Pub Date : 2026-02-01Epub Date: 2026-01-01DOI: 10.1016/j.aquatox.2025.107704
Indrajit Das , Soumen Roy , Ankur Banerjee , Poulami Sen Gupta , Subrata Karmakar , Shamee Bhattacharjee , Deba Prasad Mandal
Organophosphates are one of the major and most widely used pesticides. Globally, two of the most widely used organophosphates are chlorpyrifos (CPF) and malathion (MAL). Reports on the effect of environmentally relevant concentrations of organophosphates during embryological development are very limited.
In this study, we have exposed 2 h viable zebrafish to 100 µg/L, 200 µg/L, 400 µg/L concentrations of CPF or MAL. In addition, the embryos were also exposed to a mixture of CPF and MAL containing 200 µg/L of each of the pesticides (CPF+MAL). Morphological observations of the whole embryo, behavioural study and histopathological assessment of various organs in 120 hpf zebrafish larvae were conducted. mRNA expressions of the genes relevant to neuro and cardiac development were also analysed. Finally, intracellular ROS generation and protein expression of the oxidative stress responsive transcription factor NRF2 was assessed.
Both the pesticides have been shown to induce various types of malformations related to cardiac and neural toxicity. A significant observation of this study is the differential effect of CPF and MAL on the hatching rate of zebrafish embryos and on the locomotor activity of zebrafish larvae. Among all the experimental exposures, CPF was the most toxic, even more than the combination group which we found to be very startling.
Overall, we showed that sub-lethal concentrations of organophosphate pesticides can cause severe developmental toxicity and abnormal gene expressions without causing lethality in the embryos.
{"title":"Developmental toxicity of two organophosphate pesticides in Zebrafish embryo: Comparative and combinatorial assessment of neuro- and cardio-toxicity of sub-lethal concentrations of chlorpyrifos and malathion","authors":"Indrajit Das , Soumen Roy , Ankur Banerjee , Poulami Sen Gupta , Subrata Karmakar , Shamee Bhattacharjee , Deba Prasad Mandal","doi":"10.1016/j.aquatox.2025.107704","DOIUrl":"10.1016/j.aquatox.2025.107704","url":null,"abstract":"<div><div>Organophosphates are one of the major and most widely used pesticides. Globally, two of the most widely used organophosphates are chlorpyrifos (CPF) and malathion (MAL). Reports on the effect of environmentally relevant concentrations of organophosphates during embryological development are very limited.</div><div>In this study, we have exposed 2 h viable zebrafish to 100 µg/L, 200 µg/L, 400 µg/L concentrations of CPF or MAL. In addition, the embryos were also exposed to a mixture of CPF and MAL containing 200 µg/L of each of the pesticides (CPF+MAL). Morphological observations of the whole embryo, behavioural study and histopathological assessment of various organs in 120 hpf zebrafish larvae were conducted. mRNA expressions of the genes relevant to neuro and cardiac development were also analysed. Finally, intracellular ROS generation and protein expression of the oxidative stress responsive transcription factor NRF2 was assessed.</div><div>Both the pesticides have been shown to induce various types of malformations related to cardiac and neural toxicity. A significant observation of this study is the differential effect of CPF and MAL on the hatching rate of zebrafish embryos and on the locomotor activity of zebrafish larvae. Among all the experimental exposures, CPF was the most toxic, even more than the combination group which we found to be very startling.</div><div>Overall, we showed that sub-lethal concentrations of organophosphate pesticides can cause severe developmental toxicity and abnormal gene expressions without causing lethality in the embryos.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"291 ","pages":"Article 107704"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-15DOI: 10.1016/j.aquatox.2025.107686
Zeyan Zhang , Kejin Zhou , Yafang Chen , Kun Xie , Mo Zhao , Shimiao Zhao , Zhiqiang Xia , Wenjun Hong , Pan Ma , Xinyi Zhou
Norethindrone (NET) and levonorgestrel (LNG) are synthetic progestins frequently detected in aquatic environments, have unclear effects on lipid metabolic homeostasis during the early life stages of aquatic organisms. Although progestins commonly occur as mixtures, their combined impacts remain unclear. In this study, we investigated the individual and combined impacts of NET and LNG at environmentally relevant concentrations (2–200 ng/L) on lipid metabolism in zebrafish larvae. NET and LNG significantly disrupted early development in zebrafish. It also altered lipid profiles, as indicated by elevated triglyceride (TG) levels, reduced total cholesterol (TC), as well as alterations in key metabolic enzymes (FASN, LPL) and lipid-regulatory genes (pparγ, fasn, lpl, pparα). Co-exposure with LNG resulted in non-additive responses across multiple endpoints. Antagonistic interactions were predominant at medium and high concentrations, while occasional synergism was observed at low doses. These complex patterns were further supported by Bliss independence model analysis. Notably, combined exposure suppressed both lipid synthesis and degradation pathways more strongly than individual treatments, leading to lipid accumulation and altered energy regulation. This study advanced understanding of the ecological risks caused by progestins in aquatic environments and highlighted the necessity of mixture-based risk assessment of endocrine-disrupting compounds.
{"title":"Non-additive effects of norethisterone and levonorgestrel mixtures on lipid metabolism at environmentally relevant concentrations","authors":"Zeyan Zhang , Kejin Zhou , Yafang Chen , Kun Xie , Mo Zhao , Shimiao Zhao , Zhiqiang Xia , Wenjun Hong , Pan Ma , Xinyi Zhou","doi":"10.1016/j.aquatox.2025.107686","DOIUrl":"10.1016/j.aquatox.2025.107686","url":null,"abstract":"<div><div>Norethindrone (NET) and levonorgestrel (LNG) are synthetic progestins frequently detected in aquatic environments, have unclear effects on lipid metabolic homeostasis during the early life stages of aquatic organisms. Although progestins commonly occur as mixtures, their combined impacts remain unclear. In this study, we investigated the individual and combined impacts of NET and LNG at environmentally relevant concentrations (2–200 ng/L) on lipid metabolism in zebrafish larvae. NET and LNG significantly disrupted early development in zebrafish. It also altered lipid profiles, as indicated by elevated triglyceride (TG) levels, reduced total cholesterol (TC), as well as alterations in key metabolic enzymes (FASN, LPL) and lipid-regulatory genes (<em>pparγ, fasn, lpl, pparα</em>). Co-exposure with LNG resulted in non-additive responses across multiple endpoints. Antagonistic interactions were predominant at medium and high concentrations, while occasional synergism was observed at low doses. These complex patterns were further supported by Bliss independence model analysis. Notably, combined exposure suppressed both lipid synthesis and degradation pathways more strongly than individual treatments, leading to lipid accumulation and altered energy regulation. This study advanced understanding of the ecological risks caused by progestins in aquatic environments and highlighted the necessity of mixture-based risk assessment of endocrine-disrupting compounds.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"291 ","pages":"Article 107686"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145753415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-01-03DOI: 10.1016/j.aquatox.2026.107707
Liuqingqing Liu , Wenting Zhao , Xianxiang Luo , Xiuhui Tan , Linjia Liu , Liyan Huang , Zixi Yuan , Zhiying Li , Fengmin Li , Hao Zheng
The lethal impacts of N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine-quinone (6PPD-Q), a transformation product of tire wear antioxidant 6PPD, on salmonids pose great threats to “Ocean Health” within One Health frame. However, its sublethal effects on non-sensitive fish, especially the behaviors and the underlying mechanisms, remain poorly understood. Therefore, juvenile pearl gentian grouper (♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatus), one of the ecologically and economically important marine species, was selected to compare the effects of 6PPD-Q and 6PPD at an environmentally relevant concentration (10 µg L-1) on the personality behaviors and brain-gut axis regulation mechanism. After 30 days of exposure, 6PPD-Q significantly reduced the time spent in the thigmotaxis zone and locomotor activity by 19.40% and 14.03%, respectively, while 6PPD showed little effect, indicating that 6PPD-Q increased risk-taking propensity and decreased activity, thereby disrupting personality behavioral homeostasis in the non-sensitive fish. Mechanistically, 6PPD-Q exposure mediated the neurotoxic effects through inducing persistent neuroinflammatory responses, increasing blood-brain barrier permeability, and decreasing neuronal activity. These neurotoxic effects were associated with the downregulated DNA damage repair gene (gadd45ba) and anti-inflammatory regulator (dusp1). In parallel, 6PPD-Q impaired intestinal physicochemical barrier integrity, reduced beneficial bacteria (e.g., Muribaculaceae) and enriched pathogenic bacteria (e.g., Nautella), thereby disturbing gut microbial homeostasis and brain–gut axis regulation. From “brain–gut” axis perspective, this study elucidated the mechanisms by which 6PPD-Q at environmentally relevant concentration disrupts personality behavioral balance in non-sensitive marine fish, providing new insight for ecological risk assessment and early warning of emerging tire-derived contaminants in marine ecosystems.
{"title":"Environmentally relevant 6PPD-quinone drives personality-specific behavioral abnormalities in juvenile grouper through interplay between neuroinflammation and gut microbial dysbiosis","authors":"Liuqingqing Liu , Wenting Zhao , Xianxiang Luo , Xiuhui Tan , Linjia Liu , Liyan Huang , Zixi Yuan , Zhiying Li , Fengmin Li , Hao Zheng","doi":"10.1016/j.aquatox.2026.107707","DOIUrl":"10.1016/j.aquatox.2026.107707","url":null,"abstract":"<div><div>The lethal impacts of <em>N</em>-(1,3-dimethylbutyl)-<em>N</em>’-phenyl-<em>p</em>-phenylenediamine-quinone (6PPD-Q), a transformation product of tire wear antioxidant 6PPD, on salmonids pose great threats to “Ocean Health” within One Health frame. However, its sublethal effects on non-sensitive fish, especially the behaviors and the underlying mechanisms, remain poorly understood. Therefore, juvenile pearl gentian grouper (<em>♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatus</em>), one of the ecologically and economically important marine species, was selected to compare the effects of 6PPD-Q and 6PPD at an environmentally relevant concentration (10 µg L<sup>-1</sup>) on the personality behaviors and brain-gut axis regulation mechanism. After 30 days of exposure, 6PPD-Q significantly reduced the time spent in the thigmotaxis zone and locomotor activity by 19.40% and 14.03%, respectively, while 6PPD showed little effect, indicating that 6PPD-Q increased risk-taking propensity and decreased activity, thereby disrupting personality behavioral homeostasis in the non-sensitive fish. Mechanistically, 6PPD-Q exposure mediated the neurotoxic effects through inducing persistent neuroinflammatory responses, increasing blood-brain barrier permeability, and decreasing neuronal activity. These neurotoxic effects were associated with the downregulated DNA damage repair gene (<em>gadd45ba</em>) and anti-inflammatory regulator (<em>dusp1</em>). In parallel, 6PPD-Q impaired intestinal physicochemical barrier integrity, reduced beneficial bacteria (e.g., <em>Muribaculaceae</em>) and enriched pathogenic bacteria (e.g., <em>Nautella</em>), thereby disturbing gut microbial homeostasis and brain–gut axis regulation. From “brain–gut” axis perspective, this study elucidated the mechanisms by which 6PPD-Q at environmentally relevant concentration disrupts personality behavioral balance in non-sensitive marine fish, providing new insight for ecological risk assessment and early warning of emerging tire-derived contaminants in marine ecosystems.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"291 ","pages":"Article 107707"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-29DOI: 10.1016/j.aquatox.2025.107701
A.K.M. Munzurul Hasan , Mahesh Rachamalla , Md Helal Uddin , Sravan Kumar Putnala , Ed S. Krol , Som Niyogi , Douglas P. Chivers
Bisphenol S (BPS) is a widely used synthetic compound and is known as an endocrine-disrupting chemical (EDC). The ability of BPS to bind predominantly to estrogen receptors raises significant concern, as it can interfere with different neurological functions, leading to neurobehavioural deficits. Despite extensive research documenting various adverse effects of BPS in adult fish, its neurobehavioural effects, especially in early life stages of fish, remain poorly understood. In the present study, zebrafish embryos (4-hours post fertilization, hpf) were exposed to an environmentally relevant concentration of BPS (30 μg/L), in addition to control and DMSO (0.01%; vehicle control), until 120 hpf, followed by behavioural, biochemical, and molecular assessments. BPS exposure impaired tail coiling frequency in embryos (20 hpf), and thigmotaxis and reflexive movement behaviour (120 hpf) in zebrafish larvae. At 120 hpf, larvae showed elevated reactive oxygen species (ROS), increased apoptosis, and higher malondialdehyde (MDA) levels, indicating lipid peroxidation and oxidative damage. Biochemical analysis further demonstrated that BPS significantly increased whole body serotonin (5-HT) and acetylcholine levels at 120 hpf. Moreover, gene expression analysis at 120 hpf indicated that BPS exposure resulted in the dysregulation of genes involved in dopaminergic, serotonergic and cholinergic neurotransmitter pathways, apoptosis pathway, oxidative stress response, and neuroinflammation. These findings suggest that BPS induces oxidative stress, neuroinflammation and apoptosis, leading to the disruption of neural development and signaling pathways involved in regulating behavioural responses. Overall, our study provides new insights into the behavioural effects and underlying neurotoxic mechanisms of developmental BPS exposure in larval zebrafish.
{"title":"Developmental exposure to Bisphenol S causes neurobehavioural deficits in larval zebrafish (Danio rerio)","authors":"A.K.M. Munzurul Hasan , Mahesh Rachamalla , Md Helal Uddin , Sravan Kumar Putnala , Ed S. Krol , Som Niyogi , Douglas P. Chivers","doi":"10.1016/j.aquatox.2025.107701","DOIUrl":"10.1016/j.aquatox.2025.107701","url":null,"abstract":"<div><div>Bisphenol S (BPS) is a widely used synthetic compound and is known as an endocrine-disrupting chemical (EDC). The ability of BPS to bind predominantly to estrogen receptors raises significant concern, as it can interfere with different neurological functions, leading to neurobehavioural deficits. Despite extensive research documenting various adverse effects of BPS in adult fish, its neurobehavioural effects, especially in early life stages of fish, remain poorly understood. In the present study, zebrafish embryos (4-hours post fertilization, hpf) were exposed to an environmentally relevant concentration of BPS (30 μg/L), in addition to control and DMSO (0.01%; vehicle control), until 120 hpf, followed by behavioural, biochemical, and molecular assessments. BPS exposure impaired tail coiling frequency in embryos (20 hpf), and thigmotaxis and reflexive movement behaviour (120 hpf) in zebrafish larvae. At 120 hpf, larvae showed elevated reactive oxygen species (ROS), increased apoptosis, and higher malondialdehyde (MDA) levels, indicating lipid peroxidation and oxidative damage. Biochemical analysis further demonstrated that BPS significantly increased whole body serotonin (5-HT) and acetylcholine levels at 120 hpf. Moreover, gene expression analysis at 120 hpf indicated that BPS exposure resulted in the dysregulation of genes involved in dopaminergic, serotonergic and cholinergic neurotransmitter pathways, apoptosis pathway, oxidative stress response, and neuroinflammation. These findings suggest that BPS induces oxidative stress, neuroinflammation and apoptosis, leading to the disruption of neural development and signaling pathways involved in regulating behavioural responses. Overall, our study provides new insights into the behavioural effects and underlying neurotoxic mechanisms of developmental BPS exposure in larval zebrafish.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"291 ","pages":"Article 107701"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-28DOI: 10.1016/j.aquatox.2025.107700
Ye-bing Shi , Zu-lin Hua , Zi-wei Chen , Xiao-qing Li , Li Gu
Understanding how submerge-emerge alternation influences the fate of per- and polyfluoroalkyl substances (PFASs) in wetland plants is crucial for ecological risk assessment and optimizing phytoremediation under fluctuating hydrological regimes. This study simulated the alternation scenario (ASE), comparing it with continued submergence (CS) and continued emergence (CE) to investigate alternation’s regulatory effect on PFAS fate, considering plant growth, physiology, and metabolic profiles. Results showed that ASE inhibited PFAS accumulation in roots, while enhancing their translocation and accumulation in leaves. Specifically, the average PFAS amount in ASE roots (14.96 μg) was lower than that in CS (19.14 μg) and CE (17.28 μg), whereas in ASE leaves, they were 1.25 and 1.23 times higher than in CS and CE, respectively. Among individual PFASs, PFBA, 6:2 FTS, and PFOS exhibited pronounced bioaccumulation under ASE treatment, whereas PFOA preferentially accumulated under CS and CE treatments. Physiological analysis indicated that ASE stimulated plant growth (higher biomass and growth rate) and root development (e.g., longer root length and increased number of root tips), accompanied by elevated levels of H₂O₂, malondialdehyde, and chlorophyll, suggesting enhanced photosynthesis and transpiration. In the rhizosphere, ASE markedly increased the secretion of flavonoids and organic acids, while reducing the exudation of lipids and amino acids. The KEGG analysis further revealed upregulation of sphingolipid metabolism and fatty acid degradation pathways under ASE treatment, which were implicated in membrane integrity, protein functionality, and ion channel regulation. Collectively, these findings suggest that ASE mitigated PFAS accumulation in roots by enhancing membrane selectivity and activating rhizosphere defense mechanisms, while elevated oxidative stress and transpiration likely promoted PFAS translocation to leaves. This study provides novel insights into PFAS behavior in fluctuating hydrological environments and informs phytoremediation strategies.
{"title":"Submerge-emerge alternation regulates per(poly)fluoroalkyl substance fate in emergent plants: Insights from growth, physiology, and metabolomics","authors":"Ye-bing Shi , Zu-lin Hua , Zi-wei Chen , Xiao-qing Li , Li Gu","doi":"10.1016/j.aquatox.2025.107700","DOIUrl":"10.1016/j.aquatox.2025.107700","url":null,"abstract":"<div><div>Understanding how submerge-emerge alternation influences the fate of per- and polyfluoroalkyl substances (PFASs) in wetland plants is crucial for ecological risk assessment and optimizing phytoremediation under fluctuating hydrological regimes. This study simulated the alternation scenario (ASE), comparing it with continued submergence (CS) and continued emergence (CE) to investigate alternation’s regulatory effect on PFAS fate, considering plant growth, physiology, and metabolic profiles. Results showed that ASE inhibited PFAS accumulation in roots, while enhancing their translocation and accumulation in leaves. Specifically, the average PFAS amount in ASE roots (14.96 μg) was lower than that in CS (19.14 μg) and CE (17.28 μg), whereas in ASE leaves, they were 1.25 and 1.23 times higher than in CS and CE, respectively. Among individual PFASs, PFBA, 6:2 FTS, and PFOS exhibited pronounced bioaccumulation under ASE treatment, whereas PFOA preferentially accumulated under CS and CE treatments. Physiological analysis indicated that ASE stimulated plant growth (higher biomass and growth rate) and root development (e.g., longer root length and increased number of root tips), accompanied by elevated levels of H₂O₂, malondialdehyde, and chlorophyll, suggesting enhanced photosynthesis and transpiration. In the rhizosphere, ASE markedly increased the secretion of flavonoids and organic acids, while reducing the exudation of lipids and amino acids. The KEGG analysis further revealed upregulation of sphingolipid metabolism and fatty acid degradation pathways under ASE treatment, which were implicated in membrane integrity, protein functionality, and ion channel regulation. Collectively, these findings suggest that ASE mitigated PFAS accumulation in roots by enhancing membrane selectivity and activating rhizosphere defense mechanisms, while elevated oxidative stress and transpiration likely promoted PFAS translocation to leaves. This study provides novel insights into PFAS behavior in fluctuating hydrological environments and informs phytoremediation strategies.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"291 ","pages":"Article 107700"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-01-05DOI: 10.1016/j.aquatox.2026.107709
Jovica Lončar , Roko Žaja , Ivan Mihaljević , Jelena Dragojević Višević , Lana Vujica , Marin Kutnjak , Cecile Otten , Tvrtko Smital
As a member of the ABC transporter superfamily, ABCG2 is a half transporter that mediates the translocation of various xenobiotic substrates across cell membranes, playing an essential role in cellular detoxification. With the aim of developing a reliable in vivo model to study the role of ABCG2 and its interaction with drugs and environmental contaminants, in this study we used the CRISPR/Cas9 gene-editing technology to develop a zebrafish (Danio rerio) Abcg2a mutant line. The generated Abcg2a mutants developed normally to adulthood with no visible phenotype changes, abcg2a gene expression was reduced by more than 90% in the mutant larvae up to 5 days-post-fertilization, and overexpression of transcripts of functionally related ABC genes was detected in three out of eight monitored genes. The accumulation pattern of the specific Abcg2 fluorescent substrate pheophorbide A differed between mutants and wildtypes with a dominant signal in the gallbladder and intestine, respectively. Upon exposure to the model toxicants MLN7243 and mitoxantrone, the mutant larvae showed increased mortality compared to the wildtypes. The addition of the specific inhibitor Ko143 increased the mortality rate of the wildtype larvae to that of the mutants, indicating that the protective effect of Abcg2a had been abolished. The developed Abcg2a mutant line could be used as a reliable in vivo model in both pharmacology and ecotoxicology to further elucidate the function of Abcg2a in different tissues and cell compartments and to better understand the interaction of Abcg2a with different physiological or xenobiotic compounds.
{"title":"Zebrafish Abcg2a mutant line as an in vivo model for evaluation of the interaction of Abcg2a with drugs and contaminants","authors":"Jovica Lončar , Roko Žaja , Ivan Mihaljević , Jelena Dragojević Višević , Lana Vujica , Marin Kutnjak , Cecile Otten , Tvrtko Smital","doi":"10.1016/j.aquatox.2026.107709","DOIUrl":"10.1016/j.aquatox.2026.107709","url":null,"abstract":"<div><div>As a member of the ABC transporter superfamily, ABCG2 is a half transporter that mediates the translocation of various xenobiotic substrates across cell membranes, playing an essential role in cellular detoxification. With the aim of developing a reliable <em>in vivo</em> model to study the role of ABCG2 and its interaction with drugs and environmental contaminants, in this study we used the CRISPR/Cas9 gene-editing technology to develop a zebrafish (<em>Danio rerio</em>) Abcg2a mutant line. The generated Abcg2a mutants developed normally to adulthood with no visible phenotype changes, <em>abcg2a</em> gene expression was reduced by more than 90% in the mutant larvae up to 5 days-post-fertilization, and overexpression of transcripts of functionally related ABC genes was detected in three out of eight monitored genes. The accumulation pattern of the specific Abcg2 fluorescent substrate pheophorbide A differed between mutants and wildtypes with a dominant signal in the gallbladder and intestine, respectively. Upon exposure to the model toxicants MLN7243 and mitoxantrone, the mutant larvae showed increased mortality compared to the wildtypes. The addition of the specific inhibitor Ko143 increased the mortality rate of the wildtype larvae to that of the mutants, indicating that the protective effect of Abcg2a had been abolished. The developed Abcg2a mutant line could be used as a reliable <em>in vivo</em> model in both pharmacology and ecotoxicology to further elucidate the function of Abcg2a in different tissues and cell compartments and to better understand the interaction of Abcg2a with different physiological or xenobiotic compounds.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"291 ","pages":"Article 107709"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-04DOI: 10.1016/j.aquatox.2025.107637
Sen Feng , Lingyun Zhu , Meng Li , Pengrui Xu , Chuhan Xu , Hairong Lian , Fan Gao , Xinfeng Cheng , Xianling Xiang
Temperature-induced amplification of drug toxicity brings about mounting ecological risks, but the effects of neuroactive substances like chlorpromazine (CPZ) on non-target aquatic invertebrates under sudden temperature shifts remain unclear. We investigated the temperature-dependent neurotoxicity of CPZ in the freshwater rotifer Brachionus calyciflorus, focusing on dopaminergic signaling. We first identified and functionally validated the dopamine receptor gene BcDopR1 in B. calyciflorus, a receptor featuring a 1371-bp open reading frame (ORF) that encodes a 456-amino acid polypeptide with seven transmembrane domains. Heterologous expression in HEK293T cells showed dopamine significantly elevated intracellular cAMP in BcDopR1-transfected cells, while CPZ dose-dependently inhibited this DA-induced cAMP response, confirming BcDopR1 as a functional D1-like dopamine receptor and CPZ as its potent antagonist. Rotifers were exposed to CPZ (0–250 μg/L) under three ecologically relevant temperatures (18, 25 and 32 °C). The peak BcDopR1 expression was observed in the control group at 25 °C, and CPZ exposure inhibited its expression in a concentration- and temperature-dependent manner. As temperature increased from 18 to 32 °C, rotifers exhibited significant reductions (p < 0.05) in several morphological traits, including lorica length, posterior lateral spine length, body size, and egg size. At the population level, the maximum population density first increased and then decreased, whereas the population growth rate increased significantly (p < 0.05). Within 0–250 μg/L CPZ, rotifers at 18 and 25 °C (except 32 °C) showed a gradual increase in lorica length and body size, whereas their egg size and maximum population density first increased then decreased. These findings highlight the susceptibility of aquatic invertebrates to neuroactive contaminants and the compounding role of thermal stress in amplifying pharmaceutical ecotoxicity. BcDopR1 emerges as a promising molecular biomarker for assessing neuroactive pharmaceutical ecological risks under climate change, and advances understanding of zooplankton adaptation to multiple environmental stressors.
{"title":"Temperature-dependent dopaminergic disruption by chlorpromazine in the rotifer Brachionus calyciflorus: Evidence from receptor gene expression and population response","authors":"Sen Feng , Lingyun Zhu , Meng Li , Pengrui Xu , Chuhan Xu , Hairong Lian , Fan Gao , Xinfeng Cheng , Xianling Xiang","doi":"10.1016/j.aquatox.2025.107637","DOIUrl":"10.1016/j.aquatox.2025.107637","url":null,"abstract":"<div><div>Temperature-induced amplification of drug toxicity brings about mounting ecological risks, but the effects of neuroactive substances like chlorpromazine (CPZ) on non-target aquatic invertebrates under sudden temperature shifts remain unclear. We investigated the temperature-dependent neurotoxicity of CPZ in the freshwater rotifer <em>Brachionus calyciflorus</em>, focusing on dopaminergic signaling. We first identified and functionally validated the dopamine receptor gene <em>Bc</em>DopR1 in <em>B. calyciflorus</em>, a receptor featuring a 1371-bp open reading frame (ORF) that encodes a 456-amino acid polypeptide with seven transmembrane domains. Heterologous expression in HEK293T cells showed dopamine significantly elevated intracellular cAMP in <em>Bc</em>DopR1-transfected cells, while CPZ dose-dependently inhibited this DA-induced cAMP response, confirming <em>Bc</em>DopR1 as a functional D1-like dopamine receptor and CPZ as its potent antagonist. Rotifers were exposed to CPZ (0–250 μg/L) under three ecologically relevant temperatures (18, 25 and 32 °C). The peak <em>Bc</em>DopR1 expression was observed in the control group at 25 °C, and CPZ exposure inhibited its expression in a concentration- and temperature-dependent manner. As temperature increased from 18 to 32 °C, rotifers exhibited significant reductions (<em>p</em> < 0.05) in several morphological traits, including lorica length, posterior lateral spine length, body size, and egg size. At the population level, the maximum population density first increased and then decreased, whereas the population growth rate increased significantly (<em>p</em> < 0.05). Within 0–250 μg/L CPZ, rotifers at 18 and 25 °C (except 32 °C) showed a gradual increase in lorica length and body size, whereas their egg size and maximum population density first increased then decreased. These findings highlight the susceptibility of aquatic invertebrates to neuroactive contaminants and the compounding role of thermal stress in amplifying pharmaceutical ecotoxicity. <em>Bc</em>DopR1 emerges as a promising molecular biomarker for assessing neuroactive pharmaceutical ecological risks under climate change, and advances understanding of zooplankton adaptation to multiple environmental stressors.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"290 ","pages":"Article 107637"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145435005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-10-28DOI: 10.1016/j.aquatox.2025.107625
Nicholas T. Hayman , Zacharias Pandelides , Josiah Discar , Marienne A. Colvin , Gunther Rosen , Jennifer Arblaster , Jason Conder
Effects data for per- and poly-fluoroalkyl substances (PFAS) for marine aquatic life are lacking, limiting the assessment of site-specific ecological risks in marine ecosystems and development of marine water quality criteria. In this study, the toxicity of 10 PFAS (PFBA, PFHxA, PFOA, PFDA, PFBS, PFHxS, PFOS, PFDS, 6:2 FTS, and 8:2 FTS) were evaluated with three standard marine toxicity testing species: Mediterranean mussel (Mytilus galloprovincialis); purple sea urchin (Strongylocentrotus purpuratus); and giant kelp (Macrocystis pyrifera). Many tests failed to elicit responses exceeding 50 % adverse effect levels, despite approaching solubility limits. EC50 values were able to be derived in only 43 % of the toxicity tests, and were generally above 1 mg/L, except for PFOS and PFDA based on the most sensitive of the three species (S. purpuratus and M. galloprovincialis), with EC50s in the approximate 0.1 to 1 mg/L range. M. pyrifera, the macroalgae, was less sensitive than either invertebrate species. EC50 values for all three species decreased with perfluoroalkyl carbon chain length, as increasing toxicity was observed in longer chained compounds, and a statistically significant relationship between chain length and EC50 was detected for M. galloprovincialis. A number of other toxicological metrics (NOECs, LOECs, EC10s, and EC20s) were also generated. NOECs for sublethal endpoints were in the 0.01 to 100 mg/L range and were orders of magnitude higher than environmentally relevant concentrations. Based on the results in this study, adverse effects on these species and endpoints would not be expected to occur in the PFAS-impacted marine environment.
{"title":"Marine ecotoxicity evaluation of 10 per- and poly-fluoroalkyl acids using three USEPA short-term chronic bioassays","authors":"Nicholas T. Hayman , Zacharias Pandelides , Josiah Discar , Marienne A. Colvin , Gunther Rosen , Jennifer Arblaster , Jason Conder","doi":"10.1016/j.aquatox.2025.107625","DOIUrl":"10.1016/j.aquatox.2025.107625","url":null,"abstract":"<div><div>Effects data for per- and poly-fluoroalkyl substances (PFAS) for marine aquatic life are lacking, limiting the assessment of site-specific ecological risks in marine ecosystems and development of marine water quality criteria. In this study, the toxicity of 10 PFAS (PFBA, PFHxA, PFOA, PFDA, PFBS, PFHxS, PFOS, PFDS, 6:2 FTS, and 8:2 FTS) were evaluated with three standard marine toxicity testing species: Mediterranean mussel (<em>Mytilus galloprovincialis</em>); purple sea urchin (<em>Strongylocentrotus purpuratus</em>); and giant kelp (<em>Macrocystis pyrifera</em>). Many tests failed to elicit responses exceeding 50 % adverse effect levels, despite approaching solubility limits. EC<sub>50</sub> values were able to be derived in only 43 % of the toxicity tests, and were generally above 1 mg/L, except for PFOS and PFDA based on the most sensitive of the three species (<em>S. purpuratus</em> and <em>M. galloprovincialis</em>), with EC<sub>50</sub>s in the approximate 0.1 to 1 mg/L range. <em>M. pyrifera,</em> the macroalgae, was less sensitive than either invertebrate species. EC<sub>50</sub> values for all three species decreased with perfluoroalkyl carbon chain length, as increasing toxicity was observed in longer chained compounds, and a statistically significant relationship between chain length and EC<sub>50</sub> was detected for <em>M. galloprovincialis</em>. A number of other toxicological metrics (NOECs, LOECs, EC<sub>10</sub>s, and EC<sub>20</sub>s) were also generated. NOECs for sublethal endpoints were in the 0.01 to 100 mg/L range and were orders of magnitude higher than environmentally relevant concentrations. Based on the results in this study, adverse effects on these species and endpoints would not be expected to occur in the PFAS-impacted marine environment.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"290 ","pages":"Article 107625"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145383278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-10-28DOI: 10.1016/j.aquatox.2025.107624
Emese Balogh , Szabolcs Hócza , Nikolett Ujhegyi , Andrea Kásler , Dóra Holly , Dávid Herczeg , János Ujszegi , Zoltán Gál , Orsolya I. Hoffmann , Veronika Bókony , Zsanett Mikó
Environmental pollutants have the potential to alter sex ratios in wildlife through sex-biased mortality. Furthermore, endocrine disruptors may cause sex reversal during early ontogeny in ectothermic vertebrates, resulting in a phenotypic sex that is not concordant with the genotypic sex encoded by the sex chromosomes. Despite the wide-ranging implications of these sex-ratio biasing effects, they are rarely studied in ecotoxicology, especially in a way that allows for disentangling the two mechanisms. We investigated these effects of two synthetic pyrethroids, deltamethrin and etofenprox, that are commonly used insecticides and have been linked to adverse effects on fish and amphibian biodiversity. We assessed the effects of environmentally relevant concentrations of these two pyrethroids on phenotypic sex ratio, sex-dependent mortality, and sex reversal in agile frogs (Rana dalmatina). Tadpoles from field-collected eggs were reared in mesocosms until metamorphosis by adding 0.03 or 0.3 μg/L of deltamethrin or etofenprox three times to the water. We observed no effect in three of the four treatment groups. However, in the lower-concentration etofenprox treatment, phenotypic sex ratio was male-biased two months post-metamorphosis, and genotypic sexing revealed that this was due to female-biased mortality during metamorphosis and not to sex reversal. Although the estimation certainty of these effects was somewhat limited, they highlight that not all sex-ratio distorting effects are caused by sex reversal. Therefore, ecotoxicological studies aiming to understand the endocrine distruptor effects of environmental contaminants should strive to separate the effects on sex determination and sex-dependent mortality.
{"title":"Effects of pyrethroid insecticides on sex ratios in agile frogs (Rana dalmatina)","authors":"Emese Balogh , Szabolcs Hócza , Nikolett Ujhegyi , Andrea Kásler , Dóra Holly , Dávid Herczeg , János Ujszegi , Zoltán Gál , Orsolya I. Hoffmann , Veronika Bókony , Zsanett Mikó","doi":"10.1016/j.aquatox.2025.107624","DOIUrl":"10.1016/j.aquatox.2025.107624","url":null,"abstract":"<div><div>Environmental pollutants have the potential to alter sex ratios in wildlife through sex-biased mortality. Furthermore, endocrine disruptors may cause sex reversal during early ontogeny in ectothermic vertebrates, resulting in a phenotypic sex that is not concordant with the genotypic sex encoded by the sex chromosomes. Despite the wide-ranging implications of these sex-ratio biasing effects, they are rarely studied in ecotoxicology, especially in a way that allows for disentangling the two mechanisms. We investigated these effects of two synthetic pyrethroids, deltamethrin and etofenprox, that are commonly used insecticides and have been linked to adverse effects on fish and amphibian biodiversity. We assessed the effects of environmentally relevant concentrations of these two pyrethroids on phenotypic sex ratio, sex-dependent mortality, and sex reversal in agile frogs (<em>Rana dalmatina</em>). Tadpoles from field-collected eggs were reared in mesocosms until metamorphosis by adding 0.03 or 0.3 μg/L of deltamethrin or etofenprox three times to the water. We observed no effect in three of the four treatment groups. However, in the lower-concentration etofenprox treatment, phenotypic sex ratio was male-biased two months post-metamorphosis, and genotypic sexing revealed that this was due to female-biased mortality during metamorphosis and not to sex reversal. Although the estimation certainty of these effects was somewhat limited, they highlight that not all sex-ratio distorting effects are caused by sex reversal. Therefore, ecotoxicological studies aiming to understand the endocrine distruptor effects of environmental contaminants should strive to separate the effects on sex determination and sex-dependent mortality.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"290 ","pages":"Article 107624"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145383282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-15DOI: 10.1016/j.aquatox.2025.107651
Huan Yang , Dong-Sheng Zhao , Yu-Ting Chen , Nan Li , Xiufeng Yan , Hui-Xi Zou
Florfenicol (FFC) is a broad-spectrum antibiotic that is used in aquaculture to effectively control bacterial infections in animals by inhibiting bacterial protein synthesis. However, its widespread application in aquaculture has increased environmental residues, posing potential toxic effects on non-target organisms in aquatic ecosystems. In this study, we evaluated the toxic effects of FFC on the marine diatom Phaeodactylum tricornutum and the associated underlying mechanisms. The results showed that FFC significantly inhibited cell proliferation in a dose-dependent manner, reduced photosynthetic pigment content, and impaired photosynthetic performance, as evidenced by decreased chlorophyll fluorescence parameters. At the same time, FFC exposure induced oxidative stress, characterized by suppressed antioxidant enzyme activities, decreased soluble sugar and protein contents, and elevated malondialdehyde (MDA) levels. Transcriptomic analysis revealed that short-term exposure (24 h) primarily disrupted nitrogen metabolism-related gene expression, while prolonged exposure (96 h) significantly suppressed photosynthetic pathways. qPCR analysis further validated the downregulation of key genes involved in porphyrin metabolism and ribosome biogenesis in eukaryotes. Collectively, FFC inhibited P. tricornutum growth by disrupting the photosynthetic electron transport chain, inducing oxidative damage, and interfering with critical biological processes, including nitrogen metabolism and protein synthesis.
{"title":"Florfenicol impairs photosynthesis and triggers oxidative stress in Phaeodactylum tricornutum: Physiological and transcriptomic evidence","authors":"Huan Yang , Dong-Sheng Zhao , Yu-Ting Chen , Nan Li , Xiufeng Yan , Hui-Xi Zou","doi":"10.1016/j.aquatox.2025.107651","DOIUrl":"10.1016/j.aquatox.2025.107651","url":null,"abstract":"<div><div>Florfenicol (FFC) is a broad-spectrum antibiotic that is used in aquaculture to effectively control bacterial infections in animals by inhibiting bacterial protein synthesis. However, its widespread application in aquaculture has increased environmental residues, posing potential toxic effects on non-target organisms in aquatic ecosystems. In this study, we evaluated the toxic effects of FFC on the marine diatom <em>Phaeodactylum tricornutum</em> and the associated underlying mechanisms. The results showed that FFC significantly inhibited cell proliferation in a dose-dependent manner, reduced photosynthetic pigment content, and impaired photosynthetic performance, as evidenced by decreased chlorophyll fluorescence parameters. At the same time, FFC exposure induced oxidative stress, characterized by suppressed antioxidant enzyme activities, decreased soluble sugar and protein contents, and elevated malondialdehyde (MDA) levels. Transcriptomic analysis revealed that short-term exposure (24 h) primarily disrupted nitrogen metabolism-related gene expression, while prolonged exposure (96 h) significantly suppressed photosynthetic pathways. qPCR analysis further validated the downregulation of key genes involved in porphyrin metabolism and ribosome biogenesis in eukaryotes. Collectively, FFC inhibited <em>P. tricornutum</em> growth by disrupting the photosynthetic electron transport chain, inducing oxidative damage, and interfering with critical biological processes, including nitrogen metabolism and protein synthesis.</div></div>","PeriodicalId":248,"journal":{"name":"Aquatic Toxicology","volume":"290 ","pages":"Article 107651"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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