Fingerprinting the reactive toxicity pathways of 50 drinking water disinfection by-products

Stalter, Daniel, O'Malley, Elissa, Von Gunten, Urs and Escher, Beate I. (2016) Fingerprinting the reactive toxicity pathways of 50 drinking water disinfection by-products. Water Research, 91 19-30. doi:10.1016/j.watres.2015.12.047


Author Stalter, Daniel
O'Malley, Elissa
Von Gunten, Urs
Escher, Beate I.
Title Fingerprinting the reactive toxicity pathways of 50 drinking water disinfection by-products
Journal name Water Research   Check publisher's open access policy
ISSN 1879-2448
0043-1354
Publication date 2016-03-15
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.watres.2015.12.047
Open Access Status Not Open Access
Volume 91
Start page 19
End page 30
Total pages 12
Place of publication London, United Kingdom
Publisher I W A Publishing
Language eng
Formatted abstract
A set of nine in vitro cellular bioassays indicative of different stages of the cellular toxicity pathway was applied to 50 disinfection by-products (DBPs) to obtain a better understanding of the commonalities and differences in the molecular mechanisms of reactive toxicity of DBPs. An Eschericia coli test battery revealed reactivity towards proteins/peptides for 64% of the compounds. 98% activated the NRf2-mediated oxidative stress response and 68% induced an adaptive stress response to genotoxic effects as indicated by the activation of the tumor suppressor protein p53. All DBPs reactive towards DNA in the E. coli assay and activating p53 also induced oxidative stress, confirming earlier studies that the latter could trigger DBP's carcinogenicity. The energy of the lowest unoccupied molecular orbital ELUMO as reactivity descriptor was linearly correlated with oxidative stress induction for trihalomethanes (r2 = 0.98) and haloacetamides (r2 = 0.58), indicating that potency of these DBPs is connected to electrophilicity. However, the descriptive power was poor for haloacetic acids (HAAs) and haloacetonitriles (r2 < 0.06). For HAAs, we additionally accounted for speciation by including the acidity constant with ELUMO in a two-parameter multiple linear regression model. This increased r2 to >0.80, indicating that HAAs' potency is connected to both, electrophilicity and speciation. Based on the activation of oxidative stress response and the soft electrophilic character of most tested DBPs we hypothesize that indirect genotoxicity—e.g., through oxidative stress induction and/or enzyme inhibition—is more plausible than direct DNA damage for most investigated DBPs. The results provide not only a mechanistic understanding of the cellular effects of DBPs but the effect concentrations may also serve to evaluate mixture effects of DBPs in water samples.
Keyword Disinfection byproduct
Electrophilicity
Mutagenicity
Oxidative stress
p53 activation
QSAR
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID PIOF-GA-2012-329169
FT100100694
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
National Research Centre for Environmental Toxicology Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
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