378 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS R. L. Goldemberg, Rakuma Laboratories, Inc., P.O. Box 2083, South Hackensack, NJ 07606 The development of a new modality for plaque re- moval is described--use of a plaque-loosening dental rinse prior to brushing. The functionality of such pre-rinses mandates formulations different from products intended for postbrushing or mouth- freshening uses. The pre-brushing rinse has a higher pH and contains surfactants and analgesic ingredi- ents. Antimicrobial activity is secondary in terms of functionality of such pre-rinses. Significant effi- cacy of this dental rinse has been demonstrated in laboratory and clinical tests. Chlorhexidine•a unique chemical for control of gingivitis W. Briner, Ph.D., The Procter and Gamble Co., 11511 Reed Hartman Highway, Cincinnati, OH 45241. Chlorhexidine has been shown effective in control- ling gingivitis for months and can be a lifesaving drug in the immunosuppressed. Chlorhexidine is a bisbiguanide of the following structure: NH NF Cl- O- NH.C.NH.C.NH. (CH2)6.NH.C.NH.C.NH - \•-Cl NH NH Chemistry, Toxicity, and Uses: It has the charac- teristics of a cationic surfactant. Chlorhexidine is relatively nontoxic. It is poorly absorbed in the gut, most passing through unchanged. The reported side effects from oral use include extrinsic staining of teeth and a slight transient desquamation, neither of which limits usefulness of the drug. It is used in surgical scrubs, disinfection of contact lenses, etc. It is available in some countries as a dental gel or as a mouthrinse. Microbiology: Chlorhexidine is a broad spectrum antimicrobial agent which is effective against a number of oral microorganisms. After a single rinse with chlorhexidine, about 30% is retained in the oral cavity and this is slowly released into saliva, maintaining effective levels for several hours. This is perceived as contributing to the efficacy of chlor- hexidine in the mouth. In humans, slight (about twofold) increases in resistance of oral bacteria to chlorhexidine have been observed during mouthrins- ing. However, these increases dissipated or disap- peared after cessation of use and did not limit ef- ficacy of the drug. In vivo studies: Studies in dogs have shown chlor- hexidine effective in controlling gingivitis for up to seven years with no loss of alveolar bone. No mean- ingful increases in resistance of oral bacteria were observed. Under the severe challenge of the exper- imental gingivitis model in humans, no oral hy- giene for three weeks, a chlorhexidine mouthrinse maintained gingivial health virtually unchanged from baseline. In clinical trials of 19nger duration, chlorhexidine mouthrinses have been shown to re- duce gingivitis up to 80% in comparison with pla- cebo' while establishing a level of gingival health similar to that of chlorhexidine in the experimental gingivitis model. Reductions in the number of bac- teria in the oral cavity have been documented during rinsing with chlorhexidine. In immunosup- pressed patients undergoing bone marrow trans- plants, a chlorhexidine mouthrinse has been shown to decrease candida and candida-associated mor- bidity and mortality. In this setting it may be con- sidered a lifesaving drug. Chlorhexidine today is the standard of comparison for any agent claiming antigingivitis efficacy. In clinical trial, chlorhexidine has produced reductions in gingivitis up to 80% while maintaining excellent gingival health for months. It can be a lifesaving drug in immunosuppressed patients. Essential oils Robert C. Emling, University of Pennsylvania, School of Dental Medicine, 4001 Spruce Street, Philadelphia, PA 19104 Essential oils, such as thymol, menthol, and euca- lyptol, have been used in mouth rinses for over 100 years. These ingredients in mouth rinses have been documented to be antibacterial in laboratory tests. With the scientific association of microorganisms and plaque formation, and the suspected involve- ment of this process with carious lesions and gin- givitis, the effect of essential oils on these processes have taken on new interests. For the past decade, products containing essential oils have been studied clinically for their role in oral health status. The studies have assessed short-term effects which occur within one or two weeks. Other studies have run for six months. Some studies have been conducted with no other oral hygiene than the mouth rinse alone, while others have allowed the use of the mouth rinses in an unsupervised setting of "usual home care." Almost uniformly, the results of the studies have been favorable to the products con- taining essential oils. In general, these products have retarded the development of plaque and have reduced the severity of gingivitis. The studies have also compared products containing essential oils to control groups using only a vehicle, or against plain water rinses. The results of these assessments have generally shown products containing essential oils to be more effective than the controls, thus pointing to the fact that these agents are active ingredients. Sanguinaria/sanguinarine in the control of plaque and gingivitis G. Lee Sourhard, Ph.D., Vipont Laboratories, Inc., Fort Collins, CO 80524 In the past few years sanguinaria products have been

ABSTRACTS 379 introduced into the marketplace for the control of dental plaque. Sanguinaria is a bontanical extract obtained from the plant Sanguinaria canadensis. San- guinaria is composed of benzophenanthridine alka- loids and sanguinarine is the prominent alkaloid. Sanguinarine has a unique iminim ion chemistry that is responsible for its effectiveness against dental plaque formation. This presentation will include a review of clinical safety and efficacy studies. Both toothpaste and oral rinse clinical studies will be reviewed. Studies on the retention of sanguinarine in the oral cavity and its antimicrobial action against plaque-forming micro-organisms will be presented as a rational mechanism of action. Certain qualitative changes in plaque as a means of reducing gingivitis will also be considered. Sanguinarine rep- resents an innovative new ingredient for use in the oral cavity with potential against plaque, gingivitis, and periodontal diseases. SESSION III IN VITRO SAFETY In vitro approaches to toxicity testing: A status report Roland M. Nardone, Ph.D., Department of Bi- ology and the Center for Advanced Training in Cell and Molecular Biology, Catholic University of America, Washington, D.C. 20064 Prompted by the partial successes of short-term cell culture tests for the evaluation of the potential mu- tagenicity and carcinogenicity of chemicals and the growing concern for the use of animals for toxicity testing, programs for the evaluation of target-spe- cific chemicals are being developed. The strategies which may be employed to develop such tests and the difficulties and opportunities which they present will be described and analyzed. Ocular and neuronal in vitro test development will be emphasized. Hydrophobicity of n-lauroyl amino acid as a pa- rameter to determine primary skin and eye ir- ritation Kazutami Sakamoto, Ph.D., Ajinomoto USA, Inc., 9 West 57th Street, Suite 4625, New York, NY 1OO19 Hydrophobicity of N-lauroyl (C•2 fatty acid acyl) amino acids (LAA) were measured by reversed phase HPLC and TLC. The order of hydrophobiciry of LAA, which corresponds to the character of side- chain residue of each amino acid, is found as fol- lows: the Phe Ile Leu Val Trp Pro Ala Gyl Set Glu. The primary skin and eye irritation for rabbits is tested by the Draize method and compared to the hydrophobicity. A good relationship is found be- tween hydrophobicity and primary eye irritation, which is that lower hydrophobicity corresponds to lower irritation. A similar relationship is found for LAA between hydrophobicity and hemolysis for human red cells. In contrast, the primary skin ir- ritation is inversely proportioned to the hydropho- bicity, except for glutamic acid. As a result, it is assumed that hydrophobicity is a useful parameter to evaluate skin and eye irritation. Of the LAA's which have already been tested, N-lauroyl glutamic acid seems to be the mildest material. Determination of surfactant irritancy from the swelling behavior of a collagen membrane J. Blake-Haskins, D. Scala, L. Rhein, and C. R. Robbins, Colgate-Palmolive Co., 909 River Road, Piscataway, NJ 08854 Swelling of a collagen membrane by surfactants has been established as an in vitro method to evaluate anionic surfactant potential. The method was used to study the relationship of surfactant structure to swelling activity for alkyl sulfates and ethoxylated alcohol sulfates, in which the carbon chain number and ethylene oxide number were varied systemati- cally. Results show that the C12 homologue in- duced the most swelling and that membrane swelling is inversely proportional to ethylene oxide content. Swelling response is dose-dependent. The assay was used to investigate surfactant interactions additions of amphoteric surfactants to an anionic surfactant reduce the amount of swelling caused by the anionic alone. Results of this in vitro test cor- relate with findings from established in vitro and in vivo laboratory and clinical irritation assessments. These findings suggest a mechanism of skin irrita- tion in which collagen is disrupted, leading to swelling of the skin. SESSION IV GENERAL PAPERS Surfactant structure effects on stratum cor- neum swelling Linda D. Rhein, Ph.D., C. R. Robbins and K. Fernee, Colgate Palmolive Co., 909 River Road, Piscataway, NJ 08854 Surfactants in solution induce swelling of isolated stratum corneum (Robbins and Fernee Putterman, et al.). The highest levels of swelling observed were for anionic surfactants, and very little swelling oc- curred with cationics and nonionics. For a homol- ogous series of alkyl sulfates, swelling was maximal for the C12 homologue. We have now extended these studies to examine effects of structural variants of surfactants on swelling of stratum corneum. Swelling caused by surfactants increased with time, was dose dependent, and was saturable with in- creasing concentration. The extent of swelling was reduced with increased ethoxylation of dodecyl sul- fate and depended upon the counterion. For ho- mologous series of various anionic surfactants, max-