Mechanism-Based Cutaneous Adverse Effects

Skin irritation can be produced by nonimmune-mediated idiosyncratic cutaneous reactions resulting from cumulative toxicity, overdose, drug interactions, and metabolic alterations (Lee and Thompson, 2006). RhE skin irritation tests (SIT) have been validated and adopted by OECD as TG 439 for determining the irritation hazard from topical exposure to chemicals and mixtures (Kandarova et al., 2009 OECD, 2009). TG 439 is based on the ability of irritant chemicals to penetrate the stratum comeum and produce cytotoxicity in the underlying cell layers. The TG classifies test substances as either irritating or nonirritating based on results of the MTT viability assay. 

The EpiDerm SIT is endorsed in the ISO 10993-10 (ISO, 2015) for assessment of medical devices. However, since extracts from medical devices have very low irritation potential and may be underpredicted by the OECD TG 439 protocol, a validation study using a modified EpiDerm SIT (utilizing an extended exposure time and increased dose) is currently underway to address the concerns of the medical devices industry and ISO (Casas et al., 2013 Kandarova et al, 2015). 

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