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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 | Impact of chlorine exposure time on disinfection byproduct formation in the presence of iopamidol and natural organic matter during chloramination显示文摘Chloramines,in practice,are formed onsite by adding ammonia to chlorinated drinking water to achieve the required disinfection.While regulated disinfection byproducts(DBPs)are reduced during chloramine disinfection,other DBPs such as iodinated(iodo-)DBPs,that elicit greater toxicity are formed.The objective of this study was to investigate the impact of prechlorination time on the formation of both halogen-specific total organic halogen(TOX)and iodo/chlorinated(chloro-)DBPs during prechlorination/chloramination in source waters(SWs)containing iopamidol,an X-ray contrast medium.Barberton SW(BSW)and Cleveland SW(CSW)containing iopamidol were prechlorinated for 5–60 min and afterwards chloraminated for 72 hr with ammonium chloride.Chlorine contact time(CCT)did not significantly impact total organic iodine(TOI)concentrations after prechlorination or chloramination.Concentrations of total organic chlorine(TOCl)formed during prechlorination did not significantly change regardless of pH and prechlorination time,whileTOClappearedtodecreaseafter 72 hrchloraminationperiod.Dichloroiodomethane(CHCl_2I)formation during prechlorination did not exhibit any significant trends as a function of p H or CCT,but after chloramination,significant increases were observed at pHs 6.5 and 7.5 with respect to CCT.Iodo-HAAs were not formed during prechlorination but were detected after chloramination.Significant quantities of chloroform(CHCl_3)and trichloroacetic acid(TCAA)were formed during prechlorination but formation ceased upon ammonia addition.Therefore,prechlorination studies should measure TOX and DBP concentrations prior to ammonia addition to obtain data regarding the initial conditions. | Nana Osei B.Ackerson Alexis H.Killinger Hannah K.Liberatore Thomas A.Ternes Michael J.Plewa Susan D.Richardson Stephen E.Duirk | 2019 | Journal of Environmental Sciences2019，31，4： | 4 |
| 6 | Comparative mammalian cell cytotoxicity of wastewater with elevated bromide and iodide after chlorination,chloramination, or ozonation显示文摘Recycling wastewater is becoming more common as communities around the world try to better control their water resources against an increased frequency of either prolonged droughts or intense flooding. For communities in coastal areas, wastewaters may contain elevated levels of bromide(Br^-) and iodide(I^-) from seawater intrusion or high mineral content of source waters. Disinfection of such wastewater is mandatory to prevent the spread of pathogens, however little is known about the toxicity of wastewater after disinfection in the presence of Br^-and I^-. In this study we compared the induction of chronic cytotoxicity in mammalian cells in samples of municipal secondary wastewater effluent amended with elevated levels of Br^-/I^-after disinfection by chlorine, chloramines or ozone to identify which disinfection process generated wastewater with the lowest level of adverse biological response. Chlorination increased mammalian cell cytotoxicity by 5times as compared to non-disinfected controls. Chloramination produced disinfected wastewater that expressed 6.3 times more cytotoxicity than the non-disinfected controls and was 1.3 times more cytotoxic than the chlorinated samples. Ozonation produced wastewater with cytotoxicity comparable to the non-disinfected controls and was at least 4times less cytotoxic than the chlorine disinfected wastewaters. These results indicate that compared to chlorination and chloramination, ozonation of wastewater with high Br^-/Ilevels yielded the lowest mammalian cell cytotoxicity, suggesting its potential as a more favorable method to disinfect wastewater with minimizing the biological toxicity in mind. | Shengkun Dong Thanh H.Nguyen Michael J.Plewa | 2017 | Journal of Environmental Sciences2017，29，8： | 4 |
| 7 | Disinfection By-Products in Drinking Water, Recycled Water and Wastewater: Formation, Detection, Toxicity and Health Effects: Preface显示文摘The disinfection of drinking water was an outstanding(and perhaps the most important)public health achievement of the 20^(th) century.According to the United Nations World Health Organization,over 4 billion people have access | Michael J.Plewa Susan D.Richardson | 2017 | Journal of Environmental Sciences2017，29，8： | 3 |
| 8 | Formation of regulated and unregulated disinfection byproducts during chlorination and chloramination: Roles of dissolved organic matter type, bromide, and iodide显示文摘Algal blooms and wastewater effluents can introduce algal organic matter(AOM) and effluent organic matter(Ef OM) into surface waters, respectively. In this study, the impact of bromide and iodide on the formation of halogenated disinfection byproducts(DBPs) during chlorination and chloramination from various types of dissolved organic matter(DOM, e.g., natural organic matter(NOM), AOM, and Ef OM) were investigated based on the data collected from literature. In general, higher formation of trihalomethanes(THMs) and haloacetic acids(HAAs) was observed in NOM than AOM and Ef OM, indicating high reactivities of phenolic moieties with both chlorine and monochloramine. The formation of haloacetaldehydes(HALs), haloacetonitriles(HANs) and haloacetamides(HAMs) was much lower than THMs and HAAs. Increasing initial bromide concentrations increased the formation of THMs, HAAs, HANs, and HAMs, but not HALs. Bromine substitution factor(BSF) values of DBPs formed in chlorination decreased as specific ultraviolet absorbance(SUVA) increased. AOM favored the formation of iodinated THMs(I-THMs) during chloramination using preformed chloramines and chlorination-chloramination processes. Increasing prechlorination time can reduce the I-THM concentrations because of the conversion of iodide to iodate, but this increased the formation of chlorinated and brominated DBPs. In an analogous way, iodine substitution factor(ISF) values of I-THMs formed in chloramination decreased as SUVA values of DOM increased. Compared to chlorination, the formation of noniodinated DBPs is low in chloramination. | Yunsi Liu Keqiang Liu Michael J.Plewa Tanju Karanfil Chao Liu | 2022 | Journal of Environmental Sciences2022，34，7： | 2 |
| 9 | Investigation of nuclear enzyme topoisomerase as a putative molecular target of monohaloacetonitrile disinfection by-products显示文摘Disinfection by-products occur widely as the unintended effect of water disinfection and are associated with toxicity and adverse human health effects. Yet the molecular mechanisms of their toxicity are not well understood. To investigate the molecular basis of hyperploidy induction by monohaloacetonitriles, the interaction of monohaloacetonitriles with topoisomerase Ⅱ in Chinese hamster ovary cells was examined. We showed a concentration-dependent inhibition of DNA decatenation activity of topoisomerase under acellular conditions while in vitro monohaloacetonitrile treatment expressed mixed results. The working hypothesis, that topoisomerase Ⅱ is a molecular target of monohaloacetonitriles, was only partially supported.Nevertheless, this research serves as a starting point toward molecular mechanisms of toxic action of monohaloacetonitriles. | Yukako Komaki Michael J.Plewa | 2017 | Journal of Environmental Sciences2017，29，8： | 2 |
| 10 | 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 |
| 11 | Relationships between regulated DBPs and emerging DBPs of health concern in U.S. drinking water显示文摘A survey was conducted at eight U.S. drinking water plants, that spanned a wide range of water qualities and treatment/disinfection practices. Plants that treated heavily-wastewaterimpacted source waters had lower trihalomethane to dihaloacetonitrile ratios due to the presence of more organic nitrogen and HAN precursors. As the bromide to total organic carbon ratio increased, there was more bromine incorporation into DBPs. This has been shown in other studies for THMs and selected emerging DBPs(HANs), whereas this study examined bromine incorporation for a wider group of emerging DBPs(haloacetaldehydes, halonitromethanes). Moreover, bromine incorporation into the emerging DBPs was, in general, similar to that of the THMs. Epidemiology studies that show an association between adverse health effects and brominated THMs may be due to the formation of brominated emerging DBPs of heath concern. Plants with higher free chlorine contact times before ammonia addition to form chloramines had less iodinated DBP formation in chloraminated distribution systems, where there was more oxidation of the iodide to iodate(a sink for the iodide) by the chlorine. This has been shown in many bench-scale studies(primarily for iodinated THMs), but seldom in full-scale studies(where this study also showed the impact on total organic iodine. Collectively, the THMs, haloacetic acids, and emerging DBPs accounted for a significant portion of the TOCl, TOBr, and TOI;however, ~50% of the TOCl and TOBr is still unknown. The correlation of the sum of detected DBPs with the TOCl and TOBr suggests that they can be used as reliable surrogates. | Stuart W.Krasner Ai Jia Chih-Fen T.Lee Raha Shirkhani Joshua M.Allen Susan D.Richardson Michael J.Plewa | 2022 | Journal of Environmental Sciences2022，34，7： | 1 |
| 12 | 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 |
| 13 | 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 |
| 14 | Iodoacetic acid exposure alters the transcriptome in mouse ovarian antral follicles显示文摘Iodoacetic acid(IAA) is an unregulated water disinfection byproduct that is an ovarian toxicant. However, the mechanisms of action underlying IAA toxicity in ovarian follicles remain unclear. Thus, we determined whether IAA alters gene expression in ovarian follicles in mice. Adult female mice were dosed with water or IAA(10 or 500 mg/L) in the water for 35-40 days. Antral follicles were collected for RNA-sequencing analysis and sera were collected to measure estradiol. RNA-sequencing analysis identified 1063 differentially expressed genes(DEGs) in the 10 and 500 mg/L IAA groups(false discovery rate FDR < 0.1), respectively, compared to controls. Gene Ontology Enrichment analysis showed that DEGs were involved with RNA processing and regulation of angiogenesis(10 mg/L) and the cell cycle and cell division(500 mg/L). Pathway Enrichment analysis showed that DEGs were involved in the phosphatidylinositol 3-kinase and protein kinase B(PI3K-Akt), gonadotropin-releasing hormone(Gn RH), estrogen, and insulin signaling pathways(10 mg/L). Pathway Enrichment analysis showed that DEGs were involved in the oocyte meiosis, Gn RH, and oxytocin signaling pathways(500 mg/L). RNA-sequencing analysis identified 809 DEGs when comparing the 500 and 10 mg/L IAA groups(FDR < 0.1). DEGs were related to ribosome, translation, m RNA processing, oxidative phosphorylation, chromosome, cell cycle, cell division, protein folding, and the oxytocin signaling pathway. Moreover, IAA exposure significantly decreased estradiol levels(500 mg/L) compared to control. This study identified key candidate genes and pathways involved in IAA toxicity and can help to further understand the molecular mechanisms of IAA toxicity in ovarian follicles. | Andressa Gonsioroski Mary Laws Vasiliki E.Mourikes Alison Neff Jenny Drnevich Michael J.Plewa Jodi A.Flaws | 2022 | Journal of Environmental Sciences2022，34，7： | 0 |
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