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Toxic Chemicals Found in Tattoos: Links to Autoimmune and Inflammatory Diseases

Toxic Chemicals Found in Tattoos: Links to Autoimmune and Inflammatory Diseases

Tattooing is a long-standing human ritual that transcends historical and sociocultural boundaries, but more regulatory oversight is needed to ensure inks are not contaminated with dangerous chemical byproducts.

Debunking Tattoo Mythology: A Short History of The Tattooing Ritual

Tattoos represent a cultural rite of passage, a mode of self-expression, and a means of cultivating one’s unique identity (1). British captain, explorer, and navigator James Cook introduced the word tattoo into the European vernacular, as an amalgamation of the Polynesian word ‘ta’ to ‘strike something’ and the Tahitian word ‘tatau’ meaning ‘to mark something’ (2). 

The historical use of tattoos extends back at least seven thousand years ago, as tattoos were discovered on the extremities of a mummy from that period found in Northern Chile (3). Also, the five thousand year-old mummified remains of Ötzi the Iceman were found to contain osteochondrosis, or abnormal bone growth, in body sites where tattoos were present (2). Pesapane and colleagues (2014) likewise note that documentation of tattoos dates back to records by Roman emperor Constantine the Great in 313 AD, Pope Hadrian 1 in 787 AD, and the Old Testament (2).

Historically, tattoos were used to demarcate group identity, to protect the internal body from the exterior world, as a symbol of religious indoctrination, and in branding rituals as a form of medieval punishment. As an example of tattoos signifying group affiliation, “Crusaders used mostly Christian motifs to ensure that they received a Christian funeral in case they died in a foreign country” (3). In Japan, on the other hand, criminals were branded with tattoos as a mark of social stigmatization from the eighteenth century onward, which led to the rise of a tattooed demographic called the Yakuza (3).

Although condemned as marks of defilement by monotheistic religions, tattoos were a venerated practice in ancient Egypt and Rome, and remained a secret practice in some Christian sects such as the Sanctuary of Loreto (2). Ocean expeditions of the eighteenth century heralded a resurgence in the popularity of the tattoo, as interaction of colonialists with local South Pacific cultures led to adoption of local tattoo motifs by the former, and the eventual replacement of native designs with European-themed tattoos (3).

In the nineteenth century, a veritable “tattoo mania” was embraced by elite aristocratic European social classes (2). Celebrity figures including Tsar Nicholas II, Sir Winston Churchill, and Empress Elisabeth of Austria all sported tattoos (2, 3). However, in the late nineteenth century, the law profession contributed to the demise of the traditional meanings of the tattoo in their attempts to “conclude from the physiognomy of the exterior appearance as to the moral standards or criminal intent of a person” (3). The public perception of tattoos was also influenced by the display of tattooed persons as elements in circuses and carnivals (3).

Today, popularity of tattooing once again soars, as studies have demonstrated that nearly a third of university students, and 80 million people in the United States, are tattooed (4, 5). With its origins in pre-industrial cultural traditions and supernatural mythology, tattooing and other body modifications have been a long-standing component of the human condition. Clearly, “Tattoos and piercings can no longer be regarded as destructive acts of self mutilation practiced by fringe groups” (1, p. 115).

Histologic Reactions Secondary to Tattoos

Although the age of moralizing tattoos as an indictment of character should be long passed, concerns linger over health implications. According to Wenzel and colleagues (2013), “Medical complications after tattooing are often seen by physicians, but are generally unknown to the public” (6, p. 138). Tattoos have been associated with “allergic, lichenoid, granulomatous, and pseudolymphomatous reactions or induction of skin diseases” (2, p. 145). Other localized skin diseases, including the autoimmune disorders lichen planus and psoriasis, as well as eczema and morphea, have also been induced by tattoos (7). 

In one nationwide survey of German-speaking countries, for example, 67.5% of individuals with tattoos reported skin problems, 6% reported systemic reactions resulting from tattoos, with 1.3% reporting light sensitivity of the tattooed skin (8). The survey similarly revealed that chronic problems including burning, itching, erythema, papules, nodules, and eczema occurred in 6% of subjects (8). It is estimated that five million people in the United States have persistent skin problems secondary to tattoos, but data on toxicant-induced health problems related to tattoos has not been systematically collected (9).

According to Goldstein (1979), “The injection of any foreign material into the skin produces an inflammatory response, and some degree of necrosis, due to mechanical disruption of the tissue” (10, p. 896). Although this initial reaction normally subsides, subsequent sensitization reactions can occur along with mild fibrosis of the papillary dermis, meaning thickening and scarring of collagenous connective tissue (10). 

In addition, perivascular infiltration of lymphocytes and macrophages, meaning migration of white blood cells of the immune system to sites around slightly dilated blood vessels, is also a feature of tattooed tissues (10). Various histological abnormalities can occur, such as foreign-body type or sarcoid type granulomatous formations, comprised of aggregates of macrophage cells known as histiocytes (10). Inflammatory infiltrates characterized by significant fibroplasia, or the growth of fibrous tissue, creating nodules known as dermatofibroma and keratoses can also occur (10).

Pathological skin pigmentation, known as cutaneous dyschromia, can likewise occur due to deposition of heavy metals such as bismuth and mercury in the basement membranes of sebaceous glands and sweat ducts (10). 

Tattoo Safety: A Need For More Regulatory Oversight

Researchers state, "Tattoo inks are typically composed of negligibly soluble or insoluble pigments, dispersants in which the pigments are suspended and other additives for preservation or to alter the viscosity of the ink" (11). Although some contemporary inks can contain organic pigments, colored ink conventionally contains metals (12). Because other industrial applications of tattoo inks include paint and printing, they can harbor up to 10% impurities (9). Further, studies show that the "vast majority of tested tattoo inks contained significant amounts of NPs [nanoparticles],” which are associated with a litany of ill health effects (13).

A recent study published in the Journal of Hazardous Materials revealed that chemicals present in tattoo ink induced cytotoxicity (cell death), genotoxicity (DNA mutation), and adaptive stress response pathways (11).  Adaptive stress pathways are activated to restore cellular homeostasis, or balance, following damage incurred to cell structure, indicating that tattoo ink disrupts cellular integrity (34). Chemicals in tattoo ink can contribute to deleterious health outcomes by different modes, including binding of chemicals to enzymes and biological molecules and partitioning of chemicals into cell membranes (11).

Safety Hazards of Colored Inks

Because no color additives are approved for intradermal injection, no tattoo pigments are approved for use by the Food and Drug Administration (FDA). As articulated in a study by Arisa and Alster (2012), “The majority of tattoo ink is industrial-grade color intended for use as printer ink or automobile paint” (14).

Colored pigments, on the one hand, can decompose following light exposure into dangerous aromatic amines which are subsequently disseminated throughout the body and accumulate in lymphatic system, interfacing directly with components of the immune system (6). In a recent study, the levels of genotoxicity (DNA damage) and oxidative stress (inflammatory) pathways induced by red and yellow tattoo ink were particularly troublesome, as they generated the greatest response (11). Another study by Falconi and colleagues (2009) found that red tattoo ink significantly reduced viability of fibroblast cells, which are responsible for production of the extracellular matrix that provides the structural framework for tissues (15). 

When exposed to natural or ultraviolet light, azo pigments contained within red and yellow inks have been demonstrated to emit hazardous compounds, and they also have been shown to contain the probable human carcinogen 3,3-dichlorobenzidine as an intermediary in their production (11). Furthermore, o-anisidine and 4-aminobiphenyl, aromatic amines within red ink, can elicit genotoxic effects, damaging genetic material after metabolic activation (11, 16). Other investigations have elucidated a connection between red tattoo ink, skin irritation, and tumors (6). In various studies, “Coincidental lesions such as sarcoidosis, B-cell lymphoma, pseudolymphoma, melanoma, basal cell carcinoma, non-Hodgkin's lymphoma, and squamous cell carcinoma have also been reported to occur” (14).

Safety Hazards of Black Inks

However, black inks, which predominately consist of soot products, are also problematic (9). Carbon black in black ink is derived from the incomplete combustion of hydrocarbons, which accounts for its polycyclic aromatic hydrocarbon (PAH) content (17). PAHs represent ubiquitous pollutants derived from the burning of organic materials such as wood, petrol, oil, and coal, which elicit well-defined carcinogenic (cancer-causing), mutagenic (DNA-altering), and toxic effects (18). 

Researchers state, "Chemical analysis revealed the presence of polycyclic aromatic hydrocarbons in the tested black tattoo ink at concentrations twice the recommended level" (11). In particular, the PAHs pyrene and fluoranthene were found at the highest levels, and the possible human carcinogen naphthalene was also detected (11). PAHs are capable of absorbing ultraviolet radiation from the sun and producing a cytotoxic reactive oxygen species (ROS), singlet oxygen, as a byproduct, which can result in cell death (6). In another study, 10 of 11 black inks tested had levels of PAH exceeding the concentration recommended by the European Council, and 100% of black inks analyzed had levels of the carcinogen benzo(a)pyrene exceeding safe limits (17). 

One toxic ingredient found in black tattoo ink, hexachloro-1,3-butadiene (HCBD), is a byproduct of manufacturing processes for chlorinated solvents, and has a history of use as a fumigant or pesticide (9). It has been shown to perpetuate skin, kidney, and liver damage in rodent studies (19). 9-fluorenone, acquired from coal tar, has likewise been found in black tattoo ink and may cause phototoxic reactions, or chemically induced skin irritation following sunlight exposure (20, 21).

Hexamethylenetetramine, a preservative used in the manufacture of coatings, resins, rubber, and cosmetics, is another agent contained within some black tattoo inks (9). It releases formaldehyde, the xenobiotic toxic substance used to embalm corpses, which is associated with systemic autoimmune disease (22). It has likwewise been shown in the literature to cause respiratory allergies and contact dermatitis (9). 

Particularly alarming is the occurrence of dibenzofuran (DBF) in black tattooing agents, which is derived from “the incomplete combustion of coal biomass, refuse, diesel fuel, and residual oil, as well as tobacco smoke” 9, p. 236). When polychlorinated, or attached to chlorine atoms, it belongs to a dangerous class of persistent organic pollutants called dioxin-like chemicals (9). Dioxin-like chemicals exert gastrointestinal, hepatic, and dermal toxicity and DBF can cause respiratory irritation (9).

Components of Tattoo Ink Linked to Autoimmunity and Mitochondrial Dysfunction

Another study found that all 14 commercially available black inks analyzed contained the softener dibutyl phthalate, a sensitizing agent which “acts directly on keratinocytes and can drive Th2 responses following skin exposure via induction of thymic stromal lymphopoietin gene expression” (9, p. 231). This is to say, dibutyl phthalate can facilitate expression of a gene that tips the immune system in the direction of Th2-dominant responses, which have been implicated in some autoimmune diseases including systemic lupus erythematosus (SLE) and Sjögren's syndrome (23).

Other chemicals found within tattoos, such as formaldehyde, may induce autoimmunity by either inducing cell death, and exposing antigenic material within the cell against which the immune system may mount an attack, or by covalently binding to tissue and creating ‘neoantigens’ which incite immune responses (24, 25, 26).

Black inks likewise have been shown to induce production of reactive oxygen species (ROS) such as singlet oxygen or peroxyl radicals, which are free-radicals that can steal electrons from neighboring molecules and damage cell constituents (17). One study by Regensberger and colleagues (2010) found that in the presence of ultraviolet light, some black inks reduced activity of the energetic powerhouses of the cell, the mitochondria, of human dermal keratinocytes, the type of cell that predominates in the outermost layer of skin (27). Impaired mitochondrial activity has health implications since mitochondrial dysfunction is implicated in mood disorders, cardiovascular disease, diabetes, neurodegenerative disorders, chronic fatigue syndrome, fibromyalgia, migraine headaches, autoimmune diseases, and cancer (28).

Risk of Infection from Tattoos

Although professional tattooist organizations have improved hygienic standards, concerns about contagious exposure through tattooing remains (29). As articulated by Serup (2017), microbial pathogens such as hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency viruses (HIV) can be introduced, and “Severity of infection varies from minor to major, ultimately with life-threatening septicemia” (29, p. 30). People who are immunocompromised are often advised to refrain from tattooing (29).

Although sanitation measures are improving and risk of contracting infectious diseases from contaminated tattoo equipment has decreased, the inks themselves may harbor infectious microbes (30). Recent studies reveal that, despite 42% of products claiming sterility on their labels, 10% of unopened and 17% of previously used stock bottles of tattoo ink were contaminated with pathogenic bacteria, and that almost a third of products had leaking physical seals (31). Those inks marketed as nontoxic, which exclude alcohol and preservatives, possess greater risk of microbial contaminants, such as the Starbrite Colors tattoo inks which were removed from the market due to the presence of Pseudomonas aeruginosa and Acremonium mold (14).

How To Ensure Tattoo Safety

As an honored tradition, indelible art form, and means of forging individuation, it is incumbent upon the industry to guarantee safer options for tattoo ink. People should have the bodily autonomy to engage in tattooing practices without sacrificing their health.

For instance, vegetable-based inks, such as yellow pigments derived from turmeric, may represent a safer alternative, although they may need to be special ordered by the tattoo artist. Not dissimilar to cosmetics, the FDA has not traditionally enforced or regulated tattoo inks (32). Further, the level of transparency regarding ingredients is impeded by the proprietary nature of the tattoo inks sold by many manufacturers. 

In addition, because the term non-toxic is not legally regulated, what is advertised as nontoxic ink may still contain deleterious ingredients, such as blue pigments derived from the neurotoxin aluminum and white pigments derived from titanium dioxide nanoparticles. The latter, for example, is not only classified as possessing carcinogenic properties by both the International Agency for Research on Cancer and the National Institute for Occupational Safety and Health, but also elicits oxidative damage that can cause immunogenicity, inflammation, genotoxicity, and problems with cell integrity (33).

Consumers should demand access to safer tattoo inks and also rally for more regulatory oversight not only in this domain, but in the realms of cosmetics and personal care products as well. Further, for those suffering from toxicity as a result of tattoos, natural regimens intended to support biotransformation and elimination may be indicated, and some individuals suffering overt heavy metal toxicity may need to undergo chelation protocols supervised by an environmental medicine physician.

References

1. Stirn, A. (2007). ["My body belongs to me"--cultural history and psychology of piercings and tattoos] [Article in German]. The Umsch, 64(2), 115-119.

2. Pesapane, F. et al. (2014). A short history of tattoo. Journal of the American Medical Association: Dermatology, 150(2), 145. doi:10.1001/jamadermatol.2013.8860

3. Schmid, S. (2013). Tattoos — An historical essay. Travel Medicine and Infectious Disease, 11(6), 444-447.

4. King, K.A., & Vidourek, R.A. (2013). Getting inked: tattoo and risky behavioral involvement among university students. Social Science, Journal, 50, 540-546. 

5. Laumann, A.E., & Derick, A.J. (2006). Tattoos and body piercings in the United States: a national data set. Journal of the American Academy of Dermatology, 413-421.

6. Wenzel, S.M. et al. (2013). Adverse reactions after tattooing: review of the literature and comparison to results of a survey. Dermatology, 226, 138-147.

7. Khunger, N., Molpariya, A., & Khunger, A. (2016). Complications of tattoos and tattoo removal: stop and think before you ink. Journal of Cutaneous and Aesthetic Surgery, 8(1), 30-36.  doi: 10.4103/0974-2077.155072.

8. Klugl, I. et al. (2010). Incidence of health problems associated with tattooed skin: a nation-wide survey of German-speaking countries. Dermatology, 221, 43-50. 

9. Lehner, K. et al. (2011). Black tattoo inks are a source of problematic substances such as dibutyl phthalate. Contact Dermatitis, 231-238.

10. Goldstein, A.P. (1979). VII. Histologic reactions in tattoos. Journal of Dermatology and Surgical Oncology, 5(11), 896-900.

11. Neale, P.A. et al. (2015). Bioanalytical evidence that chemicals in tattoo ink can induce adaptive stress responses. Journal of Hazardous Materials, 296, 192-200. doi: 10.1016/j.jhazmat.2015.04.051.

12. Bäumler, W. et al. (2000). Q-switch laser and tattoo pigments: first results of the chemical and photophysical analysis of 41 compounds. Laser Surgery Medicine, 13-21.

13. Høgsberg, T. et al. (2011). Tattoo inks in general usage contain nanoparticles. British Journal of Dermatology, 165(6), 1210-1218. doi: 10.1111/j.1365-2133.2011.10561.x.

14. Arisa, O.E., & Alster, T.S. (2012). Rising Concern over Cosmetic Tattoos. Dermatologic Survey,  38(3), 424–429. doi: 10.1111/j.1524-4725.2011.02202.x

15. Falconi, M. et al. (2009). Influence of a commercial tattoo ink on protein production in human fibroblasts. Archives of Dermatology Research, 539-547.

16. Oda, Y. (2004). Analysis of the involvement of human N-acetyltransferase 1 in the genotoxic activation of bladder carcinogenic arylamines using a SOS/umu assay system. Mutation Research: Fundamental and Molecular Mechanisms of Mutagenesis, 399-406.

17. Høgsberg, T. et al. (2013). Black tattoo inks induce reactive oxygen species production correlating with aggregation of pigment nanoparticles and product brand but not with the polycyclic aromatic hydrocarbon content. Experimental Dermatology, 464-469.

18. Abdel-Shafy, H.I., & Mansour, M.S.M. (2016). A review on polycyclic aromatic hydrocarbons: Source, environmental impact, effect on human health and remediation. Egyptian Journal of Petroleum, 25(1), 107-123. 

19. Dubrat, P., & Gradiski, D. (1987). Percutaenous toxicity of hexachlorobutadiene. Acta Pharmacol Toxicol (Copenhagen), 43, 346-353.

20. Atsumi, T. et al. (1998). Cytotoxicity of photosensitizers camphorquinone and 9-fluorenone with visible light irradiation on a human submandibular-duct cell line in vitro. Archives of Oral Biology, 43, 73-81.

21. Okada, N. et al. (2008). Effects of visible light-irradiated camphorquinone and 9-fluorenone on murine oral mucosa. Dental Materials Journal, 27, 809-813.

22. Bigazzi, P.E. (1997). Autoimmunity caused by xenobiotics. Toxicology, 119, 1-21.

23. Ishida, H. et al. (1997). [An imbalance between Th1 and Th2-like cytokines in patients with autoimmune diseases--differential diagnosis between Th1 dominant autoimmune diseases and Th2 dominant autoimmune diseases]. Nixon Rinsho, 55(6), 1438-1443.

24. Pollard, K.M. (2012). Gender differences in autoimmunity associated with exposure to environmental factors. Journal of Autoimmunity, 38(2-3), J177–J186.

25. Germolec, D., Kono, D.H., Pfau, J.C. et al. (2012). Animal models used to examine the role of the environment in the deveopment of autoimmune disease: findings from an NIEHS expert panel workshop. Journal of Autoimmunity, 39(4), 285–293.

26. Griem, P. et al. (1998). Allergic and autoimmune reactions to xenobiotics: how do they arise? Immunology Today, 19(3), 133–141.

27. Regensburger, J. et al. (2010). Tattoo inks contain polycyclic aromatic hydrocarbons that additionally generate deleterious singlet oxygen. Experimental Dermatology, 19, 275-281.

28. Pieczenik, S.R., & Neustadt, J. (2007). Mitochondrial dysfunction and molecular pathways of disease. Experimental and Molecular Pathology, 83, 84-92.

29. Serup, J. (2017). Tattoo Infections, Personal Resistance, and Contagious Exposure through Tattooing. Current Problems in Dermatology, 52, 30-41. doi: 10.1159/000450777.

30. Bonadonna, L. (2015). Survey of studies on microbial contamination of marketed tattoo inks. Current Problems in Dermatology, 48, 190-195. doi: 10.1159/000369226. 

31. Høgsberg, T. et al. (2013). Microbial status and product labelling of 58 original tattoo inks. Journal of the European Dermatology and Venereology, 27(1), 73-80. doi: 10.1111/j.1468-3083.2011.04359.x.

32. Ortiz, A.E., & Alster, T.S. (2012). Rising concern over cosmetic tattoos. Dermatologic Surgery, 38(3), 424-429.

33. Skocaj, M. et al. (2011). Titanium dioxide in our everyday life; is it safe? Radiology and Oncology, 45(4), 227-247. 

34. Simmons, S.O. et al. (2009). Cellular stress response pathway system as a sentinel ensemble in toxicological screening. Toxicological Science, 111, 202-225.

 

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of GreenMedInfo or its staff.

Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

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