Tattoo industry faces an ink makeover

Today’s youth are more colorful than their parents, at least when it comes to permanent body art. Once considered taboo in mainstream cultures in the US and Europe, tattoos are more accepted socially now than they were in past generations. About 12% of people in Europe and more than 20% of people in the US have at least one tattoo, according to a report by the European Commission’s Joint Research Centre. Among adults in the US aged 26–40, the percentage is closer to 40%. The popularity of tattoos with younger generations is a trend across Western countries as a growing number of young people turn their skin into canvases.

As the prevalence of tattoos in Western countries has increased, so too have scientists’ safety questions about the inks tattooers use. Tattoo inks live in murky regulatory territory in the US. “It’s not a drug. It’s not a food. It’s not even a cosmetic. It’s its own thing, and it’s very lightly regulated,” says Mark Prausnitz, a biomedical engineer at the Georgia Institute of Technology.

Safety data for ink ingredients exist, but they were often collected in nontattoo contexts. Tattoo ink manufacturers formulate their products using ingredients originally intended for textiles, paints, and other manufacturing industries. So existing health data don’t account for these ingredients sitting in the skin for long periods. This data gap has left toxicologists and other health experts with questions about what factors cause some people with tattoos to experience adverse health events such as infections, allergic reactions, and other dermatologic problems.

Existing data have already pushed some governments to act. This year, the European Union enacted new regulations that prohibit tattoo inks from containing substances that are known to harm human health. To help guide future regulations, scientists are addressing questions about how the chemicals in inks change over time in skin and how they interact with human tissues. Meanwhile, some researchers are inventing new ink formulations that could lead to next-generation medical devices and wearable technologies.

New regulations

Randa Roland, a faculty lecturer in the chemistry department at the University of California, Santa Cruz, is covered in molecules. She got her first tattoo around 2006 and hasn’t stopped since. Many people with tattoos describe getting their first one as “breaking the seal.” A 2019 poll from the market research company Ipsos found that 33% of tattoo-sporting adults in the US reported having two tattoos, and the average across the survey participants was four tattoos of varying sizes. The same poll found that people younger than 55 were twice as likely as older adults to have at least one tattoo.

Roland’s tattoos illustrate aspects of the history of chemistry, iconic concepts, or fascinating compounds that hold a personal meaning. “They remind me that chemistry has generally got a story to go with it,” she says. Like many tattoo collectors, Roland worked closely with a licensed tattooer to carefully choose each design. Then the tattoo artist got to work bringing the art to life.

Here’s what scientists know about how the tattooing process works: Tattoo inks generally consist of a water-soluble carrier solution that helps deliver an insoluble pigment into the skin. The tattooer loads that ink into a tattoo machine that oscillates a set of needles to transfer ink particles into the middle layers of the dermis by repeatedly puncturing the skin. As the tattoo heals, blood flow increases to the affected area and begins to carry away the water-soluble components. At the same time, immune cells called macrophages surround the insoluble pigment particles. As these cells settle, they fix the ink particles in place. If all goes to plan, the final result is healed skin with the colorful art locked into place.

Tattoos like Roland’s take hours to create and require a variety of colored inks. Black and white inks, widely used for outlines, highlights, and shading, are made from the inorganic pigments carbon black and titanium dioxide, respectively. Most other inks owe their hues to organic pigments. Because these pigments are water insoluble by design, manufacturers add a cocktail of chemicals, such as glycerin and isopropyl alcohol, to solubilize these colorants and keep them shelf stable. A good ink will be formulated to flow easily into skin, stay where it’s injected, and maintain its color over time, says Michael Dirks, a chemical engineer who cofounded a consulting company, called the 3 Pylons, that specializes in tattoo ink formulations. Now, some ink manufacturers are changing their formulations.

Tattoos are generally safe, but some people experience health issues with body art beyond the uncomfortable yet expected wound-healing process. A 2016 paper by the European Commission’s Joint Research Centre describes reports of adverse tattoo-related health events, including allergic reactions, prolonged healing times, and infections. It’s difficult to know just how often these complications occur, because people don’t always go to a doctor for treatment, and doctors are the ones who would document these incidents.

And the exact cause of these adverse events can be devilish to parse. The Joint Research Centre report points to evidence that tattoo machines’ needles may leave behind nickel and chromium debris in the skin, and both these metals are common allergens. Other investigations have found tattoo ink in lymph nodes and other tissues, which suggests that insoluble pigment particles may move through our tissues more extensively than previously thought. These findings and others have prompted health officials to more closely examine tattoo ink ingredients’ toxicology.

Tattoo inks don’t fit neatly into commonly regulated consumer categories. Over the past decades, commercial tattooing products have fallen under a patchwork of regulations that differ between countries and even between states. In the US, intradermal inks used in tattoos and permanent makeup are classified as cosmetics under the Food and Drug Administration. But the FDA “traditionally has not exercised regulatory authority for color additives on the pigments used in tattoo inks,” the agency says on its website. In the European Union, some common ingredients in tattoo inks aren’t permitted for use in cosmetic products at all.

Inconsistencies in regulatory guidance on tattoo inks in EU member countries led the European Commission to adopt a new, unified ordinance under the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) program in 2020. The EU’s expanded REACH regulations will restrict the use of about 4,200 chemicals—such as known carcinogens, mutagens, and irritants that are already prohibited from use in cosmetic products—in tattoo inks. The agency allowed the tattoo industry until Jan. 4, 2022, to comply with the new REACH restrictions.

Among the thousands of restricted substances are more than 20 coloring agents. Many of these chemicals are organic molecules that contain azo bonds, a double bond between nitrogen atoms. Organic azo pigments are often used to create red, orange, and yellow inks. The building blocks that make these pigments include aromatic nitrogen compounds that are known carcinogens. The azo bonds in the pigments can break apart when exposed to light and release these soluble, toxic compounds into the bloodstream, Dirks says. Ink manufacturers have other options for replacing these warm hues of the rainbow, but not for the cool colors, he says.

The phthalocyanine compounds pigment blue 15 and pigment green 7 are among the only, and thus most widely used, blue and green pigments used in tattoo inks, Dirks says. European consumer safety officials placed these pigments on the list of prohibited cosmetic substances because of concerns that hair dyes containing these pigments potentially cause bladder cancer, but the link was never substantiated. A risk assessment report conducted by the German Federal Institute for Risk Assessment (BfR) in 2020 found that both pigment blue 15 and pigment green 7 have been used for more than a decade, during which time they have posed “a comparatively low level of toxicity” (BfR-Stellungnahmen 2020, DOI: 10.17590/20201006-102053). But the BfR notes that the data are incomplete, especially in the context of tattoos. For that reason, it recommended further research to clarify any suspicions about the pigments’ hazards. The report also cautions that a ban on pigment blue 15 and pigment green 7 could result in the use of less-investigated coloring agents in their place.

Tattooists expressed concern over the new REACH regulations’ potential impact on the tattoo industry because there are no alternative blue and green pigments. Dirks and his colleagues launched a petition with the European Parliament that has since garnered more than 178,200 cosigners in defense of the pigments.

Both pigment blue 15 and pigment green 7 are exempted from the REACH restrictions until January 2023 to provide researchers an opportunity to present updated safety data and allow the tattoo industry to seek safer replacements. But Dirks and others fear that there are no suitable alternatives to replace these pigments in inks. The tattoo industry is too small to pressure chemical manufacturers to develop new, REACH-compliant blue and green pigments, he says. There are approved blue coloring agents used in the cosmetic industry, but they are dyes, which are water soluble. Dye molecules don’t produce the same color intensity as pigments and are more easily degraded in skin, Dirks says.

Filling in the data gaps

As the EU enacts new tattoo ink regulations, scientists continue their investigations into the basic science behind tattoo ink chemistry and safety.

For John Swierk, a photochemist at Binghamton University, the question of why tattoos fade with light and laser​removal is particularly intriguing. Swierk and his team began designing experiments to study how common tattoo inks are affected by different light conditions, such as ambient office lighting and ultraviolet radiation from the sun. But they ran into an unexpected challenge in the very first steps. “We began to recognize that a lot of the inks had discrepancies between what was written on the bottle and what was actually in the ink according to our analytical testing,” he says.

Swierk realized that it would be impossible to design a standardized protocol to investigate the photochemistry of tattoo inks when their composition remained enigmatic. So his team started analyzing the ingredients in about 100 commercial inks. “A majority of things that we’ve looked at have had some level of discrepancy,” Swierk says. For example, labels misrepresented pigments or omitted carrier substances. Swierk reported his team’s findings at the American Chemical Society Fall 2022 meeting in Chicago. His lab has begun collating results in a public database called What’s in My Ink?, which he hopes to expand as this project continues.

When scientists get more information about what inks contain, they can start studying safety issues like allergic reactions to ingredients. Tattoo allergies don’t occur often, but the impact on people who develop these reactions can be significant, says Ines Schreiver, a biomedical engineer and coleader of the BfR’s Dermatotoxicology Study Centre. “Unlike other allergens like jewelry, you cannot just take it off. It’s inside of you,” she says. In fact, laser tattoo removal could lead to more severe reactions by releasing allergens into the bloodstream as the ink particles disperse in the skin.

For decades, tattooists and allergy researchers have noticed greater rates of allergic reaction in tattoos containing red pigments, especially in combination with sun exposure. In some cases, a person getting a new tattoo with red ink will experience an adverse reaction in older tattoos that were never a problem.

In 2019, Schreiver and her colleagues analyzed more than 100 skin biopsies from patients experiencing an allergic reaction from red tattoos. When the researchers analyzed these samples by X-ray diffraction and matrix-assisted laser desorption ionization tandem mass spectrometry (MALDI-MS/MS), they found that 55% of samples contained naphthol AS pigments, a class of red azo compounds (Contact Dermatitis 2019, DOI: 10.1111/cod.13423). But correlation does not equal causation. Schreiver suspects that the culprit may not be the pigments themselves. Instead, it’s possible that leftover starting materials from their synthesis, breakdown products from photodegradation, or some combination of other unknown factors could trigger allergic reactions.

Another area that Schreiver and her colleagues want to study is how ink pigments age in skin. They are working on a lab model of multilayered, healed skin tissue in a petri dish. By embedding pigments in these tissue cultures, the researchers are beginning to investigate how tattooed pigments in healed skin react to light and how a rudimentary immune system responds to those reactions (Arch. Toxicol. 2020, DOI: 10.1007/s00204-020-02825-z). It’s one of many projects that Schreiver and her colleagues are pursuing to better understand why certain people experience adverse reactions to tattoos and how to prevent them from happening in others.

Functional body art

While some scientists and engineers try to answer questions about current tattoo ink chemistry and safety, others are developing new tattoo technologies.

At Georgia Tech, Prausnitz has been developing vaccines that can be administered in the skin through microneedle patches, which are widely used in pharmaceutical and cosmetic consumer products. Recently, Prausnitz began adapting this technology to deliver tattoo inks. Each patch contains a grid of conical microneedles about 1 mm long made from a soluble polymer matrix that can be loaded with the desired ink. When the patch is placed on the skin, the needles pierce the tissue to deliver the payload. The needles quickly dissolve while the ink remains fixed like any other intradermal tattoo. Unlike tattoo machines, these microneedles don’t cause bleeding, have a low risk of infection, and can be self-​administered. Prausnitz tested his microneedle tattoo patches using different ink colors, including fluorescent inks that are visible only under ultraviolet light. In rats, these tattoos were stable a year later, though some tattoos appeared to stretch or deform as the skin aged (iScience 2022, DOI: 10.1016/j.isci.2022.105014).

Meanwhile, Ephemeral is among a new wave of companies working to bring innovative tattoo inks to consumers. Unlike permanent tattoo inks, Ephemeral’s formulation is made to fade over 9–15 months. The company offers only black ink tattoos at a handful of brick-and-mortar studio locations across the US, but more locations and color options are in the works. The company hopes to attract clients who want a traditional tattooing experience without the lifetime commitment.

“From a technical perspective, we needed a tattoo ink that behaves like a permanent ink and also disappears over time,” says Brennal Pierre, a chemical engineer and cofounder of Ephemeral. The company’s inks are made with medical-​grade, bioabsorbable particles that shrink over time. Smaller particles are easier for the body to clear away naturally until nothing is left of the original design.

When Ephemeral’s team designed its made-to-fade inks, safety was a top priority, Pierre says. Though Pierre could not disclose specific ingredients in the inks, he thinks that made-to-fade inks could also be used in healthcare settings. For example, breast cancer patients undergoing radiotherapy often get a small tattoo to mark the spot on their body where technicians aim the beam of radiation.

Biomedical applications for tattoos are also gaining momentum. As a postdoctoral researcher, biomedical engineer Ali K. Yetisen wanted to design wearable medical devices that could monitor disease biomarkers in a person’s bloodstream. As Yetisen considered strategies to integrate monitoring devices seamlessly into a person’s body for continuous use, he realized that the same blood biomarkers he wanted to measure are also found within interstitial fluid, which surrounds cells and suffuses skin tissue. “Pretty much everything that you detect in blood samples can be detected in interstitial fluid,” Yetisen says. That’s when he realized that a tattooable biosensor might work better than an implantable device.

Yetisen and his colleagues created tattoo inks using reagents that change color in response to pH, glucose levels, and albumin to monitor disease states like hypoglycemia. They used these inks to make tattoo patterns such as stars and chevrons in samples of pig skin. Then they developed a mobile app to decode the colors from the tattoos (Angew. Chem., Int. Ed. 2019, DOI: 10.1002/anie.201904416). “We can utilize this smartphone camera as a portable spectrophotometer,” he says. The data are only semiquantitative but could help patients and doctors keep tabs on medical conditions through continuous monitoring at home. Now at Imperial College London, Yetisen is working to expand the functionality of these biosensing tattoo inks.

For UC Santa Cruz’s Roland, the prospect of adding high-tech inks to her tattooed collection of chemical curios is an exciting proposition. And she will continue to lean on her tattooist to help navigate decisions about the safety of inks she uses in future designs.

Binghamton University’s Swierk and others hope their research will help consumers like Roland make informed choices about tattoo safety. “We’re not antitattoo in any way,” he says.

If people were developing tattoos for the first time today with current safety concerns in mind, “the set of pigments that get used in tattooing are not the set of pigments that you would choose in any way, shape, or form,” Swierk says. But, it’s still early days for understanding tattoo ink chemistry and safety, he says. Researchers need to learn a lot of basics before they can start designing better and safer inks.