{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:52:43Z","timestamp":1791921163749,"version":"4.3.4"},"reference-count":48,"publisher":"American Chemical Society (ACS)","issue":"40","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["42377270"],"award-info":[{"award-number":["42377270"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["42522707"],"award-info":[{"award-number":["42522707"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Aromatic disinfection byproducts (DBPs) are emerging contaminants generated during drinking water disinfection and exhibit higher cytotoxicity and genotoxicity than traditional aliphatic DBPs. However, in vivo toxicokinetic behavior of aromatic DBPs during sensitive developmental stages remains poorly understood, limiting accurate risk assessment. Here, five aromatic DBPs within three classes (halophenols, halonitrophenol, and halohydroxybenzaldehydes) were systematically investigated using zebrafish embryos to compare developmental toxicity and characterize toxicokinetics. Developmental toxicity tests showed that the median lethal concentrations (LC50) of halonitrophenol were lower than halophenols and halohydroxybenzaldehydes, and brominated analogues were consistently more toxic than chlorinated counterparts. When expressed as median lethal residues (LR50) instead of LC50, toxicity differences decreased from 13-fold to 3-fold, indicating that reliance on external concentrations may misrepresent toxic potency. Toxicokinetic analysis showed that halophenol and halonitrophenol DBPs exhibited higher uptake and slower elimination, resulting in appreciable bioaccumulation and elevated internal exposure. In contrast, halohydroxybenzaldehydes exhibited substantially lower uptake rate constants, whereas elimination rate constants were 2\u20133 orders of magnitude higher, collectively resulting in extremely low bioaccumulation and negligible internal residues. These distinct kinetic profiles provide, for the first time among aromatic DBPs, insights linking chemical structure, internal exposure, and toxicity, supporting more biologically relevant risk-based prioritization.<\/jats:p>","DOI":"10.1021\/acs.est.6c06696","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:01:43Z","timestamp":1790823703000},"page":"28363-28371","source":"Crossref","is-referenced-by-count":0,"title":["Toxicokinetics Reveal\nStructure-Related Differences\nin Developmental Toxicity among Typical Aromatic Disinfection Byproducts\nin Zebrafish Embryos"],"prefix":"10.1021","volume":"60","author":[{"given":"Xin","family":"Li","sequence":"first","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 511443"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifang","family":"Pan","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 511443"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 511443"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5200-1916","authenticated-orcid":true,"given":"Huizhen","family":"Li","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 511443"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-8339","authenticated-orcid":true,"given":"Jing","family":"You","sequence":"additional","affiliation":[{"name":"Jinan University , , ,","place":["Guangzhou, China, 511443"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"issue":"1","key":"2026101310153972200_cit1","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1021\/acs.analchem.9b05269","article-title":"Water analysis: emerging contaminants and current issues","volume":"92","author":"Richardson","year":"2020","journal-title":"Anal. Chem."},{"issue":"42","key":"2026101310153972200_cit2","doi-asserted-by":"publisher","first-page":"22334","DOI":"10.1021\/acs.est.4c13900","article-title":"Disinfection byproducts\nconfirmed over 50 years: Systematic curation,\nmodes of toxic action, and toxicogenomics","volume":"59","author":"Xiang","year":"2025","journal-title":"Environ.\nSci. Technol."},{"issue":"2","key":"2026101310153972200_cit3","doi-asserted-by":"publisher","first-page":"56","DOI":"10.14311\/334","article-title":"Formation of haloforms during chlorination\nof natural waters","volume":"42","author":"Gru\u0308nwald","year":"2002","journal-title":"Acta Polytech."},{"key":"2026101310153972200_cit4","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.watres.2019.05.024","article-title":"Disinfection byproduct formation during drinking water\ntreatment\nand distribution: A review of unintended effects of engineering agents\nand materials","volume":"160","author":"Ding","year":"2019","journal-title":"Water Res."},{"key":"2026101310153972200_cit5","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2021.151089","article-title":"Aquatic toxicity and aquatic ecological\nrisk assessment of wastewater-derived halogenated phenolic disinfection\nbyproducts","volume":"809","author":"Wang","year":"2022","journal-title":"Sci. Total Environ."},{"key":"2026101310153972200_cit6","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/698_2011_125","article-title":"Drinking\nWater Disinfection By-products","volume-title":"Emerging\nOrganic Contaminants and Human Health","author":"Richardson","year":"2011"},{"issue":"1","key":"2026101310153972200_cit7","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1021\/acs.est.1c03292","article-title":"Comparative Toxicity Analyses from\nDifferent Endpoints: Are New Cyclic Disinfection Byproducts (DBPs)\nMore Toxic than Common Aliphatic DBPs?","volume":"56","author":"Wu","year":"2022","journal-title":"Environ.\nSci. Technol."},{"issue":"3","key":"2026101310153972200_cit8","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1021\/acs.est.2c07629","article-title":"Identification of toxicity\nforcing agents from individual aliphatic and aromatic disinfection\nbyproducts formed in drinking water: implications and limitations","volume":"57","author":"Chen","year":"2023","journal-title":"Environ. Sci. Technol."},{"key":"2026101310153972200_cit9","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.watres.2014.07.024","article-title":"Comparative toxicity\nof new halophenolic DBPs in chlorinated saline\nwastewater effluents against a marine alga: halophenolic DBPs are\ngenerally more toxic than haloaliphatic ones","volume":"65","author":"Liu","year":"2014","journal-title":"Water Res."},{"key":"2026101310153972200_cit10","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.jes.2017.04.021","article-title":"CHO cell cytotoxicity and genotoxicity analyses of\ndisinfection by-products: an updated review","volume":"58","author":"Wagner","year":"2017","journal-title":"J. Environ. Sci."},{"issue":"18","key":"2026101310153972200_cit11","doi-asserted-by":"publisher","first-page":"10590","DOI":"10.1021\/acs.est.8b02831","article-title":"Halobenzoquinone-Induced\nDevelopmental Toxicity, Oxidative Stress, and Apoptosis in Zebrafish\nEmbryos","volume":"52","author":"Wang","year":"2018","journal-title":"Environ. Sci. Technol."},{"issue":"19","key":"2026101310153972200_cit12","doi-asserted-by":"publisher","first-page":"10868","DOI":"10.1021\/es401841t","article-title":"Comparative developmental toxicity of new aromatic halogenated DBPs\nin a chlorinated saline sewage effluent to the marine polychaete Platynereis dumerilii","volume":"47","author":"Yang","year":"2013","journal-title":"Environ.\nSci. Technol."},{"issue":"12","key":"2026101310153972200_cit13","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1002\/etc.5620111205","article-title":"Toxicokinetics in aquatic systems:\nModel comparisons and use in hazard assessment","volume":"11","author":"Landrum","year":"1992","journal-title":"Environ. Toxicol. Chem."},{"issue":"2","key":"2026101310153972200_cit14","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.ecoenv.2006.07.001","article-title":"Using biological\ntraits to predict species sensitivity\nto toxic substances","volume":"67","author":"Baird","year":"2007","journal-title":"Ecotoxicol. Environ. Saf."},{"issue":"22","key":"2026101310153972200_cit15","doi-asserted-by":"publisher","first-page":"9548","DOI":"10.1021\/acs.est.4c00065","article-title":"Toxicokinetics explain\ndifferential freshwater ecotoxicity of nanoencapsulated imidacloprid\ncompared to its conventional active ingredient","volume":"58","author":"Wu","year":"2024","journal-title":"Environ. Sci. Technol."},{"issue":"29","key":"2026101310153972200_cit16","doi-asserted-by":"publisher","first-page":"10532","DOI":"10.1021\/acs.est.3c01646","article-title":"Two-compartmental toxicokinetic\nmodel predicts interspecies sensitivity variation of imidacloprid\nto aquatic invertebrates","volume":"57","author":"Su","year":"2023","journal-title":"Environ. Sci. Technol."},{"issue":"9","key":"2026101310153972200_cit17","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1021\/es00046a001","article-title":"Enhancing ecotoxicological modeling and assessment.\nBody residues and modes of toxic action","volume":"27","author":"McCarty","year":"1993","journal-title":"Environ.\nSci. Technol."},{"issue":"1","key":"2026101310153972200_cit18","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/S0378-4274(99)00022-3","article-title":"Influence\nof oral administration of a quaternary mixture of trihalomethanes\non their blood kinetics in the rat","volume":"106","author":"Luciene da Silva","year":"1999","journal-title":"Toxicol.\nLett."},{"issue":"1","key":"2026101310153972200_cit19","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.cbpc.2006.09.006","article-title":"Quantitative oral\ndosing of water soluble and lipophilic contaminants in the Japanese\nmedaka (Oryzias latipes)","volume":"145","author":"Schultz","year":"2007","journal-title":"Comp. Biochem. Physiol.,\nPart C: Toxicol. Pharmacol."},{"key":"2026101310153972200_cit20","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.ecoenv.2018.07.073","article-title":"Health risk\nassessment of trihalomethanes\nmixtures from daily water-related activities via multi-pathway exposure\nbased on PBPK model","volume":"163","author":"Zhang","year":"2018","journal-title":"Ecotoxicol. Environ. Saf."},{"issue":"3","key":"2026101310153972200_cit21","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages\nof embryonic development of the zebrafish","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev.\nDyn."},{"issue":"7446","key":"2026101310153972200_cit22","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/nature12111","article-title":"The zebrafish reference genome sequence and\nits relationship to the human genome","volume":"496","author":"Howe","year":"2013","journal-title":"Nature"},{"issue":"2","key":"2026101310153972200_cit23","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.reprotox.2011.06.121","article-title":"Zebrafish\nembryos as an alternative to animal experiments\u2500A commentary\non the definition of the onset of protected life stages in animal\nwelfare regulations","volume":"33","author":"Stra\u0308hle","year":"2012","journal-title":"Reprod. Toxicol."},{"key":"2026101310153972200_cit24","article-title":"The\nZebrafish Book: A Guide for the Laboratory Use of Zebrafish (Brachydanio rerio)","author":"Westertleld","year":"1989"},{"key":"2026101310153972200_cit25","article-title":"Fish Embryo\nAcute Toxicity (FET) Test","author":"OECD.","year":"2013"},{"issue":"16","key":"2026101310153972200_cit26","doi-asserted-by":"publisher","first-page":"11547","DOI":"10.1021\/acs.est.2c03421","article-title":"Human Apparent Volume\nof Distribution Predicts Bioaccumulation of\nIonizable Organic Chemicals in Zebrafish Embryos","volume":"56","author":"Zhang","year":"2022","journal-title":"Environ. Sci. Technol."},{"issue":"7","key":"2026101310153972200_cit27","doi-asserted-by":"publisher","first-page":"3898","DOI":"10.1021\/acs.est.8b07188","article-title":"Toxicokinetics of Perfluorinated\nAlkyl Acids Influences Their Toxic Potency in the Zebrafish Embryo\n(Danio rerio)","volume":"53","author":"Vogs","year":"2019","journal-title":"Environ. Sci. Technol."},{"issue":"7","key":"2026101310153972200_cit28","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1002\/etc.175","article-title":"Bioaccumulation\nkinetics of organic xenobiotic pollutants in the freshwater invertebrate\nGammarus pulex modeled with prediction intervals","volume":"29","author":"Ashauer","year":"2010","journal-title":"Environ. Toxicol. Chem."},{"issue":"2","key":"2026101310153972200_cit29","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.70019","article-title":"Software Update:\nThe ORCA Program System, Version 6.0","volume":"15","author":"Neese","year":"2025","journal-title":"Wiley\nInterdiscip. Rev.: Comput. Mol. Sci."},{"issue":"12","key":"2026101310153972200_cit30","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1021\/acs.jcim.5b00654","article-title":"Better Informed Distance Geometry: Using What We Know\nTo Improve Conformation Generation","volume":"55","author":"Riniker","year":"2015","journal-title":"J. Chem.\nInf. Model."},{"issue":"18","key":"2026101310153972200_cit31","doi-asserted-by":"publisher","first-page":"6378","DOI":"10.1021\/jp810292n","article-title":"Universal Solvation\nModel Based on\nSolute Electron Density and on a Continuum Model of the Solvent Defined\nby the Bulk Dielectric Constant and Atomic Surface Tensions","volume":"113","author":"Marenich","year":"2009","journal-title":"J. Phys. Chem. B"},{"issue":"7","key":"2026101310153972200_cit32","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1002\/jcc.21759","article-title":"Effect of\nthe Damping Function in\nDispersion Corrected Density Functional Theory","volume":"32","author":"Grimme","year":"2011","journal-title":"J. Comput. Chem."},{"issue":"18","key":"2026101310153972200_cit33","doi-asserted-by":"publisher","first-page":"3297","DOI":"10.1039\/b508541a","article-title":"Balanced Basis Sets\nof Split Valence, Triple Zeta Valence\nand Quadruple Zeta Valence Quality for H to Rn: Design and Assessment\nof Accuracy","volume":"7","author":"Weigend","year":"2005","journal-title":"Phys. Chem. Chem. Phys."},{"key":"2026101310153972200_cit34","doi-asserted-by":"publisher","first-page":"119458","DOI":"10.1016\/j.watres.2022.119458","article-title":"Comparative cytotoxicity,\nendocrine-disrupting effects, oxidative stress of halophenolic disinfection\nbyproducts and the underlying molecular mechanisms revealed by transcriptome\nanalysis","volume":"229","author":"Li","year":"2023","journal-title":"Water Res."},{"issue":"6","key":"2026101310153972200_cit35","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1007\/s00894-007-0176-9","article-title":"Halogen bonding\nand the design of\nnew materials: organic bromides, chlorides and perhaps even fluorides\nas donors","volume":"13","author":"Politzer","year":"2007","journal-title":"J. Mol. Model."},{"issue":"22","key":"2026101310153972200_cit36","doi-asserted-by":"publisher","first-page":"9750","DOI":"10.1021\/es202420g","article-title":"Impaired gas\nbladder\ninflation in zebrafish exposed to a novel heterocyclic brominated\nflame retardant tris (2, 3-dibromopropyl) isocyanurate","volume":"45","author":"Li","year":"2011","journal-title":"Environ. Sci. Technol."},{"key":"2026101310153972200_cit37","doi-asserted-by":"publisher","first-page":"106180","DOI":"10.1016\/j.aquatox.2022.106180","article-title":"Cadmium impairs\nzebrafish swim bladder development via ROS mediated inhibition of\nthe Wnt\/Hedgehog pathway","volume":"247","author":"Zhang","year":"2022","journal-title":"Aquat. Toxicol."},{"issue":"2","key":"2026101310153972200_cit38","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.eehl.2024.02.004","article-title":"Dihalogenated nitrophenols\nin drinking water: Prevalence, resistance to household treatment,\nand cardiotoxic impact on zebrafish embryo","volume":"3","author":"Sun","year":"2024","journal-title":"Eco-Environ. Health"},{"issue":"12","key":"2026101310153972200_cit39","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1039\/b814041n","article-title":"10th Anniversary\nCritical Review: The tissue-residue approach for toxicity assessment:\nconcepts, issues, application, and recommendations","volume":"10","author":"Meador","year":"2008","journal-title":"J. Environ. Monit."},{"issue":"11","key":"2026101310153972200_cit40","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1039\/c0em00234h","article-title":"Advantages of toxicokinetic\nand toxicodynamic modelling\nin aquatic ecotoxicology and risk assessment","volume":"12","author":"Ashauer","year":"2010","journal-title":"J. Environ. Monit."},{"issue":"7","key":"2026101310153972200_cit41","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1080\/10408440591002183","article-title":"Aldehyde sources,\nmetabolism, molecular\ntoxicity mechanisms, and possible effects on human health","volume":"35","author":"O\u2019Brien","year":"2005","journal-title":"Crit. Rev. Toxicol."},{"key":"2026101310153972200_cit42","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.freeradbiomed.2012.06.025","article-title":"An overview of the\nchemistry and biology of reactive\naldehydes","volume":"59","author":"Fritz","year":"2013","journal-title":"Free Radical Biol. Med."},{"issue":"6","key":"2026101310153972200_cit43","doi-asserted-by":"publisher","first-page":"3498","DOI":"10.1021\/es204611h","article-title":"Significance of Xenobiotic Metabolism for Bioaccumulation\nKinetics of Organic Chemicals in Gammarus pulex","volume":"46","author":"Ashauer","year":"2012","journal-title":"Environ. Sci. Technol."},{"issue":"3","key":"2026101310153972200_cit44","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1021\/acs.est.5c14563","article-title":"The Dose\nMakes the Poison\u201d: Relevance of Paracelsus\u2019s Principle\nfor Modern Chemical Hazard Assessment with New Approach Methodologies","volume":"60","author":"Escher","year":"2026","journal-title":"Environ. Sci. Technol."},{"key":"2026101310153972200_cit45","doi-asserted-by":"publisher","first-page":"107489","DOI":"10.1016\/j.aquatox.2025.107489","article-title":"Application\nof TKTD models in predicting time-resolved\nbioaccumulation and toxicity of pesticides to aquatic organisms","volume":"286","author":"Li","year":"2025","journal-title":"Aquat. Toxicol."},{"key":"2026101310153972200_cit46","doi-asserted-by":"publisher","first-page":"109134","DOI":"10.1016\/j.envint.2024.109134","article-title":"Metabolite identification of emerging disinfection byproduct dibromo-benzoquinone\nin vivo and in vitro: Multi-strategy mass-spectrometry annotation\nand toxicity characterization","volume":"193","author":"Zhou","year":"2024","journal-title":"Environ. Int."},{"issue":"1","key":"2026101310153972200_cit47","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1093\/toxsci\/kfae012","article-title":"A critical review of advances in\ntumor metabolism abnormalities induced by nitrosamine disinfection\nby-products in drinking water","volume":"199","author":"Sun","year":"2024","journal-title":"Toxicol. Sci."},{"key":"2026101310153972200_cit48","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.jhazmat.2016.09.038","article-title":"Toxicity of 2, 6-dichloro-1, 4-benzoquinone and five\nregulated drinking water disinfection by-products for the Caenorhabditis\nelegans nematode","volume":"321","author":"Zuo","year":"2017","journal-title":"J. Hazard. Mater."}],"container-title":["Environmental Science &amp;\nTechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.est.6c06696","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/60\/40\/28363\/68721159\/acs.est.6c06696.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/60\/40\/28363\/68721159\/acs.est.6c06696.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:38:57Z","timestamp":1791920337000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/esthag\/article\/60\/40\/28363\/5443070\/Toxicokinetics-Reveal-Structure-Related"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":48,"journal-issue":{"issue":"40","published-online":{"date-parts":[[2026,9,30]]},"published-print":{"date-parts":[[2026,10,13]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.est.6c06696","relation":{},"ISSN":["0013-936X","1520-5851"],"issn-type":[{"value":"0013-936X","type":"print"},{"value":"1520-5851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]}}}