Electrophilic Reactivity of Sulfated Alcohols in the Context of Skin Sensitization.

Abstract

The surfactant sodium lauryl sulfate (SLS), although consistently positive in the murine local lymph node assay (LLNA) for skin sensitization, shows no evidence of being a human sensitizer and is often described as a false positive, lacking structural alerts for sensitization. However, there is evidence of the cinnamyl sulfate anion being the metabolite responsible for the sensitization potential of cinnamyl alcohol to humans and in animal tests. Here, manufacturing chemistry data and physical organic chemistry principles are applied to confirm that SLS is not reactive enough to sensitize, whereas sensitization to cinnamyl alcohol via cinnamyl sulfate is plausible. Sensitization data for several other primary alcohols, including geraniol, farnesol, and possibly hydrocortisone, are also consistent with this mechanism. It seems possible that biosulfation may play a wider role than has previously been recognized in skin sensitization.