Biocompatibility of Hydroxylated Metabolites of BISGMA and BFDGE

Unpolymerized dental monomers can leach out into the oral biophase and are bioavailable for metabolism. We hypothesize that metabolites would be less toxic than parent monomers. We first identified the formation of metabolites from bisphenol F diglycidyl ether (BFDGE) and Bisphenol A glycidyl methacrylate (BISGMA) after their exposure to liver S9 fractions. Then, the metabolites and parent compounds were subjected to in vitro cytotoxicity, mutagenicity, and estrogenicity studies. Bisphenol A bis(2,3-dihydroxypropyl) ether and bisphenol F bis(2,3-dihydroxypropyl) ether were the hydroxylated metabolites of BISGMA and BFDGE, respectively. Cytotoxicity against L929 cells showed that the metabolites were significantly (p < 0.05) less cytotoxic than the parent monomers. Only BFDGE was mutagenic in the Ames assay with strain TA100 of Salmonella typhimurium. Parent and metabolite compounds did not stimulate estrogen-dependent MCF-7 cell proliferation above solvent controls. These results indicated that the hydroxylated metabolites were non-mutagenic, non-estrogenic, and less cytotoxic than their parent monomers.

[1]  A. Glaros,et al.  In vitro biocompatibility of oxirane/polyol dental composites with promising physical properties. , 2002, Dental materials : official publication of the Academy of Dental Materials.

[2]  R. Smith,et al.  The stability of methacrylate biomaterials when enzyme challenged: kinetic and systematic evaluations. , 2001, Journal of biomedical materials research.

[3]  A. Glaros,et al.  Effects of Dental Resins on TNF-α-induced ICAM-1 Expression in Endothelial Cells , 2001 .

[4]  R. Smith,et al.  LIQUID CHROMATOGRAPHY AND PURIFICATION OF DENTAL MONOMERS , 2001 .

[5]  J. Santerre,et al.  Relation of dental composite formulations to their degradation and the release of hydrolyzed polymeric-resin-derived products. , 2001, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[6]  A. Glaros,et al.  Effects of dental resins on TNF-alpha-induced ICAM-1 expression in endothelial cells. , 2001, Journal of dental research.

[7]  R. Sueiro,et al.  Genotoxicity of the coating lacquer on food cans, bisphenol A diglycidyl ether (BADGE), its hydrolysis products and a chlorohydrin of BADGE. , 2000, Mutation research.

[8]  A. Glaros,et al.  In vitro cytotoxicity of solid epoxy-based dental resins and their components. , 1999, Dental materials : official publication of the Academy of Dental Materials.

[9]  S. Hikage,et al.  Cytotoxicity of dental resin monomers in the presence of S9 mix enzymes. , 1999, Dental materials journal.

[10]  W. Welshons,et al.  Low-dose bioactivity of xenoestrogens in animals: fetal exposure to low doses of methoxychlor and other xenoestrogens increases adult prostate size in mice , 1999, Toxicology and industrial health.

[11]  G. Schmalz,et al.  The mutagenic activity of unpolymerized resin monomers in Salmonella typhimurium and V79 cells. , 1998, Mutation research.

[12]  W. Hume,et al.  Diffusion of monomers from bonding resin-resin composite combinations through dentine in vitro. , 1996, Journal of dentistry.

[13]  G. Shambaugh,et al.  Adaptation of the diphenylamine (DPA) assay to a 96-well plate tissue culture format and comparison with the MTT assay. , 1994, BioTechniques.

[14]  G. Rottinghaus,et al.  pH-dependent cytotoxicity of contaminants of phenol red for MCF-7 breast cancer cells. , 1991, Endocrinology.

[15]  R. G. Craig,et al.  Setting Reactions and Compressive Strengths of Calcium Phosphate Cements , 1990, Journal of dental research.

[16]  H. Kuster,et al.  Hydrolysis of bisphenol A diglycidylether by epoxide hydrolases in cytosolic and microsomal fractions of mouse liver and skin: inhibition by bis epoxycyclopentylether and the effects upon the covalent binding to mouse skin DNA. , 1989, Carcinogenesis.

[17]  B. Ames,et al.  Revised methods for the Salmonella mutagenicity test. , 1983, Mutation research.

[18]  I. J. Climie,et al.  Metabolism of the epoxy resin component 2,2-bis[4](2,3]epoxypropoxy)phenyl]propane, the diglycidyl ether of bisphenol A (DGEBPA) in the mouse. Part I. A comparison of the fate of a single dermal application and of a single oral dose of 14C-DGEBPA. , 1981, Xenobiotica; the fate of foreign compounds in biological systems.