children. This was due to fewer children in the high IQ range. While the studies lacked sufficient detail for the committee to fully assess their quality and their relevance to U.S. populations, the consistency of the collective results warrant additional research on the effects of fluoride on intelligence. Investigation of other mental and physiological alterations reported in the case study literature, including mental confusion and lethargy, should also be investigated.

A few animal studies have reported alternations in the behavior of rodents after treatment with fluoride. However, the observed changes were not striking in magnitude and could have been due to alterations in hormonal or peptide activity. Animal studies to date have used conventional methodologies to measure learning and memory abilities or species-typical behaviors in novel locations. The tasks used to measure learning and memory did not require any significant mental effort. No studies were available on higher order mental functions, altered reactions to stress, responses to disease states, or supplemental reactions to known neurotoxins. Procedures are available that could test for cognitive functions, but they are labor intensive and have seldom been used in the past 60 years. One example is the reasoning test designed by Maier (1929), who found that even a small lesion of the neocortex impaired performance on the reasoning test (Maier 1932). A more recent example is the delayed matching to position test with different outcomes (Savage 2001), which have shown that damage to the hippocampus can affect learning.

As noted in Chapter 2, exposure to fluorosilicates could occur under some conditions. There are reports that such chemicals enhance the uptake of lead into the body and brain, whereas NaF does not. Further research is needed to elucidate how fluorosilicates might have different biological effects from fluoride salts.

Lipids and phospholipids, phosphohydrolases and phospholipase D, and protein content have been shown to be reduced in the brains of laboratory animals subsequent to fluoride exposure. The greatest changes were found in phosphatidylethanolamine, phosphotidylcholine, and phosphotidylserine. Fluorides also inhibit the activity of cholinesterases, including acetylcholinesterase. Recently, the number of receptors for acetylcholine

Front matter (R1-R22)

Summary (1-12)

1 Introduction (13-22)

2 Measures of Exposure to Fluoride in the United States (23-88)

3 Pharmacokinetics of Fluoride (89-102)

4 Effects of Fluoride on Teeth (103-130)

5 Musculoskeletal Effects (131-180)

6 Reproductive and Developmental Effects of Fluoride (181-204)

7 Neurotoxicity and Neurobehavioral Effects (205-223)

8 Effects on the Endocrine System (224-267)

9 Effects on the Gastrointestinal, Renal, Hepatic, and Immune Systems (268-303)

10 Genotoxicity and Carcinogenicity (304-339)

11 Drinking Water Standards for Fluoride (340-353)

References (354-410)

Appendix A Biographical Information on the Committee on Fluoride in Drinking Water (411-415)

Appendix B Measures of Exposure to Fluoride in the United States: Supplementary Information (416-438)

Appendix C Ecologic and Partially Ecologic Studies in Epidemiology (439-441)

Appendix D Comparative Pharmacokinetics of Rats and Humans (442-446)

Appendix E Detailed Information on Endocrine Studies of Fluoride (447-508)