|
Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Engineering / Faculty of Engineering >
Peer-reviewed Journal Articles, etc >
Metabolism-Coupled Cell-Independent Acetylcholinesterase Activity Assay for Evaluation of the Effects of Chlorination on Diazinon Toxicity
| Title: | Metabolism-Coupled Cell-Independent Acetylcholinesterase Activity Assay for Evaluation of the Effects of Chlorination on Diazinon Toxicity |
| Authors: | Matsushita, Taku Browse this author →KAKEN DB | | Kikkawa, Yuji Browse this author | | Omori, Kei Browse this author | | Matsui, Yoshihiko Browse this author →KAKEN DB | | Shirasaki, Nobutaka Browse this author →KAKEN DB |
| Keywords: | Drinking water | | metabolite | | oxon | | transformation product |
| Issue Date: | 20-Sep-2021 |
| Publisher: | American Chemical Society |
| Journal Title: | Chemical research in toxicology |
| Volume: | 34 |
| Issue: | 9 |
| Start Page: | 2070 |
| End Page: | 2078 |
| Publisher DOI: | 10.1021/acs.chemrestox.1c00155 |
| Abstract: | Drinking water quality guideline values for toxic compounds are determined based on their acceptable daily intake. The toxicological end point for determining the acceptable daily intake of most organophosphorus insecticides is inhibition of acetylcholinesterase (AChE). Although insecticides ingested with drinking water are partly metabolized by the liver before transport to the rest of the body, no current cell-independent AChE activity assay takes the effects of metabolism into account. Here, we incorporated metabolism into a cell-independent AChE activity assay and then evaluated the change in anti-AChE activity during chlorination of a solution containing the organophosphorus insecticide diazinon. The anti-AChE activities of solutions of diazinon or diazinon-oxon, the major transformation product of diazinon during chlorination, were dramatically changed by metabolism: the activity of diazinon solution was markedly increased, whereas that of diazinon-oxon solution was slightly decreased, clearly indicating the importance of incorporating metabolism into assays examining toxicity after oral ingestion. Upon chlorination, diazinon was completely transformed, in part to diazinon-oxon. Although diazinon solution without metabolism did not show antiAChE activity before chlorination, it did after chlorination. In contrast, with metabolism, diazinon solution did show anti-AChE activity before chlorination, but chlorination gradually decreased this activity over time. The observed anti-AChE activities were attributable solely to diazinon and diazinon-oxon having been contained in the samples before metabolism, clearly suggesting that the presence not only of diazinon but also of diazinon-oxon should be monitored in drinking water. Further examination using a combination of tandem mass spectrometry and in silico site-of-metabolism analyses revealed the structure of a single metabolite that was responsible for the observed anti-AChE activity after metabolism. However, because this compound is produced via metabolism in the human body after oral ingestion of diazinon, its presence in drinking water need not be monitored and regulated. |
| Rights: | This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Chemical research in toxicology, copyright c American Chemical Society after peer review. To access the final edited and published work see https://pubs.acs.org/articlesonrequest/AOR-RN9RYMPQ9PNBD4EY5JP6. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/86540 |
| Appears in Collections: | 工学院・工学研究院 (Graduate School of Engineering / Faculty of Engineering) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 松下 拓
|
