58 American Dental Association levels of natural or adjusted fluoride in drinking water in Great Britain (England, Scotland and Wales) had no impact on the incidence of either osteosarcoma or Ewing’s sarcoma in people aged 0-49. Water fluoride levels ranged from near zero to a maximum of approximately 1.26 ppm.120 A case-control study121 published in 2011 found no significant association between the fluoride levels in bone and osteosarcoma risk. Led by a Harvard researcher, the study analyzed fluoride levels in bone samples from 137 patients with primary osteosarcoma and bone samples from 51 patients with other newly-diagnosed malignant bone tumors who served as a control group. Conducted in nine U.S. hospitals over an eight-year period (1993 and 2000), the study was considered the most extensive to date on the issue. The vast majority of fluoride in the body is located in calcified tissue such as bone. The study hypothesized that if chronic exposure to fluoride was a risk factor for osteosarcoma, then those cases would have a significantly higher level of fluoride in bone than the controls. This was not the case. The major advantage of this study was the ability to use actual bone fluoride levels as a measure of fluoride intake rather than estimating fluoride exposure. Focusing on fluoride intake from water as a primary source of fluoride, in earlier studies122,123 members of the research team noted the difficulty in obtaining accurate information on fluoride levels of drinking water at the subjects’ homes. Even when accurate information could be obtained, that information did not reflect actual consumption of water by the study subjects. Funding for the study came from three agencies of the National Institutes of Health — the National Cancer Institute, the National Institute of Environmental Health Sciences and the National Institute of Dental and Craniofacial Research.121 The best available scientific evidence shows that fluoridated water does not cause osteosarcoma (a form of bone cancer). 34. Does fluoride, as provided by community water fluoridation, inhibit the activity of enzymes in humans? Answer. The best available scientific evidence demonstrates that the recommended levels of fluoride in drinking water, has no effect on human enzyme activity. Fact. Enzymes are organic compounds that promote chemical change in the body. The best available scientific evidence has not indicated that water fluoridated at the recommended levels has any influence on human enzyme activity. There are no available data to indicate that, in humans drinking water fluoridated at the recommended levels, the fluoride affects enzyme activities with toxic consequences.124 The World Health Organization report, Fluorides and Human Health states, “No evidence has yet been provided that fluoride ingested at 1 ppm in the drinking water affects intermediary metabolism of food stuffs, vitamin utilization or either hormonal or enzymatic activity.”125 In 2006, the National Research Council Report stated that the available data were not sufficient to draw any conclusions about potential effects or risks to liver enzymes from low-level long-term fluoride exposures such as those seen with community water fluoridation.9 The concentrations of fluoride used in laboratory studies to produce significant inhibition of enzymes are hundreds of times greater than the concentration present in body fluids or tissues.126 While fluoride could affect enzymes in an artificial environment outside of a living organism in the laboratory, it is unlikely that adequate cellular levels of fluoride to adversely alter enzyme activities would be attainable in a living organism. The two primary physiological mechanisms that maintain a low concentration of fluoride ion in body fluids are the rapid excretion of fluoride by the kidneys and the uptake of fluoride by calcified tissues.52