The combined use of biological investigations, bio chromatographic and in silico methods to solve the puzzle of badge and its derivative's toxicity

Abstract

Bisphenol A diglycidyl ether (BADGE) is a pre-polymer of BPA widely used in manufacturing of epoxy resins and plastics; due to its high reactivity, unintended by-products, such as chlorinated and hydrolysed products, can reach the human body. This research integrates multiple approaches such as computational predictions, chromatographic experiments, biological assays, and human biomonitoring studies to comprehensively evaluate the toxicological profiles of the parent compound and its derivatives. In silico predictions were first utilized to estimate the toxicological properties and interactions of BADGE derivatives, providing insights into their bioactivity. Biomimetic liquid chromatography was then used to simulate membrane permeability and biodistribution, predicting how these chemicals might cross biological membranes and accumulate in tissues. In vitro experiments assessed cellular toxicity through viability assays, identifying BADGE·2HCl as the most cytotoxic derivative. Reactive Oxygen Species (ROS) production evaluation was performed to assess the oxidative stress induced by these compounds, revealing elevated ROS levels in cells exposed to BADGE and BADGE·2HCl with a consequent significant oxidative damage. Similarly, BADGE and BADGE·2HCl were able to induce cellular death by apoptosis activation. Human serum analysis in a population sample (N = 96), showed BADGE·2H₂O as the most frequently detected metabolite, indicating a considerable human exposure and metabolic processes. The findings highlight a toxicity of BADGE derivatives similar to that of BADGE; BADGE·2HCl resulted particularly cytotoxic and BADGE·2H₂O is the most frequent detected in human serum, underscoring the need for regulatory measures to mitigate potential health risks associated with these compounds.