• Murali K Matta, Robbert Zusterzeel, Nageswara R Pilli, Vikram Patel, Donna A Volpe, Jeffry Florian, Luke Oh, Edward Bashaw, Issam Zineh, Carlos Sanabria, Sarah Kemp, Anthony Godfrey, Steven Adah, Sergio Coelho, Jian Wang, Lesley-Anne Furlong, Charles Ganley, Theresa Michele, and David G Strauss.
• Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
• JAMA. 2019 Jun 4; 321 (21): 2082-2091.

ImportanceThe US Food and Drug Administration (FDA) has provided guidance that sunscreen active ingredients with systemic absorption greater than 0.5 ng/mL or with safety concerns should undergo nonclinical toxicology assessment including systemic carcinogenicity and additional developmental and reproductive studies.ObjectiveTo determine whether the active ingredients (avobenzone, oxybenzone, octocrylene, and ecamsule) of 4 commercially available sunscreens are absorbed into systemic circulation.Design, Setting, And ParticipantsRandomized clinical trial conducted at a phase 1 clinical pharmacology unit in the United States and enrolling 24 healthy volunteers. Enrollment started in July 2018 and ended in August 2018.InterventionsParticipants were randomized to 1 of 4 sunscreens: spray 1 (n = 6 participants), spray 2 (n = 6), a lotion (n = 6), and a cream (n = 6). Two milligrams of sunscreen per 1 cm2 was applied to 75% of body surface area 4 times per day for 4 days, and 30 blood samples were collected over 7 days from each participant.Main Outcomes And MeasuresThe primary outcome was the maximum plasma concentration of avobenzone. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, and ecamsule.ResultsAmong 24 participants randomized (mean age, 35.5 [SD, 1.5] years; 12 (50%] women; 14 [58%] black or African American; 14 [58%]), 23 (96%) completed the trial. For avobenzone, geometric mean maximum plasma concentrations were 4.0 ng/mL (coefficient of variation, 6.9%) for spray 1; 3.4 ng/mL (coefficient of variation, 77.3%) for spray 2; 4.3 ng/mL (coefficient of variation, 46.1%) for lotion; and 1.8 ng/mL (coefficient of variation, 32.1%). For oxybenzone, the corresponding values were 209.6 ng/mL (66.8%) for spray 1, 194.9 ng/mL (52.4%) for spray 2, and 169.3 ng/mL (44.5%) for lotion; for octocrylene, 2.9 ng/mL (102%) for spray 1, 7.8 ng/mL (113.3%) for spray 2, 5.7 ng/mL (66.3%) for lotion, and 5.7 ng/mL (47.1%) for cream; and for ecamsule, 1.5 ng/mL (166.1%) for cream. Systemic concentrations greater than 0.5 ng/mL were reached for all 4 products after 4 applications on day 1. The most common adverse event was rash, which developed in 1 participant with each sunscreen.Conclusions And RelevanceIn this preliminary study involving healthy volunteers, application of 4 commercially available sunscreens under maximal use conditions resulted in plasma concentrations that exceeded the threshold established by the FDA for potentially waiving some nonclinical toxicology studies for sunscreens. The systemic absorption of sunscreen ingredients supports the need for further studies to determine the clinical significance of these findings. These results do not indicate that individuals should refrain from the use of sunscreen.Trial RegistrationClinicalTrials.gov Identifier: NCT03582215.

24 keywords...

hide…