Studying the metabolism of toxic chemical warfare agent-related phenylarsenic chemicals in vitro in cod liver

• Published in: Journal of hazardous materials 2020-06, Vol.391, p.122221, Article 122221
• Main Authors: Niemikoski, Hanna, Koske, Daniel, Kammann, Ulrike, Lang, Thomas, Vanninen, Paula
• Format: Article
• Language: English
• Subjects: Animals; Arsenic; Arsenicals - metabolism; Chemical warfare agent; Chemical Warfare Agents - metabolism; Fish; Gadus morhua; Glutathione - metabolism; High-resolution mass spectrometry; In vitro metabolism; Liver - metabolism; Oxidation-Reduction; Water Pollutants, Chemical - metabolism
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2020.122221

[Display omitted] •First study on in vitro metabolism of CWA-related phenylarsenic chemicals.•Novel CWA-related methylated metabolites and GSH conjugates were detected.•Structures were elucidated using synthesized reference chemicals and high-resolution MS.•Metabolites can be used for monitoring concentrations of these compounds in fish. Large quantities of chemical warfare agents (CWAs), such as phenylarsenic chemicals, were disposed by sea-dumping after World War II. Nowadays, the release of these toxic chemicals from munitions poses a potential threat to living organisms. This study investigates the fate of these chemicals in fish by exposing selected CWA-related phenylarsenic chemicals and their oxidation products to cod (Gadus morhua) liver S9 fraction in vitro. Clark I (DA), Adamsite (DM) and their corresponding oxidation products as well as triphenylarsine oxide (TPA[ox]) and phenylarsonic acid (PDCA[ox]) were used as chemicals in in vitro experiments. Glutathione (GSH) conjugates of DA, DM and PDCA-related chemicals were found to be the most dominant metabolites, and methylated metabolites were detected as well, suggesting that these compounds are metabolised in the presence of cod liver enzymes. TPA[ox] was the only compound tested that did not form a GSH conjugate or methylated metabolite, indicating a different biotransformation pathway for this compound. Furthermore, hydroxylated metabolites were detected for each tested chemical. Due to their reactive nature, GSH conjugates may be difficult to detect in fish samples from CWA dumpsites. In contrast, both methylated and hydroxylated metabolites of phenylarsenic chemicals are promising target chemicals for the detection of CWA-related contamination in fish.