Predictability of in vitro dermal assays when evaluating fatty amine derivatives.

It is widely accepted that skin assays based on reconstructed human epidermis (RhE) models can be used in place of in vivo testing to accurately predict corrosivity and/or irritancy of commodity chemicals. Due to REACH legislation, substances from various categories of fatty amines derivatives have been evaluated for dermal corrosion applying either the EpiDerm™ (EPI-200) or EpiSkin™ assay. Available data and practical experience indicated that these substances are corrosive to the skin. The substances tested are cationic surfactants which dermal effects are characterized by a delayed severe inflammatory reaction. The mechanism is thought to be related to disruption of the cellular membrane following diffusion of the long apolar tails of the molecules into the lipid bilayers. However, unexpectedly almost all obtained study results indicated that these substances are NOT corrosive in these in vitro RhE test systems. Since these results did not align with the experiences on such substances, limited in vivo rabbit studies were employed additionally. These studies confirmed that after some delay full skin tissue destruction occurs, requiring classification as Corrosive Cat.1B or 1C for GHS. The results obtained for various fatty amine derivatives shows that RhE assays do not always predict corrosivity correctly.