In Vitro Toxicology and Dermato-Cosmetology (IVTD) group , Vrije Universiteit Brussel, BE
Safety evaluation of cosmetic products in the EU is in particular based on the safety of the ingredients (chemical structure, toxicological profile and exposure). Cosmetic ingredients should be free of systemic toxicity in the concentration and application used in the cosmetic product. In this context, the margin of safety (MoS) is calculated and should preferably be much higher than 100:
MoS = (NOAEL)syst/SED, with (NOAEL)syst being the maximum systemic concentration not provoking an adverse effect and SED the systemic exposure dose.
As the dermal absorption is a critical factor with a significant impact on the SED, its experimental determination is of major importance, at least for the actives present in the formulation. The in vitro method as described in the OECD 428 guideline can be applied, taking the basic criteria into consideration as described in the “SCCS’s Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation” (SCCS/1564/15) and also taken up in opinion SCCS/1358/10. When, however, the dermal absorption is not known, the default value of 50% dermal absorption may be used as in a retrospective study on the Annex substances of cosmetic regulation 1223/2009/EC, it could be shown that 98% and 95% of 164 substances had a dermal absorption lower than 50% and 20%, respectively. In case a very low oral bioavailability for a compound is suspected by a number of specific physico-chemical properties (e.g. molecular weight, logPow, H bond acceptor/donor, melting point, topical polar surface area) pointing in that direction, it has been proposed that an extensive dermal absorption study showing a very low dermal absorption is sufficient to omit systemic exposure studies such as oral repeated dose toxicity studies in animals.