Appraisal Neurodevelopmental Disorders

Fluoride studies in rats – an example of weak research

Publication reviewed:

Neurodegenerative changes in different regions of brain, spinal cord and sciatic nerve of rats treated with sodium fluoride

Reddy PY, Reddy KP, Kumar KP — J Med Allied Sci. 2011;1(1):30-5

Dr. Gary Whitford, author of The Metabolism and Toxicity of Fluoride, appraised an example of weak research in fluoride studies in rats.

Sciatic nerve example from fluoride studies in rats


Overall, I can say that if this paper had been sent to me for review, it would not have been accepted for publication.


  • A – Strong methodology and unbiased, appeared in peer-reviewed in respected science journal
  • B – Strong methodology and unbiased, not in peer-reviewed journal
  • C – Weak methodology and/or biased
  • F – Not a scientific finding


  • High – All the peer-reviewed research to date support these findings, and a significant amount of research has been done in this area.
  • Medium – Most, but not all, peer-reviewed research to date support these findings, and a significant amount of research has been done in this area.
  • Low – Not a lot of research has been done in this area, or some, but not most, other peer-reviewed research supports these findings.
  • Not Supported – No other studies support this study’s conclusions.
  • Contradicted – Most studies contradict this study’s conclusions.


(None noted for this example of fluoride studies in rats)


The references that are cited (eg, papers by Waldbott, Mullinex, Burgstahler and Colquhoun) indicate that the authors favor publications by persons with strong biases against fluoridation and other uses of fluoride. On the other hand, they do not cite publications that could not find adverse effects of very high fluoride exposure on the central nervous system (eg, Whitford et al, Neurotox Teratol 31: 210-215, 2009). The authors say that fluoride analysis of brain was done using the electrode and nothing more. This provides virtually no information about the analytical method that they used. Note also that the Abstract refers to “20 ppm of sodium fluoride”, which is 9.1 ppm of fluoride, while the Materials and Methods refers to “20 ppm concentration of fluoride.” This adds to the confusion about how the study was conducted. Apparently the rats in both the control and fluoride groups were fed inadequately or had some disease that caused massive losses in body weight. The initial body weights averaged 180 grams. At the end of the study, the average body weights of the control and fluoride groups were 111 grams and 93 grams, respectively (Table 1). This raises the possibility that the abnormal appearance of neural tissue shown in the figures was due to starvation or disease.


There were two groups of male rats. The control group received no fluoride other than what may have been in the “tap water” and the “commercial pellet diet.” The fluoride dose given by gavage to the fluoride group is not clear. The authors say that the rats received “20 ppm concentration of fluoride by gavage feeding for two months.” The reason for the lack of clarity is this: To what does the “20 ppm” refer? It is highly unlikely that “20 ppm” refers to the concentration of fluoride in the water that was administered by stomach tube (gavage) because of the impossibly high brain fluoride concentration (864 mg/kg or 45.5 mmol/kg) shown in Table 1. It is more likely that “20 ppm” refers to the dose in terms of body weight, ie, 20 mg F/kg of body weight daily for two months. In either case the brain fluoride concentrations shown in Table 1 are impossibly high. I would say that the investigators have had little experience with analysis of fluoride in biological samples. Regardless of whether the “20 ppm fluoride” refers to the concentration in the solution administered by gavage or to the mg/kg body weight dose, the exposure level was high or extremely high compared to that of humans consuming fluoridated water.


On page 31, Mullinex et al. did not report “hyperactivity and cognitive deficits” in their paper. They simply speculated about cognitive deficits in the Discussion section but did not test for them.

The authors cite a publication by Varner et al that reported “morphological alteration in specific regions of the brain” of rats treated with high doses of aluminum fluoride. That is true but they did not cite a subsequent paper by Varner et al that reported no behavioral effects of high doses of fluoride (Behavioral and Neural Biology 61: 233-241, 1994). The tests used to evaluate possible behavioral effects were balance beam (the fluoride treated rats actually performed better) and the Morris water maze test, which tests memory. So despite possible histological changes in neural tissue associated with high fluoride exposures, behaviors remained unaffected.

Our publication (cited above) also found no adverse effects in appetitive based learning by rats after eight months of fluoride exposure up to 230 times more than that experienced by persons with typical fluoride intake from dietary sources including fluoridated water.

Overall, I can say that if this paper had been sent to me for review, it would not have been accepted for