Human Phase I in Vitro Liver Metabolism of Two Bisphenolic Diglycidyl Ethers BADGE and BFDGE

2020-06-29

Root canal sealers are commonly used to endodontically treat teeth with periapical infections. Some root canal sealers based on epoxy resin contain bisphenol A diglycidyl ether (BADGE) and bisphenol F diglycidyl ether (BFDGE). The presence of these chemicals is of concern due to the close contact to the blood stream at the apex and the long setting times of up to 24 h. These chemicals, or any of their degradation products or metabolites, can then exert their toxic effects before being excreted. This study aimed to identify the phase I in vitro biotransformation products of BADGE and BFDGE using human liver microsomes. During incubation with microsomal fractions, the epoxides were rapidly hydrolysed in a NADPH independent manner resulting in the formation of BADGE.2H2O and BFDGE.2H2O. Further, oxidative reactions, such as hydroxylation and carboxylation, generated other BADGE metabolites, such as BADGE.2H2O-OH and BADGE.H2O.COOH, respectively. For BFDGE, further oxidation of BFDGE.2H2O led to the newly reported carboxylic acid, BFDGE.H2O.COOH. In total, three specific metabolites have been identified which can serve in future human biomonitoring studies of BADGE and BFDGE.

Authors: Philippe Vervliet, Siemon de Nys, Radu Corneliu Duca, Imke Boonen, Lode Godderis, Marc Elskens, Kirsten L van Landuyt, Adrian Covaci
; Full Source: Toxicology letters 2020 Jun 29;332:7-13. doi: 10.1016/j.toxlet.2020.06.022.
; Full Source: Scientific reports 2020 Jul 2;10(1):10902. doi: 10.1038/s41598-020-67709-9.