56 American Dental Association Chronic fluoride toxicity can develop after 10 or more years of exposure to very high levels of fluoride, levels much higher than what is associated with drinking water fluoridated at recommended levels. The primary functional adverse effect associated with long-term excess fluoride intake is skeletal fluorosis.40,58 The development of skeletal fluorosis and its severity is directly related to the level and duration of fluoride intake. For example, the ingestion of water naturally fluoridated at approximately 5 mg/L or greater for 10 years or more is needed to produce clinical signs of osteosclerosis (a mild form of skeletal fluorosis that can be seen as a change in bone density on x-rays) in the general population. In areas naturally fluoridated at 5 mg/L, daily fluoride intake of 10 mg/day would not be uncommon.40 A survey of X-rays from 170,000 people in Texas and Oklahoma whose drinking water had naturally occurring fluoride levels of 4 to 8 ppm revealed only 23 cases of osteosclerosis and no cases of crippling skeletal fluorosis.98 Evidence of advanced skeletal fluorosis, or crippling skeletal fluorosis, was not seen in communities in the United States where water supplies contained up to 20 mg/L of naturally occurring fluoride.40,99 In these communities, “daily fluoride intake of 20 mg/day would not be uncommon.”40 Crippling skeletal fluorosis is extremely rare in the United States and is not associated with water fluoridated at the recommended level.40,58 Additional information on this topic can be found in this Section, Question 26. The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the nation. These sites make up the Superfund: National Priorities List (NPL) and are the sites targeted for long-term federal cleanup activities.100 The Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles for hazardous substances that describe the effects of exposure from chemicals found at these sites and acute releases of these hazardous substances.101 The ATSDR provides answers to the most frequently asked questions about exposure to hazardous substances found around hazardous waste sites and the effects of exposure on human health. The Toxicological Profile for Fluorides, Hydrogen Fluoride and Fluorine indicates that subsets of the population could be unusually susceptible to the toxic effects of fluoride and its compounds at high doses, such as what might be encountered in the cleanup of a chemical spill. However, there are no data to suggest that exposure to the low levels of fluoride associated with community water fluoridation would result in adverse effects in these potentially susceptible populations.101 The ATSDR’s Public Health Statement on Fluorides states that “when used appropriately, fluoride is effective in preventing and controlling dental caries.”102 While large doses of fluoride could be toxic, it is important to recognize the difference in the effect of a massive dose of an extremely high level of fluoride versus the recommended amount of fluoride found in optimally fluoridated water. The implication that fluoride in large doses and fluoride in trace amounts have the same effect is completely unfounded. Many substances in widespread use are very beneficial in small amounts while toxic in large quantities. The possibility of adverse health effects from continuous low level consumption of fluoride over long periods has been studied extensively. As with other nutrients, fluoride is safe and effective when used and consumed properly. No charge against the safety of fluoridation has ever been substantiated by generally accepted scientific knowledge. After more than 70 years of research and practical experience, the best available scientific evidence indicates that fluoridation of community water supplies is safe. After more than 70 years of research and practical experience, the best available scientific evidence indicates that fluoridation of community water supplies is safe. 32. Does drinking water fluoridated at the recommended levels cause or accelerate the growth of cancer? Answer. According to the best available scientific evidence, there is no association between cancer rates in humans and drinking water that is fluoridated at the recommended levels. Fact. Since community water fluoridation was introduced in 1945, more than 50 epidemiologic studies in different populations and at different times have failed to demonstrate an association between fluoridation and the risk of cancer.1 Studies have been conducted