/L; it revised its recommendation to 0.7 mg/L in 2015 (Gooch 2015). State and local governments, however, ultimately decide whether to fluoridate water systems. From the outset, the practice of fluoridating water systems has been controversial (NRC 2006), primarily because of the adverse health effects that have been associated with fluoride exposure over the years.
In 2006, the National Academies released the report Fluoride in Drinking Water: A Scientific Review of EPA’s Standards (NRC 2006), which reviewed the scientific literature on fluoride exposure and human health effects (see Box 1-1). That report found that chronic exposure to fluoride is associated with enamel fluorosis and with bone weakening that could increase the risk of fractures. However, the evidence on several outcomes was not sufficient for the committee to reach conclusions; neurotoxicity was one such outcome. A few epidemiologic studies
1 Hereafter referred to as the monograph.
indicated IQ deficits in children exposed to fluoride at 2.5–4 mg/L in drinking water. However, the committee that prepared the 2006 report concluded that “the studies lacked sufficient detail…to fully assess their quality and relevance to the U.S. populations, [but] the consistency of the results appears significant enough to warrant additional research on the effects of fluoride on intelligence” (NRC 2006, p. 8).
Since the National Academies report (NRC 2006) was released, additional scientific research has been conducted on the association between fluoride exposure and neurodevelopmental and cognitive health effects. In 2016, NTP published the results of a systematic review that examined the effects of fluoride exposure on learning and memory in animals (NTP 2016). NTP found “low to moderate level-of-evidence that suggests adverse effects on learning and memory in animal[s] exposed to fluoride” at concentrations higher than 0.7 ppm (NTP 2016, p. vii). NTP noted that few studies that examined effects near concentrations of 0.7 ppm were available, that confidence in the results of available studies was reduced because of confounding and risk-of-bias issues, and that further research was needed.
Over the last decade, epidemiologic studies of the effects of fluoride exposure on neurodevelopment and cognition have also been conducted. Given those studies and a nomination from FAN, NTP conducted a systematic review of the
evidence on fluoride exposure and neurodevelopmental and cognitive health effects and released its monograph in 2019 (NTP 2019).2 Although a primary focus was on the human evidence, the systematic review evaluated animal studies that had been published since the 2016 NTP report and mechanistic studies that might be able to shed light on a possible pathway for fluoride exposure to cause neurodevelopmental or cognitive health effects. The monograph concluded that “fluoride is presumed to be a cognitive neurodevelopmental hazard to humans. This conclusion is based on a consistent pattern of findings in human studies across several different populations showing that higher fluoride exposure is associated with decreased IQ or other cognitive impairments in children” (NTP 2019, p. 2). Although NTP did not conduct a formal dose–response assessment, it noted that effects on cognitive neurodevelopment were inconsistent at concentrations of about 0.03–1.5 ppm. NTP (2019) also stated that the evidence of cognitive effects in adults was inadequate, that the animal evidence was inadequate to support conclusions about cognitive effects, and that the possible mechanisms for the noted effects “are not well characterized.” Given the importance of the findings, NTP asked the National Academies to review its monograph.
The committee that was convened as a result of the NTP request included experts in toxicology, epidemiology, neurodevelopment, systematic review, and statistics. Appendix A provides biographic information on the committee. The committee was asked to review the monograph and ultimately to assess whether NTP’s conclusions are supported by the evidence provided in it. The verbatim statement of task is provided in Box 1-2.
The committee held several teleconferences and one in-person meeting, which included an open session at which the committee heard from the sponsor and interested stakeholders. As part of its evaluation, the committee reviewed key scientific studies from the monograph and considered materials submitted to the committee by interested parties. It is important to note that the committee did not conduct its own independent evaluation of the evidence, and it did not conduct a data audit (that is, review all the data reported in the monograph to ensure that it had been reported correctly), although it did review some key literature to enable
2 It is important to note that NTP monographs evaluate the evidence that a given exposure causes adverse health effects. As noted by NTP, the monographs might provide hazard conclusions depending on the assessment goals and available evidence (see https://ntp.niehs.nih.gov/whatwestudy/assessments/index.html). They typically do not include formal dose–response assessments, and they are not risk assessments or risk–benefit assessments. Therefore, they should not be used to reach conclusions on appropriate exposure guidance levels or standards.
its review. The committee evaluated whether presentation of the evidence in the monograph supported NTP’s conclusions and focused primarily on the human and animal evidence.
The report is organized into four chapters and one appendix. Chapter 2 provides the committee’s review of the methods and overall presentation. Chapters 3 and 4 provide the committee’s evaluation of NTP’s presentation and assessment of the animal and human evidence, respectively. Appendix A provides the biographic information on the committee.
Gooch, B.E. 2015. U.S. Public Health Service Recommendation for Fluoride Concentration in Drinking Water for the Prevention of Dental Caries. Public Health Reports 130: 318-331.
NRC (National Research Council). 2006. Fluoride in Drinking Water: A Scientific Review of EPA’s Standard. Washington, DC: The National Academies Press.
NTP (National Toxicology Program). 2016. NTP Research Report: Systematic Review of the Effects of Fluoride on Learning and Memory in Animal Studies. Research Triangle Park, NC: National Toxicology Program. Research Report 1.
NTP. 2019. Draft NTP Monograph on the Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. Office of Health Assessment and Translation, Division of the NTP, National Institute of Environmental Health Sciences, National Institutes of Health, US Department of Health and Human Services.