Sun-protection factor of zinc-oxide sunscreens: SPF_{in vitro} too low compared to SPF_{in vivo}-a brief review

Sunscreens are mainly characterized by their sun-protection factor (SPF), which is measured according to the in vivo gold standard ISO 24444. Although the SPF concept is simple, SPF values are difficult to measure, due to the rather high variability caused by the complex interaction of light and skin. For half a century, there have been attempts to correlate the costly and ethically controversial in vivo procedure with a non-invasive (in vitro) method. After decades of development, alternative non-invasive SPF methods are expected to become available as ISO standards in early 2025. In particular, sunscreen manufacturers who use zinc oxide (ZnO) in higher concentrations (conc.) (10-25%) in their formulations, are concerned that these new in vitro methods would not confirm the SPF-values on their labels that have been determined in vivo, according to ISO 24444. This brief review reveals that sunscreen formulations with high conc. of ZnO often yield SPF_{in vitro} values that are lower than the SPF_{in vivo} values. This can be explained by the fact that in vitro methods have been developed for conventional emulsions products with organic UV filters, but not for highly concentrated ZnO-alone sunscreens. Fortunately, there seems to be a fix for this problem. There is a difference in density between ordinary emulsions with organic filters (density of the residual oil phase ~ 1.0 g/ml) and highly concentrated ZnO-alone formulations (~ 1.3-1.7 g/ml). As the application of current standards is weight-based, this makes the film on the PMMA plate much thinner, which is likely to lead to lower SPF_{in vitro} values. Preliminary experiments show that using the same volume on the PMMA plates instead of the same weight as organic UV filters gives a much better correlation between in vitro and in vivo SPF results. A recent evaluation of three samples of highly concentrated ZnO sunscreens by the Dutch NVWA seems to confirm these findings. Further experimental evidence is required to fully understand this phenomenon and to adapt the in vitro method for higher conc. ZnO formulations accordingly.