Introduction – Evaluation of the skin irritation potential – POLYSOL®PGA
The ability of a substance or a medical device to induce skin irritation is a fundamental aspect for the safety assessment of the product and it is required by various regulatory authorities. For decades, the assessment of skin irritation has been based on the method described by Draize et al. (1944), but now both the European Regulation for Chemicals (REACH: Registration, Evaluation, Authorization, and Restriction of chemicals, June 2007) that the seventh amendment to the European Cosmetics Directive, have banned the use of animals for testing performed to this end (Alépée et al., 2010).
In detail, the Guideline for the testing of chemicals OECD 405 Acute dermal irritation/corrosion (2020) states that: “[…] Special attention was given to possible improvements in animal welfare and the evaluation of all existing information substances to be tested, in order to avoid the unnecessary use of animals in laboratory […] – all the information indicated on a substance and its irritant-corrosive potential must be evaluated prior to consider in vivo tests […] sufficient information may already exist to classify a substance as its irritant or corrosive potential, without the need to carry out tests on animals. “. For this reason, in 2002 ECVAM (European Centre for the Validation of Alternative Methods) has funded a pre-evaluation study of five different in vitro models to study the acute skin irritation (Fentem and Botham, 2002). The in vitro EpiSkinTM test method was validated in 2007 by EURL ECVAM as a full replacement method for the Draize acute skin irritation test and adopted in the OECD Test Guideline 439 in 2009.
Various other three-dimensional models that mimic the in vitro human epidermis have been developed, as RHE (Reconstructed Human Epidermis, SkinEthicTM), in which normal human keratinocytes proliferate and differentiate on a synthetic filter for 17 days, using a chemically defined culture medium (Rosdy and Clauss, 1990). The model consists of fully differentiated epidermis, including the basal, spinous, granular layers and stratum corneum (Tornier et al., 2006). The RHE model, since its commercialization in 1992, was mainly used for irritation studies for pharmaceutical purposes (Doucet et al., 1996; Kandàrovà et al., 2006; Tornier et al., 2006) or for discrimination between irritant and sensitizing substances (Coquette et al., 1999, 2003) but also used for phototoxicity assays (Bernard et al., 2000; Medina et al., 2001), permeability assays (Garcia et al., 2002; Barbotteau et al. , 2005) and several functional experiments (Laugier et al., 2000; Gazel et al., 2006).