In the JournalsPerspective

FDA: Some sunscreen ingredients exceed safety threshold, but still OK to use

Six active ingredients in four different commercially-available sunscreen formulations applied by healthy study participants were systemically absorbed through the skin, resulting in exposure levels that exceeded the FDA threshold for safety testing, researchers reported in JAMA.

Murali K. Matta, PhD, of the FDA’s Division of Applied Regulatory Science, and colleagues wrote that additional research is needed to determine the effect of systemic sunscreen absorption, so the clinical significance of these findings is not clearly understood. However, they stressed that individuals should continue to use sunscreen for ultraviolet protection.

The FDA recommends that active sunscreen ingredients with systemic exposure levels greater than 0.5 ng/mL undergo additional safety testing, including systemic carcinogenicity and reproductive studies, according to the researchers. In a previous study, Matta and colleagues sought to determine the systemic absorption of four active sunscreen ingredients: avobenzone, ecamsule, octocrylene and oxybenzone. In that study, researchers found that these ingredients were absorbed systemically and remained in plasma for at least 3 days after the last application. When used under maximal use conditions (at least every 2 hours), plasma concentrations of these sunscreen ingredients exceeded the FDA threshold of 0.5 ng/mL, supporting the need for additional studies investigating the safety of systemic absorption.

In the new study, researchers randomly assigned 48 patients (mean age, 38.7 years; 50% women; 48% white) in a 1:1:1:1 ratio to apply sunscreen that contained avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and/or octinoxate via an aerosol spray, lotion, nonaerosol spray or pump spray. Sunscreen was applied at 2 mg/cm2 to 75% of body surface area over 4 days. It was applied once on day 1 and four times during the remaining 3 days at 2-hour intervals. Although conducting the study outside would be more indicative of a real-life setting, the researchers conducted the study indoors, noting that “the data would have likely been more variable because of the need to control for heat, humidity, wind and cloud cover.”

Sunscreen Squeezed Into a Person's Hands 
Six active ingredients in four different commercially-available sunscreen formulations applied by healthy study participants were systemically absorbed through the skin, resulting in exposure levels that exceeded the FDA threshold for safety testing, researchers reported in JAMA. Photo source: Adobe

Matta and colleagues analyzed blood samples collected over the study and found that the geometric mean maximum plasma concentrations of all six active ingredients were greater than 0.5 ng/mL after a single application on day 1. Individual ingredient’s geometric mean maximum plasma concentrations and coefficient of the variation (CV) percentages were:

  • 3.5ng/mL for avobenzone (70.9% CV), 180.1 ng/mL for oxybenzone (57.3% CV), 6.6 mg/mL for octocrylene (78.1% CV), 23.1 mg/mL for homosalate (68% CV), and 5.1 mg/mL for octisalate (81.6% CV) in aerosol spray formulations;
  • 7.1 mg/mL for avobenzone (73.9% CV), 258.1 mg/mL for oxybenzone (53% CV), and 7.8 mg/mL for octocrylene (87.1% CV) in lotions;
  • 3.5 mg/mL for avobenzone (73% CV), 6.6 mg/mL for octocrylene (103.9% CV), 17.9 mg/mL for homosalate (61.7% CV), 5.8 mg/mL for octisalate (77.4% CV), and 7.9 mg/mL for octinoxate (86.5% CV) in nonaerosol spray formulations; and
  • 3.3 mg/mL for avobenzone (47.8% CV), 13.9 mg/mL for homosalate (70.2% CV), 4.6 mg/mL for octinoxate (97.6% CV), and 5.2 mg/mL octinoxate (68.2% CV) in spray pump formulations.

Fourteen of the participants reported a rash, but no serious drug-related adverse events were reported.

The new findings do not mean sunscreen ingredients are unsafe, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, stated in a press release.

“Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use,” Woodcock continued.

In a related editorial to the new JAMA study, Adewole S. Adamson, MD, MPP, assistant professor in the department of internal medicine at the University of Texas at Austin, and Kanade Shinkai, MD, PhD, professor in the department of dermatology at the University of California, San Francisco, encouraged sunscreen manufacturers to perform tests on their products.

“Elevating the science of the benefits and harms of sunscreen should be a priority,” Adamson and Shinkai wrote. “The sunscreen industry must begin conducting these safety studies as recommended by the FDA. Until then, the harms of absorption of sunscreen filters will remain uncertain.”

Both studies conducted by Matta and colleagues stem from an FDA proposed rule that seeks to update regulatory requirements for most sunscreen products sold in the United States, according to an FDA blog. Several dermatologists told Healio Primary Care that the proposed rule also calls for raising the maximum SPF value on sunscreen product labels from 50 plus to 60 plus and ascertaining if there is still a need for such products with a SPF value that is lower than 15.

The FDA received about 15,000 comments to the proposed sunscreen rule before the public comment period ended in June 2019, an agency spokesperson told Healio Primary Care. She did not give a timeframe for the final rule’s issuance, stating that “the FDA wants to make certain we give careful scientific and regulatory consideration to all comments.” – by Janel Miller

References:

Adamson AS, Shinkai K. JAMA. 2020;323(3):223-234.

FDA.gov. Shedding new light on sunscreen absorption. https://www.fda.gov/news-events/fda-voices-perspectives-fda-leadership-and-experts/shedding-new-light-sunscreen-absorption. Accessed Jan. 17, 2020.

Matta MK, et al. JAMA. 2020;doi:10.1001/jama.2019.20747.

Disclosures: The authors report no relevant financial disclosures.

Six active ingredients in four different commercially-available sunscreen formulations applied by healthy study participants were systemically absorbed through the skin, resulting in exposure levels that exceeded the FDA threshold for safety testing, researchers reported in JAMA.

Murali K. Matta, PhD, of the FDA’s Division of Applied Regulatory Science, and colleagues wrote that additional research is needed to determine the effect of systemic sunscreen absorption, so the clinical significance of these findings is not clearly understood. However, they stressed that individuals should continue to use sunscreen for ultraviolet protection.

The FDA recommends that active sunscreen ingredients with systemic exposure levels greater than 0.5 ng/mL undergo additional safety testing, including systemic carcinogenicity and reproductive studies, according to the researchers. In a previous study, Matta and colleagues sought to determine the systemic absorption of four active sunscreen ingredients: avobenzone, ecamsule, octocrylene and oxybenzone. In that study, researchers found that these ingredients were absorbed systemically and remained in plasma for at least 3 days after the last application. When used under maximal use conditions (at least every 2 hours), plasma concentrations of these sunscreen ingredients exceeded the FDA threshold of 0.5 ng/mL, supporting the need for additional studies investigating the safety of systemic absorption.

In the new study, researchers randomly assigned 48 patients (mean age, 38.7 years; 50% women; 48% white) in a 1:1:1:1 ratio to apply sunscreen that contained avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and/or octinoxate via an aerosol spray, lotion, nonaerosol spray or pump spray. Sunscreen was applied at 2 mg/cm2 to 75% of body surface area over 4 days. It was applied once on day 1 and four times during the remaining 3 days at 2-hour intervals. Although conducting the study outside would be more indicative of a real-life setting, the researchers conducted the study indoors, noting that “the data would have likely been more variable because of the need to control for heat, humidity, wind and cloud cover.”

Sunscreen Squeezed Into a Person's Hands 
Six active ingredients in four different commercially-available sunscreen formulations applied by healthy study participants were systemically absorbed through the skin, resulting in exposure levels that exceeded the FDA threshold for safety testing, researchers reported in JAMA. Photo source: Adobe

Matta and colleagues analyzed blood samples collected over the study and found that the geometric mean maximum plasma concentrations of all six active ingredients were greater than 0.5 ng/mL after a single application on day 1. Individual ingredient’s geometric mean maximum plasma concentrations and coefficient of the variation (CV) percentages were:

  • 3.5ng/mL for avobenzone (70.9% CV), 180.1 ng/mL for oxybenzone (57.3% CV), 6.6 mg/mL for octocrylene (78.1% CV), 23.1 mg/mL for homosalate (68% CV), and 5.1 mg/mL for octisalate (81.6% CV) in aerosol spray formulations;
  • 7.1 mg/mL for avobenzone (73.9% CV), 258.1 mg/mL for oxybenzone (53% CV), and 7.8 mg/mL for octocrylene (87.1% CV) in lotions;
  • 3.5 mg/mL for avobenzone (73% CV), 6.6 mg/mL for octocrylene (103.9% CV), 17.9 mg/mL for homosalate (61.7% CV), 5.8 mg/mL for octisalate (77.4% CV), and 7.9 mg/mL for octinoxate (86.5% CV) in nonaerosol spray formulations; and
  • 3.3 mg/mL for avobenzone (47.8% CV), 13.9 mg/mL for homosalate (70.2% CV), 4.6 mg/mL for octinoxate (97.6% CV), and 5.2 mg/mL octinoxate (68.2% CV) in spray pump formulations.

Fourteen of the participants reported a rash, but no serious drug-related adverse events were reported.

The new findings do not mean sunscreen ingredients are unsafe, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, stated in a press release.

“Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use,” Woodcock continued.

In a related editorial to the new JAMA study, Adewole S. Adamson, MD, MPP, assistant professor in the department of internal medicine at the University of Texas at Austin, and Kanade Shinkai, MD, PhD, professor in the department of dermatology at the University of California, San Francisco, encouraged sunscreen manufacturers to perform tests on their products.

“Elevating the science of the benefits and harms of sunscreen should be a priority,” Adamson and Shinkai wrote. “The sunscreen industry must begin conducting these safety studies as recommended by the FDA. Until then, the harms of absorption of sunscreen filters will remain uncertain.”

Both studies conducted by Matta and colleagues stem from an FDA proposed rule that seeks to update regulatory requirements for most sunscreen products sold in the United States, according to an FDA blog. Several dermatologists told Healio Primary Care that the proposed rule also calls for raising the maximum SPF value on sunscreen product labels from 50 plus to 60 plus and ascertaining if there is still a need for such products with a SPF value that is lower than 15.

The FDA received about 15,000 comments to the proposed sunscreen rule before the public comment period ended in June 2019, an agency spokesperson told Healio Primary Care. She did not give a timeframe for the final rule’s issuance, stating that “the FDA wants to make certain we give careful scientific and regulatory consideration to all comments.” – by Janel Miller

References:

Adamson AS, Shinkai K. JAMA. 2020;323(3):223-234.

FDA.gov. Shedding new light on sunscreen absorption. https://www.fda.gov/news-events/fda-voices-perspectives-fda-leadership-and-experts/shedding-new-light-sunscreen-absorption. Accessed Jan. 17, 2020.

Matta MK, et al. JAMA. 2020;doi:10.1001/jama.2019.20747.

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    Edward Bell

    Edward Bell

    Matta and colleagues are to be commended for conducting this study. As sunscreen products are easily available without prescription, and as they are commonly recommended for protection from the harmful effects of sun exposure, these data are important to consider. This study provides additional needed data on systemic absorption and potential systemic adverse effects of common sunscreen product ingredients. Matta’s study was well conducted, with consideration given to many important characteristics, including proper dose application, use of different dosage forms, application of more than one dose, residual skin absorption and a variety of skin type scores.

    The results demonstrate that all six of the tested active ingredients were systemically absorbed to amounts greater than the safety threshold currently established by the FDA. As the authors discuss, more data are needed to assess the safety of commonly available sunscreen product ingredients. It is important to evaluate these data from a clinical perspective. As the authors point out, additional data are needed describing the real-world effects of sunscreen application outdoors (eg, additional effects of wind, water exposure). As much published evidence exists that demonstrates the strongest relationship between sunlight exposure and skin cancer results from exposure in the childhood and adolescent years, systemic absorption data from pediatric subjects would be additionally helpful.

    Until additional data are available, so-called ‘bedside’ recommendations for sunscreen product use should not change — use a broad spectrum sunscreen product as an important part of skin cancer risk reduction and apply the product in a proper amount and frequency, as most of our patients do not.

     

    • Edward Bell, PharmD, BCPS
    • Professor of clinical sciences, Drake University College of Pharmacy
      Blank Children’s Hospital, Des Moines, Iowa
      Infectious Diseases in Children Editorial Board Member ​

    Disclosures: Bell reports no relevant financial disclosures.