Why don’t we use octisalate?

Although octyl salicylate is among the most used sunscreen filters, its tolerance profile faces growing criticism. Here are the various concerns raised against it:

Ethylhexyl salicylate: an irritating UV filter?

From a dermatological perspective, octisalate is a filter considered well tolerated, with a low sensitisation potential. A reference study conducted in 2012 by the European Multicentre Photopatch Test Study assessed skin reactivity to various UV filters in a large panel of participants. The study involved 1,031 volunteers and recorded two reactions to ethylhexyl salicylate, corresponding to a 0.19% reaction rate. Observed symptoms were localized redness without systemic reactions. Octisalate is not known to be a photoallergen; reports of allergic reactions following application and UV exposure are rare.

Can octisalate cross the skin barrier?

The issue of skin absorption and systemic distribution of octyl salicylate is drawing interest in discussions over potential endocrine effects of certain organic filters. In a study with six volunteers, penetration of ethylhexyl salicylate was assessed using the tape-stripping method, which allows analysis of the compound concentration at different levels of the stratum corneum. Two formulation types were tested: an oil-in-water emulsion gel and a petroleum jelly base.

• With the emulsion formulation, approximately 25.6% of the applied dose was found in the stratum corneum.

• With petroleum jelly, this proportion fell to 11%.

The authors observed that concentration in the superficial part of the stratum corneum was significantly higher with the emulsion than with the gel. Concentration in deeper layers remained moderate and above that of the gel. These results suggest that the formulation has a direct effect on the penetration level of octyl salicylate, without demonstrating significant systemic absorption.

Another study assessed systemic absorption of sunscreen formulations containing several chemical filters, including 5% ethylhexyl salicylate. The formulation was applied to the forearms of nine volunteers without occlusion and removed after 12 hours. Urinary analyses up to 48 hours after application estimated that only 1-2% of the total formulation was absorbed. However, the study did not specify the proportion of each UV filter in the formula (avobenzone, octocrylene, octisalate and ethylhexyl methoxycinnamate), preventing determination of the share attributable to ethylhexyl salicylate.

Is ethylhexyl salicylate an endocrine disruptor?

Octisalate is also suspected of disrupting the endocrine system and interacting with hormone receptors such as oestrogen receptors. In the case of ethylhexyl salicylate, researchers assessed this risk with reassuring results. A study using predictive modelling estimated the theoretical affinity of ethylhexyl salicylate for the oestrogen receptor (ER). After this computational approach, octisalate was classified as a compound that does not bind to the oestrogen receptor.

These results were corroborated by an experimental biological assay using a recombinant yeast system expressing the ERα receptor. This method, based on β-galactosidase induction in the presence of an oestrogenic ligand, showed that ethylhexyl salicylate produced an attenuated dose-response curve, flatter than that of oestradiol. Its relative oestrogenic potency was estimated at 1/2,000,000 that of oestradiol, indicating low to negligible biological activity.

These data seem to indicate that octisalate does not exert an oestrogenic effect.

Does octisalate pose a risk to the environment?

Like other organic sunscreen filters, ethylhexyl salicylate has environmental consequences once released into the environment, notably through swimming. Its lipophilic structure, designed to resist water, also contributes to its persistence in aquatic environments. In addition, studies have shown that octisalate can accumulate in living organisms, particularly in lipid-rich tissues. Research on zebrafish (Danio rerio) has shown that exposure to ethylhexyl salicylate during embryonic development can cause several harmful effects, such as cardiovascular malformations, abnormal lipid accumulation and impaired tissue oxygenation. These phenomena are associated with altered expression of genes involved in lipid metabolism and vascular development.

Although these results cannot be extrapolated to humans, they emphasise octisalate’s disruptive potential in aquatic ecosystems.

Moreover, although research is ongoing, ethylhexyl salicylate is suspected of contributing to coral reef degradation, like other organic UV filters such as octocrylene. Recent metabolomic profiling studies on the coral Pocillopora damicornis have shown that ethylhexyl salicylate increased stress in this organism. At 50 µg/L, this UV filter induced production of a coral steroid, (3β,5α,8α)-5,8-epidioxy-ergosta-6,24(28)-diene-3-ol, a marker of environmental stress. At 300 µg/L, the response intensified, with elevated levels of polyunsaturated fatty acids, lysophosphatidylcholines, and lysophosphatidylethanolamines, molecules linked to inflammatory responses and oxidative stress. These data suggest that octisalate exposure can disrupt coral metabolism.