IN VITRO CUTANEOUS METABOLISM OF TRIOCTANOIN AND TRANSCUTANEOUS PASSAGE OF 2-ETHYLHEXANOIC ACID

Trioctanoin (INCI name: Triethylhexanoin, CAS number: 7360-38-5) is a well-known raw material largely used in cosmetic products. The safety of Trioctanoin was evaluated by the CIR Expert Panel in 2001 and considered as safe in the present practice of use [1]. In March 2012, the safety of Trioctanoin was reassessed by French National Authorities and they mention that given the inability to characterize the toxicity profile and the lack of data on the part metabolized to 2-ethylhexanoic acid (2-EHA) (classified as reprotoxic category 2) it is not possible to conclude to the safety of use of trioctanoin as a cosmetic ingredients. The aim of this study was to determine the cutaneous metabolism of Trioctanoin into its metabolite 2-EHA and the transcutaneous passage of the two molecules on normal and altered human skin [2-4].

Trioctanoin and its metabolite, 2-EHA, were applied on fresh human abdominal skin for up to 24 hours. Franz-type diffusion static cells were used as in vitro model. Receptor liquid was sampled at 3, 6 and 24 hours for the quantification of 2-EHA and Trioctanoin. Analyses of both compounds by LC-MS/MS were performed in skin washing, stratum corneum strips, epidermis, dermis and receptor compartment washing.

After topical application of Trioctanoin on fresh dermatomed human skin pre-treated or not with a dermaroller, 2-EHA concentrations in receptor liquid were under the lower limit of quantification (LLOQ). Therefore, no biotransformation of Trioctanoin in 2-EHA occurred in the condition of the incubation.

This study supports the conclusion that:

1. 2-EHA applied on fresh human abdominal skin is able to pass through the skin.
2. The skin, particularly the dermis is able to metabolize Trioctanoin into 2-EHA.
3. Trioctanoin does not pass through the skin; it is stopped by the stratum corneum so there is no 2-EHA formation, even if the skin is slightly irritated.
4. Trioctanoin can be safely used as an ingredient in cosmetic products.