Primary irritation index and safety zone of cosmetics: retrospective analysis of skin patch tests in 7440 Korean women during 12 years S. M. An*, H. Ham*, E. J. Choi*, M. K. Shin* ,† , S. S. An ‡ , H. O. Kim § and J. S. Koh* *Dermapro Skin Research Center, DERMAPRO LTD., 4F Jiho B/D, Bangbaejoongang-Ro 30, Seocho-Gu, Seoul, South Korea, † Department of Dermatology, College of Medicine, Kyung Hee University, Seoul, South Korea, ‡ Amorepacific R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do, South Korea and § Department of Dermatology, Seoul St. Mary’s Hospital, College of Medicine, Catholic University Seoul, South Korea Received 11 July 2013, Accepted 15 September 2013 Keywords: safety testing, sensitive skin/inflammation/Allergy, statistics Synopsis BACKGROUND: Cosmetics are products used over long periods by the public, and their safety is very important. Several types of human tests are used widely for the evaluation of cosmetics includ- ing single patch tests, in-use tests, human repeated insult patch test (HRIPT). However, there is no clear and well-defined published objective and standardized criteria for primary skin irritation in regard to the large variety of cosmetic products. METHODS: This study analysed human patch tests conducted from May 2001 to December 2012 with 4606 materials of proto- type or finished cosmetic products on 7440 normal Korean women aged 18À60 years. The tested products were patched under occlu- sion for 24 or 48 h, and skin tolerance was assessed twice at 30 min and 24 h after patch removal using a 5-step scale accord- ing to the CTFA guidelines. RESULTS: Human patch tests for cosmetics were performed of 4606 cases, and 30À33 subjects participated in each case. The response in each case was calculated based on total subject num- ber, skin reaction intensity and the number of respondents. The calculated response was standardized using the z-score, and a safety zone was provided in terms of human primary irritation in accordance with the human skin reaction evaluation criteria and usage or formula of cosmetics. CONCLUSIONS: This study established the safety criteria for irritation in the cosmetics field. R esum e. CONTEXTE: Les cosm etiques sont des produits utilis es sur de longues p eriodes par le public, et leur s ecurit e est tr es importante. Plusieurs types de tests humains sont largement utilis es pour l’ eval- uation des produits cosm etiques, y compris les patch tests simples, les essais d’usage, les tests r ep et es de sensibilisation cutan ee sur humains. (HRIPT). Cependant, aucun crit ere claire et bien d efinie, objectif et standardis e publi e pour l’irritation cutan ee primaire existe  a l’ egard de la grande vari et e de produits cosm etiques. METHODES: La pr esente  etude a analys e les tests cutan es humains men es de mai 2001  a D ecembre 2012 avec 4.606  echantillons de prototype ou de produits finis cosm etiques sur 7.440 femmes cor eennes saines ^ ag es de 18-60 ans. Les produits test es ont  et e patch es sous occlusion pendant 24 ou 48 heures, et la tol erance de la peau a  et e  evalu ee deux fois,  a 30 minutes et 24 heures apr es le retrait du patch en utilisant une  echelle en 5  etapes selon les directives CTFA. RESULTATS: Les patch-tests humains pour les cosm etiques ont  et e r ealis ees sur 4.606 cas et 30-33 sujets ont particip e  a chaque cas. La r eponse dans chaque cas a  et e calcul ee selon le nombre total de sujets, l’intensit e de la r eaction de la peau, et le nombre de r epon- dants. La r eponse calcul ee a  et e normalis ee en utilisant le z-score, et une zone de s ecurit ea  et e fournie en termes d’irritation primaire humaine en conformit e avec les crit eres d’ evaluation des r eactions de la peau humaine et de l’utilisation ou la formule des produits cosm etiques. CONCLUSIONS: Cette  etude a  etabli les crit eres de s ecurit e pour l’irritation dans le domaine des cosm etiques. Introduction ‘Cosmetics’ are defined as any substance or preparation intended to be placed in contact with the various external parts of the human body (epidermis, hair system, nails, lips and external genital organs) or with the teeth and the mucous membranes of the oral cavity with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance and/or correcting body odours and/or protecting them or keeping them in good condition in EU [1]. It is very important to ensure the safety of cosmetics, and cosmetic com- panies have made great efforts to improve this safety. Despite their efforts, various types of adverse events from simple skin irritation to severe dermatitis have been reported [2–4]. The safety of cosmetics can be evaluated at various levels such as through in vitro, animal and human experiments using specialized methods [5–16]. However, the cosmetics safety assessment at the cellular or animal level could not clearly reflect the safety in the human skin. The adequacy of these tests is debatable, and safety assessment should therefore be performed at the human level [17–19]. The most important step is to evaluate skin toxicity such as the potential of cosmetics to cause irri- tation and sensitization. The human patch test is a useful method to test primary irritation in the human body caused by direct contact with the skin [14–16, 20]. Acute primary irritation is a reversible inflammatory reaction that includes redness, heat, burning, itching, stinging and swelling at the site of application of a single dose of an irritant [21, 22]. The human patch test is not standardized like in vitro tests or Correspondence: Jae Sook Koh, 4F, Jiho BD, 919-1, Bangbae-dong, Seocho-gu, Seoul 137-843, South Korea. Tel.: 82 2 597 5434; Fax: 82 2 597 5430; e-mail: dermapro@dermapro.co.kr 62 © 2013 Society of Cosmetic Scientists and the Soci et e Franc ßaise de Cosm etologie International Journal of Cosmetic Science, 2014, 36, 62–67 doi: 10.1111/ics.12095