{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:36:01Z","timestamp":1785404161348,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Provincial Center for Disease Control and Prevention","award":["2024D344"],"award-info":[{"award-number":["2024D344"]}]},{"award":["2024D344"],"award-info":[{"award-number":["2024D344"]}],"id":[{"id":"https:\/\/ror.org\/04tms6279","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health","award":["2020B1212030008"],"award-info":[{"award-number":["2020B1212030008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>6:2 Chlorinated polyfluoroether sulfonate (F-53B), an emerging per- and polyfluoroalkyl substance used as a perfluorooctane sulfonate substitute in electroplating, may co-occur with Cr(VI) in industrially affected aquatic environments. However, their combined developmental toxicity in vertebrates remains poorly understood. This study compared the effects of F-53B and Cr(VI) alone and in combination on zebrafish embryos and larvae exposed from 0 to 120 hpf at environmentally relevant concentrations (10 and 100 \u03bcg\/L). Developmental toxicity, ocular morphology, retinal histology, locomotor behavior, and ocular-development-related gene expression were assessed. Single Cr(VI) exposure produced prominent effects on hatching, locomotor activity, retinal-layer thickness, and selected transcriptional responses related to retinoic acid signaling and ocular development. F-53B alone caused developmental and ocular alterations but generally produced weaker or more selective responses than Cr(VI). Co-exposure did not uniformly intensify the toxicity of either compound. Instead, the mixture enhanced some endpoints, including malformation, heart rate, and specific ocular or retinal alterations while showing weaker or divergent responses for other endpoints, such as locomotor activity and selected transcriptional markers. These findings indicate that F-53B\/Cr(VI) co-exposure produces endpoint-dependent toxicity rather than a consistent synergistic pattern. Overall, the study highlights the importance of comparing single and combined exposures across multiple biological endpoints when assessing the developmental risks of co-occurring contaminants.<\/jats:p>","DOI":"10.3390\/toxics14060471","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:31:56Z","timestamp":1779885116000},"page":"471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Developmental Toxicity of Ecologically Relevant Concentrations of the PFOS Alternative F-53B and Hexavalent Chromium in Zebrafish, Danio rerio"],"prefix":"10.3390","volume":"14","author":[{"given":"Qunjie","family":"Feng","sequence":"first","affiliation":[{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 510430, China"},{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China"},{"name":"Guangdong Basic Research Center of Excellence for Ecological Security and Green Development, Key Laboratory of City Cluster Environmental Safety and Green Development, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximei","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 510430, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 510430, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 510430, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Tong","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 510430, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Gao","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 510430, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 510430, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4611-8069","authenticated-orcid":false,"given":"Zenghua","family":"Qi","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China"},{"name":"Guangdong Basic Research Center of Excellence for Ecological Security and Green Development, Key Laboratory of City Cluster Environmental Safety and Green Development, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyang","family":"Long","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 510430, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxin","family":"Yu","sequence":"additional","affiliation":[{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 510430, China"},{"name":"Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China"},{"name":"Guangdong Basic Research Center of Excellence for Ecological Security and Green Development, Key Laboratory of City Cluster Environmental Safety and Green Development, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106877","DOI":"10.1016\/j.envint.2021.106877","article-title":"Current understanding of hexavalent chromium [Cr(VI)] neurotoxicity and new perspectives","volume":"158","author":"Wise","year":"2022","journal-title":"Environ. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.fsi.2020.09.005","article-title":"Amelioration of hexavalent chromium-induced bioaccumulation, oxidative stress, tight junction proteins and immune-related signaling factors by Allium mongolicum Regel flavonoids in Ctenopharyngodon idella","volume":"106","author":"Zhao","year":"2020","journal-title":"Fish. Shellfish Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.watres.2017.07.024","article-title":"Emerging poly-and perfluoroalkyl substances in the aquatic environment: A review of current literature","volume":"124","author":"Xiao","year":"2017","journal-title":"Water Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jenvman.2019.05.126","article-title":"Assessment of heavy metal pollution from anthropogenic activities and remediation strategies: A review","volume":"246","author":"Vareda","year":"2019","journal-title":"J. Environ. Manag."},{"key":"ref_5","unstructured":"United States Environmental Protection Agency (2026, May 23). National Recommended Water Quality Criteria: Aquatic Life Criteria Table, Available online: https:\/\/www.epa.gov\/wqc\/national-recommended-water-quality-criteria-aquatic-life-criteria-table."},{"key":"ref_6","unstructured":"Canadian Council of Ministers of the Environment (1999). Canadian Water Quality Guidelines for the Protection of Aquatic Life: Chromium, Hexavalent Chromium and Trivalent Chromium. Canadian Environmental Quality Guidelines, Canadian Council of Ministers of the Environment."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"114907","DOI":"10.1016\/j.watres.2019.114907","article-title":"Removal of F-53B as PFOS alternative in chrome plating wastewater by UV\/Sulfite reduction","volume":"163","author":"Bao","year":"2019","journal-title":"Water Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.aquatox.2017.02.002","article-title":"6:2 Chlorinated polyfluorinated ether sulfonate, a PFOS alternative, induces embryotoxicity and disrupts cardiac development in zebrafish embryos","volume":"185","author":"Shi","year":"2017","journal-title":"Aquat. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10163","DOI":"10.1021\/es401525n","article-title":"First report of a Chinese PFOS alternative overlooked for 30 years: Its toxicity, persistence, and presence in the environment","volume":"47","author":"Wang","year":"2013","journal-title":"Environ. Sci. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.chroma.2016.01.039","article-title":"Simultaneous qualitative and quantitative analysis of fluoroalkyl sulfonates in riverine water by liquid chromatography coupled with Orbitrap high resolution mass spectrometry","volume":"1435","author":"Lin","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.scitotenv.2019.02.198","article-title":"Parental exposure to 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) induced transgenerational thyroid hormone disruption in zebrafish","volume":"665","author":"Shi","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"136130","DOI":"10.1016\/j.chemosphere.2022.136130","article-title":"Environmentally relevant concentrations of F\u201353B induce eye development disorders-mediated locomotor behavior in zebrafish larvae","volume":"308","author":"Wu","year":"2022","journal-title":"Chemosphere"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"121479","DOI":"10.1016\/j.envpol.2023.121479","article-title":"Effects of PFOS, F-53B and OBS on locomotor behaviour, the dopaminergic system and mitochondrial function in developing zebrafish (Danio rerio)","volume":"326","author":"Kalyn","year":"2023","journal-title":"Environ. Pollut."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.cbpc.2010.05.010","article-title":"Biomarkers as a tool to assess effects of chromium (VI): Comparison of responses in zebrafish early life stages and adults","volume":"152","author":"Domingues","year":"2010","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"112983","DOI":"10.1016\/j.ecoenv.2021.112983","article-title":"Chromium induced neurotoxicity by altering metabolism in zebrafish larvae","volume":"228","author":"Xu","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127040","DOI":"10.1016\/j.chemosphere.2020.127040","article-title":"Polystyrene microplastics decrease F\u201353B bioaccumulation but induce inflammatory stress in larval zebrafish","volume":"255","author":"Yang","year":"2020","journal-title":"Chemosphere"},{"key":"ref_17","first-page":"102750","article-title":"Microplastics and heavy metals contamination in Atropus atropos and associated health risk assessment in the northwest of the Persian Gulf, Iran","volume":"57","author":"Esmaeilbeigi","year":"2023","journal-title":"Reg. Stud. Mar. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113926","DOI":"10.1016\/j.ecoenv.2022.113926","article-title":"Microplastics and copper induce apoptosis, alter neurocircuits, and cause behavioral changes in zebrafish (Danio rerio) brain","volume":"242","author":"Santos","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Di Paola, D., Gugliandolo, E., Capparucci, F., Cordaro, M., Iaria, C., Siracusa, R., D\u2019Amico, R., Fusco, R., Impellizzeri, D., and Cuzzocrea, S. (2022). Early exposure to environmental pollutants: Imidacloprid potentiates cadmium toxicity on zebrafish retinal cells death. Animals, 12.","DOI":"10.3390\/ani12243484"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jes.2021.12.019","article-title":"Repairing of rutin to the toxicity of combined F-53B and chromium pollution on the biofilm formed by Pseudomonas aeruginosa","volume":"127","author":"Zhang","year":"2023","journal-title":"J. Environ. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jhazmat.2013.07.030","article-title":"Phenanthrene causes ocular developmental toxicity in zebrafish embryos and the possible mechanisms involved","volume":"261","author":"Huang","year":"2013","journal-title":"J. Hazard. Mater."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13427","DOI":"10.1021\/acs.est.9b03820","article-title":"Bioconcentration and metabolic effects of emerging PFOS alternatives in developing zebrafish","volume":"53","author":"Tu","year":"2019","journal-title":"Environ. Sci. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ntt.2015.01.002","article-title":"Embryonic exposure to cadmium (II) and chromium (VI) induce behavioral alterations, oxidative stress and immunotoxicity in zebrafish (Danio rerio)","volume":"48","author":"Jin","year":"2015","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.chemosphere.2019.07.016","article-title":"Acute exposure to environmentally relevant concentrations of Chinese PFOS alternative F-53B induces oxidative stress in early developing zebrafish","volume":"235","author":"Wu","year":"2019","journal-title":"Chemosphere"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.scitotenv.2017.12.101","article-title":"Multiple approaches to assess the effects of F-53B, a Chinese PFOS alternative, on thyroid endocrine disruption at environmentally relevant concentrations","volume":"624","author":"Deng","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lundin, L., and Keiter, S.H. (2025). Zebrafish as a Model to Investigate Nanoparticles. Nanosafety: A Comprehensive Approach to Assess Nanomaterial Exposure on the Environment and Health, Springer.","DOI":"10.1007\/978-3-031-93871-9_14"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16176","DOI":"10.1007\/s11356-021-16354-4","article-title":"Specificity of time- and dose-dependent morphological endpoints in the fish embryo acute toxicity (FET) test for substances with diverse modes of action: The search for a \u201cfingerprint\u201d","volume":"29","author":"Pannetier","year":"2022","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_28","unstructured":"OECD (2025). Test No. 236: Fish Embryo Acute Toxicity (FET) Test; OECD Guidelines for the Testing of Chemicals, Section 2, OECD Publishing."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16045","DOI":"10.1038\/s41598-022-20364-8","article-title":"Combined toxicities of cadmium and five agrochemicals to the larval zebrafish (Danio rerio)","volume":"12","author":"Hu","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.chemosphere.2019.04.064","article-title":"Joint toxic effects of cadmium and four pesticides on the earthworm (Eisenia fetida)","volume":"227","author":"Yu","year":"2019","journal-title":"Chemosphere"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yin, J., Morrissey, M.E., Shine, L., Kennedy, C., Higgins, D.G., and Kennedy, B.N. (2014). Genes and signaling networks regulated during zebrafish optic vesicle morphogenesis. BMC Genom., 15.","DOI":"10.1186\/1471-2164-15-825"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1038\/sj.embor.embor919","article-title":"Loss of eyes in zebrafish caused by mutation of chokh\/rx3","volume":"4","author":"Loosli","year":"2003","journal-title":"EMBO Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.2174\/092986711795029618","article-title":"Regulation of gene expression by retinoids","volume":"18","author":"Amann","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/jat.3519","article-title":"Long-term exposure to bisphenol S damages the visual system and reduces the tracking capability of male zebrafish (Danio rerio)","volume":"38","author":"Liu","year":"2018","journal-title":"J. Appl. Toxicol."},{"key":"ref_35","first-page":"806","article-title":"A proteome map of the zebrafish (Danio rerio) lens reveals similarities between zebrafish and mammalian crystallin expression","volume":"14","author":"Posner","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1002\/jat.4440","article-title":"Chromium exposure altered metabolome and microbiome-associated with neurotoxicity in zebrafish","volume":"43","author":"Yan","year":"2023","journal-title":"J. Appl. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"119029","DOI":"10.1016\/j.ecoenv.2025.119029","article-title":"Environmental reproductive toxicity of common pesticides: Mechanisms and implications throughout the zebrafish life cycle","volume":"304","author":"Yang","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"107108","DOI":"10.1016\/j.envint.2022.107108","article-title":"Human exposure to F-53B in China and the evaluation of its potential toxicity: An overview","volume":"161","author":"He","year":"2022","journal-title":"Environ. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"037003","DOI":"10.1289\/EHP11403","article-title":"Emerging and legacy perfluoroalkyl substances in breastfed Chinese infants: Renal clearance, body burden, and implications","volume":"131","author":"Yao","year":"2023","journal-title":"Environ. Health Perspect."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1007\/s00204-025-04247-1","article-title":"In-vivo toxicokinetics of chromium in human blood and urine after intravenous injection of chromate","volume":"100","author":"Kilo","year":"2026","journal-title":"Arch. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6656","DOI":"10.1038\/s41598-023-33919-0","article-title":"Human health risk assessment of potentially toxic elements in the breast milk consumed by infants in Western Iran","volume":"13","author":"Sharafi","year":"2023","journal-title":"Sci. Rep."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/6\/471\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:28:39Z","timestamp":1779888519000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/6\/471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["toxics14060471"],"URL":"https:\/\/doi.org\/10.3390\/toxics14060471","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]}}}