Objectives: This study describes the results of an in silico prediction approach for difunctional acrylates used as comonomers in dental resin based materials. The prediction focuses primarily on genotoxicity and carcinogenicity (rodent tumorigenicity) of ethylene glycol dimethacrylate (EGDMA), diethylene glycol dimethacrylate (DEGDMA), Triethylene glycoldimethacrylate (TEGDMA) and tetraethylene glycol dimethacrylate (TetEGDMA). Methods: DEREK (Deductive Estimation of Risk on Existing Knowledge), is a rule-based expert system that generates predictions for various endpoints of toxicity based on knowledge about reactive substructures in a given molecule. MCase (Multiple Computer Automated Structure Evaluation), predicts toxicity on the basis of discrete structural fragments found to be statistically relevant to a specific biological activity (biophore). The system also generates information on deactivating fragments (biophobes). Results: DEREK predicts all compounds to exhibit genotoxic activity in the L5178Y mouse lymphoma cell assay. According to the DEREK knowledge base a,b-unsaturated esters of this type are generally not mutagenic to Salmonella, except for the case of activated compounds with an electron-withdrawing substituent on the alpha position. However, a,b-unsaturated esters may exhibit clastogenic activities in L5178Y cells in the absence of exogenous activation (S9). MCase predicts all acrylates to be inactive as genotoxicants in bacterial test systems (i.e. Ames test). MCase predicts EGDMA to be inactive as a rodent tumorigen. For the other acrylates MCase detects one biophore indicating tumorigenicity in female rats (only FR1 database). However, this biophore (CH2- CH2-O- CH2- CH2) is not transgender or transspecies, which reduces the probability of the respective molecule being active as tumorigen. Conclusion: All compounds under question have a considerable likelihood to exhibit a genotoxic activity in the L5178Y mouse lymphoma cell assay. The compounds have a low likelihood to display a mutagenicity in the Ames test. Supported in part by the Deutsche Forschungsgemeinschaft DFG (Schw 431/8-1)

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Back to the 81st General Session of the International Association for Dental Research (June 25-28, 2003)

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