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A comparative study (Whitford, et al.,1991) of fluoride pharmacokinetics in five species (dog, cat, rat, rabbit and hamster) determined that there are major quantitative diffences in the metabolic handling of fluoride among the five species evaluated, and that plasma, renal and extra-renal (calcified tissue) values of the young adult dog, when factored for body weight, resemble those of the young adult human most closely. The 5-minute plasma fluoride concentrations were ordered as follows: dog > rabbit > rat > hamster > cat (concentrations were 110.8 +/- 14.3, 91.3 +/- 3.1, 78.4 +/- 5.3, 69.1 +/- 4.9, and 52.2 +/- 4.8 umol/L, respectively). In terms of body weight, the plasma clearances were highest in the hamster, rat, and cat (8.60, 7.34 and 7.24 mL/min/kg, respectively), intermediate in the rabbit (5.80 mL/min/kg), and lowest in the dog (3.50 mL/min/kg). This result indicates that the hamster, rat and cat cleared fluoride from their extracellular fluids more than 2 times faster than did the dog. The plasma clearance of fluoride in the rabbit was 66% faster than that of the dog.

In another study (Susheela, et al., 1982), rabbits were administered daily oral doses of 10 mg sodium fluoride/kg body weight by gavage for various periods of time and then levels of fluoride in serum, urine, noncalcified tissues, calcified tissues, and erythrocyte membrane and hemolysate were estimated at different time intervals for the purpose of understanding how much fluoride was deposited, how much is excreted, and what quantity of fluoride was in circulation. Following sodium fluoride ingestion, the circulating level of fluoride was enhanced. The increase in fluoride content was proportionate to the duration of sodium fluoride administration, at least up to 10 months. Urinary fluoride content data revealed that, due to sodium fluoride ingestion, the amount of excreted fluoride increased up to 30 days. Thereafter, for unknown reasons, fluoride excreation gradually diminished towards normal limits. Cortical and cancellous bone differed significantly in their fluoride content. Cancellous bone, upon sodium fluoride administration, showed greater affinity for fluoride uptake, possibly due to its greater surface area exposed to circulation. Fluoride content data of non-calcified tissues showed that less fluoride was taken up when compared to calcified tissue. However, in non-calcified tissues it was evident that different organ tissues varied in their affinity for fluoride and in their fluoride content. Upon sodium fluoride administration, all soft tissues investigated, including the erythrocyte membrane and hemolysate, showed enhanced fluoride content.

In an earlier study, Zipkin and Likins (1957) investigated the absorption of various fluorine compounds from the gastrointestinal tract of the rat. Sodium fluoride, as well as sodium fluorosilicate (Na2SiF6), sodium fluorophosphate (Na2PO3F) and stannous fluoride (SnF2) were absorbed through the gastrointestinal tract of the rat to the same extent (mean 48.4 +/- 1.6%), whereas potassium hexafluorophosphate (KPF6), tetraethylammonium hexafluorophosphate (EtNPF6) and potassium fluoroborate (KBF4) were absorbed to a significantly greater degree (73.6 +/- 2.0%). The results suggest that the difference in rate of absorption of the two groups of fluorine compounds is related to their dissimilarity in electronic structure. In compounds with lower rates of absorption, fluorine is electrovalently bound and is present as the fluoride ion, whereas in compounds with greater rates of fluorine absorption, fluorine is covalently bound.