levels and corresponded maximally to 0.014% of the topically applied dose. No radioac- tivity was measured in blood or feces sampled up to 120 h after application. In vitro, 24 h after a 4-h application, Mexoryl SX remained primarily on the skin surface. The mean in vitro absorption over 24 h, adding up the amounts found in the dermis and receptor fl uid, was 0.16% of the applied dose. It was concluded from the in vivo pharmacokinetic results that the systemically absorbed dose of Mexoryl SX was less than 0.1%. This study dem- onstrated that, under realistic exposure conditions, the human systemic exposure to this UVA fi lter is negligible and poses no risk to human health (62). Cinnamate Derivatives. Hu man exposure to ethylh exyl (octyl) methoxycinnamate (EHMC/ OMC) is signifi cant, and it can pose a risk for human health. EHMC has been found to be absorbed through the skin, and it was detected in human biomatrices, such as urine, blood, and human breast milk. Several studies have proven the toxic potential of EHMC, such as endocrine-disrupting effect in vitro and in vivo. However, it is reported and estab- lished that EHMC experiences degradation by two primary pathways, photolysis and photoisomerization. One of the products of photoisomerization is also cis-EHMC. When EHMC is exposed to sunlight, the commonly present trans-EHMC may be transferred to cis-EHMC (cis/trans isomerization, also called geometric isomerization). The isomeric form in which EHMC appears may impact its toxicity potential. Researchers studied the s kin permeation of the parental trans-EHMC and its cis-isomer. The trans-EHMC geometric isomer along with its laboratory-produced cis-EHMC coun- terpart was added in a commercial sunscreen lotion, which was applied on the skin (fore- arm) of two volunteers (2 mg cm-2). The combined product was left on the skin for 8 h, and then tape stripping was used to remove the horny layer. A total protein assay was applied, and the thickness of the given SC was measured spectrophotometrically. The HPLC-DAD method was used to estimate the concentration of the isomers present in the extracted SC. The kinetic parameters [diffusion coeffi cient (D), partition coeffi cient (K), and permeability coeffi cient (k)] were calculated from the measured depth-concentration profi le in six replicates (six application sites on the skin) with the use of Fick’s second law [D cis-EHMC = 1.62 ± 0.83 × 1014 (m2 s-1), D trans-EHMC = 1.58 ± 0.84× 1014 (m2 s-1)]. The values of calculated diffusion coeffi cients and permeability coeffi cients of cis-EHMC were slightly higher than those of trans-EHMC. However, the Wilcoxon nonparametric test showed no statistical difference in either k or D of both isomers (p 0.05). Although the Wilcoxon nonparametric test showed no statistical difference in dermatotoxicokinetic parameter of both isomers (p 0.05), the studies by Necasova et al. and Sharma et al. (63,64) showed that the cis-EHMC can cause more signifi cant risk than trans-EHMC in the scenario of female population exposure (ages 16–65) after daily application of several kinds of personal cosmetic products. Even though the permeation of both isomers seems to be similar, the emergent cis-EHMC causing greater DNA damage can be more harmful than trans-EHMC in the same depth of SC. In vitro genotoxic effects of trans- and cis- EHMC on adult human liver stem cells HL1–hT1 and human-derived lymphoblastoid cells TK-6 using a high-throughput comet assay were studied. TK-6 cells treated with cis-EHMC showed a high level of DNA damage when compared with untreated cells in concentrations 1.56–25 μgmL-1. Trans-EHMC showed genotoxicity after exposure to the two highest concentrations, 12.5 and 25 μgmL-1. It still remains crucial to conduct diffe rent toxicological studies of isomeric forms and defi ne their dermatotoxicokinetic parameters to decipher the risks imposed on the human skin (65). DISTRIBUTION OF UV FILTERS ON THE SKIN 311

The group of cinnamate analogues also inc ludes the UVB fi lter OCR. Studies showed that 16–24 h after application of OCR (8–10%) on the surface of skin samples, most of the OCR remained on the surface of the skin as non-penetrated material ( 95%), and detectable amounts of the applied dose were found in the SC, and in low amounts or below the detec- tion limit in other skin layers (epidermis, dermis, or receptor medium). None of the authors determined a percentage of dermal absorption. Hayden’s study showed that only 0.4% of OCR was found in the epidermis and approximately 0.05% in the fl uid receptor (40). Therefore, it can be concluded that transdermal absorption of OCR is very low. The sensitizing potential of OCR has been extensively reviewed in the scientifi c literature, and contact al- lergy to OCR is very rare in the general population. Photocontact allergy cases to OCR have been reported but are rare in the general population (66). It is photostable with a good photostabilizing effect, particularly toward BMDBM. BMDBM exhibits high absorptive capacity in the UVA region, but it suffers from marked decom- position under sunlight irradiation, which leads to a reduction in the protective effi cacy of the sunscreen preparation during solar exposure. In addition, its photo-fragmentation results in the formation of free radicals, which may directly or indirectly initiate skin damage. The instability of BMDBM under sunlight can be reduced by the addition of UVB fi lters, such as OCR or methylbenzylidene camphor, with triplet energy similar to BMDBM and acting as quenchers of its triplet state. In the case of irradiation, energy transfer between OCR and BMDBM takes place in the exited state (triplet state). Triazones . The UVB fi lters ethylhexyl triazone (EHT), diethylhexyl butamido triazone (DEBT, iscotrizinol, Uvasorb HEB), and the broad-spectrum UV fi lter bis-ethylhexy- loxyphenol methoxyphenyl triazine (BEMT, bemotrizinol, Tinosorb S/BASF Care Cre- ations, Germany) have a molecular weight over 500 Da because of the extension and multiplication seed in their chromophoric groups. The benefi ts of these UV fi lters in- clude the development of high absorption coeffi cients, anti-infl ammatory properties while being effi cient and also photostable (67,68). Tinosorb S can also optimize the pho- tostability of other UV fi lters in a sunscreen (69). T riazones are an integral part of an increasing number of skincare and sunscreen products, and this has to do with their benefi cial properties. A particle size less than 100 nm and a molecular weight of 823.1 Da make Tris-biphenyl triazine (Tinosorb A2B) the fi rst UV fi lter to be ideally included in care products around Europe. It offers great skin protection against UV radiation between 290 and 340 nm, bridging the gap between “conventional” UVA or UVB fi lters. In addition, it has water-dispersible action, it is broad-spectrum, and it is micronized. Benzo triazoles. The UV fi lters drometrizole trisiloxane (DTS, Mexoryl XL) and methylene bis- benzotriazolyl tetramethylbutylphenol (MBBT, Bisoctrizole, Tinosorb M) are also catego- rized within the 500 Da rule. They have a minor skin penetration property, while they rarely cause (photo) allergic reactions (37,70). Mexoryl XL, the fi rst photostable UV fi l- ter, offers skin protection over the whole UVB and UVA ranges. A combination of Mexo- ryl SX and XL also offers a synergistic effect on their protection properties (71). Tinoso rb M is produced in the form of organic microfi ne particles and can be dispersed in the water phase of a sunscreen. Also, it offers all the properties of organic and inorganic UV fi lters, while it refl ects, scatters, and absorbs UV radiation. Furthermore, it exhibits suffi cient photostability and broad-spectrum ability over the whole UVB, UVA-I, and UVA-II range (72). JOURNAL OF COSMETIC SCIENCE 312