In order to ensure the safety of cosmetic products, it is important to determine how much of the active ingredient can be absorbed into and through the skin. These values are used in a risk assessment together with other toxicological information gained from regulatory studies that have characterised the hazard potential of the active. When this information is assembled in a regulatory dossier, a margin of safety is used to ensure that the amount of the active that could reach the systemic circulation is much lower than the amount known to cause an adverse effect in an animal study, or an equivalent regulatory-approved predictive in vitro study. These so-called “safety factors” are conventionally arbitrary values (often 10 or 100) that are used to provide a significant separation between the quantities of the cosmetic ingredient in question known to cause an adverse effect and the actual quantities that reach the systemic circulation via the dermal route. We accept that these safety factors must be conservative due to potential differences in response between species and to ensure that susceptible individuals are sufficiently protected. We all wish to minimise the extent to which animals are used to define toxicological end points, and clearly, if an in silico or in vitro approach is deemed fit-for-purpose, we would all advocate using alternative approaches for the safety testing of cosmetics.
The development of the in vitro test guideline OECD 428 for dermal absorption testing makes an interesting story, since this is one area of safety assessment where the in vitro approach has been shown to be more predictive of human systemic exposure than animal studies. Donated human skin is now used extensively by industry for dermal absorption studies, and is recognised by the WHO/IPCS as the “gold standard” for human risk assessment in this area. The SCCS have specific guidance for in vitro dermal absorption testing that encompasses the myriad of exposure scenarios for products as diverse as hair dyes, sunscreens and leave-on cosmetics. This in vitro approach will be described, including key aspects of the method that define the absorbed/penetrated dose and the unabsorbed skin-bound dose, including how this is influenced by physicochemistry and specific formulation components. A new approach will be presented for the screening and development of new cosmetic ingredients and formulations and how dermal absorption is best placed in the overall sequence of safety testing in order to improve the development, safety and registration of new cosmetic products.
Professor Jon Heylings is speaking at the Novel strategies towards regulatory compliance after Regulation (EC) 1223/2009 was set in motion workshop at in-cosmetics on Tuesday 14 April 2015, 09:00 – 13:00 Workshop Room CC5.3