Toxic Byproducts Generated in Disinfected Drinking Water Contaminated with Pharmaceuticals

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 by-products (DBPs), both of which are highly genotoxic and/or cytotoxic in mammalian cells. ICM are widely used at medical centers to enable medical imaging of soft tissues (e.g., organs, veins, blood vessels), they are almost completely excreted in urine or feces within 24 h, and they 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 water treatment plants that had no detectable iodide or very low iodide in their source waters. When 10 of the original 23 cities’ source waters were re-sampled, four ICM were found—iopamidol, iopromide, iohexol, and diatrizoate—with iopamidol most frequently detected, in 6 of the 10 plants sampled, up to 2700 ng/L. Subsequent controlled laboratory reactions of iopamidol with chlorine and monochloramine in buffered deionized water (in the absence of natural organic matter (NOM)), produced only very low 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-DBPs were generally higher at higher pH (8.5) for chlorine, but were higher at lower pH (6.5) for monochloramine. Iodate was also formed and was maximized at pH 7.5 and 8.0. Extracts from chloraminated natural source waters with and without iopamidol as well as from chlorinated natural source water with iopamidol were the most cytotoxic samples in mammalian cells. Source water with iopamidol but no disinfection were the least cytotoxic. While extracts from chlorinated and chloraminated natural 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 or chloraminated drinking water. Background In a previous 23-city occurrence study, we measured the widespread presence of iodinated disinfection by-products (iodo-DBPs)—iodo-acids and iodo-trihalomethanes (iodo-THMs)—in chloraminated and chlorinated drinking water in the United States and Canada at μg/L levels (up to 10.2 μg/L or 1.7 μg/L for individual iodo-THMs or iodo-acids, respectively (Richardson et al. 2008). Iodo-DBPs are highly genotoxic and cytotoxic, with iodoacetic acid being the most genotoxic DBP identified to date in mammalian cell systems (Plewa et al. 2004). The primary source of iodine in iodo-DBPs is believed to be from natural iodide in source waters. However, natural iodide levels were very low or not detected in some cases such that iodo-DBP formation could not be accounted for by natural iodide concentrations in the source waters (Richardson et