Comparative Toxicity Analyses from Different Endpoints: Are New Cyclic Disinfection Byproducts (DBPs) More Toxic than Common Aliphatic DBPs?

Abstract

In recent years, dozens of halogenated disinfection byproducts (DBPs) with cyclic structures were identified and detected in drinking water globally. Previous in vivo toxicity studies have shown that a few new cyclic DBPs possessed higher developmental toxicity and growth inhibition rate than common aliphatic DBPs; however, in vitro toxicity studies have proved that the latter exhibited higher cytotoxicity and genotoxicity than the former. Thus, to provide a more comprehensive toxicity comparison of DBPs from different endpoints, 11 groups of cyclic DBPs and nine groups of aliphatic DBPs were evaluated for their comparative in vitro and in vivo toxicity using human hepatoma cells (Hep G2) and zebrafish embryos. Notably, results showed that the in vitro Hep G2 cytotoxicity index of the aliphatic DBPs was nearly eight times higher than that of the cyclic DBPs, whereas the in vivo zebrafish embryo developmental/acute toxicity indexes of the cyclic DBPs were roughly 48–50 times higher than those of the aliphatic DBPs, indicating that the toxicity rank order differed when different endpoints were applied. For a broader comparison, a Pearson correlation analysis of DBP toxicity data from nine different endpoints was conducted. It was found that the observed Hep G2 cytotoxicity and zebrafish embryo developmental/acute toxicity in this study were highly correlated with the previously reported in vitro CHO cytotoxicity and in vivo toxicity in aquatic organisms (P < 0.01), respectively. However, the observed in vitro toxicity had no correlation with the in vivo toxicity (P > 0.05), suggesting that the toxicity rank orders obtained from in vitro and in vivo bioassays had large discrepancies. According to the observed toxicity data in this study and the candidate descriptors, two quantitative structure–activity relationship (QSAR) models were established, which help to further interpret the toxicity mechanisms of DBPs from different endpoints.

Emerging Disinfection Byproduct 2,6-Dichlorobenzoquinone-Induced Cardiovascular Developmental Toxicity of Embryonic Zebrafish and Larvae: Imaging and Transcriptome Analysis

“…Briefly, two male and two female adult fish in each tank were separated the night before the collection of fertilized eggs. In a previous study of acute toxicity of aromatic DBPs on zebrafish embryos, the doses of DBPs ranged from 0.1 to 1000 μM . Exposure of zebrafish embryos to16 μM 2,6-DCBQ caused a high mortality rate (80%) .…”

Occurrence and Cytotoxicity of Aliphatic and Aromatic Halogenated Disinfection Byproducts in Indoor Swimming Pool Water and Their Incoming Tap Water

“…70 Another study also demonstrated that the HepG2 cell cytotoxicity of DBPs was significantly correlated with both the CHO cell cytotoxicity and the T24 cell cytotoxicity, suggesting that the cytotoxicity results of HepG2 cells were reliable for the in vitro cytotoxicity evaluation of DBPs. 45 In our previous studies, HepG2 cells have been adopted for the cytotoxicity tests of iodinated DBPs, which was a well-established method for the cytotoxicity evaluation of DBPs. 42,46 Thus, we also adopted this method to clarify the comparative toxicity of the aliphatic and aromatic halogenated DBPs in swimming pool water and their incoming tap water in this study.…”

“…It has been reported that the toxicity rank orders obtained from in vitro and in vivo bioassays had large discrepancies. 45 Thus, in future studies, in vivo toxicity assays may also be conducted to comprehensively clarify the risks posed by different categories of DBPs in swimming pool water. Furthermore, the concentration-cytotoxicity contributions were limited to the five categories of aliphatic halogenated DBPs and six categories of aromatic halogenated DBPs in this study, while other unknown categories of aliphatic and aromatic halogenated DBPs were not able to be included (especially for the large number of unknown aromatic halogenated DBPs).…”

Halocyclopentadienes: An Emerging Class of Toxic DBPs in Chlor(am)inated Drinking Water

“…23 An extensive new toxicology study of cyclic versus aliphatic DBPs by Wu et al demonstrates that aliphatic DBPs are much more cytotoxic, but cyclic DBPs have higher adverse developmental effects and acute toxicity in zebrafish embryos. 24 T h i s c o n t e n t i s Studies also show that >50% of total organic halogen (TOX) in chlorinated drinking water, >70% of TOX in chloraminated drinking water, and ∼40% of TOX in ozonated−chlorinated water are attributed to unknown DBPs, 25−29 and it was recently suggested that aromatic halo-DBPs might contribute ∼30% of the TOX in chlorinated drinking water. 23 To improve the safety of drinking water consumed daily by billions of people throughout the world, it is important to identify the structures of the unknown DBPs comprising a dominant portion of this water.…”

“…A recent paper by Diana et al suggests that non-nitrogenous DBPs, such as halocyclopentenoic acids, halofuranones, and haloquinones, may help to explain the risk of bladder cancer, and another study by Han et al suggests that aromatic halogenated DBPs might help to explain adverse developmental effects observed in epidemiologic studies . An extensive new toxicology study of cyclic versus aliphatic DBPs by Wu et al demonstrates that aliphatic DBPs are much more cytotoxic, but cyclic DBPs have higher adverse developmental effects and acute toxicity in zebrafish embryos …”