Common antimicrobials disrupt early zebrafish development through immune-cardiac signaling

The global production and use of antimicrobial chemicals surged during and after the COVID-19 pandemic, yet their developmental toxicity in aquatic organisms at environmentally relevant concentrations remains poorly understood. Here, we investigate and compare the developmental effects of two restri...

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Main Authors: Yueyue Liu, Chen Wang, Zhiyou Fu, Yingchen Bai, Guomao Zheng, Fengchang Wu
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Environmental Science and Ecotechnology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666498425000213
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author Yueyue Liu
Chen Wang
Zhiyou Fu
Yingchen Bai
Guomao Zheng
Fengchang Wu
author_facet Yueyue Liu
Chen Wang
Zhiyou Fu
Yingchen Bai
Guomao Zheng
Fengchang Wu
author_sort Yueyue Liu
collection DOAJ
description The global production and use of antimicrobial chemicals surged during and after the COVID-19 pandemic, yet their developmental toxicity in aquatic organisms at environmentally relevant concentrations remains poorly understood. Here, we investigate and compare the developmental effects of two restricted antimicrobial chemicals—triclosan (TCS) and triclocarban (TCC)—and three alternative antimicrobials—benzalkonium chloride (BAC), benzethonium chloride (BEC), and chloroxylenol (CX)—on zebrafish embryos (Danio rerio) at concentrations of 0.4, 4, and 40 μg L−1. We find that BAC induces the most severe reduction in hatching rates, followed by TCS, TCC, BEC, and CX. BAC also exhibits the strongest inhibition of heart rate, with toxicity levels comparable to those of TCS and TCC. All tested chemicals, except CX, cause significant teratogenic effects. Transcriptomic analysis reveals substantial disruptions in immune-related coagulation cascades and mitogen-activated protein kinase signaling pathways. Further validation via protein-protein interaction network analysis and real-time quantitative polymerase chain reaction confirms that altered expression of key hub genes in these pathways impacts bone and heart development, as well as immune system function, potentially driving developmental toxicity. This study provides the first systematic comparison of developmental toxicity among currently used antimicrobials at environmentally relevant concentrations, revealing that the alternative antimicrobial BAC poses greater developmental risks than the banned TCS and TCC. These findings raise concerns about the safety of BAC as a widespread substitute and highlight the necessity for more rigorous environmental risk assessments of alternative antimicrobials before their large-scale application.
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spelling doaj-art-d6cec4e1d6ff4f8481982f57d78bb4e22025-08-20T02:54:39ZengElsevierEnvironmental Science and Ecotechnology2666-49842025-03-012410054310.1016/j.ese.2025.100543Common antimicrobials disrupt early zebrafish development through immune-cardiac signalingYueyue Liu0Chen Wang1Zhiyou Fu2Yingchen Bai3Guomao Zheng4Fengchang Wu5State key laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China; College of Water Science, Beijing Normal University, Beijing, 100875, ChinaState key laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China; Corresponding author.State key laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, ChinaState key laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, ChinaSchool of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen, 518055, ChinaState key laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China; Corresponding author.The global production and use of antimicrobial chemicals surged during and after the COVID-19 pandemic, yet their developmental toxicity in aquatic organisms at environmentally relevant concentrations remains poorly understood. Here, we investigate and compare the developmental effects of two restricted antimicrobial chemicals—triclosan (TCS) and triclocarban (TCC)—and three alternative antimicrobials—benzalkonium chloride (BAC), benzethonium chloride (BEC), and chloroxylenol (CX)—on zebrafish embryos (Danio rerio) at concentrations of 0.4, 4, and 40 μg L−1. We find that BAC induces the most severe reduction in hatching rates, followed by TCS, TCC, BEC, and CX. BAC also exhibits the strongest inhibition of heart rate, with toxicity levels comparable to those of TCS and TCC. All tested chemicals, except CX, cause significant teratogenic effects. Transcriptomic analysis reveals substantial disruptions in immune-related coagulation cascades and mitogen-activated protein kinase signaling pathways. Further validation via protein-protein interaction network analysis and real-time quantitative polymerase chain reaction confirms that altered expression of key hub genes in these pathways impacts bone and heart development, as well as immune system function, potentially driving developmental toxicity. This study provides the first systematic comparison of developmental toxicity among currently used antimicrobials at environmentally relevant concentrations, revealing that the alternative antimicrobial BAC poses greater developmental risks than the banned TCS and TCC. These findings raise concerns about the safety of BAC as a widespread substitute and highlight the necessity for more rigorous environmental risk assessments of alternative antimicrobials before their large-scale application.http://www.sciencedirect.com/science/article/pii/S2666498425000213DisinfectantsHatchabilityDevelopmental toxicityTranscriptomic analysisZebrafish
spellingShingle Yueyue Liu
Chen Wang
Zhiyou Fu
Yingchen Bai
Guomao Zheng
Fengchang Wu
Common antimicrobials disrupt early zebrafish development through immune-cardiac signaling
Environmental Science and Ecotechnology
Disinfectants
Hatchability
Developmental toxicity
Transcriptomic analysis
Zebrafish
title Common antimicrobials disrupt early zebrafish development through immune-cardiac signaling
title_full Common antimicrobials disrupt early zebrafish development through immune-cardiac signaling
title_fullStr Common antimicrobials disrupt early zebrafish development through immune-cardiac signaling
title_full_unstemmed Common antimicrobials disrupt early zebrafish development through immune-cardiac signaling
title_short Common antimicrobials disrupt early zebrafish development through immune-cardiac signaling
title_sort common antimicrobials disrupt early zebrafish development through immune cardiac signaling
topic Disinfectants
Hatchability
Developmental toxicity
Transcriptomic analysis
Zebrafish
url http://www.sciencedirect.com/science/article/pii/S2666498425000213
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AT chenwang commonantimicrobialsdisruptearlyzebrafishdevelopmentthroughimmunecardiacsignaling
AT zhiyoufu commonantimicrobialsdisruptearlyzebrafishdevelopmentthroughimmunecardiacsignaling
AT yingchenbai commonantimicrobialsdisruptearlyzebrafishdevelopmentthroughimmunecardiacsignaling
AT guomaozheng commonantimicrobialsdisruptearlyzebrafishdevelopmentthroughimmunecardiacsignaling
AT fengchangwu commonantimicrobialsdisruptearlyzebrafishdevelopmentthroughimmunecardiacsignaling