This study was conducted to test the hypothesis that the margin of saf
e fluoride exposure is narrowed in rats that are physiologically compr
omised by renal dysfunction. The study objective was to determine whet
her 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-op
erated control rats received 0 mu g/ml, 5 (0.26 mmol/l), 15 (0.79), or
50 mu g/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 anal
yzed. Selected tissues were saved for histology, and bone marrow cells
were harvested for determining the frequency of sister chromatid exch
ange, a marker of genetic damage. In spite of significantly higher lev
els of fluoride in the tissues of the animals with renal insufficiency
, there were no clinically adverse, fluoride-induced, extraskeletal ph
ysiological, biochemical, or genetic effects of chronic exposure to co
mmon levels of fluoride in these rats.