Occurrence of iodinated X-ray contrast media and their biotransformation products in the urban water cycle.

A LC tandem MS method was developed for the simultaneous determination of four iodinated X-ray contrast media (ICM) and 46 ICM biotransformation products (TPs) in raw and treated wastewater, surface water, groundwater, and drinking water. Recoveries ranged from 70% to 130%, and limits of quantification (LOQ) varied between 1 ng/L and 3 ng/L for surface water, groundwater and drinking water, and between 10 ng/L and 30 ng/L for wastewater. In a conventional wastewater treatment plant, iohexol, iomeprol, and iopromide were transformed to >80%, while iopamidol was transformed to 35%. In total, 26 TPs were detected above their LOQ in WWTP effluents. A significant change in the pattern of ICM TPs was observed after bank filtration and groundwater infiltration under aerobic conditions. Predominately, these TPs are formed at the end of the microbial transformation pathways in batch experiments with soil and sediment. These polar ICM TPs, such as iohexol TP599, iomeprol TP643, iopromide TP701A, and iopromide TP643, were not or only partially removed during drinking water treatment. As a consequence, several ICM TPs were detected in drinking water, at concentration levels exceeding 100 ng/L, with a maximum of 500 ng/L for iomeprol TP687.

Formation of toxic iodinated disinfection by-products from compounds used in medical imaging.

Iodinated X-ray contrast media (ICM) were investigated as a source of iodine in the formation of iodo-trihalomethane (iodo-THM) and iodo-acid disinfection byproducts (DBPs), both of which are highly genotoxic and/or cytotoxic in mammalian cells. ICM are widely used at medical centers to enable imaging of soft tissues (e.g., organs, veins, blood vessels) and are designed to be inert substances, with 95% eliminated in urine and feces unmetabolized within 24 h. ICM are not well removed in wastewater treatment plants, such that they have been found at elevated concentrations in rivers and streams (up to 100 µg/L). Naturally occurring iodide in source waters is believed to be a primary source of iodine in the formation of iodo-DBPs, but a previous 23-city iodo-DBP occurrence study also revealed appreciable levels of iodo-DBPs in some drinking waters that had very low or no detectable iodide in their source waters. When 10 of the original 23 cities' source waters were resampled, four ICM were found--iopamidol, iopromide, iohexol, and diatrizoate--with iopamidol most frequently detected, in 6 of the 10 plants sampled, with concentrations up to 2700 ng/L. Subsequent controlled laboratory reactions of iopamidol with aqueous chlorine and monochloramine in the absence of natural organic matter (NOM) produced only trace levels of iodo-DBPs; however, when reacted in real source waters (containing NOM), chlorine and monochloramine produced significant levels of iodo-THMs and iodo-acids, up to 212 nM for dichloroiodomethane and 3.0 nM for iodoacetic acid, respectively, for chlorination. The pH behavior was different for chlorine and monochloramine, such that iodo-DBP concentrations maximized at higher pH (8.5) for chlorine, but at lower pH (6.5) for monochloramine. Extracts from chloraminated source waters with and without iopamidol, as well as from chlorinated source waters with iopamidol, were the most cytotoxic samples in mammalian cells. Source waters with iopamidol but no disinfectant added were the least cytotoxic. While extracts from chlorinated and chloraminated source waters were genotoxic, the addition of iopamidol enhanced their genotoxicity. Therefore, while ICM are not toxic in themselves, their presence in source waters may be a source of concern because of the formation of highly toxic iodo-DBPs in chlorinated and chloraminated drinking water.

Biotransformation of selected iodinated X-ray contrast media and characterization of microbial transformation pathways.

Iodinated X-ray contrast media (ICM) are commonly detected in the aquatic environment at concentrations up to the low microgram per liter range. In this study, the biotransformation of selected ICM (diatrizoate, iohexol, iomeprol, and iopamidol) in aerobic soil-water and river sediment-water batch systems was investigated. In addition, microbial transformation pathways were proposed. Diatrizoate, an ionic ICM, was not biotransformed, while three nonionic ICM were transformed into several biotransformation products (TPs) at neutral pH. Iohexol and iomeprol were biotransformed to eleven TPs and fifteen TPs, respectively, while eight TPs were detected for iopamidol. Since seven of the TPs detected during biotransformation had not been previously identified, mass fragmentation experiments were completed to elucidate the chemical structures. Oxidation of primary alcoholic moieties, cleavage of the N-C bonds (i.e., deacetylation and removal of hydroxylated propanoic acids), and decarboxylation are potential reactions that can explain the formation of the identified TPs. Iohexol and iomeprol had similar biotransformation rates, while iopamidol was biotransformed slower and to a lesser extent. A LC tandem MS method confirmed the presence of ICM TPs in aqueous environmental samples. Fifteen of the ICM TPs were even detected in drinking water with concentrations up to 120 ng/L.

Multistep approach for the structural identification of biotransformation products of iodinated X-ray contrast media by liquid chromatography/hybrid triple quadrupole linear ion trap mass spectrometry and (1)H and (13)C nuclear magnetic resonance.

This study investigated the application of a hybrid triple quadrupole linear ion trap mass spectrometer (Qq-LIT-MS) in combination with NMR to elucidate the chemical structures of 27 biotransformation products (TPs) of the nonionic iodinated X-ray contrast media (ICM), iohexol, iomeprol, and iopamidol, formed in contact with soil. The combination of MS(2) and MS(3) spectra with Qq-LIT-MS was essential to determine the MS fragmentation pathways crucial for structural elucidation. (1)H and (13)C NMR analyses were needed to confirm the chemical structures of TPs proposed by MS fragmentation. Biotransformation occurred exclusively at the side chains of the iodinated X-ray contrast media, while the iodinated benzene ring remained unaltered. Several of the newly identified TPs of the ICM were found in surface water, groundwater, and even drinking water. Concentrations as high as 1450 +/- 110 ng/L (iomeprol TP629) were detected in groundwater that is influenced by wastewater infiltration, and as high as 289 +/- 41 ng/L (iomeprol TP643) in drinking water.