. "10 Genotoxicity and Carcinogenicity." Fluoride in Drinking Water: A Scientific Review of EPA's Standards. Washington, DC: The National Academies Press, 2006.
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Fluoride in Drinking Water: A Scientific Review of EPA’S Standards
TABLE 10-4 Evidence Summary for Carcinogenicity of Fluoride: Epidemiologic Studies and Rodent Lifetime Bioassays
Cancer Site/Type
Individual-Based Epidemiology Studies
Ecologic Epidemiology Studies
Animal Data
Osteosarcoma
Case-control studies ambiguous (additional comprehensive hospital-based case-control study including bone fluoride measurements is under way).
Mixed.
Male F344/N rats: Borderline positive.
Male F344 rats: inconclusive
Oral cavity
NCI incidence elevated in males, but no mortality trends. Several other reports positive.
Nonstatistically significant increase in male rats.
Thyroid
Nonstatistically significant increase in male rats.
Kidney and/or bladder
Occupational cohort: positive finding, inhalation route, high exposures.
Some positive reports.
Uterine
One positive report.
Respiratory
Occupational cohort positive finding, inhalation route, high exposures.
One positive report.
TABLE 10-5 Evidence Summary for Carcinogenicity of Fluoride: Genotoxicity and Mechanistic Assays
Type of Effect and Assay
Strength of Evidence
Mitogenesis
Well established.
Cytogenetic effects: human in vivo exposure, in vitro assay.
Inconsistent; and the positive findings were from weak papers.
Cytogenetic effects: human in vitro exposure, in vitro assay.
Inconsistent.
Cytogenetic effects: other mammalian systems.
Inconsistent.
Transformation.
Inconsistent; the positive results are consistent with a promotion mechanism.
DNA repair mechanism: human.
Suggestive positive finding regarding tumor suppressor gene, small case series.
