Monomer Structure-Hazard Relationships in Photo-Curable (Meth)acrylates: Electrophilicity, Functionality, Molecular Architecture, Cross-Reactivity and Limits of Read-Across

Photo-curable (meth)acrylates share structural motifs that invite structure-activity reasoning, particularly the alpha,beta-unsaturated carbonyl system of acrylates and the alpha-methyl substitution of methacrylates. Experimental studies show that electrophilic reactivity toward glutathione can vary by orders of magnitude and that alpha-methyl substitution reduced thiol reactivity for selected acrylate/methacrylate pairs. Guinea-pig sensitisation studies likewise demonstrate meaningful differences between multifunctional acrylates, but they do not support a simple monotonic rule based on functionality count alone. Closely related bisphenol-A/epoxy-derived di(meth)acrylates showed sharply different sensitising capacities, with impurities identified as a potentially important confounder. Contemporary reviews of methacrylate skin-sensitisation methods show that in vitro, in chemico, animal and in silico approaches do not perform identically across even a deliberately bounded chemical series. Clinical literature further shows asymmetric cross- and co-sensitisation patterns. ER-94 therefore separates five questions: molecular electrophilicity, intrinsic sensitisation endpoint, exposure/mobility, technical-grade composition, and clinical cross-reactivity. Structure can support hypothesis-driven read-across only when the endpoint, applicability domain, impurities and contradictory data are addressed. It cannot establish that one untested monomer is "safer" than another.