Chlorination of Source Water Containing Iodinated X-ray Contrast Media: Mutagenicity and Identification of New Iodinated Disinfection Byproducts

Abstract

Iodinated contrast media (ICM) are non-mutagenic agents administered for X-ray imaging of soft tissues. ICM can reach µg/L levels in surface waters because they are administered in high doses, excreted largely un-metabolized, and poorly removed by wastewater treatment. Iodinated disinfection by-products (I-DBPs) are highly genotoxic and have been reported in disinfected waters containing ICM. We assessed the mutagenicity in Salmonella of extracts of chlorinated *

Inability of GSTT1 to activate iodinated halomethanes to mutagens in Salmonella

“…Recently, we assessed the impact of four iodinated contrast media, which are used to enhance medical X‐ray imaging for soft tissues, on the mutagenicity of source water after the contrast media‐containing water was chlorinated (Postigo et al, 2018). We found that organic extracts of the chlorinated waters containing either of two of the contrast media, iopamidol (IPAM) and iohexol (IHX), were more mutagenic in the GSTT1‐expressing strain of Salmonella (RSJ100) than in the non‐expressing strain (TPT100).…”

“…Because nothing was known at the time about the ability of the I‐THMs to be activated by GSTT1, we ascribed the enhanced mutagenicity of these water extracts by GSTT1 to the Br‐THMs, which we had detected in the waters and that are activated by GSTT1. Beyond five halonitromethanes (Kundu et al, 2004b), none of the other halonitromethanes is activated by GSTT1, nor is iodoacetic acid (Postigo et al, 2018); no other DBPs have been evaluated for their ability to be activated to mutagens by GSTT1. The I‐THM data reported here support our original conclusion, eliminating the I‐THMs as a contributor to the enhanced mutagenicity of the IPAM‐ or IHX‐containing waters in RSJ100 that we reported in Postigo et al (2018).…”

“…However, unlike all but CDIM among the I‐THMs, all the I‐HAAs induce DNA damage in CHO cells as assessed by the comet assay (Richardson et al, 2008; Plewa et al, 2010) and are more genotoxic than their brominated or chlorinated analogues (Wagner and Plewa, 2017); they are also 8 times more mutagenic at the Hprt locus in CHO cells than their chlorinated or brominated analogues (Zhang et al, 2010). We have shown that iodoacetic acid (IAA) is also mutagenic in Salmonella TA100 and not activated by GSTT1 (Postigo et al, 2018).…”

“…As assessed by Richardson et al (2008) in chlorinated and chloraminated drinking waters from 23 cities in the U.S. and Canada, as well as reviewed by Postigo and Zonja (2019) and Dong et al (2019), various I‐DBPs have been found in drinking water during the disinfection of waters containing iodide and/or organic iodine. The types and concentrations of I‐DBPs are influenced by the concentration of iodide (Richardson et al, 2008; Jones et al, 2012; Postigo et al, 2017), the molecular size of the natural organic matter (NOM) (Zhang et al, 2016), and the presence of iodinated X‐ray contrast media in the source water (Duirk et al, 2011; Wendel et al, 2014; Xu et al, 2017; Postigo et al, 2018; Ackerson et al, 2020). A U.S. nationwide DBP occurrence study found that the concentrations of I‐THMs increased with chloramination more than with chlorination, with most I‐THMs present at sub‐ to low‐μg/L concentrations among various drinking water samples (Weinberg et al, 2002; Krasner et al, 2006).…”

“…The Br‐THMs are activated to mutagens in Salmonella by GSTT1 (DeMarini et al, 1997; Pegram et al, 1997), as are five halonitromethanes (Kundu et al, 2004b). Although iodoacetic acid is not activated to a mutagen by GSTT1 (Postigo et al, 2018), it is the most genotoxic among the HAAs (Plewa et al, 2002, 2004b; Attene‐Ramos et al, 2010; Zhang et al, 2010) and induces cell transformation in NIH3T3 cells (Wei et al, 2013). No other DBPs have been evaluated for their ability to be activated to mutagens in Salmonella by GSTT1, including the I‐THMs.…”