.l. Soc. Cosmet. Chem., 24, 815-828 (December 9, 1973• Interfaces of Laboratory and Clinical Assessment of Therapeutic Dentifrices JOHN J. HEFFERREN, Ph,D.* Presented December 11, 1972, New York City Synopsis-The character and frequency of use has led many researchers to consider the dentifrice as a vehicle to deliver specific agents to the oral cavity. FLUORIDE-containing DENTIFRICES are an accomplished fact illustrating the success of this approach. The dentifrice oral vehicle approach requires a consumer-acceptable formulation, one that does its job of cleaning the teeth and refreshing the •nouth while delivering agents to the oral cavity. Supervised brushing studies have always ,provided a more positive agent response than unsupervised studies, because good supervision ensures consistent adherence to study protocol. Laboratory assessment of a dentifrice formulation involves the usual physical criteria of a cleansing dentifrice, i.e., dispersion, cohesion, extrusion, flavor, etc., as well as other procedures designed to reflect the character and quantity of special agents added to the formulation. Total ion or entity content will assess manufacturing control soluble ion content will indicate availability. Chemical availability, however, may differ from clinical availability and thus additional laboratory procedures must be designed to assess clinical availability. Whether these procedures are called in vitro, in vivo, or bioavailability, clinical reference should be established. The interfaces of LABORATORY and CLINICAL EVAL- UATIONS constitute the milieu of today's and tomorrow's products. INTRODUCTION The human oral cavity is a dynamic place. Air, food, and drink necessary for life pass through this orifice. It is not surprising that the soft and hard tissues of the mouth require periodic refreshment. The most general oral cleansing aid has been the dentifrice. The abl'asive-detergent system of the dentifrice has been used to remove the oral debris collecting on the tooth surfaces, while the dentifrice-flavoring system provides general refreshment to the oral cavity. Dental floss, oral irrigators, and mouthwashes have also been used to clean and refresh the oral cavity. The dynamic interaction of food substrates, salivary fluids, and the oral microbiota results in periodic dissolution and remineralization of tooth sur- faces. When the balance of the interaction overshifts to dissolution, dental *Council on Dental Therapeutics, American Dental Assn., 211 East Chicago Ave., Chicago, Ill. 60611. 815

816 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS caries occurs. This carions process is not a generalized process but one re- stricted to specific tooth sites. At other sites, often on the same tooth, mineral- ization may be favored. Tooth mortality studies in Sweden (1) have indicated that dental caries is the cause for 75% of the tooth extractions occurring in the first 25 years of life. After 50 years of age, tooth Koss due to soft tissue (periodontal) disease becomes more significant, but even then dental caries remains a maior cause of tooth loss. Dental caries is probably not a single disease entity. Socransky (2) has listed four types of dental caries differentiating them on the basis of the specific site of activity and the microorganisms present at the site, i.e., smooth surface, pit and fissure, root surface (cementum), and deep dentin caries. Smooth surface dental caries requires dental plaque with good adhesive prop- erties. A few strains of streptococci produce this adhesive dextran plaque from sucrose. Pit and fissure dental caries occurs when acid-producing micro- organisms are packed into the tooth crevices. These crevices are located pri- marily on the occlusal or chewing surfaces of the teeth and thus the term oc- clusal caries is frequently used. These microorganisms have a less specific biochemical character, and because of the protective shelter of the tooth crevice they do not require plaque for adhesion to the tooth surfaces. Dental caries occurring on the root surfaces of teeth afflicted with periodontal disease may be a by-product of a somewhat different, mildly acidiogenic group of microorganisms common to the gingival crevice area. The fourth type of den- tal caries, deep dentin caries, may be caused by microorganisms different from those initiating the lesion in the enamel surface. In the design of an anticaries agent, there would appear to be a number of routes and points of attack. Some of these general approaches might include: antibacterial, antibacterial metabolite, substrate (tooth structure) alteration, fluid phase (saliva) alteration, and diet control. Many of these approaches and their ramifications have been reviewed previously (3). At present, sub- strate alteration is most important and successful in retardation of the dental caries process. Although physical protection of the tooth surface with the use of a sealant on the occlusal surface has enjoyed some success (4), improve- ment of the chemical resistance to dissolution is most important. Dietary fluoride through communal fiuoridation is the most effective and efficient route to the reduction of dental caries (5). The dietary fluoride is incorporated into the tooth structure at the time of mineralization and effec- tively produces a more perfect structure. Subsequent topical administration of fluoride at substantially higher concentrations (dentifrice-0.1% fluoride, and professionally applied preparations-l.2 to 10% fluoride) supplement the dietary fluoride. It should be recognized that the prime site for fluoride activity is the tooth mineral. However, the effect of fluoride in some vehicles may be due in part to