Hunting for aquatic bladder carcinogens

Epidemiological studies have consistently found an association between the consumption of chlorinated water and an increased risk of developing bladder cancer. This risk has been attributed to disinfection byproducts (DBPs) – undesirable products formed during the disinfection of drinking water – but the individual compounds responsible remain unknown. This project aims at assessing which individual or groups of DBPs may be implicated in the bladder cancer association. By comparing the structures of bladder carcinogens and probable DBPs in a review of the literature (published in Water Research), halocyclopentenoic acids, halofuranones and haloquinones were selected as potentially critical DBP candidates. Eleven phenolic compounds previously used as surrogates for natural organic matter in drinking water were chlorinated under 91 different conditions (different precursors, pH, chlorine and bromide doses). UV spectroscopy was used as a screening method to identify which conditions lead to the formation of stable UV-absorbing DBPs. Ten chlorinated samples were prioritised, in which 3 chlorophenols and bromoform were tentatively identified by GC-MS. Using HPLC-HRMS, the chemical formulas of 55 DBPs were elucidated and possible products were proposed for 44 of them. 31 of these were never reported before as DBPs. A novel pathway was proposed for the formation of 15 out of a total of 35 furan-like products tentatively identified using HPLC-HRMS. It consists of the opening of the oxidised phenolic ring followed by the formation of a 5-membered ring by intramolecular nucleophilic addition. These results indicate6that the formation of furan-like DBPs may be far more widespread in drinking water than previously appreciated. Among the mechanistically plausible DBPs tentatively identified, 11 were predicted to be bladder carcinogens using a quantitative structure-toxicity relationship theoretical model. Prioritising critical DBPs will enable future research to assess their occurrence, confirm their toxicity and control their concentration in drinking water, ultimately reducing the bladder cancer risk