Electrochemical simulation of triclosan metabolism and toxicological evaluation

Abstract

Tricolsan (TCS), an antimicrobial agent, is considered as emerging pollutant due to its wide dispersive use in personal care products and high aquatic toxicity. In the present study, phase I metabolism of triclosan was investigated through laboratory electrochemical simulation studies. The products formed in the electrochemical (EC) cell were identified by online and offline coupling with QTRAP and high-resolution FTICR mass spectrometers, respectively. The sequential formation and disappearance of each product, with the continuous increase of voltage from 0 to 3500 mV, was observed to reveal the transformation pathways of TCS. The toxic potential of TCS and the identified products was estimated using Quantitative structure-activity relationship (QSAR) modeling on 16 target proteins. The toxicity change of TCS during simulated metabolism and toxicological effects of reaction mixture were assessed by Fish embryo toxicity (FET) test (Danio rerio) and quantitative real-time polymerase chain reaction (qPCR). Eight metabolites formed during the simulated metabolism of TCS mainly via the mechanisms of hydroxylation, ether-bond cleavage and cyclization. In FET test, the reaction mixture (LC_{50, 48h}=1.28 mg/L) after electrochemical reactions showed high acute toxicity on zebrafish embryos, which was comparable to that of triclosan (LC_{50, 48h}=1.34 mg/L). According to the modeling data, less toxic products formed only via ether-bond cleavage of TCS while the products formed through other mechanisms showed high toxicity. AhR-mediated dioxin-like effects on zebrafish embryos, such as developmental retardation in skeleyton and malformations in cardiovascular system, were also observed after exposure to the TCS reaction mixture in FET test. Activation of the AhR by the reaction mixture in zebrafish embryos was further proved in cyp1a gene expression analysis.

Keywords: AhR mediated activity; Electrochemistry-mass spectrometry; Metabolism; Toxicity; Triclosan.