Assessing the skin irritation and sensitizing potential of concentrates of water chlorinated in the presence of iodinated X-ray contrast media.

Chemical disinfection of water provides significant public health benefits. However, disinfectants like chlorine can react with naturally occurring materials in the water to form disinfection byproducts (DBPs). Natural levels of iodine have been reported to be too low in some source waters to account for the levels of iodinated DBPs detected. Iodinated X-ray contrast media (ICM) have been identified as a potential source of iodine. The toxicological impact of ICM present in source water at the time of disinfection has not been fully investigated. Iopamidol, iohexol, iopromide, and diatrizoate are among the ICM most frequently detected in water. In this study, source water containing one of these four ICM was chlorinated; non-chlorinated ICM-containing water samples served as controls. Reactions were conducted at an ICM concentration of 5 µM and a chlorine dose of 100 µM over 72 hr. Water concentrates (20,000-fold) were prepared by XAD-resin/ethyl acetate extraction and DMSO solvent exchange. We used the MatTek® reconstituted human epithelial skin irritation model to evaluate the water concentrates and also assessed the dermal irritation and sensitization potential of these concentrates using the LLNA:BrdU ELISA in BALB/c mice. None of the water concentrates tested (2500X) resulted in a skin irritant response in the MatTek® skin irritation model. Likewise, none of the concentrates (2500X, 1250X, 625X, 312.5X, 156.25X) produced a skin irritation response in mice: erythema was minimal; the maximum increase in ear thickness was less than 25%. Importantly, none of the concentrates produced a positive threshold response for allergic skin sensitization at any concentration tested in the LLNA:BrdU ELISA. We conclude that concentrates of water disinfected in the presence of four different ICM did not cause significant skin irritation or effects consistent with skin sensitization at the concentrations tested.