Dihalogenated Nitrophenols in Drinking Water: Prevalence, Resistance to Household Treatment, and Cardiotoxic Impact on Zebrafish Embryo

Overview

Journal Eco Environ Health

Date 2024 Apr 22

PMID 38646095

Authors

Hongjie Sun

Yingying Liu

Chunxiu Wu

Lena Q Ma

Dongxing Guan

Huachang Hong

Haiying Yu

Hongjun Lin

Xianfeng Huang

Peng Gao

Affiliations

Soon will be listed here.

Abstract

Dihalogenated nitrophenols (2,6-DHNPs), an emerging group of aromatic disinfection byproducts (DBPs) detected in drinking water, have limited available information regarding their persistence and toxicological risks. The present study found that 2,6-DHNPs are resistant to major drinking water treatment processes (sedimentation and filtration) and households methods (boiling, filtration, microwave irradiation, and ultrasonic cleaning). To further assess their health risks, we conducted a series of toxicology studies using zebrafish embryos as the model organism. Our findings reveal that these emerging 2,6-DHNPs showed lethal toxicity 248 times greater than that of the regulated DBP, dichloroacetic acid. Specifically, at sublethal concentrations, exposure to 2,6-DHNPs generated reactive oxygen species (ROS), caused apoptosis, inhibited cardiac looping, and induced cardiac failure in zebrafish. Remarkably, the use of a ROS scavenger, N-acetyl-l-cysteine, considerably mitigated these adverse effects, emphasizing the essential role of ROS in 2,6-DHNP-induced cardiotoxicity. Our findings highlight the cardiotoxic potential of 2,6-DHNPs in drinking water even at low concentrations of 19 μg/L and the beneficial effect of N-acetyl-l-cysteine in alleviating the 2,6-DHNP-induced cardiotoxicity. This study underscores the urgent need for increased scrutiny of these emerging compounds in public health discussions.

References

Chen B, Jiang J, Yang X, Zhang X, Westerhoff P . Roles and Knowledge Gaps of Point-of-Use Technologies for Mitigating Health Risks from Disinfection Byproducts in Tap Water: A Critical Review. Water Res. 2021; 200:117265. PMC: 8634687. DOI: 10.1016/j.watres.2021.117265. View

Zhang X, Qiu X, Yuan F, Wang J, Zhao C, Li R . TBX5 loss-of-function mutation contributes to familial dilated cardiomyopathy. Biochem Biophys Res Commun. 2015; 459(1):166-71. DOI: 10.1016/j.bbrc.2015.02.094. View

Hinits Y, Pan L, Walker C, Dowd J, Moens C, Hughes S . Zebrafish Mef2ca and Mef2cb are essential for both first and second heart field cardiomyocyte differentiation. Dev Biol. 2012; 369(2):199-210. PMC: 3927553. DOI: 10.1016/j.ydbio.2012.06.019. View

Lyons I, Parsons L, Hartley L, Li R, Andrews J, Robb L . Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. Genes Dev. 1995; 9(13):1654-66. DOI: 10.1101/gad.9.13.1654. View

Lundgren C, Sjostrand D, Biner O, Bennett M, Rudling A, Johansson A . Scavenging of superoxide by a membrane-bound superoxide oxidase. Nat Chem Biol. 2018; 14(8):788-793. PMC: 6379055. DOI: 10.1038/s41589-018-0072-x. View

Tanaka M, Chen Z, Bartunkova S, Yamasaki N, Izumo S . The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development. 1999; 126(6):1269-80. DOI: 10.1242/dev.126.6.1269. View

Liu J, Zhang X, Li Y, Li W, Hang C, Sharma V . Phototransformation of halophenolic disinfection byproducts in receiving seawater: Kinetics, products, and toxicity. Water Res. 2018; 150:68-76. PMC: 6390291. DOI: 10.1016/j.watres.2018.11.059. View

Yang X, Ou W, Xi Y, Chen J, Liu H . Emerging Polar Phenolic Disinfection Byproducts Are High-Affinity Human Transthyretin Disruptors: An in Vitro and in Silico Study. Environ Sci Technol. 2019; 53(12):7019-7028. DOI: 10.1021/acs.est.9b00218. View

de Pater E, Clijsters L, Marques S, Lin Y, Garavito-Aguilar Z, Yelon D . Distinct phases of cardiomyocyte differentiation regulate growth of the zebrafish heart. Development. 2009; 136(10):1633-41. PMC: 2673760. DOI: 10.1242/dev.030924. View

10.

Lu J, Wang W, Xu W, Zhang C, Zhang C, Tao L . Induction of developmental toxicity and cardiotoxicity in zebrafish embryos by Emamectin benzoate through oxidative stress. Sci Total Environ. 2022; 825:154040. DOI: 10.1016/j.scitotenv.2022.154040. View

11.

Yang M, Zhang X . Comparative developmental toxicity of new aromatic halogenated DBPs in a chlorinated saline sewage effluent to the marine polychaete Platynereis dumerilii. Environ Sci Technol. 2013; 47(19):10868-76. DOI: 10.1021/es401841t. View

12.

Liang Q, de Windt L, Witt S, Kimball T, Markham B, Molkentin J . The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo. J Biol Chem. 2001; 276(32):30245-53. DOI: 10.1074/jbc.M102174200. View

13.

Zhang Z, Zhu Q, Huang C, Yang M, Li J, Chen Y . Comparative cytotoxicity of halogenated aromatic DBPs and implications of the corresponding developed QSAR model to toxicity mechanisms of those DBPs: Binding interactions between aromatic DBPs and catalase play an important role. Water Res. 2019; 170:115283. DOI: 10.1016/j.watres.2019.115283. View

14.

Du Z, Wang G, Gao S, Wang Z . Aryl organophosphate flame retardants induced cardiotoxicity during zebrafish embryogenesis: by disturbing expression of the transcriptional regulators. Aquat Toxicol. 2015; 161:25-32. DOI: 10.1016/j.aquatox.2015.01.027. View

15.

Hu S, Gong T, Xian Q, Wang J, Ma J, Li Z . Formation of iodinated trihalomethanes and haloacetic acids from aromatic iodinated disinfection byproducts during chloramination. Water Res. 2018; 147:254-263. DOI: 10.1016/j.watres.2018.09.058. View

16.

Hunter P . Household water treatment in developing countries: comparing different intervention types using meta-regression. Environ Sci Technol. 2009; 43(23):8991-7. DOI: 10.1021/es9028217. View

17.

Ma S, Gan Y, Chen B, Tang Z, Krasner S . Understanding and exploring the potentials of household water treatment methods for volatile disinfection by-products control: Kinetics, mechanisms, and influencing factors. J Hazard Mater. 2016; 321:509-516. DOI: 10.1016/j.jhazmat.2016.08.053. View

18.

Reiter J, Alexander J, Rodaway A, Yelon D, Patient R, Holder N . Gata5 is required for the development of the heart and endoderm in zebrafish. Genes Dev. 1999; 13(22):2983-95. PMC: 317161. DOI: 10.1101/gad.13.22.2983. View

19.

Verhaagen B, Fernandez Rivas D . Measuring cavitation and its cleaning effect. Ultrason Sonochem. 2015; 29:619-28. DOI: 10.1016/j.ultsonch.2015.03.009. View

20.

Weinberg H, Pereira V, Singer P, Savitz D . Considerations for improving the accuracy of exposure to disinfection by-products by ingestion in epidemiologic studies. Sci Total Environ. 2005; 354(1):35-42. DOI: 10.1016/j.scitotenv.2004.12.016. View