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). -Updated May 2, 2023 (EC).

NTP 1990 Cancer Study: Thyroid and Oral Cancer

The United States Congress mandated the National Toxicology Program (NTP) to conduct animal studies to determine if fluoride causes cancer. After a few aborted attempts in the early 1980s, the NTP successfully began a 2-year study on rats and mice in 1985. Battelle Columbus Laboratories was retained by NTP to perform the study.

The NTP released their report in 1990.

Two of the most controversial findings revolved around the findings of osteosarcoma and liver cancer. The senior toxicologist for the Environmental Protection Agency, William Marcus, expressed concerns about the “systematic downgrading” of cancers throughout the report.

There were also increases in oral and thyroid cancers, but they were not considered statistically significant. We include the findings below.

Oral Cancers

“A second potential target site for sodium fluoride when given in drinking water is the upper digestive tract and oral cavity. Squamous cell neoplasms of the oral mucosa (tongue, palate, or gingiva) occurred with marginally increased incidences in dosed males and female rats over the rates in controls. The increased incidences of these neoplasms were not statistically significant when compared with the incidences in concurrent controls; however, the incidences in the high-dose groups were significantly higher than the incidences observed in historical control animals (0.7% male rats; 0.6% female rats).
As with lesions of the bone, a direct comparison with the historical rates for oral cavity neoplasms is not completely accurate because of the increased attention given to the oral cavity and teeth in the sodium fluoride studies compared to previous NTP studies. Rates for oral cavity neoplasms similar to those observed in high-dose male and female rats in the sodium fluoride studies (4%) have been observed twice for males and once for females in the historical control database of 42 dosed feed or water studies. Neoplasms of the oral cavity were observed in control male and female rats in the current studies; one was observed in an age-matched control male rat and one occurred in a control female rat in the main study.
An argument could be made for combining the male and female rat studies for analysis of oral cavity neoplasms because a marginal increase occurred in both groups. An analysis for significance of the combined P values for the logistic regression trend tests for males and female rats resulted in a nonsignificant P value of 0.065.
In contrast to osteosarcomas, for which there are no recognized benign or preneoplastic counterparts (Litvinov and Soloviev, 1973), squamous cell hyperplasias of the oral cavity are considered preneoplastic precursor lesions of squammous cell neoplasms of the oral cavity (Brown and Hardisty, 1990). Squamous cell hyperplasia occurred in no more than one animal in any of the dosed or control groups in the current studies. Thus, based on the absence of statistical significance versus the concurrent controls, the occurrence of these tumors in control animals, and the lack of a dose-related increase in non-neoplastic precursor lesions, it is concluded that there is insufficient evidence to relate tumors of the oral cavity with administration of sodium fluoride to male or female rats. Glattre and Wiese (1979) reported an association between a decrease in human mortality due to oral cavity neoplasia and increasing fluoride content in water over the range of 0 to 0.5 ppm.”
SOURCE: National Toxicology Program [NTP] (1990). Toxicology and Carcinogenesis Studies of Sodium Fluoride in F344/N Rats and B6C3f1 Mice. Technical report Series No. 393. NIH Publ. No 91-2848. National Institute of Environmental Health Sciences, Research Triangle Park, N.C. p. 73-74.

Thyroid Cancers:

“Follicular cell neoplasms of the thyroid gland appeared with a marginally increased incidence in high-dose male rats compared with controls. This increase is not statistically significant compared with controls unless control animals from both interim groups (27 and 66 weeks) and the age-matched controls are pooled with the main study control group. If this is done, the logistic regression P value for the trend is 0.027. Thyroid follicular cell neoplasms typically occur with an incidence of 1.2% in historical control animals.Incidences of 6% have previously been observed in untreated control groups for gavage studies. The incidence of these neoplasms in the high-dose groups was 5/90 (5.5%;includes 10 animals from the 66-week interim sacrifice, one of which had a thyroid follicular cell carcinoma). Three of these tumors were adenomas. The incidence of carcinomas did no differ across the dosed groups and the incidence of follicular cell hyperplasia was not increased. No increase in the incidence of these tumors occurred in female rats. Based on these considerations, follicular cell neoplasms of the thyroid are not considered related to sodium fluoride administration.”
SOURCE: National Toxicology Program [NTP] (1990). Toxicology and Carcinogenesis Studies of Sodium Fluoride in F344/N Rats and B6C3f1 Mice. Technical report Series No. 393. NIH Publ. No 91-2848. National Institute of Environmental Health Sciences, Research Triangle Park, N.C. p. 74.

Interviews with EPA Scientists About NTP Study:


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