As regulatory scrutiny around ingredient safety intensifies, especially regarding salicylate exposure and its conversion to salicylic acid, robust data on dermal absorption has become increasingly important. In response to a Scientific Committee on Consumer Safety (SCCS) inquiry and industry-wide discussions, the Research Institute for Fragrance Materials (RIFM) conducted an in vitro study examining the skin absorption of ethyl salicylate, pentyl salicylate, and (Z)-3-hexenyl salicylate—three widely used fragrance ingredients.
CosmeticsDesign spoke with Dr. Kaushal Joshi, Principal Scientist at RIFM, about the study’s findings and what they mean for formulators, safety assessors, and regulators navigating evolving standards in cosmetic product development.
CDU: What prompted this study, and why focus on these particular salicylates?
Dr. Kaushal Joshi: Salicylates are widely used in fragrance formulations across many consumer products, but until now, there has been limited skin absorption data for several of these compounds. It was initiated due to an SCCS inquiry and discussions from a working group led by Cosmetics Europe.
Furthermore, with increased regulatory focus on salicylate exposure from cosmetic and personal care products, especially its conversion to salicylic acid, we saw a need to generate high-quality, human-relevant data. Ethyl salicylate, pentyl salicylate, and (Z)-3-hexenyl salicylate were selected because they are commonly used and represent different structural variations, allowing us to explore how structure impacts skin permeation.
CDU: One of the key takeaways was the impact of occlusion. Can you elaborate on that?
Dr. Joshi: Absolutely. Typically, occlusion is considered a more conservative approach.
We tested each salicylate under unoccluded and occluded conditions, simulating scenarios like a cream being left open to air versus being covered over with a bandage. Across the board, occlusion increased permeation.
For example, ethyl salicylate absorption nearly doubled under occlusion. This reinforces how real-world use conditions can significantly affect exposure levels, crucial for accurate safety assessments.
CDU: You also tracked salicylic acid as a degradation product. Why was that important?
Dr. Joshi: While the study didn’t directly aim to assess metabolism, we knew from previous work that salicylate esters could break down into salicylic acid in the skin. We could calculate the total absorbed dose by measuring both the parent compounds and salicylic acid.
CDU: Did the vehicle used (cream vs ethanol/water solution) significantly influence the results?
Dr. Joshi: Yes, particularly for pentyl salicylate. We tested it both in a cream and a 70/30 ethanol/water solution, a common vehicle in fragrance skin absorption studies.
The ethanol/water solution notably increased absorption, underscoring how formulation choice can dramatically affect dermal delivery. It’s a reminder that safety assessments should consider realistic, consumer-relevant product formats.
CDU: What are the broader implications of this study for formulators and regulators?
Dr. Joshi: For formulators, our findings emphasize the importance of considering not just ingredient selection but also formulation type and usage conditions when evaluating safety. For regulators, this data helps fill critical gaps in dermal absorption, supporting more accurate systemic exposure estimates.
Ultimately, this work contributes to responsible innovation by ensuring that commonly used fragrance ingredients are effective and safe.
CDU: What’s next in this line of research?
Dr. Joshi: We’re continuing our collaboration with An-eX Analytical Services to examine more fragrance ingredients under similar conditions. The goal is to develop a robust, transparent dataset to inform regulatory risk assessments globally.
We also hope to explore in vivo–in vitro correlations and refine predictive models for skin absorption.
Source: Toxicology in Vitro, 2025, 106019, doi: 10.1016/j.tiv.2025.106019, “In vitro human skin absorption of ethyl salicylate, pentyl salicylate, and (Z)-3-hexenyl salicylate from topical formulations: Effects on permeation and distribution.” Authors: Joshi, K. et al.