Spotlight on CDER Science: New FDA Study Shines Light on Sunscreen Absorption
In a study recently published in the Journal of the American Medical Association (JAMA), 1 CDER scientists conducted a pilot study and learned that four active ingredients commonly found in sunscreen (avobenzone, oxybenzone, octocrylene, and ecamsule) were absorbed through the skin into the body.
These results do not mean that the ingredients are unsafe. Rather the results support the need for further absorption testing and other safety studies of these ingredients for repeated use. While industry and other interested parties develop further data, the public should continue to use sunscreens with other sun protective measures. Broad spectrum sunscreens with sun protection factor (SPF) values of at least 15 remain a critical element of a skin-cancer prevention strategy.
Today, sunscreens, which are regulated as over-the-counter (OTC) drug products, are used with greater frequency, in larger amounts, and by more consumers than ever before. Moreover, sunscreen formulations have changed, yielding higher SPFs and better broad-spectrum protection. Lab technologies have also evolved, improving our capacity to detect the absorption of active ingredients.
Some concerns have been raised about the safety and effects of sunscreen ingredients on human health, in part because we have limited evidence of absorption for some sunscreen ingredients. There is a need for more rigorous and systematic research specifically evaluating the bloodstream concentration of sunscreen ingredients when users apply sunscreen as directed on the label.
In February 2019, the agency announced a proposed rule to update regulations on sunscreens. In the proposed rule, the FDA requested more safety data from manufacturers for 12 sunscreen active ingredients, including some of the ingredients that the FDA tested in the JAMA study. The information obtained from this study, along with other safety/toxicology studies, would help determine if these ingredients meet the agency’s criteria for a product to be designated as “generally recognized as safe and effective” (GRASE) for its intended use. Only two sunscreen ingredients – zinc oxide and titanium dioxide – currently meet GRASE criteria.
Conducting the Study
To conduct the study, FDA scientists used a maximal usage trial (MUsT) design to evaluate the absorption of four sunscreen ingredients in commercially available products, using maximum dose limits and intervals (e.g., every two hours, four times per day) consistent with the product’s label. 2 A MUsT is a standardized method for evaluating the absorption of topical drug products, such as lotions, creams and sprays that are applied to the skin.
Twenty-four healthy study participants, enrolled from July to August 2018, were randomly assigned to four treatment groups, with equal numbers of men and women in each group. Each group received a different sunscreen product (either one of two sprays or a lotion or a cream), with each product containing a combination of four sunscreen active ingredients (avobenzone, oxybenzone, octocrylene, and ecamsule).
Each participant had one of the sunscreen formulations applied in a standardized amount four times a day for four days, to 75 percent of body surface area, which is typically the percentage of skin exposed by normal swimwear. The researchers then collected blood samples over a seven-day period.
In addition to measuring absorption rates, the researchers also explored how the ingredient moved through the body (e.g., pharmacokinetics), including the time it took for each ingredient to reach maximum concentration overall and the time for each ingredient to be removed from the body.
Results showed that all four tested ingredients were absorbed into the body at amounts exceeding the FDA threshold of 0.5 nanograms per milliliter (ng/mL), for potentially waiving some additional studies for sunscreens. 2 This threshold for testing the safety of sunscreen active ingredients is based on the principle that the approximate cancer risk associated with plasma concentrations below this threshold would be less than 1 case in 100,000 after a single dose. The major observations from this clinical study include:
- Maximum plasma concentrations (blood levels) of all tested ingredients exceeded the threshold after a single day of sunscreen application;
- The maximum plasma concentration of three tested ingredients (avobenzone, oxybenzone, octocrylene) also exceeded the threshold for seven days (three days after applying the sunscreen products);
- The total drug exposure and maximum plasma concentration increased from day one to day four for oxybenzone, avobenzone and octocrylene.
Details about other pharmacokinetic parameters are discussed in detail in the published JAMA article. 1
A second part of the systemic absorption study is underway using a different design to investigate additional questions raised by part one of this study. Part two will study the maximum concentration of the ingredients in the blood after a single application, the concentration up to 17 days after the last dose, and the absorption of other commonly used active ingredients, including octinoxate, homosalate and octisalate.
Of note, part one of this study did not address certain variables that may influence systemic absorption, such as differences in absorption by formulation type, variations in skin type, and the age of study participants.
While safety testing continues, the agency advises that the public continue to use sunscreen products in combination with other sun protective measures, such as wearing protective clothing, sunglasses and hats, and avoiding direct sunlight whenever possible during the peak hours of 10 am to 2 pm. Skin cancer remains the most commonly diagnosed cancer in the United States, and skin cancer rates continue to rise. Broad spectrum sunscreens with SPF of at least 15 help guard the skin from both UVA and UVB rays. When used with other sun protective measures, broad spectrum sunscreens with SPF values of at least 15 help prevent skin cancer, sunburn, and other ultraviolet damage to skin cells.
- 1. a. b. Matta MK, et al. Effect of Sunscreen Application Under Maximal Use Conditions on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial. JAMA. 2019;321(21):2082-2091.
- 2. a. b. US Food and Drug Administration, HHS, Guidance for industry: Maximal Usage Trials for Topically Applied Active Ingredients Being Considered for Inclusion in an Over-The-Counter Monograph: Study Elements and Considerations, May 2019.