174 JOURNAL OF COSMETIC SCIENCE Table I. Physician Assessment (PA) of Hand Condition at Baseline and 14 Days Post Treatment Baseline 14 Days Post Treatment Dorsal Palmar Dorsal PaJmar Erythema 2.0 2.0 + Scorel + Scorel Scaling 2.0 2.0 + Scorel + Scorel Fissuring 1.0 1.0 0 (healed) 0 (healed) Xerosis 2.0 2.0 + ScoreI + Score! Edema 0 0 0 0 Vesiculation 0 0 0 0 Lichenification 0 0 0 0 0, no identifiable signs and symptoms +, slight involvement 1, mild 2, moderate 3, moderately severe 4, very severe. Figure 1. Transepidennal Water Loss (TEWL) values observed at day 7 and 14 for the dorsal and palmar surface sites alone. 60 50 40 30 20 10 0 Baseline El IVlean Dorsal Value Day 7 Day 14 ■ IVlean Palrrar Value □ Untreated Site

2007 ANNUAL SCIENTIFIC MEETING 175 A REVIEW OF SKIN IRRITATION PROTOCOLS FOR THE EVALUATION OF SKIN IRRITATION POTENTIAL Introduction Ward L. Billhimer and James P. Bowman Hill Top Research Corporation Skin irritation is one of the most common adverse effects in humans. It is an immediate, non- immunological inflammatory response to a physical, chemical, or biological insult. Inflammation produced in the skin can be objectively observed ( erythema, edema or heat) or subjectively described (pain, stinging, itching, or burning). The irritant response tends to be universal, unlike most other inflammatory responses which are individual and specific. Irritant contact dermatitis can occur in all individuals provided the irritants are in contact with the skin for a sufficient length of time and in sufficiently high concentration. Testing for potential adverse skin effects is a key component of both the overall safety assessment and the evaluation of potential improvements in mildness of many consumer products. This presentation will provide a review of some key protocols used to assess the irritation potential of a broad base of consumer products and their ingredients as well as provide support for product claims. Principles of Skin Irritation An irritant is any agent that, when applied to the skin, has the capacity to produce cell damage with a local inflammatory reaction but without involvement of immunological processes. Virtually any substance, even water, can be an irritant under certain conditions. A multitude of factors are involved in the development and persistence of skin irritation. Strong irritants produce inflammation or cellular damage after a single exposure - primary irritation. However, most irritants produce inflammation after repeated or prolonged exposures - cumulative irritation. While the different types of irritants exert their effects through different mechanisms, their common point of attack is on the stratum corneum. Strategies for Evaluation of Skin Irritation Potential Historically, the prophetic patch test has been the method of choice for assessing the irritation potential of consumer products and their ingredients. It originated as a diagnostic tool for identifying allergens and subsequently evolved into a predictive tool for premarket screening for allergens and ranking irritants. Two basic approaches are typically used - single application and repetitive application of the test materials. Due to the diversity of factors influencing the development and intensity of skin irritation, a large number of testing protocols have been developed to evaluate product safety or to substantiate label or advertising claims. These patch tests simulate exaggerated exposure conditions and are used to define the safety of the materials under extreme exposures or "worse case" scenarios. Single application protocol: Numerous versions of the original 24 hour patch test have been designed to evaluate the primary irritation potential of test materials following a single patch application. It has even been refined and standardized as a 4 hour patch test capable of classifying the irritation hazard of substances with significant irritation potential while avoiding unacceptable strong reactions. Cumulative irritation patch tests: Kligman and Wooding developed a test designed to evaluate the irritation potential of products that have low irritation potential or tend to be used repetitively. It requires the application of occlusive patches ( exaggerated exposure) of the test material to the same skin site for 21 consecutive days. Berger and Bowman showed that cumulative irritation scores for a 14-day test have a positive correlation to the 21-day test and that 95% of the data is effectively generated in the first 14 days. Traditional patch testing approaches are not always good predictors of the actual consumer experience because they can not simulate or duplicate the almost infinite combination of factors that lead to irritation under use. For this reason, controlled usage tests and consumer home use testing have become a part of the product assessment process.