Proliferation Toxicity and Mechanism of Novel Mixed Bromine/Chlorine Transformation Products of Tetrabromobisphenol a on Human Embryonic Stem Cell

Abstract

Mixed bromine/chlorine transformation products of Tetrabromobisphenol A (ClyBrxBPAs) are a kind of mixed halogenated compounds recently identified in electronic waste dismantling sites, resulting in a lack of toxicity data. To study their reproduction and development toxicity, the proliferation toxicity was investigated using human embryonic stem cells (hESC) exposed to the lowest effective dose of two ClyBrxBPA analogues (2-chloro-2′,6-dibromobisphenol A and 2,2′-dichloro-6-monobromobisphenol A). For comparison, Tetrabromobisphenol A, 2,2′,6-tribromobisphenol A, and bisphenol A were also assessed. It was observed that ClyBrxBPAs inhibited hESCs proliferation in a concentration-dependent manner. The cell bioaccumulation efficiency of ClyBrxBPAs was higher than that of Tetrabromobisphenol A. Also, ClyBrxBPAs were more toxic than Tetrabromobisphenol A, with 2,2′-dichloro-6-monobromobisphenol A exhibiting the most potent toxicity. Furthermore, flow cytometry and oxidative stress results showed that increased reactive oxygen species raised the degree of apoptosis and reduced DNA synthesis. Metabolomics analysis on the effect of ClyBrxBPAs on metabolic pathway alteration showed that ClyBrxBPAs mainly interfered with four metabolic pathways related to amino acid metabolism and biosynthesis. These results provide an initial perspective on the proliferation toxicity of ClyBrxBPAs, indicated development and reproduction toxicity on children.

Keywords: Tetrabromobisphenol A, transformation products, human embryonic stem cell, proliferation toxicity, metabolic pathway