Percutaneous Absorption of Mexoryl SX^® in Human Volunteers: Comparison with in vitro Data

Abstract

The potential human health risk of UV filters depends on their toxicity and the human systemic exposure which is a function of the extent of percutaneous absorption of the topically applied substance into the human organism. Using a ‘mass balance’ approach, a study was designed to investigate the systemically absorbed dose of [¹⁴C]-Mexoryl SX^® in humans after topical application of a typical sunscreen emulsion. In addition, to assess the correlation with in vitro experiments, the percutaneous absorption of this UVA filter through isolated human skin was measured under identical exposure conditions. When applied in vivo for a period of 4 h, 89–94% of the applied radioactivity was recovered from the wash-off samples. In urine samples, the radioactivity slightly exceeded background levels and corresponded maximally to 0.014% of the topically applied dose. No radioactivity was measured in blood or faeces sampled up to 120 h after application. In vitro, 24 h after a 4-hour application, [¹⁴C]-Mexoryl SX remained primarily on the skin surface. The mean in vitro absorption over 24 h, adding up the amounts found in the dermis and receptor fluid, was 0.16% of the applied dose. It is concluded from the in vivo pharmacokinetic results that the systemically absorbed dose of [¹⁴C]-Mexoryl SX is less than 0.1%. The order of magnitude of this value correlates well with the corresponding in vitro data which overestimate the in vivo results as previously observed with other hydrophilic compounds. This study demonstrates that, under realistic exposure conditions, the human systemic exposure to this UVA filter is negligible and poses no risk to human health.

In vitro Percutaneous Absorption and in vivo Stratum Corneum Distribution of an Organic and a Mineral Sunscreen

“…These factors can induce fluctuations in the quantification, thus affecting the accuracy of the recovery. However, the values obtained are similar to those previously published in in vitro and in vivo percutaneous penetration studies of sunscreens using nonradiolabeled [1] and radiolabeled [2,8] molecules, and these values comply with COLIPA guidelines [15] .…”

“…Many other studies, in vitro and in vivo, with lipophilic organic filters [9] , insoluble TiO 2 [3,7] and the organic pigment MBBT [16] , have confirmed this distribution in the SC with 1 90% of the dose recovered in the first 5-15 tape strippings. In contrast, with Mexoryl SX [8] only 0.008 % of the applied dose was recovered in 16 tape strippings, and 91.9% was found at the skin surface. The hydrophilic properties of Mexoryl SX limit its SC diffusion, but the very low recovery in the SC is probably the result of the harsh washing procedure (10 wipings with a cotton swab impregnated with 5% lauryl ether sulphate) carried out in that experiment [8] .…”

“…In contrast, with Mexoryl SX [8] only 0.008 % of the applied dose was recovered in 16 tape strippings, and 91.9% was found at the skin surface. The hydrophilic properties of Mexoryl SX limit its SC diffusion, but the very low recovery in the SC is probably the result of the harsh washing procedure (10 wipings with a cotton swab impregnated with 5% lauryl ether sulphate) carried out in that experiment [8] .…”

“…In this work between 89 and 93% of the compounds applied was recovered in the skin ( table 1 ). The loss of between 11 and 7% of the compounds could be due to several factors [8,14] , such as the difficulty to apply a homogeneous film of the formulation on the skin, or the multiple steps required in the analytical procedure for extracting the sunscreens from the tape strippings and the skin compartments. These factors can induce fluctuations in the quantification, thus affecting the accuracy of the recovery.…”

“…Using tape stripping in combination with UV/visible spectroscopy, Weigmann et al [7] obtained a precise localization of TiO 2 with a direct correlation to the SC profile. Using the mass balance approach, an in vivo investigation was carried out to evaluate the percutaneous absorption of a UVA filter in human volunteers [8] . Topical application of the radiolabeled molecule showed that the human systemic exposure was negligible.…”