This study was conducted to test the hypothesis that the margin of safe fluoride exposure is narrowed in rats that are physiologically compromised by renal dysfunction. The study objective was to determine whether increases in fluoride retention and tissue fluoride levels in rats with surgically induced renal insufficiency result in toxic fluoride effects not ordinarily observed in healthy animals. Uremic and sham-operated control rats received 0 microg/ml, 5 (0.26 mmol/l), 15 (0.79), or 50 microg/ml (2.63 mmol/l) of fluoride in their drinking water for 3 or 6 months. Fluoride retention was monitored, and, following euthanasia, tissue fluoride and biochemical markers of tissue function were analyzed. Selected tissues were saved for histology, and bone marrow cells were harvested for determining the frequency of sister chromatid exchange, a marker of genetic damage. In spite of significantly higher levels of fluoride in the tissues of the animals with renal insufficiency, there were no clinically adverse, fluoride-induced, extraskeletal physiological, biochemical, or genetic effects of chronic exposure to common levels of fluoride in these rats.

To determine the potential adverse effects, if any, of long-term fluoride ingestion in humans, samples were collected from 25 adult females taking daily doses of fluoride (mean, 23 mg elemental F) for the treatment of osteoporosis and from 38 osteoporotic female controls. Patients in the fluoride group had been receiving therapy for approximately 18 months with a mean duration of 4.2 years and had serum fluoride values of at least 10 μmol/l. Laboratory analyses for fluoride were conducted on plasma, urine and drinking water samples collected from each panelist. Blood was also collected for blood chemistry analyses and plasma lymphocytes were examined for the frequency of sister chromatid exchange (SCE). Plasma and urine fluoride levels were significantly different between the two groups, while water fluoride was not. The SCE frequency, a measurement of potential genotoxicity, did not differ between the two groups. Of the blood chemistry parameters measured, albumin, alkaline phosphatase, sodium, chloride, the albumin/globulin (A/G) ratio, indirect bilirubin, lactate dehydrogenase (LDH), and γ-glutamyl transferase (GGT) were found to be significantly different between the two groups (P ≤ 0.05). However, none of the mean group values were outside stated normal ranges for any of these parameters. We conclude that the risk of developing adverse systemic effects from the ingestion of fluoride, at dosages and for a duration comparable with that of our panel, is minimal.