Zebrafish have been used in many fluoride studies involving both inorganic and organic fluoride compounds, including studies on thyroid hormone metabolism and action.
They have also been used as a model to study "dental fluorosis" (Bartlett et al., 2005; Zhang et al., 2016) as well as skeletal fluorosis (Fan & Gao, 2019; Gong et al., 2022; Wang et al., 2025).
Most of the research on fluoride effects on zebrafish has been conducted in China.
Inorganic Fluoride
Abdul Wazith MJ, Taju G, Abdul Majeed S, Rajkumar V, Mithra S, Kanimozhi K, Zaheer Ahmed S, Sahul Hameed AS - "Amelioration of Fluoride Induced Toxicity by trans-Chalcone in Zebrafish Larvae and Its Gill Cell Line: An In Vivo and In Vitro Approach" Environ Toxicol (2025) doi: 10.1002/tox.70014.
https://onlinelibrary.wiley.com/doi/10.1002/tox.70014
Babu S, Velmani NS, Manoharan S, Perumal E - "Esculin, a Coumarin Glucoside Prevents Fluoride-Induced Oxidative Stress and Cardiotoxicity in Zebrafish Larvae" Environmental Toxicology 40(4):636-649 (2025)
https://doi.org/10.1002/tox.24445
Bartlett JD, Dwyer SE, Beniash E, Skobe Z, Payne-Ferreira TL - "Fluorosis: a new model and new insights" J Dent Res 84(9):832-836 (2005)
https://doi.org/10.1177/154405910508400910
Cao J, Feng C, Xie L, Li L, Chen J, Yun S, Guo W, Wang T, Wu Y, Meng R, Wang G, He X, Luo Y - "Sesamin attenuates histological alterations, oxidative stress and expressions of immune-related genes in liver of zebrafish (Danio rerio) exposed to fluoride" Fish Shellfish Immunol 106:715-723 (2020) doi: 10.1016/j.fsi.2020.08.039
https://www.sciencedirect.com/science/a ... 4820306033
Castro TFD, Paiva IM, Carvalho AFS, Assis IL, Palmieri MJ, Andrade-Vieira LF, Marcussi S, Solis-Murgas LD - "Genotoxicity of spent pot liner as determined with the zebrafish (Danio rerio) experimental model" Environ Sci Pollut Res Int 25(12):11527-11535 (2018) doi: 10.1007/s11356-018-1404-9
https://link.springer.com/article/10.10 ... 018-1404-9
Chen J, Luo Y, Cao J, Xie L - "Fluoride exposure changed the expression of microRNAs in gills of male zebrafish (Danio rerio)" Aquat Toxicol 233:105789 (2021) doi: 10.1016/j.aquatox.2021.105789
https://www.sciencedirect.com/science/a ... 5X21000485
Chen J, Xue W, Cao J, Song J, Jia R, Li M - “Fluoride caused thyroid endocrine disruption in male zebrafish (Danio rerio)” Aquatic Toxicology 171:48-58 (2016)
https://doi.org/10.1016/j.aquatox.2015.12.010
"The transcriptional levels of ...iodothyronine I (DIO1), and thyroid hormone receptor alpha (TRα) were also elevated in all fluoride-exposed male fish after 90 days of exposure...The results indicated that the growth of the male zebrafish used in the experiments was significantly inhibited, the thyroid microtrastructure was changed, and the levels of T3 and T4 were disturbed in fluoride-exposed male fish."
Chen J, Xu M, Li L, Lu Y, Luo Y, Cao J - "Chronic fluoride induces neurotoxicity in zebrafish through the gut-brain axis" Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 292:110157 (2025)
https://doi.org/10.1016/j.cbpc.2025.110157
"These indicate that fluoride can result in neurotoxicity and behavioral changes by disrupting intestinal permeability and causing intestinal damage caused by imbalance of gut microbiota nucleotide metabolism, and the abnormal expression of dopamine related genes in the gut in zebrafish. Male zebrafish are more sensitive than female zebrafish."
Chen J, Wang T, Cao J, Luo Y, Shi L, Gao R - "A study on the toxic effects of fluoride on zebrafish embryo/larval development" Journal of Environmental Sciences 43(11):422-430 (2023)
Cheng J, Liu Y, Li Y, Yang B, Yang X, Chen X, Zhou Y, Li B, Guo L, Wang F, Tang D - "Asparagus Saponin Officinalisnin-II Alleviates Fluoride-Induced Neurotoxicity Via Activation of the SIRT1/BDNF Signaling Pathway" Biol Trace Elem Res Online ahead of print (2026)
https://doi.org/10.1007/s12011-026-05116-3
Di Paola D, Capparucci F, Lanteri G, Crupi R, Marino Y, Franco GA, Cuzzocrea S, Spanò N, Gugliandolo E, Peritore AF - "Environmental Toxicity Assessment of Sodium Fluoride and Platinum-Derived Drugs Co-Exposure on Aquatic Organisms" Toxics 10(5):272 (2022) doi: 10.3390/toxics10050272.
https://www.mdpi.com/2305-6304/10/5/272
Dondossola ER, Pacheco SD, Visentin SC, Mendes NV, Baldin SL, Bernardo HT, Scussel R, Rico EP - "Prolonged fluoride exposure alters neurotransmission and oxidative stress in the zebrafish brain" Neurotoxicology 89:92-98 (2022)
https://pubmed.ncbi.nlm.nih.gov/35065950/
Fan Y, Gao Y - "A New Animal Model for Skeletal Fluorosis: Zebrafish" Chinese Journal of Endemiology 38(2):169-172 (2019) PFPC Library
Gong Y, Shu L, Chen F, Zheng D, Guan Z, Lou D - "Effects of fluoride on zebrafish skeletal development and its correlation with the OPG/RANKL pathway" Chinese Journal of Endemiology 41(2):93-99 (2022)
"Fluoride exposure affected zebrafish skeletal development, and the effect was associated with changes in the OPG/RANKL pathway."
Guo W, Wang T, Xue W, Wang G, He X, Wu P, Chen J, Cao J - "Interference effects of fluoride on thyroid endocrine function in zebrafish" Acta Scientiae Circumstantiae 39(4):1340-1347 (2019) PFPC Library
https://doi.org/10.13671/j.hjkxxb.2018.0464
viewtopic.php?p=8306#p8306
- also cited as: Guo W, Wang T, Xue W, Wang G, He X, Wu P, Chen J, Cao J - "Interfering effect of fluorine on thyroid endocrine function in zebrafish" Journal of Environmental Science, 39(4):1340-1347 (2019)
Guo L, Yang B, Chen F, Yuan X, Cheng J, Chen X, Zhou Y, Yang X, Li Y, Liu Y, Tang D, Wang F - "Disruption of the SIRT1/PI3K/AKT Signaling Axis Mediates Fluoride-Induced Cardiotoxicity: Evidence from in Vitro and Zebrafish Models" Biol Trace Elem Res 204(4):2411-2426 (2026)
https://doi.org/10.1007/s12011-025-04828-2
Jin T, Yang X, Zhu Y, Yan C, Yan R, Yang Q, Huang H, An Y - "Analysis of Acute and Short-Term Fluoride Toxicity in Zebrafish Embryo and Sac-Fry Stages Based on Bayesian Model Averaging" Toxics 12(12):902 (2024)
https://doi.org/10.3390/toxics12120902
Karaman M, Toraman E, Sulukan E, Baran A, Bolat İ, Yıldırım S, Kankaynar M, Ghosigharehagaji A, Budak H, Ceyhun SB - "Fluoride exposure causes behavioral, molecular and physiological changes in adult zebrafish (Danio rerio) and their offspring" Environ Toxicol Pharmacol 97:104044 (2023) doi: 10.1016/j.etap.2022.104044
https://www.sciencedirect.com/science/a ... 892200237X
Lan A, Gong Y, Li X, Wang Y, Zheng D, Tang H, Wang S, Tang W, Huang C, Guan Z, Lou D - "The correlation between fluoride-induced bone damage and reduced DLAV formation in Zebrafish Larvae" Ecotoxicol Environ Saf 288:117366 (2024) doi: 10.1016/j.ecoenv.2024.117366
https://www.sciencedirect.com/science/a ... 1324014428
Li Junjun, Zhao Qiaoyu, Li Yue, Bao Ying, Li Bingyang, Yan Huazhu, Huo Si Meng, Fan Yumei, Yang Yanmei, Gao Yanhui - "Effects of embryonic fluoride exposure on skeletal development in zebrafish" Chinese Journal of Endemic Diseases 37(1):24-29 (2018). DOI: 10.3760/cma.j.issn.2095-4255.2018.01.006
"Low-dose fluoride exposure made zebrafish embryos bone sclerotic, and high-dose fluoride exposure made zebrafish embryos osteoporotic."
Li M, Cao J, Chen J, Song J, Zhou B, Feng C, Wang J - "Waterborne fluoride exposure changed the structure and the expressions of steroidogenic-related genes in gonads of adult zebrafish (Danio rerio)" Chemosphere 145:365-75 (2016) doi: 10.1016/j.chemosphere.2015.11.041
https://pubmed.ncbi.nlm.nih.gov/26692514/
Li M, Cao J, Zhao Y, Wu P, Li X, Khodaei F, Han Y, Wang J - "Fluoride impairs ovary development by affecting oogenesis and inducing oxidative stress and apoptosis in female zebrafish (Danio rerio)" Chemosphere 256:127105 (2020) doi: 10.1016/j.chemosphere.2020.127105
https://pubmed.ncbi.nlm.nih.gov/32450357/
Liu H, Lu H, Wang R, Zhang X, Guo T, Dong Y, Ma Y, Ma C, Xing M - "Integrating network toxicology, transcriptomics and experimental validation to elucidate the potential mechanisms of fluoride-induced neurotoxicity in zebrafish" Comp Biochem Physiol C Toxicol Pharmacol 306:110549 (2026). doi: 10.1016/j.cbpc.2026.110549
https://www.sciencedirect.com/science/a ... 5626001079
"The underlying mechanism involves fluoride activation of the TLR4/NF-κB pathway, which upregulates NLRP3 inflammasome expression. This will cause neurons to undergo pyroptosis and trigger severe neuroinflammation." NOTE: NLRP3 is regulated by Gq/11
Lu Y, Zhang X, Chen J, Cao J, Feng C, Yun S, Cheng Y, Cheng F - "Sex-specific effects of fluoride and lead on thyroid endocrine function in zebrafish (Danio rerio)" Chem Biol Interact 110151 (2022). doi: 10.1016/j.cbi.2022.110151
https://www.sciencedirect.com/science/a ... 9722003568
Lu H, Wang R, Zhang X, Dong Y, Liu H, Zhang Y, Ma C, Xing M - "Assessing the health risks of environmentally relevant concentrations of fluoride and phenanthrene: Neurobehavioral toxicity induced in zebrafish through disruption of the microbiome-gut-brain axis and suppression of Wnt/β-catenin signalling" Environmental Chemistry and Ecotoxicology 8:352-367 (2026)
https://doi.org/10.1016/j.enceco.2025.11.035
"Collectively, these findings indicate that fluoride and phenanthrene induce anxiety behavior and neurotoxicity, associated with perturbations in 5-HT metabolism, gut microbiota composition, oxidative stress, apoptosis, and neuroinflammation."
Mondal P, Shaw P, Bandyopadhyay A, Dey Bhowmik A, Chakraborty A, Sudarshan M, Chattopadhyay A - "Mixture effect of arsenic and fluoride at environmentally relevant concentrations in zebrafish (Danio rerio) liver: Expression pattern of Nrf2 and related xenobiotic metabolizing enzymes" Aquat Toxicol 213:105219 (2019) doi: 10.1016/j.aquatox.2019.06.002
https://pubmed.ncbi.nlm.nih.gov/31195325/
Mukhopadhyay D, Priya P, Chattopadhyay A - "Sodium fluoride affects zebrafish behaviour and alters mRNA expressions of biomarker genes in the brain: Role of Nrf2/Keap1" Environ Toxicol Pharmacol 40(2):352-9 (2015) doi: 10.1016/j.etap.2015.07.003
https://pubmed.ncbi.nlm.nih.gov/26245810/
Mukhopadhyay D, Srivastava R, Chattopadhyay A - "Sodium fluoride generates ROS and alters transcription of genes for xenobiotic metabolizing enzymes in adult zebrafish (Danio rerio) liver: expression pattern of Nrf2/Keap1 (INrf2)" Toxicol Mech Methods 25(5):364-73 (2015) doi: 10.3109/15376516.2015.1025348
https://www.tandfonline.com/doi/abs/10. ... 15.1025348
Mukhopadhyay D, Chattopadhyay A - "Induction of oxidative stress and related transcriptional effects of sodium fluoride in female zebrafish liver" Bull Environ Contam Toxicol 93(1):64-70 (2014) doi: 10.1007/s00128-014-1271-0
https://pubmed.ncbi.nlm.nih.gov/24705702/
Mukherjee S, Sarkar O, Islam S, Chattopadhyay A - "Oxidative stress in zebrafish gut induced by individual and combined exposure to amoxicillin, arsenic and fluoride: engagement of Nrf2-Keap1-ARE pathway" Journal of Applied Toxicology 45(11):2278-2288 (2025) Analytical Science Journals
https://doi.org/10.1002/jat.4842
Mukherjee S, Bhattacharya R, Sarkar O, Islam S, Biswas SR, Chattopadhyay A - "Gut microbiota perturbation and subsequent oxidative stress in gut and kidney tissues of zebrafish after individual and combined exposure to inorganic arsenic and fluoride" Sci Total Environ 957:177519 (2024)
https://doi.org/10.1016/j.scitotenv.2024.177519
Ottappilakkil H, Perumal E - "Fluoride exposure modulates skeletal development and mineralization in zebrafish larvae" Environ Toxicol 40(5):835-847 (2025)
https://doi.org/10.1002/tox.24474
Ottappilakkil H, Yesudas GH, Sreedharan T, Perumal E - "Fisetin modulates fluoride induced osteochondral toxicity in zebrafish larvae" Comp Biochem Physiol C Toxicol Pharmacol 299:110351 (2026)
https://doi.org/10.1016/j.cbpc.2025.110351
Singh R, Khatri P, Srivastava N, Jain S, Brahmachari V, Mukhopadhyay A, Mazumder S - "Fluoride exposure abates pro-inflammatory response and induces in vivo apoptosis rendering zebrafish (Danio rerio) susceptible to bacterial infections" Fish Shellfish Immunol 63:314-321 (2017) doi: 10.1016/j.fsi.2017.02.022. Epub 2017 Feb 20. PMID: 28223109.
https://pubmed.ncbi.nlm.nih.gov/28223109/
Wang X, Li J, Fan Y, Zhang X, Yang Y, Gao Y - "Zebrafish larvae as a model for investigating dual effects of fluoride on bone development" Toxicol Appl Pharmacol 117357 (2025) doi: 10.1016/j.taap.2025.117357
https://www.sciencedirect.com/science/a ... 8X25001334
Wang G, Wang T, Zhang X, Chen J, Feng C, Yun S, Cheng Y, Cheng F, Cao J - "Sex-specific effects of fluoride and lead exposures on histology, antioxidant physiology, and immune system in the liver of zebrafish (Danio rerio)" Ecotoxicology 31(3):396-414 (2022)
https://pubmed.ncbi.nlm.nih.gov/35088223/
NOTE: Biphasic and sex-specific effects.
Wang T, Wu S, Chen J, Li L, Cao J - "Sesamin alleviated fluoride-induced thyroid endocrine disruption in zebrafish (Danio rerio)" Aquat Toxicol 261:106625 (2023) doi: 10.1016/j.aquatox.2023.106625
https://www.sciencedirect.com/science/a ... 5X2300228X
viewtopic.php?f=7&t=5483
Wang F, Chen F, Song W, Li Y, Wu H, Tian T, Tian M, Tang D, Liu Y - "Sodium Fluoride Exposure Induces Developmental Toxicity and Cardiotoxicity in Zebrafish Embryos" Biol Trace Elem Res. 2024 Sep 17. doi: 10.1007/s12011-024-04381-4
https://pubmed.ncbi.nlm.nih.gov/39287768/
Wang Z, Zhou B, Zhang Y, Cao Y, Zhang Y, Han X, Wang Y, Zhao H - "Combined toxicity of nanoplastics and sodium fluoride to zebrafish liver: Impact on gut-liver axis homeostasis and lipid metabolism" Aquat Toxicol 291:107682 (2026) doi: 10.1016/j.aquatox.2025.107682.
https://www.sciencedirect.com/science/a ... 5X25004461
Wei YL, Lin XC, Liu YY, Lei YQ, Zhuang XD, Zhang HT, Wang XR - “Effects of water fluoridation on early embryonic development of zebrafish” Ecotoxicology and Environmental Safety 270:115907 (2024)
https://doi.org/10.1016/j.ecoenv.2023.115907
Wu Y, Zhang X, Chen J, Cao J, Feng C, Luo Y, Lin Y - "Self-recovery study of fluoride-induced ferroptosis in the liver of zebrafish (Danio rerio)" Aquat Toxicol 251:106275 (2022) doi: 10.1016/j.aquatox.2022.106275
https://www.sciencedirect.com/science/a ... 5X22002016
Xu M, Lu Y, Sun Y, Niu X, Han X, Luo Y, Chen J, Cao J - "Neurotoxic effects of fluoride on zebrafish embryos/larvae" Acta Scientiae Circumstantiae 44(3):459-467 (2024) PFPC Library
"There was no significant difference in BDNF and th gene expression in zebrafish larvae in the 20 mg·L-1 NaF group compared with the control group. In the 40 and 80 mg·L-1 NaF groups, expression was significantly lower than that in the control group. BDNF expression was significantly decreased by 23.70% and 51.42%, respectively, and th expression was significantly decreased by 30.52% and 62.23%, respectively (p<0.05)."
Xue Wenjuan - "Study on the interference effect of fluoride on the hypothalamic-pituitary-thyroid axis in zebrafish" Dissertation (2015)
http://cdmd.cnki.com.cn/Article/CDMD-10 ... 623693.htm
viewtopic.php?f=21&t=2193
Xiu Ruiqin, Gao Shirong, Xu Yongxiang, et al. - "Study on joint toxicity of fluoride and selenium to fish" China Environmental Science 15(5):348-350 (1995)
https://europepmc.org/article/cba/285541
"The joint toxicity of fluoride and selenium to zebrafish (B. rerio) was studied using acute and long-term exposure tests. The additive index method was used to evaluate the combined toxic effects. The results showed that, in acute toxicity tests using a toxicity ratio of 1:1, the combined toxicity was antagonistic at 24 h, 48 h, and 96 h. However, when the compounds were combined at a concentration ratio of 1:1, the combined toxicity was antagonistic at 24 h, additive at 48 h, and synergistic at 96 h. In the long-term exposure test, the combined toxicity to fish was synergistic."
Yang X, Zhang X, Jian G, Zhu Y, Chen H, Mu X, Li J, Zhu B, Lu H, An Y, Jin T - "Environmental standard limit fluoride exposure prioritizes neurotoxicity over osteotoxicity in larval zebrafish: A benchmark dose analysis" Aquatic Toxicology 293:107749 (2026)
https://doi.org/10.1016/j.aquatox.2026.107749
Yang YF, Li WG, Wen PP, Jia PP, Li YZ, Li TY, Pei DS - "Exposure to Sri Lanka's local groundwater in a CKDu prevalent area causes kidney damage in zebrafish" Aquat Toxicol 251:106276 (2022) doi: 10.1016/j.aquatox.2022.106276
https://www.sciencedirect.com/science/a ... 5X22002028
Zhang Y, Zhang Y, Zheng X, Xu R, He H, Duan X - "Grading and quantification of dental fluorosis in zebrafish larva" Arch Oral Biol 70:16-23 (2016) doi: 10.1016/j.archoralbio.2016.05.021
https://pubmed.ncbi.nlm.nih.gov/27300491/
Zhang X, Cao J, Chen J, Wang G, Li L, Wei X, Zhang R - "Combined Effects of Fluoride and Dietary Seleno-L-Methionine at Environmentally Relevant Concentrations on Female Zebrafish (Danio rerio) Liver: Histopathological Damages, Oxidative Stress and Inflammation" Biological Trace Element Research 202(5):2314-2326 (2024)
https://doi.org/10.1007/s12011-023-03837-3
Zhang Y, Mao S, Wen X, Liu Z, Hao Y, Duan X - "CFTR and ClC-3 Transport Fluoride Differently and Cause Dental Fluorosis in Different Ways" Biomolecules 16(7):982 (2026)
https://doi.org/10.3390/biom16070982
Organic Fluoride [PFAS]
Annunziato KM, Jantzen CE, Gronske MC, Cooper KR - "Subtle morphometric, behavioral and gene expression effects in larval zebrafish exposed to PFHxA, PFHxS and 6:2 FTOH" Aquat Toxicol 208:126-137 (2019)
https://doi.org/10.1016/j.aquatox.2019.01.009
Avidan L, English CD, McDonnell KA, Ivantsova E, Martyniuk CJ - "Transcriptome and Behavioral Assessment in Larval Zebrafish (Danio rerio) Following Exposure to Perfluorononanoic Acid (PFNA)" Genes (Basel) 17(5):558 (2026)
https://doi.org/10.3390/genes17050558
Bai S, Li T, Hu Q - "Effects of perfluorohexanesulfonic acid (PFHxS) exposure on zebrafish embryonic development and energy metabolism" Feed Research 48(17):48-52 (2025)
Blanc M, Kärrman A, Kukucka P, Scherbak N, Keiter S - "Mixture-specific gene expression in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3',4,4',5-pentachlorobiphenyl (PCB126)" Sci Total Environ 590-591:249-257 (2017)
https://doi.org/10.1016/j.scitotenv.2017.02.232
"PFHxA demonstrated that it could affect gene expression patterns in zebrafish embryos when combined to PFOS and PCB126, suggesting that such mixture may affect lipid metabolism and epigenetic mechanisms."
Cai Z, Zhou G, Yu X, Du Y, Man Q, Wang WC - "Perfluorooctanoic acid disrupts thyroid hormone biosynthesis by altering glycosylation of Na+/I- symporter in larval zebrafish" Ecotoxicol Environ Saf 297:118249 (2025) doi: 10.1016/j.ecoenv.2025.118249
https://www.sciencedirect.com/science/a ... 1325005858
"The dysfunction of NIS is due to its improper glycosylation caused by PFOA through the TSH-dependent signaling pathway."
Chen L, Tang L, Bai Y - "Combination effect of perfluorobutanesulfonate and probiotics on thyroid endocrine system of zebrafish" Journal of Henan Normal University (Natural Science Edition) 50(1):1-11 (2022)
"Exposure to PFBS alone could cause thyroid endocrine system disruption in zebrafish, while in the combination of PFBS and probiotics, probiotics could modulate these effects of PFBS through thyroid hormone levels and gene expression."
Chen J, Zheng L, Tian L, Wang N, Lei L, Wang Y, Dong Q, Huang C, Yang D - "Chronic PFOS Exposure Disrupts Thyroid Structure and Function in Zebrafish" Bull Environ Contam Toxicol 101(1):75-79 (2018)
https://doi.org/10.1007/s00128-018-2359-8
"Our findings demonstrated that chronic PFOS exposure altered thyroid hormone level, thyroid follicular cell structure and thyroid hormone related gene expression, suggesting the validity of zebrafish as an alternative model for PFOS chronic toxicity screening."
Du J, Wang S, You H - "Effects of combined exposure to perfluorooctyl sulfonate (PFOS) and nano-zinc oxide (Nano-ZnO) on hypothalamic-pituitary-thyroid axis function in zebrafish" Journal of Ecotoxicology 10(6):144-153 (2015)
https://doi.org/10.7524/AJE.1673-5897.20150528004
"The combined exposure group significantly increased the levels of thyroid hormones in the juvenile fish. The combined exposure significantly increased T3 levels while inhibiting T4 levels. Compared to the single exposure group, the combined exposure group significantly induced the expression of CRF and NIS genes, while inhibiting the expression of TSHβ and TG genes."
Godfrey A, Hooser B, Abdelmoneim A, Horzmann KA, Freeman JL, Sepulveda MS - "Thyroid Disrupting Effects of Halogenated and Next Generation Chemicals on the Swim Bladder Development of Zebrafish" Aquat Toxicol 193:228-235 (2017)
https://doi.org/10.1016/j.aquatox.2017.10.024
"Overall, our results suggest thyroid disruption by the halogenated compounds tested via the swim bladder surfactant system."
Guelfo JL, Ferguson PL, Beck J, Chernick M, Doria-Manzur A, Faught PW, Flug T, Gray EP, Jayasundara N, Knappe DRU, Joyce AS, Meng P, Shojaei M - "Lithium-ion battery components are at the nexus of sustainable energy and environmental release of per- and polyfluoroalkyl substances" Nat Commun 15:5548 (2024)
https://doi.org/10.1038/s41467-024-49753-5
Gui W, Guo H, Wang C, Li M, Jin Y, Zhang K, Dai J, Zhao Y - "Comparative developmental toxicities of zebrafish towards structurally diverse per- and polyfluoroalkyl substances" Sci Total Environ 902:166569 (2023)
https://doi.org/10.1016/j.scitotenv.2023.166569
Gui W, Guo H, Chen X, Wang J, Guo Y, Zhang H, Zhou X, Zhao Y, Dai J - "Emerging polyfluorinated compound Nafion by-product 2 disturbs intestinal homeostasis in zebrafish (Danio rerio)" Ecotoxicol Environ Saf 249:114368 (2023)
https://doi.org/10.1016/j.ecoenv.2022.114368
"Overall, the results demonstrate that Nafion BP2 disrupts the intestinal homeostasis of zebrafish by inducing intestinal toxicity, intestinal microbial dysbiosis and metabolic disorder, which provide insights into the environmental toxicity of emerging PFECAs."
Guo JS, Wu PH, Cao JL, Luo YJ, Chen JJ, Wang GD, Guo WJ, Wang TY, He XJ - "The PFOS disturbed immunomodulatory functions via NFκB signaling in liver of zebrafish (Danio rerio)" Fish and Shellfish Immunology 91(8):87-98 (2019)
https://www.sciencedirect.com/science/a ... 4819305741
"PFOS-induced pro-inflammatory effect of hepatocytes was observed, and the involvement of NF-κB signaling pathway was participated in its action mechanism. These findings provide further evidence that PFOS interferes with the immune regulation of liver of male zebrafish under in vivo conditions."
Gutsfeld S, Wray C, Schweiger N, Röhrig A, Paschke H, Fu Q, Kasmanas JC, Abdulkadir N, Kader S, Rocha U, Ebert A, Tal T - "N-Ethyl Perfluorooctane Sulfonamide (N-EtFOSA) Exposure Alters Microbiome Composition and Causes Microbiome-Dependent Behavior Effects in Larval Zebrafish" Environ Sci Technol 60(20):14276-14291 (2026)
https://doi.org/10.1021/acs.est.5c16330
Jantzen CE, Annunziato KM, Cooper KR - "Behavioral, morphometric, and gene expression effects in adult zebrafish (Danio rerio) embryonically exposed to PFOA, PFOS, and PFNA" Aquat Toxicol 180:123-130 (2016)
https://doi.org/10.1016/j.aquatox.2016.09.011
"This study demonstrates that acute, embryonic exposure (5 days) to individual PFASs result in significant biochemical and behavioral changes in young adult zebrafish 6 months after exposure. These three PFASs have long term and persistent impacts following short term embryonic exposure that persists into adulthood."
Jantzen CE, Annunziato KA, Bugel SM, Cooper KR - "PFOS, PFNA, and PFOA sub-lethal exposure to embryonic zebrafish have different toxicity profiles in terms of morphometrics, behavior and gene expression" Aquat Toxicol 175:160-170 (2016)
https://doi.org/10.1016/j.aquatox.2016.03.026
"PFOS, PFNA, and PFOA exposure resulted in significantly altered responses in terms of morphometric, locomotion, and gene expression endpoints, which could be manifested in field exposed teleosts."
Kim J, Lee G, Lee YM, Zoh KD, Choi K - "Thyroid disrupting effects of perfluoroundecanoic acid and perfluorotridecanoic acid in zebrafish (Danio rerio) and rat pituitary (GH3) cell line" Chemosphere 262:128012 (2021) doi: 10.1016/j.chemosphere.2020.128012
https://www.sciencedirect.com/science/a ... 3520322074
"In GH3 cells, exposure to PFUnDA and PFTrDA upregulated Tshβ gene, suggesting that these PFCAs increase thyroid hormone synthesis through stimulation by Tsh."
Kim S, Stroski KM, Killeen G, Smitherman C, Simcik MF, Brooks BW - "8:8 Perfluoroalkyl phosphinic acid affects neurobehavioral development, thyroid disruption, and DNA methylation in developing zebrafish" Sci Total Environ 736:139600 (2020) doi: 10.1016/j.scitotenv.2020.139600
https://www.sciencedirect.com/science/a ... 972033120X
"At 144 h, several genes related to thyroid hormones that are essential for neurodevelopment, including corticotropin releasing hormone b (crhb), iodothyronine deiodinase 3a (dio3a), thyroid-stimulating hormone receptor (tshr) and nkx2 homeobox1 (nkx 2.1), were up-regulated by 8:8 PFPiA at 5.79 μM."
Kim S, Ji K, Lee S, Lee J, Kim J, Kim S, Kho Y, Choi K - "Perfluorooctane Sulfonic Acid Exposure Increases Cadmium Toxicity in Early Life Stage of Zebrafish, Danio rerio" Environ Toxicol Chem 30(4):870-877 (2011)
https://doi.org/10.1002/etc.443
"Significant down-regulation of mRNAs related to thyroid function (thyroid hormone receptor-alpha [THRα], thyroid hormone receptor-beta [THRβ], hematopoietically expressed homeobox [hhex], and paired box gene 8 [pax8]) and decrease of throxine (T4) levels were observed in the PFOS preexposure group, suggesting that PFOS preexposure would influence the performance of thyroid gland in the later stages of life."
Kong AX, Johnson M, Chi J, Eno AF, Pham K, Zhang P, Gu H, Geng Y - "Proteome-Wide Reverse Molecular Docking Reveals Folate Receptor as a Mediator of PFAS-Induced Neurodevelopmental Toxicity" J Hazard Mater 509:142012 (2026)
https://doi.org/10.1016/j.jhazmat.2026.142012
"We found that embryonic exposure to PFNA, PFOA, and PFOS induced social deficits in zebrafish, recapitulating one of the hallmark behavioral deficits in autistic individuals."
Liang H, Zhang Y, Huang Z, Du S, Zhang J, Zhao S - "Endocrine Disrupting Effects of Typical Short-Chain Perfluorinated Substitutes PFBA and PFBS on Zebrafish" Asian Journal of Ecotoxicology (5):103-111 (2023) PFPC Library
Both compounds altered vitellogenin and thyroid hormone levels. PFBA inhibited T3 and T4, while PFBS produced an inverted U-shaped response, with the strongest inhibition of T3 and T4 reported in the high-concentration group.
Liu C, Deng J, Yu L, Ramesh M, Zhou B - "Endocrine disruption and reproductive impairment in zebrafish by exposure to 8:2 fluorotelomer alcohol" Aquat Toxicol 96(1):70-76 (2010)
https://doi.org/10.1016/j.aquatox.2009.09.012
"All these findings suggest that 8:2 FTOH might act as a weak xenoestrogen and disturb the HPG axis in zebrafish."
Liu Y, Wang J, Fang X, Zhang H, Dai J - "The Thyroid-Disrupting Effects of Long-Term Perfluorononanoate Exposure on Zebrafish (Danio rerio)" Ecotoxicology 20(1):47-55 (2011)
https://doi.org/10.1007/s10646-010-0555-3
"Our results provide the first evidence for the thyroid-disrupting effects of long-term PFNA exposure in zebrafish."
Mahoney H, Cantin J, Rybchuk J, Xie Y, Giesy JP, Brinkmann M - "Acute Exposure of Zebrafish (Danio rerio) to the Next-Generation Perfluoroalkyl Substance, Perfluoroethylcyclohexanesulfonate, Shows Similar Effects as Legacy Substances" Environ Sci Technol 57(10):4199-4207 (2023) doi: 10.1021/acs.est.2c08463
https://pubs.acs.org/doi/10.1021/acs.est.2c08463
Qi X, Xu H, Long J, Yan C, Han X, Liu H - "Perfluorooctane sulfonate (PFOS) on intestinal structure and microbiota of zebrafish (Danio rerio)" Acta Hydrobiologica Sinica 49(4):042506 (2025)
https://doi.org/10.7541/2025.2024.0290
Qian M, Sun W, Cheng L, Wu Y, Wang L, Liu H - "Transcriptome-based analysis reveals the toxic effects of perfluorononanoic acid by affecting the development of the cardiovascular system and lipid metabolism in zebrafish" Comp Biochem Physiol C Toxicol Pharmacol 289:110108 (2025)
https://doi.org/10.1016/j.cbpc.2024.110108
Rericha Y, Simonich M, Truong L, Tanguay RL - "Review of the Zebrafish as a Model to Investigate per- and Polyfluoroalkyl Substance Toxicity" Toxicol Sci kfad051 (2023) doi: 10.1093/toxsci/kfad051
https://academic.oup.com/toxsci/advance ... 51/7176390
Shi X, Liu C, Wu G, Zhou B - "Waterborne exposure to PFOS causes disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae" Chemosphere 77(7):1010-8 (2009) doi: 10.1016/j.chemosphere.2009.07.074
https://www.sciencedirect.com/science/a ... 3509009126
"A significant increase in NIS and Dio1 gene expression was observed at 200 microg L(-1) PFOS exposure, while TG gene expression was down-regulated at 200 and 400 microg L(-1) PFOS exposure."
Shi X, Du Y, Lam PK, Wu RS, Zhou B - "Developmental Toxicity and Alteration of Gene Expression in Zebrafish Embryos Exposed to PFOS" Toxicol Appl Pharmacol 230(1):23-32 (2008)
https://doi.org/10.1016/j.taap.2008.01.043
"We investigated the effects of PFOS on marker genes related to early thyroid development (hhex and pax8) and genes regulating the balance of androgens and estrogens (cyp19a and cyp19b). For thyroid development, the expression of hhex was significantly up-regulated at all concentrations tested, whereas pax8 expression was significantly up-regulated only upon exposure to lower concentrations of PFOS (0.1, 0.5, 1 mg/L)."
Shi G, Cui Q, Zhang H, Cui R, Guo Y, Dai J - "Accumulation, Biotransformation, and Endocrine Disruption Effects of Fluorotelomer Surfactant Mixtures on Zebrafish" Chem Res Toxicol (2019) 32(7):1432-1440
https://pubmed.ncbi.nlm.nih.gov/31251046/
(T3 and T4 levels decreased in the 50 and 500 μg/L females and increased T4 level in 500 μg/L exposed males.)
Shi G, Cui Q, Wang J, Guo H, Pan Y, Sheng N, Guo Y, Dai J - "Chronic exposure to 6:2 chlorinated polyfluorinated ether sulfonate acid (F-53B) induced hepatotoxic effects in adult zebrafish and disrupted the PPAR signaling pathway in their offspring" Environ Pollut 249:550-559 (2019)
https://doi.org/10.1016/j.envpol.2019.03.032
"Overall, our results provided the first line of evidence that F-53B exposure caused adverse effects in adult zebrafish and their offspring."
Singh S, Gautam K, Mir SS, Anbumani S - "Genotoxicity and cytotoxicity assessment of 'forever chemicals' in zebrafish (Danio rerio)" Mutat Res Genet Toxicol Environ Mutagen 897:503788 (2024)
https://doi.org/10.1016/j.mrgentox.2024.503788
"The results confirm the cytotoxic and genotoxic potential of PFOS and its alternatives and indicate that zebrafish are useful model organisms in risk assessment of these compounds."
Tompach MC, Gridley CK, Li S, Clark JM, Park Y, Timme-Laragy AR - "Comparing the effects of developmental exposure to alpha lipoic acid (ALA) and perfluorooctanesulfonic acid (PFOS) in zebrafish (Danio rerio)" Food Chem Toxicol 186:114560 (2024)
https://doi.org/10.1016/j.fct.2024.114560
"Together, this work demonstrates that ALA and PFOS have similar effects on lipid uptake and metabolism during embryonic development in zebrafish."
Ulhaq ZS, Tse WKF - "Perfluorohexanesulfonic acid (PFHxS) induces oxidative stress and causes developmental toxicities in zebrafish embryos" J Hazard Mater 457:131722 (2023). doi: 10.1016/j.jhazmat.2023.131722
https://www.sciencedirect.com/science/a ... 9423010051
Wang J, Shi G, Yao J, Sheng N, Cui R, Su Z, Guo Y, Dai J - "Perfluoropolyether carboxylic acids (novel alternatives to PFOA) impair zebrafish posterior swim bladder development via thyroid hormone disruption" Environ Int 134:105317 (2020) doi: 10.1016/j.envint.2019.105317
https://pubmed.ncbi.nlm.nih.gov/31733528/
"For genes related to TH synthesis, the transcription levels of dio2 increased in the PFOA, PFO3OA, and PFO5DoDA-treated groups."
Wang Q, Liu Y, Zhang M, Liu S, Wan N, Li M, Tu W - "Novel PFOS alternative OBS inhibits body growth of developing zebrafish by triggering thyroid function disorder and osteoclast differentiation" Chemosphere 341:140068 (2023) doi: 10.1016/j.chemosphere.2023.140068
https://linkinghub.elsevier.com/retriev ... 23)02338-X
"This study systematically explored the inhibitory effects of PFOS and OBS exposure on body development and tightly linked the toxic effects to thyroid function disorder and osteoclast differentiation."
Wang Y, Jiang S, Wang B, Chen X, Lu G - "Comparison of Developmental Toxicity Induced by PFOA, HFPO-DA, and HFPO-TA in Zebrafish Embryos" Chemosphere 311(Pt 1):136999 (2023)
https://doi.org/10.1016/j.chemosphere.2022.136999
"Our results showed that although PFOA alternatives may have less toxicity in the early stages of zebrafish embryos, they may have similar effects on the thyroid endocrine system...Significant increases in corticotrophin-releasing hormone (crh) and transthyretin (ttr) gene expression were also observed when the zebrafish larvae were treated with 12 mg/L PFHxA, except iodothyronine deiodinases (dio1), which decreased obviously at that point"
Wasel O, Thompson KM, Freeman JL - "Assessment of unique behavioral, morphological, and molecular alterations in the comparative developmental toxicity profiles of PFOA, PFHxA, and PFBA using the zebrafish model system" Environ Int 170:107642 (2022). doi: 10.1016/j.envint.2022.107642.
https://www.sciencedirect.com/science/a ... 2022005694
Wu Y, Meng R, Zhang X, Wang G, Chen J, Cao J - "Effects of Inorganic Fluoride and Organic Fluoride on the Antioxidant Capacity, Non-Specific Immunity and Organization Structure in Liver of Danio rerio" Journal of Nuclear Agricultural Sciences 35(8):1893-1899 (2021) PFPC Library
https://www.hnxb.org.cn/EN/10.11869/j.i ... 21.08.1893
"In conclusion, single and combined exposure to NaF and PFOS can cause toxic effects on the tissue structure and antioxidant and immune functions of zebrafish liver to varying degrees."
Wu L, Wang J, Ye H, Yao Y, Hu M, Cheng J, Kong L, Liu W, Ge F - "Impacts of hexafluoropropylene oxide tetrameric acid (HFPO-TeA) on neurodevelopment and GABAergic signaling in zebrafish larvae" Ecotoxicol Environ Saf 289:117424 (2025)
https://doi.org/10.1016/j.ecoenv.2024.117424
"These findings reveal the developmental neurotoxicity of HFPO-TeA and highlight the need for further investigation into its ecological and health risks."
Wu L, Gu J, Duan X, Ge F, Ye H, Kong L, Liu W, Gao R, Jiao J, Chen H, Ji G - "Insight into the Mechanisms of Neuroendocrine Toxicity Induced by 6:2FTCA Via Thyroid Hormone Disruption" Chemosphere 341:140031 (2023)
https://doi.org/10.1016/j.chemosphere.2023.140031
"Simultaneously, the thyroid development of zebrafish larvae was partially hindered, accompanied by decreased T3 levels, altered genes associated with the expression of thyroid hormone synthesis, transformation and transportation and neurotransmitters associated with tryptophan and tyrosine metabolic pathways. Molecular docking results showed that 6:2 FTCA has a robust binding energy with the thyroid hormone receptor (TRβ). Moreover, exogenous T3 supplementation can partially restore the adverse outcomes."
Xia J, Niu C - "Acute toxicity effects of perfluorooctane sulfonate on sperm vitality, kinematics and fertilization success in zebrafish" Chinese Journal of Oceanology and Limnology 35(4):723-728 (2017)
https://doi.org/10.1007/s00343-017-6086-5
Xiao J, Yang D, Hu B, Zha W, Li W, Wang Y, Liu F, Liao X, Li H, Tao Q, Zhang S, Cao Z - "Perfluorodecanoic acid induces the increase of innate cells in zebrafish embryos by upregulating oxidative stress levels" Comp Biochem Physiol C Toxicol Pharmacol 287:110037 (2025)
https://doi.org/10.1016/j.cbpc.2024.110037
"Our results suggest that PFDA may induce innate immune response by accumulation of oxidative stress in zebrafish at early developmental stages."
Xu M, Legradi J, Leonards P - "A comprehensive untargeted metabolomics study in zebrafish embryos exposed to perfluorohexane sulfonate (PFHxS)" Sci Total Environ 887:163770 (2023) doi: 10.1016/j.scitotenv.2023.163770
https://www.sciencedirect.com/science/a ... 9723023914
Ye J, Ji Y, Liu Y, Wang Q, Zhang M, Deng M, Wu Y, Liu S - "Toxic Effects of PFAS Mixtures from Wastewater Treatment Plant Effluents in Zebrafish Larvae: A Simulation Study" Asian Journal of Ecotoxicology 21(1):85-101 (2026) PFPC Library
https://doi.org/10.7524/AJE.1673-5897.20250903003
Yao D, Wu H, Jiang M - "Effects of Perfluorooctane Sulfonate on the Liver Metabolism of Danio rerio" Asian Journal of Ecotoxicology 13(6):97-106 (2018) PFPC Library
"Based on the physiological functions of the identified metabolites and the analysis of their metabolic pathways, it was speculated that PFOS exerts toxic effects on Danio rerio liver mainly by interfering the metabolic pathways of taurine and hypotaurine, glycolysis or glucose production, and some lipid metabolism."
Yi S, Wang J, Wang R, Liu M, Zhong W, Zhu L, Jiang G - "Structure-Related Thyroid Disrupting Effect of Perfluorooctanesulfonate-like Substances in Zebrafish Larvae" Environ Sci Technol (2024) 58(1):182-193. doi: 10.1021/acs.est.3c07003 3.
https://pubs.acs.org/doi/10.1021/acs.est.3c07003
"PFOS-like substances could competitively replace THs to bind with TH plasma and membrane transporters, thereby disrupting TH transport and action, respectively. Moreover, they are also potent to disrupt TH synthesis and activation through Na+/K+-dependent transport of I- or competitive binding to the sites of deiodinases...Collectively, our results provide a comprehensive comparison of the thyroid-disrupting effects of four PFOS-like substances.""[/color][/i]
Zhang S, Guo X, Lu S, He J, Wu Q, Liu X, Han Z, Xie P - "Perfluorohexanoic acid caused disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae" Ecotoxicol Environ Saf 232:113283 (2022) doi: 10.1016/j.ecoenv.2022.113283
https://www.sciencedirect.com/science/a ... 1322001233
"Treatment with PFHxA significantly downregulated dio2 gene transcription (0.79- and 0.79-fold) in the 2.4 and 12 mg/L exposure groups. The level of the dio1 gene was also decreased when exposed to 12 mg/L PFHxA."
Zhang S, Guo X, Lu S, Sang N, Li G, Xie P, Liu C, Zhang L, Xing Y - "Exposure to PFDoA causes disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae" Environ Pollut 235:974-982 (2018) doi: 10.1016/j.envpol.2018.01.015
https://www.sciencedirect.com/science/a ... 9117326453
BI-PHASIC: "Upregulation and downregulation of iodothyronine deiodinases (dio1) gene expression were observed upon the treatment of 1.2 mg/L and 6 mg/L PFDoA, respectively."
Zhang Z, Huang D, Gao B, Wu Y, Sun Z, Zhou Z, Liu Y, Liu S, Zhang M, Wang Q - "Comparative Reproductive Toxicity of 6:2 FTS and PFOS in Female Zebrafish (Danio rerio): From Histopathology to Molecular Response" Ecotoxicol Environ Saf 322:120337 (2026)
https://doi.org/10.1016/j.ecoenv.2026.120337
"Consistently, gnrh-family genes and lhβ were upregulated, whereas fshβ and 17β-hsd were downregulated. These endocrine disturbances were associated with abnormal oocyte development, increased follicular atresia, reduced spawning output, and higher offspring malformation risk. IBRv2 analysis indicated that although 6:2 FTS caused lower overall toxicity than PFOS, it still impaired reproduction mainly through HPG-axis disruption."
Zhao X, Meng X, Yang D, Dong S, Xu J, Chen D, Shi Y, Sun Y, Ding G - "Thyroid disrupting effects and the developmental toxicity of hexafluoropropylene oxide oligomer acids in zebrafish during early development" Chemosphere 361:142462 (2024)
https://doi.org/10.1016/j.chemosphere.2024.142462
"The transcription levels of genes related to thyroid hormone regulation (crh), biosynthesis (tpo and tg), function (trα and trβ), transport (transthyretin, ttr), and metabolism (dio1, dio2 and ugt1ab), were differently altered after the exposures, which induced the thyroid disrupting effects and decreased the heart rate. In addition, the transcription levels of some genes related to the nervous system development were also significantly affected, which was associated with the thyroid disrupting effects and consequently affected the locomotor activity of zebrafish."
Zhao X, Liu Y, Yang D, Dong S, Xu J, Li X, Li X, Ding G - "Thyroid endocrine disruption effects of OBS in adult zebrafish and offspring after parental exposure at early life stage" Aquat Toxicol 276:107125 (2024)
https://doi.org/10.1016/j.aquatox.2024.107125
"These findings indicated that chronic exposure to OBS at early life stage could interfere with thyroid endocrine system in adult zebrafish and further affect the thyroid hormone levels in offspring."
Zhao X, Yang D, Kamstra JH, Dong S, Xu J, Li X, Chen D, Shi Y, Sun Y, Ding G - "Parental exposure to hexafluoropropylene oxide trimer acid induces transgenerational developmental toxicity and thyroid endocrine disruption effects in zebrafish" Ecotoxicology and Environmental Safety 307:119476 (2025)
https://doi.org/10.1016/j.ecoenv.2025.119476
Parental HFPO-TA exposure in zebrafish was associated with thyroid axis disruption and measurable developmental and behavioral deficits in subsequent, unexposed generations, with maternal transfer and promoter DNA methylation implicated as contributors.
see also:
Duan M, Zhang J, Liu J, Qian L, Chen X, Zhao F, Zhao W, Zhong Z, Yang Y, Wang C - "Toxic effects of broflanilide exposure on development of zebrafish (Danio rerio) embryos and its potential cardiotoxicity mechanism" Environ Pollut 286:117481 (2021)
https://pubmed.ncbi.nlm.nih.gov/34126520/
Norfloxacin
Wang Dongmei et al. - "Toxic effect of norfloxacin on zebrafish embryo development and its effect on TGF-β1" Biotechnology Bulletin No. 1 (2016)
http://www.cqvip.com/qk/90799x/2016001/667729303.html
Levofloxacin
Zhang Y, Mo C, Li Y, Xu K - "Effects of Levofloxacin Exposure on Intestinal Microbes of Zebrafish" Ecology and Environmental Sciences 34(4):593-607 (2025) PFPC Library
https://doi.org/10.16258/j.cnki.1674-5906.2025.04.009
Enrofloxacin
Qiu W, Zheng M, Sun J, Tian Y, Fang M, Zheng Y, Zhang T, Zheng C - "Photolysis of enrofloxacin, pefloxacin and sulfaquinoxaline in aqueous solution by UV/H2O2, UV/Fe(II), and UV/H2O2/Fe(II) and the toxicity of the final reaction solutions on zebrafish embryos" Sci Total Environ 651(Pt 1):1457-1468 (2019)
https://doi.org/10.1016/j.scitotenv.2018.09.315
Jiang Y, Zhao Q, Su Z, Zheng J, Chen Y, Hu CB, Zhou J, Fan D, Xiang L, Zhang H, Wang W, Shao J, Chen Y - "Chronic exposure to environmental concentrations of enrofloxacin impairs neutrophil function in zebrafish via HPT axis disruption and hematopoietic dysregulation" J Hazard Mater 495:138885 (2025)
https://doi.org/10.1016/j.jhazmat.2025.138885
"This study demonstrates that enrofloxacin disrupts zebrafish immune defenses by impairing thyroid signaling and the renal microenvironment."
Fluoxetine
Huang J, Liu K, Chen S, Tang H, Li R, Wang X, Sun H - "Thyroid Endocrine Disrupting Potential of Fluoxetine in Zebrafish Larvae" J Appl Toxicol 45(6):916-924 (2025) doi: 10.1002/jat.4755
https://pubmed.ncbi.nlm.nih.gov/39875209/
"The exposure resulted in decreased thyroid hormones (THs) levels, indicating thyroid endocrine disruption. Moreover, thyroid-stimulating hormone (TSH) content was significantly inhibited in a concentration-dependent manner after exposure to FLX...The increased gene transcription of deiodinases (dio2) and uridinediphosphate-glucuronosyltransferase (ugt1ab) might be responsible for the decrease of TH contents. In addition, a significant inhibition in thyroid hormone receptors (trα and trβ) gene expression was observed upon treatment with FLX. All these results demonstrated that FLX could alter THs and TSH content as well as gene transcription in the HPT axis, exerting an endocrine disruption of the thyroid system in zebrafish larvae."
Mishra P, Gong Z, Kelly BC - "Assessing biological effects of fluoxetine in developing zebrafish embryos using gas chromatography-mass spectrometry based metabolomics" Chemosphere 188:157-167 (2017)
https://doi.org/10.1016/j.chemosphere.2017.08.149
"The results indicate fluoxetine exposure causes perturbation of energy and amino acid metabolism, which may adversely impact embryogenesis due to depletion of energy reserves."
Zindler F, Stoll S, Baumann L, Knoll S, Huhn C, Braunbeck T - "Do environmentally relevant concentrations of fluoxetine and citalopram impair stress-related behavior in zebrafish (Danio rerio) embryos?" Chemosphere 261:127753 (2020)
https://doi.org/10.1016/j.chemosphere.2020.127753
"Findings provide evidence that environmentally relevant concentrations of fluoxetine reduce stress-related behavior of zebrafish embryos, while these effects may be enhanced by the interaction of multiple SSRIs and their metabolites in environmental exposure scenarios."
Zindler F, Tisler S, Loerracher AK, Zwiener C, Braunbeck T - "Norfluoxetine Is the Only Metabolite of Fluoxetine in Zebrafish (Danio rerio) Embryos That Accumulates at Environmentally Relevant Exposure Scenarios" Environ Sci Technol 54(7):4200-4209 (2020)
https://doi.org/10.1021/acs.est.9b07618
Citalopram
North RJ, Cooper G, Mears L, Bothner B, Dlakic M, Merzdorf CS - "Persistent and Dose-Dependent Neural and Metabolic Gene Expression Changes Induced by Transient Citalopram Exposure in Zebrafish Embryos" Int J Mol Sci 26(23):11288 (2025)
https://doi.org/10.3390/ijms262311288
"All four citalopram doses suggested synaptic and neurotransmitter alterations, implying that persistent neurodevelopmental impacts resulted from a limited early window of exposure. These data highlight that transient, low-level SSRI exposures shape long-term embryonic gene expression."
Kazi KJ, English CD, Ivantsova E, Souders CL, Martyniuk CJ - "Transcriptome networks and physiology related to cardiac function and motor activity are perturbed in larval zebrafish (Danio rerio) following exposure to the antidepressant citalopram" Environ Pollut 361:124767 (2024)
https://doi.org/10.1016/j.envpol.2024.124767
Bachour RL, Golovko O, Kellner M, Pohl J - "Behavioral effects of citalopram, tramadol, and binary mixture in zebrafish (Danio rerio) larvae" Chemosphere 238:124587 (2020)
https://doi.org/10.1016/j.chemosphere.2019.124587
"The results of this study conclude that tramadol and citalopram produce hypoactivity in 144 hpf zebrafish larvae.
Co-exposure with Chemo drugs:
Di Paola D, Capparucci F, Lanteri G, Crupi R, Marino Y, Franco GA, Cuzzocrea S, Spanò N, Gugliandolo E, Peritore AF - “Environmental Toxicity Assessment of Sodium Fluoride and Platinum-Derived Drugs Co-Exposure on Aquatic Organisms” Toxics 10(5):272 (2022)
https://doi.org/10.3390/toxics10050272
Co-exposure with nanoplastics
Wang Z, Zhou B, Zhang Y, Cao Y, Zhang Y, Han X, Wang Y, Zhao H - "Combined toxicity of nanoplastics and sodium fluoride to zebrafish liver: Impact on gut-liver axis homeostasis and lipid metabolism" Aquat Toxicol 291:107682 (2026) doi: 10.1016/j.aquatox.2025.107682.
https://www.sciencedirect.com/science/a ... 5X25004461
Fluconazole
Wei W, Tang L, Wang Y, Jiang Y - "Toxicity and Mechanism of Fluconazole Exposure on Cardiovascular Development in Zebrafish Juveniles" Journal of Adverse Drug Reactions 28(5):335-342 (2026)
https://doi.org/10.3760/cma.j.cn114015-20250609-00311
"Transcriptome sequencing detected 478 differentially expressed genes (175 upregulated and 303 downregulated), mainly enriched in the vascular endothelial growth factor [VEGF] signaling pathway, myocardial adrenergic signaling pathway, and p53 signaling pathway."
Fluazinam
Zheng S, Wang X, Zhao Y - “The Toxic Effect of Fluazinam on Mitochondrial Respiratory Function and Dopamine Neural System in Zebrafish Embryos” Asian Journal of Ecotoxicology 2018(4):170-178 (2018) PFPC Library
The residues of fluazinam in the aquatic environment have long been a significant environmental concern; therefore, studying the toxic mechanism of fluazinam on zebrafish embryos is of great importance. Fluazinam is a widely used agricultural fungicide.
Wang XH, Souders CL, Zhao YH, Martyniuk CJ - "Fluazinam impairs oxidative phosphorylation and induces hyper/hypo-activity in a dose specific manner in zebrafish larvae" Chemosphere 210:633-644 (2018)
https://doi.org/10.1016/j.chemosphere.2018.07.056
Meperfluthrin
"Meperfluthrin is one of the top-selling sanitary insecticide species in the domestic market..." [China]
Li R, Zhou N, Wu M, Xu W, Tao L, Zhang Y - "Toxicity and oxidative damage of meperfluthrin on cardiac development of zebrafish embryos and larvae" Chinese Journal of Pesticide Science 26(1):149-159 (2024) PFPC Library
https://doi.org/10.16801/j.issn.1008-7303.2023.0102
"The results of this paper indicate that meperfluthrin exposure has significant toxicity to the cardiac development of zebrafish embryos and is associated with oxidative damage."
Tefluthrin
Wang H, Xu W, Li L - "Tefluthrin induced toxicities in zebrafish: Focusing on enantioselectivity" Pestic Biochem Physiol 195:105572 (2023)
https://doi.org/10.1016/j.pestbp.2023.105572
Trifluralin
Song C, Chen J, Hu G, Meng S, Fan L, Qiu L, Zheng Y, Liu Y, Wu W - "Effects of herbicide trifluralin and its degradation on the oxidative stress of zebrafish" Ecology and Environmental Sciences 26(3):468-472 (2017)
https://doi.org/10.16258/j.cnki.1674-5906.2017.03.015
Metaflumizone
Chen X, Li W - "Metaflumizone Disrupts Swim Bladder Development in Zebrafish (Danio rerio)" Asian Journal of Ecotoxicology 17(3):454-461 (2022)
https://doi.org/10.7524/AJE.1673-5897.20210319001 PFPC Library
Cyflumetofen
Zhang Y, Li L, Yang L, Kong Z, Li J, Francis F, Li M, Fan B - "Endocrine Disruption Induced by Environmental Exposure to the Acaricide Cyflumetofen and Its Main Metabolite" Toxics 14(4):272 (2026)
https://doi.org/10.3390/toxics14040272
Bisphenol AF
Wei Q, Liang J, Zhu J, Zheng Y, Pan C, Yang M, Chen Z - "Acute and sub-chronic exposure to bisphenol AF induces cardiac inflammatory response in zebrafish through lncRNA/circRNA-miRNA-mRNA regulatory networks" Ecotoxicol Environ Saf 312:119911 (2026)
https://doi.org/10.1016/j.ecoenv.2026.119911
Kwon B, Kho Y, Kim PG, Ji K - "Thyroid Endocrine Disruption in Male Zebrafish Following Exposure to Binary Mixture of Bisphenol AF and Sulfamethoxazole" Environ Toxicol Pharmacol 48:168-174 (2016)
https://doi.org/10.1016/j.etap.2016.10.018
"These results imply that both BPAF and SMX can disrupt thyroid endocrine system in zebrafish and possibly interact each other for disrupting thyroid function."
Haloxyfop-p-methyl
Liu Y, Guo J, Liu W, Yang F, Deng Y, Meng Y, Cheng B, Fu J, Zhang J, Liao X, Wei L, Lu H - "Effects of haloxyfop-p-methyl on the developmental toxicity, neurotoxicity, and immunotoxicity in zebrafish" Fish Shellfish Immunol 132:108466 (2023)
https://doi.org/10.1016/j.fsi.2022.108466
"These results indicate that haloxyfop-p-methyl induces developmental toxicity, neurotoxicity, and immunotoxicity in zebrafish, providing a perspective on the toxicological mechanism of haloxyfop-p-methyl in teleosts."
Flumioxazin & Butafenacil
Leet JK, Lindberg CD, Bassett LA, Isales GM, Yozzo KL, Raftery TD, Volz DC - "High-Content Screening in Zebrafish Embryos Identifies Butafenacil as a Potent Inducer of Anemia" PLoS One 9(8):e104190 (2014)
https://doi.org/10.1371/journal.pone.0104190
"We identified butafenacil as a potent inducer of anemia, as exposure from 0.39 to 3.125 µM butafenacil completely abolished arterial circulation in the absence of effects on all other endpoints evaluated."
Fipronil
Domingues AG, Dourado DN, Cunha LR, de Lima WG, de Barros ALC, Martucci MEP, Quaresma AV, Rubio KTS - "Hepatic and Morphological Impairments Induced by Subchronic Exposure to Fipronil Chlorination Byproducts in Adult Zebrafish (Danio rerio)" Environ Toxicol Chem 45(5):1285-1300 (2026)
https://doi.org/10.1093/etojnl/vgag056
Tetraconazole
Aksakal Fİ, Şi̇şman T, Gür C, Şenol O, Aksakal Ö - "Developmental and Systemic Toxicity of the Triazole Fungicide Tetraconazole in Zebrafish: Integrated Evidence from ER Stress, Apoptosis, and Metabolomic Disruption" J Hazard Mater 512:142405 (2026)
https://doi.org/10.1016/j.jhazmat.2026.142405
Dexamethasone
Wei Y, Wang C, Cai X, Zhan Y, Jia X - "Establishment of Zebrafish Osteopenia Model Induced by Dexamethasone" Acta Pharmaceutica Sinica 48(2):255-260 (2013) PFPC Library
Fluorinated diiodine alkanes
Lu L, Chang J, Chang Y, Ma J - "Fluorinated diiodine alkanes exert developmental toxicity on embryo-larval stages of zebrafish strain AB via regulating the expression of the specific endocrine-related genes" J Appl Toxicol 39(12):1691-1700 (2019)
https://doi.org/10.1002/jat.3893
Inorganic Fluoride Nanoparticles
Khan IA, Yu T, Li Y, Hu C, Zhao X, Wei Q, Zhong Y, Yang M, Liu J, Chen Z - "In vivo toxicity of upconversion nanoparticles (NaYF4:Yb, Er) in zebrafish during early life stages: Developmental toxicity, gut-microbiome disruption, and proinflammatory effects" Ecotoxicol Environ Saf 284:116905 (2024)
https://doi.org/10.1016/j.ecoenv.2024.116905
Fluorinated Liquid Crystal monomers
Wang J, Ma S, Li S, He S, Wei K, Guo X, He J, Wu F - "Mitochondrial dysfunction and AMPK-associated metabolic reprogramming in zebrafish exposed to fluorinated liquid crystal monomers" Ecotoxicol Environ Saf 311:119894 (2026)
https://doi.org/10.1016/j.ecoenv.2026.119894
Li W, Wang S, Fan H, Wang Z, Liu Y, You H - "Insights into hepatotoxicity of fluorinated liquid crystal monomer 1-ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (EDPrB) in adult zebrafish at environmentally relevant concentrations: Metabolic disorder and stress response" J Hazard Mater 486:136858 (2025)
https://doi.org/10.1016/j.jhazmat.2024.136858
"The findings elucidate EDPrB-induced hepatotoxicity and underlying mechanisms, which contribute to assessing the ecological risk and pollution control of FLCMs."
He S, He J, Ma S, Wei K, Wu F, Xu J, Jin X, Zhao Y, Martyniuk CJ - "Liquid crystal monomers disrupt photoreceptor patterning of zebrafish larvae via thyroid hormone signaling" Environ Int 188:108747 (2024)
https://doi.org/10.1016/j.envint.2024.108747
"We demonstrate that FLCMs can act as thyroid hormone disruptors to induce visual dysfunction in zebrafish via several molecular mechanisms."
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Fluoride & Thyroid
Chen J, Xue W, Cao J, Song J, Jia R, Li M - “Fluoride caused thyroid endocrine disruption in male zebrafish (Danio rerio)” Aquatic Toxicology 171:48-58 (2016)
https://doi.org/10.1016/j.aquatox.2015.12.010
Chen J, Wang T, Cao J, Luo Y, Shi L, Gao R - "Toxic effects of fluoride on zebrafish embryos/larvae development" Acta Scientiae Circumstantiae 43(11):422-430 (2023)
https://doi.org/10.13671/j.hjkxxb.2023.0142
NOTE: U Curves, biphasic effects
https://doi.org/10.13671/j.hjkxxb.2018.0464
viewtopic.php?p=8306#p8306
Lu Y, Zhang X, Chen J, Cao J, Feng C, Yun S, Cheng Y, Cheng F - “Sex-specific effects of fluoride and lead on thyroid endocrine function in zebrafish (Danio rerio)” Chemico-Biological Interactions 367:110151 (2022)
https://doi.org/10.1016/j.cbi.2022.110151
Wang T, Wu S, Chen J, Li L, Cao J - “Sesamin alleviated fluoride-induced thyroid endocrine disruption in zebrafish (Danio rerio)” Aquatic Toxicology 261:106625 (2023)
https://doi.org/10.1016/j.aquatox.2023.106625
Xue W - “Study on the interfering effects of fluoride on the hypothalamic-pituitary-thyroid axis in zebrafish” Shanxi Agricultural University Master’s Thesis (2015) PFPC Library
"The experimental results showed that fluoride exposure can affect the growth and development of zebrafish by affecting the morphology of the thyroid and liver tissues and thyroid hormone levels, and that the effect gradually increases as the exposure concentration increases and the exposure time is prolonged. Fluoride affected the expression of all 10 related genes in the zebrafish HPT axis, and the magnitude of the effect was related to exposure concentration, time, and sex, suggesting that fluoride can interfere with thyroid hormone levels in the body by affecting gene expression in the zebrafish HPT axis, thereby affecting growth and development."
SEE also:
- Parsons AE, Lange A, Hutchinson TH, Miyagawa S, Iguchi T, Kudoh T, Tyler CR - "Expression dynamics of genes in the hypothalamic-pituitary-thyroid (HPT) cascade and their responses to 3,3',5-triiodo-l-thyronine (T3) highlights potential vulnerability to thyroid-disrupting chemicals in zebrafish (Danio rerio) embryo-larvae" Aquat Toxicol 225:105547 (2020)
https://doi.org/10.1016/j.aquatox.2020.105547
"We conclude that the T3-driven HPT gene expression profiles defined in zebrafish embryo-larvae may provide a foundation for understanding the thyroid-disrupting effects of chemicals in this life stage."