What's the Deal with Nanoparticles in Sunscreens?

It is well known that applying a generous amount of broad-spectrum sunscreen daily, even on cloudy days, is important to protect our skin.^[1] Regular sunscreen use has been shown to prevent sunburns and skin cancer occurrence in several studies. ^[2,3] The term “broad-spectrum” refers to ingredients that protect against both ultraviolet light type A and B. Two common broad-spectrum active ingredients in sunscreen are Zinc Oxide (ZnO) and Titanium Dioxide (TiO2).^[4] In traditional sunscreens, ZnO and TiO2 appeared as a cosmetically unappealing thick white paste that was difficult to blend into the skin.  

In the last decade, however, the development of “nanoparticle” sunscreen formulas has led to sunscreens that appear transparent, blend more easily, and appear smoother under makeup.^[5] A nanoparticle is defined as a tiny particle with a diameter of less than 100 nanometers. Nanoparticles have become a hot interest in the skin care industry in many different products.^[6] In 1999, the Food and Drug Administration (FDA) approved sunscreen to be formulated with nanoparticles.^[4]

The use of sunscreen that is transparent and less-thick appeals to many consumers and may improve the regular use of sunscreen.^[7] However, people across the world have questioned the safety of nanoparticles on both humans and on the environment.^[8] In the United States, the use of nanoparticles is a regulatory problem because the FDA does not require specific labeling on nanoparticle size or quality.^[9] Currently, little is known about the long-term safety of using nanoparticle sunscreen. Some of the topics of concern include: 

1. Do nanoparticles in sunscreens create damaging reactive oxygen species (ROS)?
2. Do nanoparticles penetrate the epidermis(the most superficial layer of skin)?
3. Is it harmful to inhale nanoparticles?

ZnO and TiO2 Nanoparticles and Harmful Reactive Oxygen Species

ZnO and TiO2 are known as photocatalysts, which means that when exposed to sunlight they can create reactive oxygen species (ROS). Reactive oxygen species are harmful free-radicals that can damage cells and DNA.[10] However, it is still not clear if ZnO and TiO2 nanoparticles release free radicals that can damage the skin.  When a ray of ultraviolet (UV) light hits the ZnO or TiO2 nanoparticles, free radicals can react with proteins, lipids and DNA found in cells, potentially leading to damage.^[11,12]  One study found that exposing TiO2 to light that was similar to sunlight lead to the release of ROS that lead to damage in laboratory-grown skin cells.^[13,14] However, this study did not look at nanoparticles of Ti02.  In another experiment using mice, ZnO nanoparticles exposed to UV type B light lead to ROS based damage in the skin.^[11] It is important to note that none of these studies have been performed in human skin and we do not know if the findings would hold true. 

Additionally, the potential toxicity of these nanoparticles would only manifest if they are able to pass beyond the outermost layer of skin (epidermis) and are absorbed systemically.^[15] Until we have evidence that this occurs, the risk remains theoretical. 

Nanoparticles Getting into the Skin

Several studies have shown that ZnO and TiO2 nanoparticles do not penetrate beyond the stratum corneum (outermost layer) in healthy, unbroken skin.^[16-20] However, in a 2016 study at the National Institute of Health (NIH), TiO2 nanoparticles were found to penetrate into the dermis surrounding the hair follicles.^[21]  Studies suggest that ZnO nanoparticles also do not penetrate beyond the epidermis in human skin.^[15,22,23] In fact, in one human study, volunteers applied ZnO nanoparticle sunscreen twice daily for five days.  Researchers found that only 0.01% of the Zinc got into the blood.^[24] Currently, the Center for Drug Evaluation and Research of the FDA has concluded that “there is no significant penetration of TiO(2) nanoparticles through the intact normal epidermis.”^[25] When used as an ultraviolet filter, the FDA has stated that ZnO, is “generally recognized as safe.”^[26] The possibility that TiO¬2 may penetrate into the skin needs to be evaluated further. ^[21]

Potential Risk of Inhaling Sunscreen Nanoparticles

Toxicologists feel the greatest risk of nanoparticles is due from inhalation of zinc oxide or titanium dioxide nanoparticles.^[27] According to the International Agency for Research on Carcinogens, titanium dioxide may be a carcinogen if high doses are inhaled.^[28] The Environmental Working Group advises against using any spray or loose powder sunscreens that contain ZnO or TiO2 to avoid the potential toxicity from inhalation.^[9] One study examined if TiO2 particles are able to distribute across biological barriers, such as the blood brain barrier (BBB).  However, this study did not prove that nanoparticles actually cross the BBB, but may alter the physiology of the BBB. It concluded that we still do not yet know the risks associated with systemic absorption.^[29] 

Risk of Nanoparticles in Sunscreens

At this time ZnO nanoparticles in sunscreen do not appear to be dangerous when applied as a lotion to healthy skin, based on evidence that ZnO nanoparticles do not cross the epidermis.  The role of TiO2 nanoparticles is unclear as pilot studies show that they may penetrate to the dermis.  Studies in humans are missing and needed to assess if TiO2 nanoparticles release ROS in response to exposure to UV light. Inhalation of zinc oxide and titanium dioxide nanoparticles may have associated lung-based absorption. The current evidence is based on mouse studies and human studies are needed. The risk of using inhaling nanoparticles with powdered sunscreens on the face will need further study, and there needs to be more detailed work to understand if there is a safe way that these types of particles can be applied. Further research and more descriptive labeling may be important components for analyzing the safety and effectiveness of nanoparticles in sunscreen.  

At this time, both zinc oxide and titanium dioxide nanoparticles are approved for the formulation of sunscreens.  However, clinical research is limited and more long-term studies involving human skin under real sunlight exposure may help establish their safety profiles.  Both nanoparticles have the potential for cell damage if they cross the epidermis, but neither has demonstrated significant skin penetration in clinical studies, although TiO2 may be able to penetrate deeper than ZnO.^[21,30] It is important for ongoing research to identify risks associated with nanoparticles of ZnO and TiO2 in sunscreens. 

Sunscreens with regular zinc oxide and titanium dioxide, which are not in nanoparticle form, remain a widely available option as a broad-spectrum sunscreen. Good sun protective habits include the diligent use of sun protective clothing, avoidance of intense sunlight, and the daily use of broad-spectrum sunscreens.