Greater Boston Physicians for Social Responsibility

REPORT: In Harm’s Way: Toxic Threats to Child Development

Chapter 6: Known and Suspected Developmental Neurotoxicants (full PDF)


Since the 1950’s, in many communities throughout the US and other areas of the world, fluoride has been added to community drinking water supplies with the intention of reducing tooth decay. Controversy about the safety of that practice centers around concerns about increased risks of tooth staining and brittleness (dental fluorosis), bone brittleness (skeletal fluorosis), bone cancer, hormone disruption (melatonin), premature puberty, and altered neurological development. In addition, some critics argue that fluoridating the water supply has a minimal impact on tooth decay. The practice has been staunchly defended by the American Dental Association and heralded by the Centers for Disease Control and Prevention as one of the major public health success stories of the 20th century. We do not intend to review the entire controversy here. Recent reviews are found elsewhere (149, 150, 151). Rather, here we comment briefly on concerns about neurodevelopmental impacts of prenatal exposure to fluoride.

The US EPA sets a Recommended Maximum Contaminant Level of 4.0 ppm fluoride in drinking water. The National Institute for Dental Research considers fluoride at 1 PPM optimal for preventing dental caries. This level may be exceeded in some communities. Additional sources of fluoride, including topical fluoride treatments, fluoride tablets, and fluoride toothpaste, add to the total fluoride burden.

In an animal study, pregnant rats were given 0.13 mg sodium fluoride/kg by injection on 9 separate occasions from days 14-18 or 17-19 during pregnancy (152). Offspring of treated animals and controls were monitored by videotape that was then computer-analyzed in order to quantify various behavioral characteristics. Offspring exposed to fluoride on days 17-19 of pregnancy showed significant hyperactivity. They tended to move from one activity to another more frequently than unexposed animals. This study has been criticized for using excessive fluoride exposures. The authors respond by noting that the blood levels of fluoride in the treated animals were similar to the levels measured in people who are exposed through fluoridated water. Another criticism centered on the lack of biological plausibility that the results would differ in the two groups exposed at similar times during pregnancy (153). The authors, however, point out that vulnerable developmental stages change rapidly during this time window and argue that the findings are entirely plausible (154).

Another study found that the offspring of rats given 5, 15, 50 PPM fluoride in drinking water during pregnancy and lactation had significantly elevated acetylcholinesterase levels when tested at 80 days of age (155). Maternal acetylcholinesterase levels were also increased. Though not measured in this study, a likely result of elevated acetylcholinesterase activity is decreased acetylcholine levels. As we have noted, the enzyme, acetylcholinesterase, and the neurotransmitter, acetylcholine, play important roles in brain development. Changes in the concentrations of any neurotransmitter during development may have permanent neurological consequences. The largest effect was seen at 5 PPM, decreasing at the higher levels.

Two reports from China identify significantly lower childhood IQs in communities where fluoride exposure is elevated. In one community, where drinking water naturally contains 4.12 PPM fluoride, IQs were significantly lower than in a nearby community with fluoride levels at 0.91 PPM (average IQ 98 vs. 105) (156). This difference persisted when the study population was controlled for parental educational level. The authors describe similar occupations, living standards, and social customs in the two communities. The ecologic design of this study imposes some limits on the conclusions that may be drawn since the exposure (fluoride) and outcome (IQ) were compared on a population-wide basis without any attempt to associate individual fluoride exposure levels with individual IQs. Nonetheless, an IQ shift of 7 points in an entire population has large population-wide implications, as well as impacting individual members, and these results deserve close attention.

In the other study, investigators used dental fluorosis and urinary fluoride levels to stratify children into four quartiles (157). Elevated fluoride exposures were associated with decreased IQs in this population. That is, the distribution of IQ scores in children in each quartile of fluoride exposure shifted progressively downward as the fluoride exposures increased.


Studies in animals and human populations suggest that fluoride exposure, at levels that are experienced by a significant proportion of the population whose drinking water is fluoridated, may have adverse impacts on the developing brain. Though no final conclusions may be reached from available data, the findings are provocative and of significant public health concern. Perhaps most surprising is the relative sparseness of data addressing the central question of whether or not this chemical, which is intentionally added to drinking water, may interfere with normal brain development and function. Focused research should address this important matter urgently.

149. Hileman B. Fluoridation of water. Chem Eng News 66:26-42, 1988.
150. Connett P. Fluoride: a statement of concern. Waste Not #459. Canton NY.
151. CDC. Fluoridation of drinking water to prevent dental caries. MMWR 48:986-993, 1999.
152. Mullenix PJ, Denbesten PK, Schunior A, Kernan W. Neurotoxicity of sodium fluoride in rats. Neurotoxicol Teratol17(2):169-177, 1995.
153. Ross J, Daston G. Letter to the editor. Neurotoxicol Teratol 17(6):685-686, 1995.
154. Mullenix P, Denbesten P, Schunior A, Kernan W. Reply. Neurotoxicol Teratol 17(6):687-688, 1995.
155. Zhao XL, Wu JH. Actions of sodium fluoride on acetylcholinesterase activities in rats. Biomed Environ Sci 11(1):1-6, 1998.
156. Zhao LB Liang GH, Zhang DN, et al. Effect of a high fluoride water supply on children’s intelligence. Fluoride 29(4):190-192, 1996.
157. Li XS, Zhi JL, Gao RO, Effect of fluoride exposure on intelligence in children. Fluoride 28(4):189-192, 1995.

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