“…This is not a new concept-the idea of Mechanistically-Defined Chemical Mixtures, is a conceptual framework introduced more than 20 years ago, whereby components of a formulation can alter the active component/s' absorption thereby altering pharmacological and toxicological effects. 90,[102][103][104] Complex effects at different depths of the skin from the surface are also possible (Figure 3b,c). This includes the skin surface (e.g., chemical−chemical interactions, altered physicochemical properties, altered evaporation, binding to adnexal structure or their products such as sweat or sebum), stratum corneum (lipid extraction, altered partitioning into or through corneocytes/lipids), epidermis (biotransformation) and dermis (blood flow).…”