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Some individuals develop a tolerance to chronic irritant exposure, a process referred to as the hardening phenomenon. Although the exact mechanisms remain unclear, structural and biochemical adaptationssuch as epidermal thickening (acanthosis [patches of thickened, velvety, darkened skin that appear within body folds and creases] and hyperkeratosis), alterations in stratum corneum lipid composition, changes in barrier permeability, and modulation of inflammatory mediator expression may contribute to this adaptive response