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.

Mutation: mammalian systems.

Inconsistent.

Mutation: microorganisms.

Negative.



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