Oxirane-based dental monomers have proven useful in restorative resins. However, the potential for gene toxic effects exists because of their reactive characteristics. Previously we reported a computer method to improve design of dental monomers by identifying components in their chemical structure that contribute to mutagenic effects. Objective: Development of QSARs with Bisphenol A and F based oxiranes relative to Ames data and determine chemical structures that attenuate potential for genotoxicity. Method: Laboratory (Ames Test, TA100) and QSAR were combined to identify chemical substituents that suppress mutagenic effects on the oxirane monomer Araldite^tm GY281 (Bisphenol F diglycidyl ether monomer). The semi-empirical method AMPAC was used to optimize 192 theoretical structures, which were then tested against a QSAR (R²=0.947, F=49.30) of related known mutagenic structures using statistical method CODESSA. Results: The model established equations for mutagenic response based on chemical substituents in the QSAR. Removal of phenolic oxygen (phenyl glycidyl ether changed to phenyl propylene oxide, PPO) produced a 60% reduction in mutagenicity relative to those molecules retaining this feature. Structures with two aromatic rings (ln TA100=-2.478) were superior to those with one aromatic ring (lnTA100=-0.236) supporting current di-aromatic monomer design. Aromatic methoxy meta to the side chain reduced PPO mutagenicity in PPO (methoxyPPO/ GY281 ln TA100 ratio=0.13). Challenging the QSAR with molecules of measured mutagenicity supported the computational results. The GY281 laboratory value was statistically similar to the computer-predicted value (p<0.01). Conclusions: These studies define a method to improve the biocompatibility of existing dental resins through rational redesign. Supported by NIH/NIDCR DE09696. yourteed@umkc.edu

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