JOURNAL OF COSMETIC SCIENCE 546 makeup inks decompose when exposed to light (46,47). The use of photocatalytically active TiO2 may further accelerate sun-induced fading. The in vitro toxicological method described here should be useful both to manufacturers formulating inks and organiza- tions charged with overseeing the safety of these inks. REFERENCES (1) C. S. Zwerling, A. C. Walker, and N. F. Goldstein, Micropigmentation, State of the Art (C. S. Zwerling, Chapel Hill, NC, 1993). (2) Food and Drug Administration, Tattoos, FDA Med. Bull., 24, 8 (1994). (3) Food and Drug Administration, Tattoos and permanent makeup (2008). http://www.fda.gov/Cosmetics/ ProductandIngredientSafety/ProductInformation/ucm108530.htm. (4) D. Papameletiou, A. Zenie, D. Schwele, and W. Bäumler, Working paper on health effects and risks from tattoos, body piercing and related practices, European Commission, Ispra, Italy (2003). http:// phdres.caregate.net/curriculum/Reading%20fi les/EU_health0603.pdf. (5) D. Papameletiou, A. Zenie, and D. Schwele, Regulatory review on the safety of tattoos, body piercing and related practices, European Commission, Ispra, Italy (2003). http://ec.europa.eu/consumers/cons_safe/ news/eis_tattoo_reg_052003_en.pdf. (6) A. E. Laumann and A. J. Derick, Tattoos and body piercings in the United States: A national data set. J. Am. Acad. Dermatol., 55, 413–421 (2006). (7) W. Bäumler, E. T. Eibler, U. Hohenleutner, J. Sauer, and M. Landthaler, Q-Switch laser and tattoo pig- ments: First results of the chemical and photophysical analysis of 41 compounds, Lasers Surg. Med., 26, 13–21 (2000). (8) G. Lehmann and P. Pierchalla, Tätowierungsfarbstoffe, Derm. Beruf Umwelt, 36, 152–156 (1988). (9) S. M. Wenzel, J. Wenzel, C. Hafner, M. Landthaler, and W. Bäumler, Permanent make-up colorants may cause severe skin reactions, Contact Dermatitis, 63, 223–227 (2010). (10) M. Straetemans, L. M. Katz, and M. Belson, Adverse reactions after permanent-makeup procedures, N. Engl. J. Med., 356, 2753 (2007). (11) K. C. Klontz, L. A. Lambert, R. E. Jewell, and L. M. Katz, Adverse effects of cosmetic tattooing: An illustrative case of granulomatous dermatitis following the application of permanent makeup, Arch. Dermatol., 141, 918–919 (2005). (12) M. Falconi, G. Teti, M. Zago, A. Galanzi, L. Breschi, M. Pelotti, A. Ruggeri, and G. Mazzotti, Infl uence of commercial tattoo ink on protein production in human fi broblasts, Arch. Dermatol. Res., 301, 539– 547 (2009). (13) N. Bendsoe, C. Hansson, and O. Sterner, Infl ammatory reactions from organic pigments in red tattoos, Acta Derm. Venereol., 71, 70–73 (1991). (14) A. Bjornberg, Reactions to light in yellow tattoos from cadmium sulfi de, Arch. Dermatol., 88, 83–87 (1963). (15) D. De Argila, A. Chaves, and J. C. Moreno, Erbium: YAG laser therapy of lichenoid red tattoo reaction, J. Eur. Acad. Dermatol. Venereol., 18, 332–333 (2004). (16) M. Goldstein, Mercury-cadmium sensitivity in tattoos, Ann. Intern. Med., 67, 484–489 (1967). (17) C. Jäger, W. Harschuh, and U. Jappe, Sonnenlichtgetriggerte granulomotöse reaktion auf permanent lip-liner, Hautarzt, 56, 63–65 (2005). (18) A. Tourlaki, V. Boneshi, D. Tosi, P. Pigatto, and L. Brambilla, Granulomatous tattoo reaction induced by intense pulse light treatment, Photodermatol., Photoimmunol. Photomed., 26, 275–276 (2010). (19) I. Waldmann and F. Vakilzadeh, Allergische spätypreaktion auf rotten azofarbstoff in tätowierungen, Hautarzt, 9, 666–670 (1997). (20) H. Yazdian-Tehrani, M. M. Shibu, and N. C. Carver, Reaction in a red tattoo in the absence of mercury, Br. J. Plast. Surg., 54, 555–556 (2001). (21) J. W. Kim, J. W. Lee, Y. H. Won, J. H. Kim, and S. C. Lee, Titanium, a major constituent of blue ink, causes resistance to Nd-YAG (1064 nm) laser: Results of animal experiments, Acta. Derm. Venereol., 86, 110–113 (2006). (22) E. V. Ross, S. Yashar, N. Michaud, R. Fitzpatrick, R. Geronemus, W. D. Tope, and R. R. Anderson, Tattoo darkening and nonresponse after laser treatment: A possible role for titanium dioxide, Arch. Dermatol., 137, 33–37 (2001).

PHOTOCYTOTOXICITY OF TITANIUM DIOXIDE 547 (23) L. Thorington, “Spectral, Irradiance and Temporal Aspects of Natural and Artifi cial Light,” in The Medical and Biological Effects of Light, R. J. Wurtman, M. J. Baum, and J. T. Potts, Eds. (New York Academy of Sciences, New York, 1985), pp. 28–54. (24) J. H. Braun, Titanium dioxide—A review, J. Coatings Tech., 69, 59–72 (1997). (25) G. Forte, F. Petrucci, A. Cristaudo, and B. Bocca, Market survey on toxic metals contained in tattoo inks, Sci. Total Environ., 407, 5997–6002 (2009). (26) A. L. Timko, C. H. Miller, F. B. Johnson, and E. Ross, In vitro quantitative chemical analysis of tattoo pigments, Arch. Dermatol., 137, 143–147 (2001). (27) M. I. Cabrera, O. M. Alfano, and A. E. Cassano, Absorption and scattering coeffi cients of titanium di- oxide particulate suspensions in water, J. Phys. Chem., 100, 20043–20050 (1996). (28) T. Berger, M. Sterrer, E. Knözinger, D. Panayotov, T. L. Thompson, and J. T. Yates, Light-induced charge separation in anatase TiO2 particles, J. Phys. Chem. B., 109, 6061–6068 (2005). (29) A. L. Linsebigler, L. Guangquan, and T. Y. John, Photocatalysis on TiO2 surfaces: Principals, mecha- nisms, and selected results, Chem. Rev., 95, 735–758 (1995). (30) R. Konaka. E. Kasahara, W. C. Dunlap, Y. Yamamota, K. C. Chien, and M. Inoue, Irradiation of titanium dioxide generates both singlet oxygen and superoxide anion, Free Radic. Biol. Med., 27, 294–300 (1999). (31) Y. Nosaka, T. Daimon, A. Y. Nosaka, and Y. Murakami, Singlet oxygen formation in photocatalytic TiO2 aqueous suspension, Phys. Chem. Chem. Phys., 6, 2917–2918 (2004). (32) W. G. Wamer, J.-J. Yin, and R. R. Wei, Oxidative damage to nucleic acids photosensitized by titanium dioxide, Free Radic. Biol. Med., 23, 851–858 (1997). (33) K. Hirakawa, M. Mori, M. Yoshida, S. Oikawa, and S. Kawanishi, Photo-irradiated titanium dioxide catalyzes site specifi c DNA damage via generation of hydrogen peroxide, Free Radic. Res., 38, 439–447 (2004). (34) P. N. Maness, S. Smolinski, D. M. Blake, Z. Huang, E. J. Wolfram, and W. A. Jacoby, Bactericidal ac- tivity of photocatalytic TiO2 reaction: Toward an understanding of its killing mechanism, Appl. Environ. Microbiol., 65, 4094–4098 (1999). (35) Y. Nakagawa, S. Wakuri, K. Sakamoto, and N. Tanaka, The photogenotoxicity of titanium dioxide particles, Mutation Res., 394, 125–132 (1997). (36) L. Tiano, T. Armeni, E. Venditti, G. Barucca, L. Mincarelli, and E. Damiani, Modifi ed TiO2 particles differentially affect human skin fi broblasts exposed to UVA light, Free Radic. Biol. Med., 49, 408–415 (2010). (37) S. Kim and S. H. Ehrman, Photocatalytic activity of a surface-modifi ed anatase and rutile titania nano- particle mixture, J. Colloid Interface Sci., 338, 304–307 (2009). (38) C. M. Sayes, R. Wahi, P. A. Kurian, Y. Liu, L. L. West, K. D. Ausman, D. B. Warheit, and V. L. Colvin, Correlating nanoscale titania structure with toxicity: A cytotoxicity and infl ammatory response study with human dermal fi broblasts and human lung epithelial cells, Toxicol. Sci., 92, 174–185 (2006). (39) A. Sclafani and J. M. Herrmann, Comparison of the photoelectronic and photocatalytic activities of various anatase and rutile forms of titania in pure liquid organic phases and in aqueous solutions, J. Phys. Chem., 100, 13655–13661 (1996). (40) M. E. Carlotti, E. Ugazio, S. Sapino, I. Fenoglio, G. Greco, and B. Fubini, Role of particle coating in controlling skin damage photoinduced by titania nanoparticles, Free Radic. Res., 43, 312–322 (2009). (41) T. Picatonotto, D. Vione, and M. E. Carlotti, Effect of some additives used in the cosmetic fi eld on the photocatalytic activity of rutile, J. Dispers. Sci. Technol., 23, 845–852 (2002). (42) A. Rampaul, I. P. Parkin, and L. P. Cramer, Damaging and protective properties of inorganic components of sunscreens applied to cultured human skin cells, J. Photochem. Photobiol. A, 191, 138–148 (2007). (43) V. Brezová, S. Gabc ˇová, D. Dvoranová, and A. Staško, Reactive oxygen species produced upon photoex- citation of sunscreens containing titanium dioxide (an EPR study), J. Photochem. Photobiol. B, 79, 121– 134 (2005). (44) W. G. Wamer and J.-J. Yin, Phototoxicity, crystalline form and light-induced free radical formation for tattoo inks containing TiO2, Free Radic. Biol. Med., Suppl.1, 320 (2007). (45) R. R. Anderson, Shedding some light on tattoos? Photochem. Photobiol., 80, 155–156 (2004). (46) R. Vasold, N. Naarmann, H. Ulrich, D. Fischer, B. Köning, M. Landthaler, and W. Bäumler, Tattoo pigments are cleaved by laser light—The chemical analysis in vitro provides evidence for hazardous compounds. Photochem. Photobiol., 80, 185–190 (2004). (47) Y. Cui, A. P. Spann, L. H. Couch, N. V. Gopee, F. E. Evans, M. I. Churchwell, L. D. Williams, D. R. Doerge, and P. C. Howard, Photodecomposition of Pigment Yellow 74, a pigment used in tattoo inks, Photochem. Photobiol., 80, 175–184 (2004).