appearance on the skin, which is most noticeable in dark-skin individuals. New formulations were encouraged by decreasing the particle size, culminating in the usage of nanoparticles. Oxidative stress and cellular toxicity would be a serious concern about ZnO and TiO2 in case they could penetrate the SC, enter the dermis, and ultimately the blood supply. Fortunately, both in vivo and in vitro studies have found that systemic absorption is not possible because their permeation reaches only the SCSC. This could be due to the nanoparticles’ tendency to concentrate into larger structures (30–150 nm), which cannot penetrate into the skin (43–45). However, they might be dangerous when inhaled, and thus there use, as spray sunscreen products, containing nanoparticles, is restricted. ORGANIC UV FILTERS Organic UV fi lters belong to several organic categories that are classifi ed as UVA and UVB fi lters because of their absorption properties. A great number of organic UV fi lters contain aromatic moieties conjugated with carbonyl groups. Excited delocalized electrons of the aromatic moieties make absorption into the UV range possible. Further substitution affects the absorption strength of various UV fi lter classes. Dibenzo ylmethane (1,3-diphenyl-1,3-propanedione) Derivatives. Cosmet ic products contain the most common UVA fi lter, i.e., butyl methoxydibenzoylmethane (BMDBM), which replaced the former 4-isopropyl dibenzoylmethane (I-DBM), in accordance with the de- mands of a balanced UVA/UVB protection. The production of BMDBM was interrupted in 1993 because it was thought to be photo-allergizing. It is also implied that photodeg- radation products can also be reactive and may cause further contact allergies (46-48). However, photodegradation can be minimized, by using a UV fi lter combination or by encapsulation (16). Benzophen one Derivatives. BP-3 and BP-4 are proven to have good photostability and broad-spectrum protection against the whole UVB and UVA ranges. That is why their use is extended to sunscreens and various skincare products. However, they do not offer complete UVA protection, unless they are combined. According to various studies, BP-3 tends to permeate the human skin, leaving traces in urine and breast milk, and is consid- ered to have endocrine potential, as mentioned earlier (toxicity studies) (9,49,50). Twenty-fi ve volunteers applied a commercially available sunscreen containing 4% BP-3 morning and night for 5 d. Their urine was measured during those 5 d and further 5 d after the last application. They were divided into groups A (unirradiated) and B. Group B received UV radiation according to the skin type. BP-3 in urine was analyzed with a high- performance liquid chromatography method (HPLC). The volunteers excreted 1.2–8.7% (mean 3.7%) of the total amount of BP-3 applied. There was no signifi cant difference between the two groups (p 0.99, t-test). It has been proven that there is a positive correlation between the use of cosmetics con- taining BPs and their presence in human milk. Human milk samples were collected from mothers of three different cohorts in 2004, 2005, and 2006, who gave birth to a singleton child at the University Women’s Hospital Basel. The age of the mothers across all three study cohorts was similar, with a mean of 32.3 years. Milk samples were taken in August/ September, October, and November/December 54.72% of the study participants used sunscreens and 60.38% used other cosmetic products containing UV fi lters. UV fi lters were detected in 46 of 54 or 85.19% of breast milk samples (BP-3: 13.21% of total) (51). DISTRIBUTION OF UV FILTERS ON THE SKIN 309

The most com mon photo allergens are considered to be BP-3 and BP-4. Over the 3-year period, between January 2003 and December 2005, 1,693 patients underwent patch testing to extended British Contact Dermatitis Society standard series 553 of these patients (33%) were also patch-tested to an extended facial/cosmetic series that included a selection of chemical UV fi lters supplied by Trolab (Hermal, Reinbek, Germany) and Chemotechnique (Crawford Pharmaceuticals, Milton Keynes, UK). BP-4 was the most frequently positive chemical UV fi lter that was tested (13 patients). It also pro- duced the third most frequently positive patch test results overall. Of the 13 patients who patch-tested positively to BP-4, fi ve were male and eight were female. None of the other UV fi lters that we added, for this study, gave any appreciable numbers of positive results. BP-3, which previously had been routinely patch-tested in the British Contact Dermatitis Society facial/cosmetic series, gave positive results in three patients (0.5%) (52,53). P-Aminobenzoate Derivatives. One of the most widely used and commercially promoted UV fi lters, worldwide, is the UVB fi lter, 4-aminobenzoic acid (PABA) (54). Never- theless, it was proven that not only PABA but also its derivatives could cause photo- allergic reactions (55,56). In the year 2008, PABA was prohibited in the EU, as a UV fi lter in cosmetic products. Similarly, the use of ethylhexyl dimethyl p-aminobenzoic acid (padimate O) has also been limited and almost been replaced by different UV fi lters. Salicylate Derivat ives. This group of ana logues is typically characterized by two UVB fi lters, EHS and homosalate. Salicylate derivatives are not strong UVB absorbers, but they are able to enhance other UVB fi lters, as they are highly water resistant, because of their water insolubil- ity. Salicylates used in cosmetics are known to cause no allergic or photoallergic reactions, while at the same time, they do not permeate into the skin (57). Photostability and solubility make EHS a particularly suitable ingredient of sunscreens. In addition, triethanolamine sa- licylate, a water-soluble UV absorber, acts typically as a photo-protective agent in haircare products (58). Camphor Derivatives . The camphor deriva tives, 3-benzylidene camphor and 4-MBC, were widely used, for a long time, because of their perfect photostability, as UVB fi lters. In 1994, almost 30% of sunscreen products contained 4-MBC. During 2004–2006, 4-MBC was still widely used in sunscreen products. However, mainly because of their endocrine potential, the camphor derivatives have been strongly criticized in the past years. Produced and patented by L’Oréal (Paris, France) in 1982 and approved by the EU in 1991, terephthalylidene dicamphor sulphonic acid (TDSA, Mexoryl SX) has been found to be an effective UV fi lter. The use of Mexoryl SX in the sunscreen “Anthelios SX” was approved by the FDA in 2006. TDSA exhibits suffi cient sun protection against the nega- tive effect of UVA rays, including pigmentation, epidermal hyperplasia, and even the limitation of skin hydration and elasticity. Also, TDSA is photostable and not percutane- ously absorbed (59-61). A study was designed to i nvestigate the systemically absorbed dose of Mexoryl SX in humans after topical application of a typical sunscreen emulsion. In addition, to assess the correlation with in vitro experiments, the percutaneous absorption of this UVA fi lter through isolated human skin was measured under identical exposure conditions. When applied in vivo for a period of 4 h, 89–94% of the applied radioactivity was recovered from the wash-off samples. In urine samples, the radioactivity slightly exceeded background JOURNAL OF COSMETIC SCIENCE 310