Energy of the Lowest Unoccupied Molecular Orbital, Thiol Reactivity, and Toxicity of Three Monobrominated Water Disinfection Byproducts

Justin A. Pals, Elizabeth D. Wagner, Michael J. Plewa

Research output: Contribution to journalArticle

Abstract

Disinfection of drinking water protects public health against waterborne pathogens. However, during disinfection, toxic disinfection byproducts (DBPs) are formed. Exposure to DBPs was associated with increased risk of bladder cancer in humans. DBPs are generated at concentrations below their carcinogenic potencies; it is unclear how exposure leads to adverse health outcomes. We used computational estimates of the energy of the lowest unoccupied molecular orbital (ELUMO) to predict thiol reactivity and additive toxicity among soft electrophile DBPs. Bromoacetic acid (BAA) was identified as non-thiol-reactive, which was supported by in chemico and in vitro data. Bromoacetonitrile (BAN) and bromoacetamide (BAM) were thiol-reactive. Genotoxicity induced by these compounds was reduced by increasing the thiol pool with N-acetyl l-cysteine (NAC), while NAC had little effect on BAA. BAN and BAM shared depletion of glutathione (GSH) or cellular thiols as a molecular initiating event (MIE), whereas BAA induces toxicity through another pathway. Binary mixtures of BAM and BAN expressed a potentiating effect in genotoxicity. We found that soft electrophile DBPs could be an important predictor of common mechanism groups that demonstrated additive toxicity. In silico estimates of ELUMO could be used to identify the most relevant DBPs that are the forcing factors of the toxicity of finished drinking waters.

Original languageEnglish (US)
Pages (from-to)3215-3221
Number of pages7
JournalEnvironmental Science and Technology
Volume50
Issue number6
DOIs
StatePublished - Mar 15 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Environmental Chemistry

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