Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial

Abstract

Importance: A prior pilot study demonstrated the systemic absorption of 4 sunscreen active ingredients; additional studies are needed to determine the systemic absorption of additional active ingredients and how quickly systemic exposure exceeds 0.5 ng/mL as recommended by the US Food and Drug Administration (FDA).

Objective: To assess the systemic absorption and pharmacokinetics of the 6 active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate) in 4 sunscreen products under single- and maximal-use conditions.

Design, setting, and participants: Randomized clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) was conducted in 48 healthy participants. The study was conducted between January and February 2019.

Interventions: Participants were randomized to 1 of 4 sunscreen products, formulated as lotion (n = 12), aerosol spray (n = 12), nonaerosol spray (n = 12), and pump spray (n = 12). Sunscreen product was applied at 2 mg/cm2 to 75% of body surface area at 0 hours on day 1 and 4 times on day 2 through day 4 at 2-hour intervals, and 34 blood samples were collected over 21 days from each participant.

Main outcomes and measures: The primary outcome was the maximum plasma concentration of avobenzone over days 1 through 21. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, homosalate, octisalate, and octinoxate over days 1 through 21.

Results: Among 48 randomized participants (mean [SD] age, 38.7 [13.2] years; 24 women [50%]; 23 white [48%], 23 African American [48%], 1 Asian [2%], and 1 of unknown race/ethnicity [2%]), 44 (92%) completed the trial. Geometric mean maximum plasma concentrations of all 6 active ingredients were greater than 0.5 ng/mL, and this threshold was surpassed on day 1 after a single application for all active ingredients. For avobenzone, the overall maximum plasma concentrations were 7.1 ng/mL (coefficient of variation [CV], 73.9%) for lotion, 3.5 ng/mL (CV, 70.9%) for aerosol spray, 3.5 ng/mL (CV, 73.0%) for nonaerosol spray, and 3.3 ng/mL (CV, 47.8%) for pump spray. For oxybenzone, the concentrations were 258.1 ng/mL (CV, 53.0%) for lotion and 180.1 ng/mL (CV, 57.3%) for aerosol spray. For octocrylene, the concentrations were 7.8 ng/mL (CV, 87.1%) for lotion, 6.6 ng/mL (CV, 78.1%) for aerosol spray, and 6.6 ng/mL (CV, 103.9%) for nonaerosol spray. For homosalate, concentrations were 23.1 ng/mL (CV, 68.0%) for aerosol spray, 17.9 ng/mL (CV, 61.7%) for nonaerosol spray, and 13.9 ng/mL (CV, 70.2%) for pump spray. For octisalate, concentrations were 5.1 ng/mL (CV, 81.6%) for aerosol spray, 5.8 ng/mL (CV, 77.4%) for nonaerosol spray, and 4.6 ng/mL (CV, 97.6%) for pump spray. For octinoxate, concentrations were 7.9 ng/mL (CV, 86.5%) for nonaerosol spray and 5.2 ng/mL (CV, 68.2%) for pump spray. The most common adverse event was rash, which developed in 14 participants.

Conclusions and relevance: In this study conducted in a clinical pharmacology unit and examining sunscreen application among healthy participants, all 6 of the tested active ingredients administered in 4 different sunscreen formulations were systemically absorbed and had plasma concentrations that surpassed the FDA threshold for potentially waiving some of the additional safety studies for sunscreens. These findings do not indicate that individuals should refrain from the use of sunscreen.

Trial registration: ClinicalTrials.gov Identifier: NCT03582215.

Figure 1.. Flow of Participants in Study

Randomization was conducted in block sizes of 4 and included equal numbers of women and men in each treatment group.

Figure 2.. Pharmacokinetic Profiles of Sunscreen Active Ingredients by Product on Multiple Applications

Concentration profiles for each participant are shown for the study duration. A single application was applied at time 0 on day 1. The gray vertical lines indicate the 6-hour window (eg, at 0, 2, 4, and 6 hours) of sunscreen application on days 2, 3, and 4. The black horizontal line denotes 0.5 ng/mL. The lower limit of quantitation (LLOQ) was 0.2 ng/mL for avobenzone and 0.4 ng/mL for oxybenzone, octocrylene, homosalate, octisalate, and octinoxate (horizontal gray line). All samples below the LLOQ were set to 0.1 ng/mL for plotting individual profiles in this figure.

Figure 3.. Pharmacokinetic Profiles of Sunscreen Active Ingredients by Product on Single Application

Concentration profiles for each participant are shown for day 1. The arrows indicate sunscreen application at 0 hours. The black horizontal line denotes 0.5 ng/mL. The lower limits of quantitation (LLOQ) was 0.2 ng/mL for avobenzone and 0.4 ng/mL for oxybenzone, octocrylene, homosalate, octisalate, and octinoxate (horizontal gray line). All samples below the LLOQ were set to 0.1 ng/mL for plotting individual profiles in this figure.

Figure 4.. Residual Sunscreen Active Ingredient Amount in Skin

Amount of each analyte in skin detected on day 7 and day 14 for each participant and product. Observations for the same participant are connected by a solid black line. Amounts are summarized by product (along x-axis) and normalized to surface area of tape strips (ng/cm²). There were 10, 10, and 10 paired avobenzone, oxybenzone, and octocrylene observations, respectively, for lotion; there were 11, 10, 10, 11, and 11 paired avobenzone, oxybenzone, octocrylene, homosalate, and octisalate observations, respectively, for aerosol spray; there were 9, 9, 9, 9, and 9 paired avobenzone, octocrylene, homosalate, octisalate, and octinoxate observations, respectively, for nonaerosol spray; and there were 8, 6, 6, and 7 paired avobenzone, homosalate, octisalate, and octinoxate observations, respectively, for pump spray.