820 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 3O 22 o IO • ...,,..a• u NTRE AT E D ./o'"'•' SnCIs,- ENAMEL . .,,.•' X..,,. •' • ........ •NaF - ENAMEL • • .•' .-Z ................ / -- •SnF• - ENAMEL • ,x•. ' .X Z -• •WATER - BLANK X'•.Z' • ........... tO 20 30 40 70 80 90 I00 I10 50 eO MINUTES 120 Figure 2. Dissolution curves of powdered human dental enamel treated with 0.1% fluoride and 0.3% stannous equivalent aqueous concentrations o[ sodium fluoride, stannous fluoride, and stannous chloride in pH 4, 0.2M acetate Although the general shape of dissolution curves of powdered enamel treated with tin and fluoride compounds (Fig. 4) are similar to comparable data with intact enamel surfaces (9, 17), the reaction rate and extent of reac- tion are substantially different. Partially demineralized enamel (white spot enamel) has been used as the prime substrate for enamel solubility reduction tests of dentifrice slurries. The test (18) described in the Methods section responds to the stannous and fluoride ions in the concentrations available in dentifrices (9). By utilizing the etched enamel surface solubility as a base line, multiple tests can be run with the same set of teeth, providing the teeth are conditioned (etched) between tests to remove all traces of previous treat- ments. In vivo enamel solubility tests have been suggested as providing evidence of protection against acid attack in the mouth (19, 20). These tests are useful in confirmatory studies but the physical nature of the test makes it difficult for detailed studies. Considerable effort has been spent in developing procedures for the study of anticaries agents in experimental animals (21). The albino rat is the most frequently used animal with the cotton rat and Syrian hamster distinct second and third choices. The experimental animal has been particularly useful in determining the effect of microorganisms and diet on the caries process. By utilizing particular strains of caries-susceptible rats and innoculating them

THERAPEUTIC DENTIFRICES 821 8O 7O 6O 5O 4O 3O 2O \\ e• % ESR - A-B A= UNTREATED ENAMEL TREATED ----? I0 20 30 40 50 60 MINUTES Figure 3. Dissolution curves of powdered human dental enamel treated with dentifrice- water (1: 3) slurries in pH 4, 0.2M acetate buffer X--- X Control ß • ß Stannous fluoride paste A •x iX Stannous fluoride paste B with known caries-producing microorganisms, the reproducibility of animal studies in defining anticaries activity is increased (21). After complete physical and chemical characterization of the active ingre- dient alone and in its dentifiice formulation, demonstration of anticaries ac- tivity for the formulation in experimental animals, and determination of bio- availability by a combination of carefully chosen in vitro and in vivo tests, the question arises of what else must be done to prove anticaries effectiveness. The immediate response has been two, or better three, clinical studies lasting 3 years with several hundred children. Even this quantity of clinical evidence may not be adequate for a new type of active ingredient. The initial review of the stannous fluoride dentifrice data was based upon seven clinical studies (22). How much data is required for minor modifications of an existing den- tifrice system which has already been demonstrated to be clinically effective?