Possible Risks of Tattoo Removal Using Laser Therapy Wolfgang Bäumler Department of Dermatology, University of Regensburg, Germany

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1 Possible Risks of Tattoo Removal Using Laser Therapy Wolfgang Bäumler Department of Dermatology, University of Regensburg, Germany Abstract In the EU and the USA there are up to 100 million people with tattoos and since a few years the number is clearly increasing. Decorative tattooing is not considered to be a medical treatment and thus, there was no need for a clinical approval for the application of tattoo pigments and consequently no pharmacologic or toxicologic studies. Most of the coloured pigments used are organic compounds (e.g. azo compounds) originally manufactured by the chemical industry to stain consumer goods. A significant number of people request removal of their tattoos due to a desire to improve self-image or reduce social stigmatization. In contrast to the production of a tattoo its removal from the skin is usually performed by physicians in different fields. Laser light, at very high intensities, is applied to the skin in order to destroy tattoo pigments. Due to the high laser intensities, the tattoo pigment was heated up to a few hundred degrees Centigrade leading to a cleavage of the pigment molecules. However, while the laser induced cleavage of tattoo pigments the resultant decomposition products have been not investigated. Recently, experiments related to laser induced cleavage of tattoo pigments were performed for the first time by the Department of Dermatology and the Institute of Organic Chemistry (University of Regensburg, Germany). The results clearly showed that the high laser intensities cleaved azo compounds and an increase of decomposition products such as 2-methyl-5-nitroaniline, 2-5-dichloranilin and 4- nitro-toluol were measured. These products are proven to be toxic or even carcinogenic. After tattooing or laser treatment, the pigment plus unknown admixtures and decomposition products are not only present in the skin but are additionally transported through the blood vessels and the lymphatic system into the human body. It is known that these chemical compounds are present in the lymph nodes, however, to date there has been no investigation of this issue. Additionally, there has been no review in the literature of adverse reactions to tattoos and laser treatment and no discussion of the long-term effects. Thus, there is a significant need for further research in the field of chemical analysis of tattoo pigments and its laser induced decomposition products. Moreover, research has to be performed regarding the transport and the location of these compounds in the human body.

2 Introduction In the Western world tattooing is considered to be a sign of self-destructive and rebellious behavior (1). 100 of millions of people have at least one decorative tattoo. Cosmetic tattoos, in which black, red or flesh-toned pigments are used to mimic eye, lip or eyebrowliner, have also become increasingly popular (2). In the past, coloring agents used were inorganic pigments, whereas for dark-blue amateur tattoos, commercially available ink is still in use. Since tattoo compounds in comparison to cosmetics are not officially controlled, the origin and chemical structure of these colouring agents are unknown and neither the tattoo artist nor the tattooed patient have any information about the compounds introduces into the skin. Recently, an extensive analysis of a large number of tattoo compounds was performed for the first time (3). Most commercially available tattoo compounds are organic pigments, which are classified by their chemical constitution (4). A rough distinction is made between azo and non-azo (polycyclic) pigments. Generally, the pigments used for tattooing are well tolerated by the skin. Nevertheless, adverse reactions have been published in the literature (5-8). Moreover, several malignant lesions have occurred in tattoos (maybe coincidential) (9-11). Due to an improved self-image or social stigmatization issues, a significant number of people undergo tattoo removal, which is predominantly performed using laser therapy. The laser light penetrates the skin and is absorbed selectively by the pigment molecules which are agglomerated inside the dermis to small particles of a few µm in size. According to the principles of selective photothermolysis (12) the laser impulses selected are of high intensity and ultrashort pulse duration of a few nano seconds (Q-switched lasers). Due to interaction with laser pulses the shape and the size of the tattoo particles are changed abruptly and this has been confirmed by histology (13). However, the exact mechanisms of action regarding the destruction of tattoo pigments are still unclear. After being absorbed in the pigment molecule, the energy of the laser light is either converted to heat or breaks chemical bonds inside the molecule. The ultra short heating (~ns) of the pigment may lead to disruption of the pigment. At the same time, the extremely hot surface of the pigment causes a rapid expansion of the surrounding water inducing a negative pressure and a shock wave near to the surface of the pigment. As demonstrated for a suspension of small particles in water these shock waves may help to destroy the tattooed compounds (14). As a response, a multitude of mechanisms may occur at the same time. Particles pulverize and form a solution of pigment molecules. Molecules can break up, resulting in decomposition products or molecular structure change.

3 Due to fragmentation of the tattoo particles, small pigment particles, unknown decomposition products and newly generated chemical compounds may then be removed from the skin via lymphatic system. This mechanism induces a decrease of the color strength of the pigments and is responsible for a noticeable clearance of the tattoo. Since there is no requirement for clinical approval of tattoo pigments introduced into the skin, there is no investigation regarding the decomposition products produced by laser therapy. One goal of this study was the investigation and chemical analysis of decomposition products of tattoo pigments induced by high laser intensities. In addition, there have been no studies that examine the transport of tattoo pigments and decomposition products in the skin, sentinel lymph nodes and the rest of the human body. Tattoo removal At least 10 % of the millions of tattooed people decide to remove their tattoos. Besides adverse reactions (15-20) of the tattoo pigments itself, the main reasons for removing tattoos are improved self-image or social stigmatization. Traditional modalities are the removal of the pigment using salabrasion (21,22), cryosurgery (22,24), surgical excision (25,26) or laser application (27,28). However, these methods induce permanent scarring. Selective photothermolysis has been published (12) for the treatment of vascular lesions. The tattoo pigments have smaller diameters as compared to the vessels. Thus, the application of laser pulses with a high intensity (~ 107 W/cm²) and an ultrashort pulse duration of a few nano seconds is necessary to destroy the pigments inside the skin. Using such laser pulses a selective therapy is achieved showing a very low rate of scarring. Therefore, the removal of tattoos by laser irradiation is a widespread therapy used by physicians in different fields. It is estimated that about 10 % of tattoos are removed by laser therapy which equates to millions of patients. Tattoos are treated using different laser systems such as ruby lasers (694 nm), alexandrite lasers (755 nm) or Nd:YAG lasers (532, 1064 nm) at the respective wavelength (29-31). Laser light is absorbed in the pigment molecule with the corresponding energy converted predominantly to heat which leads to a substantial increase of the temperature of the molecule and consequently inside the pigment particle. It is well known that azo pigments cleave thermally when a temperature of 280 C is achieved (32). Since shock waves were produced by pigments after an ultra-short heating (10-9 s) using laser pulses it is obvious that high temperatures inside the pigments were achieved (14). Moreover, the laser irradiation of tattoo pigments inside the skin leads to small explosions. Histology of the skin shows small vacuoles in places the pigments particles were located prior to irradiation (13).

4 In spite of the numerous patients treated with lasers by physicians there are no investigations of the decomposition products of compounds. Recently however, experiments of laser induced cleavage of tattoo pigments in pigment suspensions - were performed for the first time by the Department of Dermatology and the Institute of Organic Chemistry (University of Regensburg, Germany). The first two tattoo pigments tested (Cardinal Red, I8) showed the presence of hazardous decomposition products. The heat energy of the absorbed laser light leads to the cleavage of the azo group of the pigment molecules. As a result 2- methyl-5-nitroanilin (2-MNA), 4-nitrotoluol (4-NT), 2-5-dichloroanilin (2,5-DCA), 1-4-dichlorobenzene (1,4-DCB), naphthol-as or 1-amino-naphthol-AS appeared in the suspension. Due to laser irradiation of the tattoo pigments the concentration of these decomposition products increased significantly. When using Cardinal Red, the concentration of 2-MNA or 4-NT increased 33-fold or 45 fold, respectively. After laser irradiation of I8 the concentration of 2,5-DCA or 1,4-DCB increased 7-fold or 33-fold, respectively. Conclusion Since up to hundred million people in the EU and USA have a tattoo and millions of people undergo laser treatment of their tattoos, there is a significant and urgent need of research. The problems are as following: The pigments used for tattoos are mostly unknown There is no disclosure of admixtures There is no clinical approval for tattoo colors The amount of pigment inside the skin is unknown Therefore, the amount of decomposition products due to laser treatment is unknown The transport mechanisms of pigments and its admixtures in the human body is unknown The amount of pigments and its admixtures outside the skin is unknown (e.g. lymph nodes, liver) There is nothing known about systemic health effects of tattoos, in particular about long-term effects (e.g. cancer) There is no review on adverse reactions regarding tattoos and laser treatment, only case reports In order to quantify and to judge the problems and the health risks of tattoos and laser treatment, the following research is necessary: chemical analysis of tattoo colors chemical analysis and quantification of laser induced decomposition products tattoo pigments, admixtures and decomposition products o transport mechanisms o concentrations outside the skin (e.g. lymph node, liver)

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