Reaction mass of Limestone and calcium fluoride and calcium sulfate

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result:
Data are available for calcium fluoride from animal and human studies. Varying levels of bioavailability are reported; the fluoride that is absorbed is largely retained by the skeleton.
Short description of key information on absorption rate:
No data are available, however the chemical nature of the substance indicates that dermal absorption is likely to be negligible.

Additional information

The kinetics of fluoride in man are well characterised. Absorbed fluoride is distributed primarily in the blood, 75% in the plasma and 25% associated with erythrocytes. Half of the plasma fluoride may be bound to organic molecules. Fluoride is rapidly distributed and is sequestered in the bones and teeth, where exchange with hydroxyl groups results in incorporation into the bone and tooth structure. Levels of fluoride in bones and teeth are directly correlated with exposure levels. Fluoride is excreted rapidly as a consequence of glomerular filtration, with a plasma half-life of 2-9 hours. The half-life for skeletal fluoride in humans is reported to be 8-20 years. The absorption of fluoride from calcium fluoride appears to be variable following oral administration and is strongly influenced by the concentration and form in which it is administered. Effects are considered likely to be due to its low water solubility. The dermal absorption of calcium fluoride is considered likely to be negligible due to its low water solubility and ionic nature.

Discussion on bioaccumulation potential result:

Rat study with calcium fluoride

In a study using 12 paired groups of albino rats, the authors administered fluoride in the form of calcium fluoride or cryolite in the drinking water for 14 weeks. Total fluoride intake (from the basal diet and drinking water) amounted to a dose level of approximately 0.75 mg/kg bw/d. Bodyweight gain and food consumption were retarded in both dose groups. Clinical signs were limited to transient haematuria in both groups, and the appearance of dental striations in all animals from Week 8 -10. Analytical determinations at necropsy revealed fluoride retention of approximately 59%, and that the large majority of the fluoride in the body was present in the skeleton (~96%). No differences were apparent between the treated groups. The authors conclude that the effects of fluoride from these two insoluble salts are comparable (Lawrenz et al, 1939).

Human volunteer studies with calcium fluoride

In a review of a number of volunteer studies, the absorption of fluoride from the gastrointestinal tract is reported to be remarkably effective, with nearly complete absorption of sodium and calcium fluoride in solution (96 -97%) and lower absorption from solid calcium fluoride (62%). Approximately half of the absorbed fluoride is excreted and half retained in the skeleton. Evidence suggests that excretion is urinary, with the small proportion of orally administered fluoride excreted in faeces representing the unabsorbed fraction. The excretion of fluoride in sweat may also be significant (Largent, 1960).

The dissolution rate of calcium fluoride tablets in vitro and the degree of fluoride absorption in vivo after calcium fluoride and sodium fluoride tablet intake in man were investigated. The calcium fluoride tablets were more than 50% dissolved after 1 hour in simulated gastric fluid, but were negligibly soluble in water or phosphate buffer. In spite of the moderate dissolution of the calcium fluoride tablets seen in vitro in simulated gastric fluid, no absorption of fluoride was apparent in human volunteers as measured by plasma levels; values at all timepoints were ~20 ng/mL plasma. In contrast, a marked elevation of plasma fluoride levels (~5 -6 times pre-dosing levels) to ~100 -120 ng/mL plasma was seen in the volunteers administered sodium fluoride. The bioavailability of fluoride from calcium fluoride in vivo is therefore shown to be very low (Afseth et al, 1987), however it was acknowledged that this may be due to the physical form in which it was administered in this study.

The absorption of fluoride was investigated in pregnant female volunteers administered calcium fluoride or sodium fluoride supplements. Elevated maternal fluoride levels were seen in all treated groups and were comparable following supplementation with sodium fluoride or calcium fluoride. In all groups, umbilical cord fluoride levels were consistently slightly higher than maternal levels. The study therefore indicates the comparable bioavailability of sodium fluoride and calcium fluoride (Caldera et al, 1988).

Tsunoda & Lu (1985) investigated the bioavailability of fluoride administered in different forms (calcium fluoride and sodium fluoride). In the group administered sodium fluoride, serum levels increased rapidly from background to peak at 0.341 ppm at 30 minutes. Levels subsequently dropped gradually to reach background at 24 hours. Urinary excretion over 24 hours accounted for 48.1% of the administered fluoride. In the group administered calcium fluoride, serum fluoride levels were slightly raised after one hour and reached a peak concentration of 0.073 ppm at two hours. Individual serum fluoride values were much more variable than in the other group. Urinary excretion over 24 hours accounted for 8.5% of the administered fluoride. The authors conclude that the gastrointestinal absorption of fluoride is influenced by the solubility of the form in which it is administered.

Discussion on absorption rate:

No specific data on the dermal absorption of calcium difluoride are available, however the low water solubility of the substance and its ionic nature indicate that dermal absorption is likely to be negligible.