Decreased electrophilicity of chemicals carcinogenic only at the maximum tolerated dose

While there was no significant difference between the actual or predicted mutagenicity and clastogenicity of a group of chemicals carcinogenic only at the maximum tolerated dose (MTD) and a group of chemicals carcinogenic below the MTD, as a group, the chemicals carcinogenic below the MTD exhibited a significantly decreased LUMO (Lowest Unoccupied Molecular Orbital) energy, indicative of increased electrophilicity (i.e. DNA reactivity). These findings suggest that chemicals carcinogenic only at the MTD either require increased doses of "weak" electrophiles to be carcinogenic or that they may act by a "non-genotoxic" mechanism.