title: Use of orbitrap-MS/MS and QSAR analyses to estimate mutagenic transformation products of iopamidol generated during ozonation and chlorination.
abstract: The effects of two water purification processes (ozonation, and chlorination after ozonation) on the mutagenicity of a solution containing iopamidol (X-ray contrast medium) were investigated by using the Ames assay. No mutagenicity was observed during ozonation. In contrast, mutagenicity was induced by the ozone-treated iopamidol-containing solution after subsequent chlorination, indicating that mutagenic transformation-products (TPs) were generated. Ten of 70 peaks detected on the LC/MS total ion chromatogram (TIC) of the ozone-treated iopamidol-containing solution after chlorination had a positive correlation (r(2) > 0.6) between their peak areas and the observed mutagenicity, suggesting that TPs detected as these peaks may induce mutagenicity. To narrow down the possible contributors to the observed mutagenicity, we compared the areas of the peaks on the TIC-charts with and without chlorination. Of the ten peaks, six were also detected in the ozone-treated iopamidol-containing solution without chlorination, which did not induce mutagenicity, indicating that these peaks were not related to the observed mutagenicity. Accurate m/z values and MS/MS analysis with an orbitrap MS of the remaining four peaks revealed that two of them represented the same TP in the negative and positive ion modes. The three remaining TPs were assessed in four quantitative structure-activity relationship models for predicting Ames mutagenicity. At least one model predicted that two of the three TPs were mutagenic, whereas none of the models predicted that the other TP was a mutagen, suggesting that the former TPs, estimated as N1-acetyl-5-amino-6-chloro-2-iodobenzene-1,3-dicarboxamide and 3-hydroxy-2-{3-[(2-hydroxyethoxy)carbonyl]-2,4,6-triiodo-5-nitrobenzoyl}amino)propanoic acid, could be the candidate compounds that contributed to the observed mutagenicity.
authors.affiliation: Faculty of Engineering, Hokkaido University, N13W8, Sapporo 060-8628, Japan. Electronic address: taku-m@eng.hokudai.ac.jp.
authors.forename: Taku
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Graduate School of Engineering, Hokkaido University, N13W8, Sapporo 060-8628, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hashizuka
authors.affiliation: Graduate School of Engineering, Hokkaido University, N13W8, Sapporo 060-8628, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kuriyama
authors.affiliation: Faculty of Engineering, Hokkaido University, N13W8, Sapporo 060-8628, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Matsui
authors.affiliation: Faculty of Engineering, Hokkaido University, N13W8, Sapporo 060-8628, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Shirasaki
mesh_terms: D002713:Chlorine / Q000737:chemistry*; D002853:Chromatography, Liquid; D054879:Halogenation; D007479:Iopamidol / Q000737:chemistry / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D010126:Ozone / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000633:toxicity*; D018508:Water Purification / Q000379:methods*
chemical_list: D009153:Mutagens; D014874:Water Pollutants, Chemical; D002713:Chlorine; D010126:Ozone; D007479:Iopamidol
keywords: Ames assay; Disinfection by-product; Drinking-water treatment; Mutagenicity; X-ray contrast medium