for sunscreens, in a phase 1 randomized controlled study of 24 healthy volunteers.
Wavebreakmedia Ltd/Thinkstock
In the open-label study, 24 people (mean age 35.5 years) were randomized to one of four commercially available sunscreens (two sprays, one lotion, or one cream formulation); 2 mg of sunscreen per 1 cm2 was applied to 75% of their body surface four times a day for 4 days (described as “maximal use conditions consistent with current sunscreen labeling”), and 30 blood samples were collected over 7 days.
The primary outcome was the maximum plasma concentration of avobenzone, from days 1-7; secondary outcomes were maximum plasma concentrations of sunscreen ingredients oxybenzone, octocrylene, and ecamsule over the same period of time.
All but one participant completed the study. “All four sunscreen active ingredients tested resulted in exposures exceeding 0.5 ng/mL,” reported Murali Matta, PhD, of the FDA’s Center for Drug Evaluation and Research, and coauthors. “The clinical effect of plasma concentrations exceeding 0.5 ng/mL is unknown, necessitating further research,” they added.
According to the study, FDA sunscreen guidance and the proposed rule for over-the-counter sunscreen monograph, nonclinical toxicology studies, such as carcinogenicity and reproductive studies, “may be waived if results of an adequately conducted human pharmacokinetic maximal usage trial show a steady state blood level less than 0.5 ng/mL and an adequately conducted toxicology assessment does not reveal any potential safety concerns.”
The results of this study “do not indicate that individuals should refrain from the use of sunscreen,” the authors concluded, adding that the “systemic absorption of sunscreen ingredients supports the need for further studies to determine the clinical significance of these findings.” The study was published in JAMA.
In an accompanying editorial, former FDA commissioner Robert Califf, MD, professor of cardiology, Duke University, Durham, N.C., and JAMA Dermatology Editor Kanade Shinkai, MD, PhD, of the department of dermatology, University of California, San Francisco, noted that “the demonstration of systemic absorption well above the FDA guideline does not mean these ingredients are unsafe” (JAMA. 2019 May 6. doi: 10.1001/jama.2019.5528). But, they added, the results “raise many important questions about sunscreen and the process by which the sunscreen industry, clinicians, specialty organizations, and regulatory agencies evaluate the benefits and risks of this topical OTC medication. First and foremost, it is essential to determine whether systemic absorption of sunscreen poses risks to human health. Second, the effects of different sunscreen formulations, clinical characteristics (that is, skin type, age, presence of skin diseases that disrupt the skin barrier), physical activity level, and exposure to sun and water on systemic sunscreen levels require further study.”
In a statement, former American Academy of Dermatology President Darrel Rigel, MD, of the department of dermatology, New York University, said that he was concerned that the results were misleading. “We have always known that there is a very small amount of absorption of sunscreens in the bloodstream,” and there are no data that this is a problem, he said, adding: “Tens of millions of people use sunscreens in the U.S. every summer weekend for many years with no incidence. Daily use of a broad-spectrum SPF of at least 30 is the best way to protect yourself from skin cancer. For many people, the chemical formulations cited in the study are the only ones that feel cosmetically elegant enough to wear. Consumers should continue to use their preferred formulation if it means they will actually wear it.”
SOURCE: JAMA. 2019 May 6. doi: 10.1001/jama.2019.5586