Beyond skin deep: The emerging science of tattoo toxicology

Jonas J. Calsbeek, Jeremy A. MacMahon & Pamela J. Lein, PhD from University of California, Davis, explain the emerging science of tattoo toxicology

Tattooing has existed in diverse cultures since at least the late Neolithic period as evidenced by the specimen of tattooed skin from the body of Őtzi the Iceman, dating to between 3370 and 3100 BC. Over the past 20 years, the prevalence of tattooing has increased significantly worldwide. In Western societies, up to 44% of people under the age of 35 have tattoos or permanent make-up. There is a common perception that tattooing is safe; however, the reality is that up to 70% of tattooed individuals report adverse health effects. The field of tattoo toxicology has emerged to grapple with outstanding questions of why tattoos trigger these responses and how to identify which chemicals used in tattoo inks are toxic.

Tattoo concerns

Tattooing involves the use of sharp tools to pierce the protective outer epidermal layer of the skin to deposit pigments into the inner dermal layer of the skin. Tattoo ink typically consists of insoluble coloured pigments, aka colourants, suspended in a mixture of water, solvents, viscosity regulators, and diverse preservatives. Because they are relatively insoluble, tattoo pigments persist in the dermis; however, they are not biologically inert. There is experimental evidence that cells in the dermis can metabolise at least some tattoo pigments, which may result in the formation of hazardous by-products. In addition, both human and experimental animal studies demonstrate that immune cells migrating through the dermis can pick up pigments, particularly metal oxide nanoparticles, and transport them to other tissues in the body, most notably lymph nodes.

The chemicals in tattoo inks include known human health hazards. Historic and modern inks often contain soot-related compounds, such as carbon black, which includes polyaromatic hydrocarbon (PAH) contaminants, along with shading additives, such as titanium dioxide or iron oxides. Carbon black and PAHs are suspected or known human carcinogens, while titanium and iron oxides cause skin sensitisation. The trend towards more colourful tattoos has increased the use of organic pigments, with azo dyes being the most common. Azo pigments are prone to photodecomposition, and some decomposition products, for example, the cleavage products of pigment yellow 74 or orange 13, are suspected or known human carcinogens.

Further, interactions of PAHs and organic ink components with ultraviolet (UV) radiation can form reactive oxygen species, which trigger inflammatory responses in the skin and induce DNA strand breaks in dermal cells. Modern tattoo inks often contain metals such as colourants, shading additives, or preservatives, or unintentional contaminants. Titanium, barium, aluminium, and copper are used as colourants, whereas antimony, arsenic, cadmium, chromium, cobalt, lead and nickel are common contaminants. Many of these metals are toxic, and levels detected in some tattoo inks are above regulatory limits. Another source of metals in tattoos is metal debris from chromium and nickel-containing tattoo needles.

While the main health risk historically was infection, the introduction of rigorous health and safety standards for tattoo parlours has significantly reduced infections following tattooing. However, a 2018 study by the United States Food and Drug Administration (U.S. F.D.A.) found that up to 50% of unopened bottles of commercial inks, including those labelled as sterile, were contaminated with microbes. The typical response is a superficial skin infection localised to the site of ink injection, but systemic infection with bacteria, fungi, or viruses, such as hepatitis C or B or HIV can occur, and in exceptional cases, may result in life-threatening sepsis.

Tattoos can also cause chronic health effects. Hypersensitivity reactions to tattoo inks or “itchy” tattoos, are the most common chronic complications. Hypersensitivity may appear after a latency of several months or years and is often resistant to standard medical treatments. Most reactions are inflammatory and can range from skin ulceration in severe allergy to excessive epidermal hyperplasia. Specific colourants, particularly red, seem to elicit allergic and hypersensitivity reactions, and the risk of reaction is increased by powerful contact allergens, such as nickel.

A current debate is the potential for tattoo inks to cause cancer. The widespread presence of genotoxic and carcinogenic chemicals in tattoo inks drives cancer concerns. Additionally, the initial skin trauma caused by tattooing, and the subsequent inflammatory reaction that can persist over a lifetime, are cancer risk factors. At present, with the exception of keratoacanthoma (a slow-growing benign skin tumour) on red tattoos, skin cancer has not been strongly associated with tattoos. However, epidemiological data are scarce, and the long latency of cancer will require large cohorts to identify associations.

Removal of tattoos does not necessarily negate toxicity concerns. Laser irradiation, which breaks down pigments via thermophotolysis, is the most common method of tattoo removal. However, laser irradiation of tattoo pigments can produce carcinogenic compounds.

Regulatory challenges

In the U.S., the F.D.A. regulates tattoo inks as cosmetics; thus, pre-market review or approval of tattoo inks is not required. While colourants require submission of a petition to establish safety, no colour additives have yet been approved for injection. In the EU, apart from a general law requiring manufacturers not to market unsafe products, there are no regulations on what components can go into tattoo inks, and tattoo legislation in Europe is based on an exposure scenario of placing a product on top of the skin, rather than into the living tissue beneath the epidermal skin barrier.

A major problem for the risk assessment of tattoo inks is the absence of sufficient data regarding ink composition and toxicology. While the final formulation might be simple, given the increasing number of substances to choose from, the problem of control is complex. Further complicating the development of effective regulatory policies is the lack of an appropriate model for evaluating the toxicological effects of tattoo pigments injected into the dermis; simple patch testing of tattoo pigments is not predictive of allergenic or hypersensitivity reactions.

International measures for consumer protection are urgently needed. Industry needs to take a more proactive stance on tattoo safety. Regulators and scientists need to address tattoo inks differently from cosmetic products. This will require focused research efforts to understand the migration, metabolism and potential toxic effects of pigments following intradermal application.

*Please note: This is a commercial profile