(606g) A Metabolism-Inspired Assay to Predict Toxicity in Drinking Water Systems

Water quality analysis is essential in the identification of chemical contaminants in drinking water distribution facilities. In vivo biotransformation of these compounds often generates reactive intermediates that can covalently bind to cells inducing cancer, cytotoxicity and hepatotoxicity. Analytical techniques such as GC/MS and HPLC/MS are frequently used to determine the concentration of toxic compounds offering sensitivity and selectivity. However, such a detailed analysis requires expensive equipment, long processing times and lab personnel with extensive expertise in the analysis of water samples, all of which can limit its use and application. In the case of biological toxicity assays, in vivo or in vitro models involve the manipulation of fragile systems such as bacteria, algae, perfused liver, microsomes, tissue, and cells, yet their use is limited due to shelf life issues. In contrast, bio-inspired chemistries can determine toxicity using more stable compounds. The purpose of this work is to develop a bio-inspired toxicity assay for Phase I and II metabolism by monitoring glutathione (GSH) depletion. Metalloporphyrins are employed as structures that imitate the active site of cytochrome P450 (CYP450) in Phase I metabolism, and Phase II metabolism is carried out by GSH conjugation of metabolites by using a reverse micelle system comprised of cetyltrimethylammonium bromide (CTAB), catalyst that mimics the role of glutathione transferase (GST) in the detoxfication step. Assays of this kind can be utilized to rapidly estimate toxicity in water samples by electrochemically measuring GSH depletion. The fabrication of a microfluidic device will permit the implementation of this technology be used as a portable toxicity assay.