TITANIUM DIOXIDE AND ZINC OXIDE NANOPARTICLES IN SUNSCREENS 231 The lack of penetration through the epidermis is considered as the main reason for the absence of skin carcinogenesis–promoting effects. INTERACTIONS OF SUNSCREENS WITH OTHER SUBSTANCES Sunscreens are not only dermal preparations applied on the skin. Many cosmetic prepara- tions, dermocosmeceutic, and dermal preparations are applied every day. It is important to investigate potential interactions between sunscreens containing NPs, to fi nd out whether sunscreens enhance or block resorption. Effects of drugs applied to the skin for many diseases can be modulated and disturbed. Peire et al. have researched interactions with amphotericin. TiO2 NPs can modulate the transdermal permeation of the ampho- tericin. The main reason is the superfi cial chemistry of TiO2 (51). ROS generated by TiO2 and ZnO NPs can increase skin permeability. Transdermal drug and other substances (dyes, pesticides, and toxins) penetration can be favored or reduced by modulating the TiO2 surface charge (coating) and its oxidative potential (crystalline phases), so the enhancer effect of TiO2 NPs can be adjusted and converted up or down- ward (52,53). People are encouraged to use sunscreens when they are exposed to sunlight, and it is often on fields where pesticides are applied. The dermal penetration of the herbicide 2,4-dicholorophenoxyacetic acid (2,4-D) is enhanced by the formulations containing chem- ical UV absorbers, the absorbers themselves, and the insect repellent DEET. Brand et al. investigated whether commercially available sunscreens containing TiO2 or ZnO enhance the transdermal absorption of pesticides. For in vitro studies, hairless mouse skin was used. In vitro permeability studies were performed with the pesticides: parathion, mala- thion, 2,4-D, and paraquat. The data demonstrate that there was signifi cant penetration enhancement of malathion, parathion, and paraquat when compared with controls. The difference between ZnO and TiO2 was noticed because ZnO can interfere with 2,4-D penetration and TiO2 had no effect. Although, the risk-benefi t analysis gives the recom- mendation for using sunscreens (54). CONCLUSION There are conclusive pieces of evidence that TiO2 and ZnO NPs do not penetrate through intact and healthy human skin, but further studies are necessary to confi rm their penetra- tion through damaged and sensitive skin. Of paramount importance is the fi nding that most studies do not demonstrate NPs’ skin penetration and that no signifi cant concentra- tions are found in layers of viable cells. It must be emphasized that cytotoxic and patho- logical outcomes are presented in studies using high concentrations of NPs, which are impossible to be used for human purpose. Results of in vivo–in vitro and human–animal studies should be cautiously extrapolated. Some studies have given conclusive pieces of evidence about the potential of NPs to in- duce ROS in vitro, which largely mediate NP-induced cytotoxicity and genotoxicity, but the important real-situation information is that NPs used in sunscreens have modifi ed the surface so it has less possibility to produce ROS, even after UV exposure. Sunscreens also contain antioxidants to neutralize generated ROS, and endogenous antioxidants can
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