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| 1 | CHO cell cytotoxicity and genotoxicity analyses of disinfection by-products: An updated review显示文摘The disinfection of drinking water is an important public health service that generates high quality, safe and palatable tap water. The disinfection of drinking water to reduce waterborne disease was an outstanding public health achievement of the 20 th century.An unintended consequence is the reaction of disinfectants with natural organic matter,anthropogenic contaminants and bromide/iodide to form disinfection by-products(DBPs).A large number of DBPs are cytotoxic, neurotoxic, mutagenic, genotoxic, carcinogenic and teratogenic. Epidemiological studies demonstrated low but significant associations between disinfected drinking water and adverse health effects. The distribution of DBPs in disinfected waters has been well defined by advances in high precision analytical chemistry. Progress in the analytical biology and toxicology of DBPs has been forthcoming.The objective of this review was to provide a detailed presentation of the methodology for the quantitative, comparative analyses on the induction of cytotoxicity and genotoxicity of103 DBPs using an identical analytical biological platform and endpoints. A single Chinese hamster ovary cell line was employed in the assays. The data presented are derived from papers published in the literature as well as additional new data and represent the largest direct quantitative comparison on the toxic potency of both regulated and emerging DBPs.These data may form the foundation of novel research to define the major forcing agents of DBP-mediated toxicity in disinfected water and may play an important role in achieving the goal of making safe drinking water better. | Elizabeth D.Wagner Michael J.Plewa | 2017 | Journal of Environmental Sciences2017，29，8： | 70 |
| 2 | TIC-Tox: A preliminary discussion on identifying the forcing agents of DBP-mediated toxicity of disinfected water显示文摘The disinfection of drinking water is a major public health achievement; however, an unintended consequence of disinfection is the generation of disinfection by-products(DBPs). Many of the identified DBPs exhibit in vitro and in vivo toxicity, generate a diversity of adverse biological effects, and may be hazards to the public health and the environment.Only a few DBPs are regulated by several national and international agencies and it is not clear if these regulated DBPs are the forcing agents that drive the observed toxicity and their associated health effects. In this study, we combine analytical chemical and biological data to resolve the forcing agents associated with mammalian cell cytotoxicity of drinking water samples from three cities. These data suggest that the trihalomethanes(THMs) and haloacetic acids may be a small component of the overall cytotoxicity of the organic material isolated from disinfected drinking water. Chemical classes of nitrogen-containing DBPs, such as the haloacetonitriles and haloacetamides, appear to be the major forcing agents of toxicity in these samples. These findings may have important implications for the design of epidemiological studies that primarily rely on the levels of THMs to define DBP exposure among populations. The TIC-Tox approach constitutes a beginning step in the process of identifying the forcing agents of toxicity in disinfected water. | Michael J.Plewa Elizabeth D.Wagner Susan D.Richardson | 2017 | Journal of Environmental Sciences2017，29，8： | 15 |
| 3 | The impact of iodinated X-ray contrast agents on formation and toxicity of disinfection by-products in drinking water显示文摘The presence of iodinated X-ray contrast media(ICM) in source waters is of high concern to public health because of their potential to generate highly toxic disinfection by-products(DBPs). The objective of this study was to determine the impact of ICM in source waters and the type of disinfectant on the overall toxicity of DBP mixtures and to determine which ICM and reaction conditions give rise to toxic by-products. Source waters collected from Akron,OH were treated with five different ICMs, including iopamidol, iopromide, iohexol,diatrizoate and iomeprol, with or without chlorine or chloramine disinfection. The reaction product mixtures were concentrated with XAD resins and the mammalian cell cytotoxicity and genotoxicity of the reaction mixture concentrates was measured. Water containing iopamidol generated an enhanced level of mammalian cell cytotoxicity and genotoxicity after disinfection. While chlorine disinfection with iopamidol resulted in the highest cytotoxicity overall, the relative iopamidol-mediated increase in toxicity was greater when chloramine was used as the disinfectant compared with chlorine. Four other ICMs(iopromide, iohexol, diatrizoate, and iomeprol) expressed some cytotoxicity over the control without any disinfection, and induced higher cytotoxicity when chlorinated. Only iohexol enhanced genotoxicity compared to the chlorinated source water. | Clara H.Jeong Edward J.Machek Morteza Shakeri Stephen E.Duirk Thomas A.Ternes Susan D.Richardson Elizabeth D.Wagner Michael J.Plewa | 2017 | Journal of Environmental Sciences2017，29，8： | 11 |
| 4 | Chloramination of wastewater effluent: Toxicity and formation of disinfection byproducts显示文摘The reclamation and disinfection of waters impacted by human activities(e.g., wastewater effluent discharges) are of growing interest for various applications but has been associated with the formation of toxic nitrogenous disinfection byproducts(N-DBPs). Monochloramine used as an alternative disinfectant to chlorine can be an additional source of nitrogen in the formation of N-DBPs. Individual toxicity assays have been performed on many DBPs, but few studies have been conducted with complex mixtures such as wastewater effluents. In this work, we compared the cytotoxicity and genotoxicity of wastewater effluent organic matter(Ef OM) before and after chloramination. The toxicity of chloraminated Ef OM was significantly higher than the toxicity of raw Ef OM, and the more hydrophobic fraction(HPO)isolated on XAD-8 resin was more toxic than the fraction isolated on XAD-4 resin.More DBPs were also isolated on the XAD-8 resin. N-DBPs(i.e., haloacetonitriles or haloacetamides) were responsible for the majority of the cytotoxicity estimated from DBP concentrations measured in the XAD-8 and XAD-4 fractions(99.4% and 78.5%, respectively).Measured DBPs accounted for minor proportions of total brominated and chlorinated products, which means that many unknown halogenated compounds were formed and can be responsible for a significant part of the toxicity. Other non-halogenated byproducts(e.g.,nitrosamines) may contribute to the toxicity of chloraminated effluents as well. | Julien Le Roux Michael J.Plewa Elizabeth D.Wagner Maolida Nihemaiti Azra Dad Jean-Philippe Croué | 2017 | Journal of Environmental Sciences2017，29，8： | 8 |
| 5 | Monohalogenated acetamide-induced cellular stress and genotoxicity are related to electrophilic softness and thiol/thiolate reactivity显示文摘Haloacetamides(HAMs) are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an S_N2 reaction mechanism.Toxicity of the monohalogenated HAMs(iodoacetamide, IAM; bromoacetamide, BAM;or chloroacetamide, CAM) varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity and toxicological properties of HAMs, measured as induction of oxidative/electrophilic stress response and genotoxicity. Additionally, we wanted to determine how well in silico estimates of electrophilic softness matched thiol/thiolate reactivity and in vitro toxicological endpoints.Each of the HAMs significantly induced nuclear Rad51 accumulation and ARE signaling activity compared to a negative control. The rank order of effect was IAM > BAM > CAM for Rad51, and BAM ≈ IAM > CAM for ARE. In general, electrophilic softness and in chemico thiol/thiolate reactivity provided a qualitative indicator of toxicity, as the softer electrophiles IAM and BAM were more thiol/thiolate reactive and were more toxic than CAM. | Justin A.Pals Elizabeth D.Wagner Michael J.Plewa Menghang Xia Matias S.Attene-Ramos | 2017 | Journal of Environmental Sciences2017，29，8： | 1 |
| 6 | Mammalian cell cytotoxicity and genotoxicity analysis of drinking water disinfection by‐products显示文摘 | Michael J.Plewa YahyaKargalioglu DanielleVankerk Roger A.Minear Elizabeth D.Wagner | 2002 | Mutagen2002，，2： | 1 |
| 7 | DNA damage and toxicogenomic analyses of hydrogen sulfide in human intestinal epithelial FHs 74 Int cells显示文摘 | Matias S.Attene‐Ramos Gerardo M.Nava Mark G.Muellner Elizabeth D.Wagner Michael J.Plewa H. RexGaskins | 2010 | Environ Mol Mutagen2010，，4： | 1 |
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