Given the modeling and predictive abilities of quantitative structure activity relationships (QSARs) for genotoxic carcinogens or mutagens that directly affect DNA, the present research investigates structural alert (SA) intermediate- predicted correlations A(SA) of electrophilic molecular structures with observed carcinogenic potencies in rats (observed activity, A = Log[1/TD(50)], i.e., A(SA) = f (X(1)(SA), X(2)(SA),...)). The present method includes calculation of the recently developed residual correlation of the structural alert models, i.e., ARA(SA) = f (A - A(SA) X(1)(SA) X(2)(SA),...). We propose a specific electrophilic ligand-receptor mechanism that combines electronegativity with chemical hardness-associated frontier principles, equality of ligand-reagent electronegativities and ligand maximum chemical hardness for highly diverse toxic molecules against specific receptors in rats. The observed carcinogenic activity is influenced by the induced SA-mutagenic intermediate effect, alongside Hansch indices such as hydrophobicity (LogP), polarizability (POL) and total energy (Etot), which account for molecular membrane diffusion, ionic deformation, and stericity, respectively. A possible QSAR mechanistic interpretation of mutagenicity as the first step in genotoxic carcinogenesis development is discussed using the structural alert chemoinformation and in full accordance with the Organization for Economic Co-operation and Development QSAR guidance principles.