Fluoride Action Network

Protected: The National Toxicology Program

Apologies, under construction for a few days. The Fluoride Action Network is in the process of adding all the information and documents it has on the National Toxicology Program’s (NTP) long involvement with the fluoride issue into this dedicated section. We expect this process to be complete by the end of February 2021.

Part 3: 2019-2020

The two Draft NTP Systematic Reviews of Fluoride’s Neurotoxicity

The National Toxicology Program (NTP) review of fluoride’s neurotoxicity was initiated in response to a nomination from the Fluoride Action Network (FAN). The NTP began the review in 2016 and released its draft in September 2019. This draft was sent to the National Academies of Sciences, Engineering and Medicine (NAS) for peer-review.

The NAS committee held a meeting for the public on November 6, 2019, to discuss NTP’s review and to accept public comment. Fluoride Action Network’s research director, Chris Neurath, and senior advisor, Bill Hirzy, PhD, attended the meeting. An excerpt from a news report by Bloomberg Law noted,

Risk Greater Than Recognized

Fluoride poses a greater risk than NTP’s draft report suggests, Chris Neurath, research director for the Fluoride Action Network, told the committee.

NTP’s report consistently paid less attention to studies that found low concentrations of fluoride could be harmful, he said.

The scientific evidence showing fluoride can harm children’s developing brains is as strong or stronger than was the data that emerged in the 1990s—and faced fierce criticism—showing low levels of lead were neurotoxic, Neurath said.

It took two decades for public health officials to accept that at a low level lead was indeed neurotoxic. “Millions of children suffered loss of IQ and behavioral problems during those two decades of critical indecision,” he said.

The academies should pay heed, he said.

The NAS recommended that NTP make several changes.

On September 16, 2020, NTP sent their second draft review to NAS, incorporating the changes they requested.

The members of the NAS committee that peer-reviewed the NTP Review are in Part 4.

Conclusion of NTP’s 2019 first draft Review (page 2):

NTP concludes 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. However, the consistency is based primarily on higher levels of fluoride exposure (i.e., >1.5 ppm in drinking water).

Conclusion of NTP’s 2020 second draft Review, page 2:

NTP concludes that fluoride is presumed to be a cognitive neurodevelopmental hazard to humans. This conclusion is based on a moderate level of evidence that shows a consistent and robust pattern of findings in human studies across several different populations demonstrating that higher fluoride exposure (e.g., >1.5 mg/L in drinking water) is associated with lower IQ and other cognitive effects in children. Limited and weaker evidence is considered to provide an inadequate level of evidence that fluoride is associated with cognitive effects in adults.

What is a “presumed” rating?

The NTP used the OHAT* method for rating fluoride’s hazard. The five ratings are: Known, Presumed, Suspected, Not classifiable, or Not identified to be a hazard to humans.

The NTP rating of “presumed” is the highest confidence rating without doing a controlled human experiment, which would be illegal.

Comparison of NTP monographs for other chemicals found only the chemical warfare agent Sarin to receive the confidence rating “known hazard” and that was because there were controlled human experiments.

* OHAT is the abbreviation for Office of Health Assessment and Translation, which is within the Division of the National Toxicology Program at the National Institute of Environmental Health Sciences.


Fluoride Action Network’s submissions

The Director of FAN, Paul Connett, PhD, noted in his comments submitted to NASEM,

“The most revealing observation from the NIH funded studies on fluoride’s neurotoxicity (Bashash 20171, 20182; Green 20193; Till 20204) is that the most vulnerable period of exposure for neurological harm from fluoride is during fetal development and during early infancy (particularly from bottle feeding).”

Chris Neurath, research director for FAN submitted substantive comments to both NASEM and the NTP on the 2020 Review (see all his submissions at the bottom).

Chris identifies with specificity the downgrading of evidence in the Review in his full submission with tables and figures. It will shock those who have read the literature to learn that the NTP Review excluded the Bashash  20171  study.

Downgraded evidence in the 2020 Review:

• Excluded the largest effect in the strongest study: Bashash 2017.
• Excluded strongest low-dose studies from dose-response meta-analysis.
• Unnecessary division of studies lowers power in dose-response meta-analyses.
• Simplistic exposure assessment underestimates hazard at doses relevant to US.
• NTP’s simplistic dose-response meta-analysis methods underestimated effects at low doses because they used the mean exposure while most studies had individual-level exposures that ranged well below the mean.
• Improperly downgraded the animal evidence to “inadequate” despite the NTP 2016 review of the animal evidence concluding it was “low to moderate”.
• The NTP monograph deviated from the OHAT guidelines in its section “Generalizability to the U.S. Population”.
• Meta-analyses have inadequate documentation.

Connett noted in his comments,

“In my view, the timing of exposure is equally important as the dose. In the Bashash 20171 study of 4 year-olds – cognitive effects were observed down to 0.2 ppm of fluoride in mother’s urine with no obvious threshold. Incredibly, the NTP managed to ignore this finding in its meta-analysis of all the studies, erroneously suggesting that Bashash, 20171 showed NO LOWERING of IQ!”

Chris Neurath identified the following strengths and weaknesses of the 2020 Review:

Strengths

• The revised and updated review has identified substantially more higher quality studies with the number going from 18 to 29.

• Of the 29 higher quality studies, 27 found statistically significant adverse effects, which is a very high degree of consistency.

• The NTP has addressed recommendations of both NASEM and FAN to improve the clarity and validity of quality scoring methods.

• The addition of meta-analyses also improves clarity of the evidence.

• The conclusion of “presumed developmental neurotoxity” has thus grown substantially stronger and is solidly supported by the body of evidence.

Weaknesses

• Our written submission has detailed discussion of weaknesses.

• By far the greatest weakness is the ad hoc section titled “Generalizability to the US Population”. This is, in effect, a risk assessment requiring a valid exposure assessment and dose-response assessment, but NTP has done neither. The NTP’s methods led to an underestimate of the confidence that fluoride causes harm at exposures below 1.5 mg/L.

• The NTP made the fundamental error of equating drinking water concentration with internal dose.

• The NTP’s exposure assessment consisted of a single one-sentence footnote referenced to a CDC database that is restricted and not available to the public.

• There was no proper dose-response assessment. The only planned dose-response assessment was a dose-response meta-analysis, yet it was not carried out for the 10 highest quality studies with individual-level exposure data. These 10 highest quality studies were also those finding affects at the lowest doses. The failure to conduct a dose-response meta-analysis on the strongest studies at low doses leads to a severe underestimate of the confidence of adverse effects at low doses.

• For the dose-response meta-analysis of group-level studies, NTP improperly used just the mean doses to define doses, even though many studies had a wide range of exposures in each exposure group, including exposures that fell below the cut-off level 1.5 mg/L.

• We are conducting a dose-response meta-analysis with the 10 individual-level studies and will supply it to the NAS.

• When proper dose-response assessments are made with the 29 higher quality studies, we found remarkable consistency of adverse effects. 18 studies were at exposures below 1.5 mg/L and 17 of those found adverse effects.

• Therefore, the evidence below 1.5 mg/L is as strong and consistent as that above 1.5 mg/L.

• Finally, a fundamental goal of the OHAT systematic review method is to ensure consistency of NTP evaluations across different chemicals.

Chris concluded this list with,

• When comparing the fluoride monograph to those for other chemicals we find a dramatic double standard, with fluoride needing to pass a far higher bar to reach a conclusion of presumed hazard than other chemicals.

• We believe the NASEM committee and NTP must take a larger perspective and ensure fluoride is treated in the same way as any other chemical being evaluated by NTP.


Documents on NTP’s Review

News Articles are at http://fluoridealert.org/news/?country=national-toxicology-program


Videos

This short video is a good introduction to the NTP’s Systematic Review of Fluoride’s Neurotoxicity


More Public Comments from Chris Neurath on the Fluoride Review (October 2020)

Documents and Submissions

Year

Documents and Submissions

2019
NTP
September 6, 2019. Draft NTP Monograph on the Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. National Toxicology Program.
2019
NTP
October 22. Draft NTP Monograph on the Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. National Toxicology Program. Dated September 6, 2019; available October 22, 2019.
LINK:
http://fluoridealert.org/wp-content/uploads/2019.ntp_.draft-fluoride-systematic-review.online-Oct-22.pdf
2019
NTP
November 6. Presentation to the National Academies on the draft NTP Monograph on the Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects, byKyla W. Taylor, PhD, Office of Health Assessment and Translation, Division of the National Toxicology Program, National Institute of Environmental Health Sciences.
2019
News
Article
November 6. Public Trust in Tap Water May Hinge on Fluoride Link to Child IQ. By Pat Rizzuto. Bloomberg Law.
2020
NTP
March 5. Review of the Draft NTP Monograph: Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects (2020). National Academy of Science, Engineering and Medicine.
LINK:  http://fluoridealert.org/wp-content/uploads/nas-review-of-ntp-review.march-5-2020.pdf
2020
NTP

September 16. Draft NTP Monograph on the Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects*.

**The September 6, 2019 draft monograph was peer reviewed by a committee convened by the National Academy of Sciences, Engineering, and Medicine (NASEM). This current draft incorporates changes in response to that review and is being submitted to the same NASEM committee for an additional round of peer review.
LINK:http://fluoridealert.org/wp-content/uploads/ntp.revised-monograph.9-16-2020.pdf

2020
NTP
September 16. Committee on Peer Review of the NTP Monograph on Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects.
LINK:http://fluoridealert.org/wp-content/uploads/ntp.nasem-committee-to-review.fluoride.2020.pdf
2020
NTP
September 16. Protocol for the Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. Project Leader: Kyla Taylor, PhD.
LINK: http://fluoridealert.org/wp-content/uploads/ntp-f-protocol_revised.sept-16-2020.pdf
2020
NTP
September 16. Literature Search Results for the Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects. 
LINK:http://fluoridealert.org/wp-content/uploads/ntp.literature-search.9-16-20.pdf
2020
FAN
October 6. National Toxicology Program confirms fluoride a brain hazard, according to Fluoride Action Network. Press Release from FAN.
2020
ADA
October 16. Comments submitted from the American Dental Association to the National Academies on the “Revised NTP Monograph on Fluoride Exposure and Neurodevelopmental and Cognitive Health.
LINK:http://fluoridealert.org/wp-content/uploads/ntp.ada_.comments.10-16-20.pdf
2020
Neurath
October 19. Submission from Chris Neurath on behalf of FAN to the National Academies Committee to Review the Revised National Toxicology Program’s Monograph on Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects.
LINK:
http://fluoridealert.org/wp-content/uploads/ntp.neurath.submission-to-nas-on-revised-ntp-monograph.10-19-20.pdf
2020
Neurath
October 19. Outline with figures of submission from Chris Neurath on behalf of FAN to the National Academies Committee to Review the Revised National Toxicology Program’s Monograph on Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects.
LINK: http://fluoridealert.org/wp-content/uploads/ntp.neurath.outline-with-figures-of-submission-to-nas.10-19-20.pdf
2020
Neurath
October 19. Oral comments from Chris Neurth on behalf of FAN on the NTP’s Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects to the National Academies Committee to Review the Revised National Toxicology Program’s Monograph.
LINK:http://fluoridealert.org/wp-content/uploads/ntp.neurath-oral-comments-to-nas.10-19-20.pdf
2020
Connett
October 19. Comments from Paul Connett of FAN to the National Academies Committee to Review the Revised National Toxicology Program’s Monograph on Systematic Review of Fluoride Exposure and Neurodevelopmental and Cognitive Health Effects.
LINK: http://fluoridealert.org/wp-content/uploads/ntp.paul-connett.comments-to-nas.10-19-20.corrected-1.pdf
2020
Neurath
December 4. The NTP Review: A Video Summary from Chris Neurath. Fluoride Action Network.
2020
Neurath
NEURATH: DOSE RESPOSE DOCUMENTS:
FAN dose-response assessment of Nov. 30, 2020
Appendix which provides the computer code used to generate the meta-analyses and meta-regressions
Data file in Excel format.xlsx”
Updated ISEE 2020 Conference poster
Supporting details for dose-response analysis summaries shown in ISEE 2020 Conference poster
and a
A zip file for:
Dose response analysis
Meta-analysis data high quality NTP studies

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