Fluoride Action Network

The National Toxicology Program

This section is dedicated to the National Toxicology Program’s (NTP) long involvement with the issue of fluoride's toxicity. The NTP is the scientific research arm for U.S. regulatory agencies. It comes under the aegis of the National Institute of Environmental Health Sciences (NIEHS). The NIEHS, in turn, comes under the umbrella of the National Institutes of Health (NIH).

NTP: Government-funded Fluoride Studies

It’s important to stress that from 1950, when the U.S. government approved the deliberate addition of fluoride into the drinking water of millions of Americans, no government agency has ever performed an assessment of the risks of this practice for the most vulnerable in our society,

  • the pregnant woman living in a fluoridated community
  • the fetus of a woman living in a fluoridated community
  • the bottle-fed infant living in a fluoridated community

Yet the public is told that community water fluoridation is “safe.”

Under the leadership of Dr. Linda Birnbaum, the director of the NIEHS and NTP from 2009 to 2019, the following government agencies began to fund the studies on fluoride’s neurotoxicity.

  • NIEHS (National Institutes of Environmental Health Studies) has responsibility for the NTP
  • NIH (National Institutes of Health) has responsibility for the NIEHS
  • EPA (Environmental Protection Agency) has responsibility for ensuring “safe” fluoride levels in drinking water

The human studies funded by U.S. government agencies (Bashash 2017, Green 2019 and Till 2020) reveal that in fluoridated communities the fetus and the formula-fed infant are the most vulnerable to fluoride’s neurotoxicity. Certain high levels of fluoride in the pregnant women’s urine were found to significantly impact the IQ, or neurodevelopment, of the offspring. These high urinary fluoride levels are found in pregnant women living in fluoridated areas as well as in naturally-occurring high fluoride areas.

The National Institute of Dental and Craniofacial Research (NIDCR) funded the Broadbent et al. 2015 study (see below) which found no association between exposure to fluoride and reduced IQ.

Not all studies funded by U.S. agencies are listed below, but we will attempt to identify all the studies as we find them.

April 2022 Update:
The U.S. Goverment-funded fluoride studies are now at https://fluoridealert.org/researchers/f-studies-funded-by-us-govt/human-studies-neurotoxicity/

Updated January 31, 2022

Year,
Grants

Author, Study

Finding

2021
NIEHS
Dec 7: Adkins & Brunst: Impacts of Fluoride Neurotoxicity and Mitochondrial Dysfunction on Cognition and Mental Health: A Literature Review. “… there is no agreed-upon mechanism for the neurotoxic effects of fluoride; however, fluoride can induce mitochondrial damage, including decreasing circulating mitochondrial DNA content, dysregulating biogenesis, and circular structure loss. Additionally, many neurodevelopmental conditions have mitochondrial underpinnings. More work is needed to elucidate the impact and timing of fluoride exposure on mental health and the role of mitochondrial function as a biological mechanism.”

2021

NIEHS

Nov 24: Mailin et al., Fluoride Exposure and Age of Menarche: Potential Differences Among Adolescent Girls and Women in the United States. “… we observed a significant interaction between plasma fluoride and race/ethnicity in association with age of menarche (p = 0.01). Among Non-Hispanic Black adolescents, each IQR increase in plasma fluoride was associated with a 5-month earlier age of menarche (B = 0.42, 95%CI –  0.61, – 0.23, p < 0.001). Potential impacts of chronic low-level fluoride exposure on reproductive health outcomes are an important area of study. Current study findings, as well as potential health disparities due to disproportionate fluoride exposure should be examined in prospective studies…”

2021

NIEHS

Oct 29: Adkins et al. Fluoride exposure during early adolescence and its association with internalizing symptoms.

• Adolescents with elevated urinary fluoride concentrations exhibit more somatization symptoms.

• Males may represent an at-risk population for fluoride-related internalizing behaviors.

• While somatization is typically comorbid with anxiety and depression, fluoride concentrations were not associated with increased depressive or anxiety symptoms.

“This is the first study to link fluoride exposure and internalizing symptoms, specifically somatization. Somatization represents an interface of physical and psychological health. Continued follow-up will help shed light on the sex-specific relationship between fluoride and mental health and the role of somatization.”

2021

NIEHS

Aug 31: Cantoral et al. Dietary fluoride intake during pregnancy and neurodevelopment in toddlers: A prospective study in the Progress Cohort. “These findings suggest that the development of nonverbal abilities in males may be more vulnerable to prenatal fluoride exposure than language or motor abilities, even at levels within the recommended intake range.”

2021

NIEHS

June 8: Grandjean et al., A Benchmark Dose Analysis for Maternal Pregnancy Urine-Fluoride and IQ in Children. The analysis found that a maternal urine fluoride concentration of 0.2 mg/L was enough to lower IQ by 1 point.  This level is exceeded 4 to 5 times in pregnant women living in fluoridated communities.

2020

NIEHS

Sept: Farmus et al., Critical Windows of Fluoride Neurotoxicity in Canadian Children

• The strongest association between fluoride and Performance IQ was during the prenatal window; the association was also significant during infancy.

• Within sex, the association between fluoride and PIQ significantly differed across the three exposure windows; among boys, the strongest association was during the prenatal window, whereas among girls, the strongest association was during infancy.

• The susceptibility of infants to fluoride from drinking water is further amplified by their higher level of water intake than adults on a per body-weight basis (Snodgrass, 1992) and lower ability to detoxify exogenous compounds than adults. In particular, formula-fed infants, whose formula is made with fluoridated water, have an approximate 70-fold higher fluoride intake than exclusively breastfed infants (Ekstrand, 1981; Zohoori et al., 2018; US EPA, 2010). Thus, level and timing of fluoride exposure are critical for determining the window of greatest vulnerability for neurodevelopmental outcomes.

2021

NIEHS, EPA

June 26: Castiblanco-Rubio et al., Dietary Influences on Urinary Fluoride over the Course of Pregnancy and at One-Year Postpartum. No significant observations made in this study.

2021

NIEHS

June 26: Ayele et al., Neuro-medical manifestations of fluorosis in populations living in the Main Ethiopian Rift Valley. Headache and joint pain reported by 67.1% and 56.3% of the participants as the most common neurological manifestation.

2021

NIH

Jan 29: Kyzer et al., Metabolism and Toxicity of Fluorine Compounds. The use of fluorine in pharmaceuticals and agrochemicals has expanded dramatically since its first use in the 1950s. Its use is often tied to improved metabolic stability, selectivity, and solubility, which has been demonstrated for a variety of products. However, fluorinated compounds are not immune to metabolism and liberation of fluoride or low molecular weight fluorinated molecules from fluorine-containing drugs, and candidates must be monitored to avoid potentially lethal toxicity.

2021

NIEHS

Feb 18: Cunningham et al., Fluoride exposure and duration and quality of sleep in a Canadian population-based sample.

2021

NIH, EPA

June: Signes-Pastor et al., Exposure to a Mixture of Metals and Growth Indicators in 6–11-Year-Old Children from the 2013–2016 NHANES.

2021

NIEHS

Oct 15: Khattak et al. Groundwater fluoride across the Punjab plains of Pakistan and India: Distribution and underlying mechanisms. Science of the Total Environment.

2021

NIEHS, NIH

Sept 7: Saylor et al. Early childhood fluoride exposure and preadolescent kidney function. Environmental Research.

2020

NIEHS

Till et al., Fluoride exposure from infant formula and child IQ in a Canadian birth cohort.

Lowered IQ

2020

NIH, EPA

Uyghurturk et al., Maternal and fetal exposures to fluoride during mid-gestation among pregnant women in northern California. The first U.S. study of urinary fluoride levels  in pregnant women as well as fluoride levels in serum and the amniotic fluid of pregnant women.

NIEHS

2020

Farmus et al., Critical Windows of Fluoride Neurotoxicity in Canadian Children. Within sex, the association between fluoride and performance IQ significantly differed across the three exposure windows (p = .01); among boys, the strongest association was during the prenatal window,  whereas among girls, the strongest association was during infancy.

2020

NIEHS

Green et al., Sex-Specific Neurotoxic Effects of Early-Life Exposure to Fluoride: a Review of the Epidemiologic and Animal Literature. Compared with females, male offspring appear to be more sensitive to prenatal, but not postnatal, exposure to fluoride. We discuss several sex-specific mechanisms and emphasize the need for future research.

2020

NIEHS, NIH

Green et al., Associations between Urinary, Dietary, and Water Fluoride Concentrations among Children in Mexico and Canada. We found that childhood urinary fluoride levels are comparable among children in Mexico City and fluoridated Canadian communities, despite distinct sources of exposure. Community water fluoridation is a major source of fluoride exposure for Canadian children.
2020
NIEHS, NIH, EPA
Liu et al., Association between fluoride exposure and cardiometabolic risk in peripubertal Mexican children. • We examined the cross-sectional association between peripubertal exposure to fluoride and markers of cardiometabolic risk in 280 girls and 256 boys at age 10-18 years living in Mexico City.
• We found that higher peripubertal fluoride exposure at the levels observed in this study population was significantly associated with increased levels of cardiometabolic risk factors in Mexican girls but not boys.

2020

NIEHS, NIH

Godebo et al., Bone quality in fluoride-exposed populations: A novel application of the ultrasonic method.

2019

NIEHS

Green et al., Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada.

Lowered IQ

2019

NIEHS

Grandjean, Developmental fluoride neurotoxicity: an updated review. Conclusion: The recent epidemiological results support the notion that elevated fluoride intake during early development can result in IQ deficits that may be considerable. Recognition of neurotoxic risks is necessary when determining the safety of fluoride-contaminated drinking water and fluoride uses for preventive dentistry purposes.

 

2019

NIEHS, NIH, EPA

Liu et al. Fluoride exposure and pubertal development in children living in Mexico City. “Childhood fluoride exposure, at the levels observed in our study, was associated with later pubertal development among Mexican boys at age 10-17 years. Further research is needed to confirm these findings.”

2019

NIEHS

Malin et al., Fluoride exposure and liver function among adolescents in the United Stares: NHANES, 2013-2016. See Mt. Sinai press release on study.

2018

NIEHS, NIH

Bashash et al., Prenatal fluoride exposure and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6–12 years of age in Mexico City.

Higher concentration of maternal urinary fluoride was associated with more ADHD-like symptoms in school-age children.

Prenatal exposure to fluoride was most strongly associated with behavioral ratings of inattention

2018

NIEHS, NIH

Till et al., Community Water Fluoridation and Urinary Fluoride Concentrations in a National Sample of Pregnant Women in Canada. The first national survey in Canada of urinary fluoride levels in pregnant women.
2018
NIH
Zelko F. 2018. Optimizing nature: Invoking the “natural” in the struggle over water fluoridation. On the history of fluoridation.
“…One of the attractions of water fluoridation is its affordability: the fluoride compounds are sourced from the phosphate and aluminum industries, for whom they would otherwise constitute an annoying waste disposal problem. Despite this, proponents have nonetheless succeeded in shaping a narrative that casts fluoridation as “natural” or at least mimicking nature.”

2017

NIEHS, NIH, EPA

Bashash et al., 2017, Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6–12 Years of Age in Mexico

Lowered IQ

2015

NIDCR

Broadbent et al. – Community Water Fluoridation and Intelligence: Prospective Study in New Zealand. This is one of eight (8) fluoride IQ studies that found no association between exposure to fluoride and reduced IQ. [72 studies found the opposite effect.] The NTP rated this study as relatively low quality and high risk of bias. There are several glaring problems with this study including the fact that virtually all of the children in the “non-fluoridated” community used fluoride supplements (a prescription drug designed to deliver the same amount of fluoride a child would get from drinking fluoridated water). FAN discusses these problems here.

Animal Studies

2018

NTP, NIEHS, NIH, HHS

McPherson et al., An Evaluation of Neurotoxicity Following Fluoride Exposure from Gestational Through Adult Ages in Long-Evans Hooded Rats.

This study was hailed by fluoridation proponents who said that no adverse neurotoxic effects were found in this study.

Spencer & Limeback identified flaws in the study.

Another flaw in this study that hasn’t been mentioned is that the rats were dosed with fluoride in drinking water from gestational day 6. The average gestation time for black hooded Long Evans rats is 20 to 23 days (Janvier Labs). The average gestation time for other rats, not identified as to species, is 21 to 23 days (Merck). (EC)

1990

NTP

Toxicology and Carcinogenesis Studies of Sodium Fluoride in F344/N Rats and B6C3F1 Mice (Drinking Water Studies).

The principal finding of NTP’s study, performed by Battelle Columbus Laboratories, was a dose-dependent increase in osteosarcoma (bone cancer) among the fluoride-treated male rats.

However, despite the fact that

1) the cancer occurred in the target organ (bone) for fluoride accumulation,
2) the increase in bone cancer was statistically-significant,
3) the doses of fluoride were low for an animal cancer study, and
4) NTP acknowledged it is “biologically plausible” that fluoride could induce bone cancer,

the NTP ruled that the study only provided “equivocal evidence” that fluoride was the cause of the cancer.
See more here AND here

.

The Sprando & Collins Animal Studies

EPA invested a lot of credence in the Sprando and Collins rat studies. Their studies found negligible effects of sodium fluoride on developmental toxicity and male reproduction at levels up to 250 ppm NaF. One of the findings that raises serious questions about these studies is the notably low incidence and severity of dental fluorosis in their treated animals. Even in the highest dosed animals (250 ppm NaF) the only dental fluorosis that was observed, according to the authors, was mild in nature. This is in stark contrast to most other studies which typically find severe changes to tooth enamel at concentrations < 100 ppm. (Den Besten et al. 1984,1985; NTP 1990). In the 1990 NTP cancer study, for instance, at 79 ppm, animals exhibited severe fluorosis of the enamel. Thus, the abnormally mild nature of the fluorosis observed in the Sprando and Collins studies suggests that the level of bio-available fluoride in these studies may be less than the authors assumed.

In contrast to the findings of over 150 animal studies from other research teams, the Sprando & Collins team reported virtually no evidence of reproductive toxicity among animals treated with very high levels of fluoride exposure. The reasons for this discrepancy remains unclear.

Comments on the Sprando & Collins studies
submitted to the National Research Council in 2004
submitted to the EPA in 2005

Grants
from

Date Published

Author, Study

FDA 2001 Colins, Sprando, et al. Multigenerational evaluation of sodium fluoride in rats.
FDA 2001 Collins, Sprando, et al., Developmental toxicity of sodium fluoride measured during multiple generations.
FDA 1998 Sprando, Collins, et al. Testing the potential of sodium fluoride to affect spermatogenesis: a morphometric study.
FDA 1997 Sprando, Collins, et al. Testing the potential of sodium fluoride to affect spermatogenesis in the rat.
FDA 1996 Sprando, et al. Effect of intratesticular injection of sodium fluoride on spermatogenesis.
FDA 1995 Collins, Sprando, et al. Developmental toxicity of sodium fluoride in rats.

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