Chemical name/INN/XAN Name of common ingredients glossary Maximum concentration in ready-for-use preparation (%) Sodium salt of 2,2′ acid/bisdisulizole disodium (USAN) Disodium phenyl dibenzimidazole tetrasulfonate (DPDT) 10 (as acid) 2,2’-(6-(4-Methoxyphenyl)-1,3,5-triazine-2,4-di yl)bis(5-((2-ethylhexyl)oxy) phenol)/Bemotrizinol Bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT) 10 Dimethicodiethylbenzalmalonate Polysilicone-15 10 TiO2 TiO2 25 TiO2(nano) TiO2(NANO) 25 Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl], hexylester Diethylamino hydroxybenzoyl hexyl benzoate 10 1,3,5-Triazine, 2,4,6-tris(1,1′ including as nanomaterial Tris-biphenyl triazine/Tris-biphenyl triazine (NANO) 10 ZnO ZnO 25 ZnO (nano) ZnO (NANO) 25 3,3-(1,4-Phenylene)bis(5,6-diphenyl-1,2,4-triazine) Phenylene bis-diphenyltriazine 2-Ethoxyethyl (2Z)-2-cyano-2-[3-(3-methoxypropylamino) cyclohex-2-en-1- ylidene]acetate Methoxypropylamino 3 Cyclohexenylidene Ethoxyethylcyanoacetate Table I Continued DISTRIBUTION OF UV FILTERS ON THE SKIN 301

compounds, lipid nanoparticles and NCs are considered colloidal carriers (22). These car- riers allow shielding of chemical compounds against photodegradation phenomena, ensure bioavailability optimization, and allow controlled release, while at the same time, they can be produced in great numbers. These exact colloidal carriers have been proven to amplify the accumulation of UV fi lters on the upper skin layers, as they have been designed to strengthen their photo-protective properties (23). The size of lipid nanocarriers makes skincare products easy to formulate and apply. Melt-emulsifi ed lipids are the base of solid lipid nanoparticle (SLN) formulation, are stable under room-temperature condi- tions, and are made of well-tolerated and biodegradable raw materials (24,25). The h armful effects associated with the exposure to UV radiation are well documented. As a result, the development of a new generation of UV fi lters that can provide effective protection against the entire UV spectrum radiation has become major concern. These protective systems should be carefully designed by selecting substances of highly reliable stability, to ensure optimal safety and effi ciency during the entire time of sun exposure. The a im of this review was to present the methods (in vitro/in vivo) used for the estimation of skin penetration of sunscreens regularly used (some sunscreens listed in both FDA monograph and EU Annex are no longer used because they have an unpleasant feel, irritate skin, or are no longer produced), the studies conducted on their toxicity, the evaluation of margin of safety (MoS), and the current situation and perspectives by using new carriers. IN VI TRO AND IN VIVO METHODS FOR CUTANEOUS PENETRATION AND TRANSDERMAL PERMEATION OF ORGANIC UV FILTERS The s tratum corneum (SC) is the outermost layer of the epidermis. It consists of 10–25 layers of dead, elongated, fully keratinized corneocytes, which are embedded in a matrix of lipid bilayers. Ceramides form the major two-tailed component of the SC lipid matrix. Free fatty acids and cholesterol form the other two dominant components of SC lipids. On most body sites, the SC is 12–16 cell layers thick, but it can vary from as little as nine cell layers on the forehead or eyelids to as much as 25 on the dorsum of the hand and up to 50 or more on the palms or the soles of the feet. The crossing of the SC is the rate-limiting step in the sequence of percutaneous absorption. The desirable site of action of UV fi lters is restricted to the skin surface or within the uppermost layers of the SC. Ideally, a sunscreen should impregnate the SC and create a fi lter against UV radiation, but not penetrate into the underlying viable tissue. Table II UV Filter Substances Categorized According to the FDA GRASEa for use in sunscreens Not GRASEb for use in sunscreens Insuffi cient data for use in sunscreensc ZnO and TiO2 Aminobenzoic acid (PABA) and trolamine salicylate Cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, OCR, padimate O, sulisobenzone, oxybenzone, and avobenzone a GRASE = generally recognized as safe and effective. b These ingredients are not currently marketed. c For those ingredients in the “insuffi cient data” category, the FDA proposes that it needs additional data to determine that sunscreens with these ingredients would be GRASE. JOURNAL OF COSMETIC SCIENCE 302