{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:30:02Z","timestamp":1786980602517,"version":"build-2736575974"},"reference-count":75,"publisher":"American Chemical Society (ACS)","issue":"13","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2018YFC1406403"],"award-info":[{"award-number":["2018YFC1406403"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["41877498"],"award-info":[{"award-number":["41877498"]}],"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":["41991313"],"award-info":[{"award-number":["41991313"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019062","name":"Tianjin Research Innovation Project for Postgraduate Students","doi-asserted-by":"crossref","award":["2019YJSB051"],"award-info":[{"award-number":["2019YJSB051"]}],"id":[{"id":"10.13039\/501100019062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Given the persistence and toxic potencies of metal contaminants in ecosystems, animals, and human beings, they are considered to be hazardous global pollutants. While the lethality of metal toxicities (e.g., LC50) can significantly vary, even within the same species, the underlying mechanisms are less well-understood. In this study, we developed a subcellular two-compartment toxicokinetic-toxicodynamic (TK-TD) model for zebrafish larvae when exposed to four metals (cadmium, lead, copper, and zinc) to reveal whether differences in metal toxicity (LC50 values) were dominated by the TK or TD processes. Results showed that the subcellular TK and TD parameters of the four metals were significantly different, and the bioconcentration factor (BCF) value of copper was higher than those of the other metals. We also found that the TD parameter internal threshold concentration (CIT) was significantly positively correlated to the LC50 values (R2 = 0.7), suggesting a dominant role of TD processes in metal toxicity. Furthermore, the combined parameter CIT\/BCF for a metal-sensitive fraction (BCFMSF), which linked exposure to effects through the TK-TD approach, explained up to 89% of the variation in toxicity to the four metals. The present study suggests that the observed variation in toxicity of these four metals was mainly determined by TD processes but that TK processes should not be ignored, especially for copper.<\/jats:p>","DOI":"10.1021\/acs.est.0c08725","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T13:52:10Z","timestamp":1623765130000},"page":"8965-8976","source":"Crossref","is-referenced-by-count":26,"title":["Role\nof Toxicokinetic and Toxicodynamic Parameters\nin Explaining the Sensitivity of Zebrafish Larvae to Four Metals"],"prefix":"10.1021","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5896-4150","authenticated-orcid":true,"given":"Lanpeng","family":"Yang","sequence":"first","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, P. R. China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4003-9458","authenticated-orcid":true,"given":"Jianfeng","family":"Feng","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, P. R. China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfei","family":"Gao","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, P. R. China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, P. R. China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"2026081710283376500_cit1","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1021\/acs.est.9b04089","article-title":"Size-Dependent Sensitivity\nof Aquatic Insects to Metals","volume":"54","author":"Cadmus","year":"2020","journal-title":"Environ. Sci.\nTechnol."},{"key":"2026081710283376500_cit2","doi-asserted-by":"publisher","first-page":"4199","DOI":"10.1021\/acs.est.7b06654","article-title":"Model for\nPredicting Toxicities of Metals and Metalloids in Coastal Marine Environments\nWorldwide","volume":"52","author":"Mu","year":"2018","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit3","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.ecoenv.2018.05.026","article-title":"Effect of Cd on growth, physiological\nresponse, Cd\nsubcellular distribution and chemical forms of Koelreuteria paniculata","volume":"160","author":"Yang","year":"2018","journal-title":"Ecotox. Environ. Safe"},{"key":"2026081710283376500_cit4","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.ecoenv.2016.11.003","article-title":"Contamination\nand\nhealth risks of heavy metals in street dust from a coal mining city\nin eastern China","volume":"138","author":"Tang","year":"2017","journal-title":"Ecotox. Environ. Safe"},{"key":"2026081710283376500_cit5","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1007\/s11434-012-5403-9","article-title":"Prediction\nof metal toxicity in aquatic organisms","volume":"58","author":"Wang","year":"2013","journal-title":"Environ.\nChem."},{"key":"2026081710283376500_cit6","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.envint.2013.09.019","article-title":"Pollution\nstatus of the Bohai Sea:\nAn overview of the environmental quality assessment related trace\nmetals","volume":"62","author":"Gao","year":"2014","journal-title":"Environ. Int."},{"key":"2026081710283376500_cit7","doi-asserted-by":"publisher","first-page":"9717","DOI":"10.1021\/acs.est.6b03301","article-title":"Linking Oxidative Stress and Magnitude\nof Compensatory\nResponses with Life-Stage Specific Differences in Sensitivity of White\nSturgeon (Acipenser transmontanus) to Copper or Cadmium","volume":"50","author":"Tang","year":"2016","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit8","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1007\/s12665-011-1022-z","article-title":"Distribution\nof AVS-SEM, transformation mechanism and risk assessment of heavy\nmetals in the Nanhai Lake in China","volume":"64","author":"He","year":"2011","journal-title":"Environ.\nEarth Sci."},{"key":"2026081710283376500_cit9","doi-asserted-by":"publisher","first-page":"9549","DOI":"10.1073\/pnas.1321082111","article-title":"Organic chemicals\njeopardize the health of freshwater ecosystems on the continental\nscale","volume":"111","author":"Malaj","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026081710283376500_cit10","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1890\/15-0346","article-title":"Evolutionary\npatterns and physicochemical properties explain macroinvertebrate\nsensitivity to heavy metals","volume":"26","author":"Malaj","year":"2016","journal-title":"Ecol. Appl."},{"key":"2026081710283376500_cit11","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.ecoenv.2006.07.001","article-title":"Using biological traits to predict species sensitivity\nto toxic substances","volume":"67","author":"Baird","year":"2007","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2026081710283376500_cit12","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1002\/etc.1868","article-title":"Physiological sensitivity of freshwater macroinvertebrates to heavy\nmetals","volume":"31","author":"Malaj","year":"2012","journal-title":"Environ. Toxicol. Chem."},{"key":"2026081710283376500_cit13","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s10646-013-1147-9","article-title":"Can commonly measurable\ntraits explain differences in metal accumulation and toxicity in earthworm\nspecies?","volume":"23","author":"Qiu","year":"2014","journal-title":"Ecotoxicology"},{"key":"2026081710283376500_cit14","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.envpol.2015.07.045","article-title":"Body size-dependent\ntoxicokinetics\nand toxicodynamics could explain intra- and interspecies variability\nin sensitivity","volume":"206","author":"Gergs","year":"2015","journal-title":"Environ. Pollut."},{"key":"2026081710283376500_cit15","doi-asserted-by":"publisher","first-page":"6025","DOI":"10.1021\/acs.est.9b00893","article-title":"Modeling the Sensitivity of Aquatic Macroinvertebrates\nto Chemicals Using Traits","volume":"53","author":"Van\nden Berg","year":"2019","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit16","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1016\/j.scitotenv.2016.08.049","article-title":"Sensitivity\nof a\ntropical micro-crustacean (Daphnia lumholtzi) to trace metals tested\nin natural water of the Mekong River","volume":"574","author":"Dao","year":"2017","journal-title":"Sci. Total\nEnviron."},{"key":"2026081710283376500_cit17","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.ecoenv.2018.06.054","article-title":"Comparative\nstudy of the sensitivity\nof Daphnia galeata and Daphnia magna to heavy metals","volume":"162","author":"Cui","year":"2018","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2026081710283376500_cit18","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1002\/etc.4419","article-title":"Sensitivity\nof a Large and Representative Sample of Antarctic Marine Invertebrates\nto Metals","volume":"38","author":"Kefford","year":"2019","journal-title":"Environ. Toxicol. Chem."},{"key":"2026081710283376500_cit19","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1177\/0748233712472519","article-title":"Comparative toxicity\nof eight metals on freshwater fish","volume":"31","author":"Shuhaimi-Othman","year":"2015","journal-title":"Toxicol.\nInd. Health"},{"key":"2026081710283376500_cit20","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1002\/etc.3382","article-title":"Sensitivity\nof six subantarctic marine\ninvertebrates to common metal contaminants","volume":"35","author":"Holan","year":"2016","journal-title":"Environ. Toxicol. Chem."},{"key":"2026081710283376500_cit21","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1016\/j.scitotenv.2017.06.010","article-title":"Sensitivity\nof the glochidia (larvae) of freshwater mussels (Bivalvia: Unionida:\nHyriidae) to cadmium, cobalt, copper, lead, nickel and zinc: Differences\nbetween metals, species and exposure time","volume":"601\u2013602","author":"Markich","year":"2017","journal-title":"Sci.\nTotal Environ."},{"key":"2026081710283376500_cit22","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.jhazmat.2017.11.013","article-title":"Quantifying the interactions among\nmetal mixtures in toxicodynamic process with generalized linear model","volume":"345","author":"Feng","year":"2018","journal-title":"J. Hazard. Mater."},{"key":"2026081710283376500_cit23","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.aquatox.2011.07.010","article-title":"Metal uptake and\nacute toxicity in zebrafish: common\nmechanisms across multiple metals","volume":"105","author":"Alsop","year":"2011","journal-title":"Aquat. Toxicol."},{"key":"2026081710283376500_cit24","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.aquatox.2019.04.022","article-title":"Systematic analysis of freshwater\nmetal toxicity with WHAM-FTOX","volume":"212","author":"Tipping","year":"2019","journal-title":"Aquat. Toxicol."},{"key":"2026081710283376500_cit25","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1897\/08-361.1","article-title":"Influence\nof pH, hardness, dissolved\norganic carbon concentration, and dissolved organic matter source\non the acute toxicity of copper to Daphnia magna in soft waters: implications\nfor the biotic ligand model","volume":"28","author":"Ryan","year":"2009","journal-title":"Environ. Toxicol.\nChem."},{"key":"2026081710283376500_cit26","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.envpol.2014.08.020","article-title":"The relationship between metal toxicity\nand biotic ligand binding affinities in aquatic and soil organisms:\na review","volume":"195","author":"Ardestani","year":"2014","journal-title":"Environ. Pollut."},{"key":"2026081710283376500_cit27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2020.123205","article-title":"Predicting copper toxicity\nin zebrafish larvae under complex water chemistry conditions by using\na toxicokinetic-toxicodynamic model","volume":"400","author":"Gao","year":"2020","journal-title":"J. Hazard.\nMater."},{"key":"2026081710283376500_cit28","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.cbpc.2008.05.015","article-title":"Effects\nof water chemistry variables\non gill binding and acute toxicity of cadmium in rainbow trout (Oncorhynchus\nmykiss): A biotic ligand model (BLM) approach","volume":"148","author":"Niyogi","year":"2008","journal-title":"Comp. Biochem. Physiol., Part C: Toxicol. Pharmacol."},{"key":"2026081710283376500_cit29","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.aquatox.2012.03.019","article-title":"Subcellular\ndifferences in handling\nCu excess in three freshwater fish species contributes greatly to\ntheir differences in sensitivity to Cu","volume":"118\u2013119","author":"Eyckmans","year":"2012","journal-title":"Aquat.\nToxicol."},{"key":"2026081710283376500_cit30","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1021\/es802888u","article-title":"Biodynamics to explain\nthe difference of copper body\nconcentrations in five marine bivalve species","volume":"43","author":"Pan","year":"2009","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit31","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.chemosphere.2018.12.197","article-title":"Toxicokinetic\nand toxicodynamic (TK-TD) modeling to study oxidative stress-dependent\ntoxicity of heavy metals in zebrafish","volume":"220","author":"Gao","year":"2019","journal-title":"Chemosphere"},{"key":"2026081710283376500_cit32","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.1021\/es103092a","article-title":"General unified threshold\nmodel of survival--a toxicokinetic-toxicodynamic framework for ecotoxicology","volume":"45","author":"Jager","year":"2011","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit33","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1021\/acs.est.8b07095","article-title":"Making Acute Tests\nMore Ecologically Relevant: Cadmium Bioaccumulation and Toxicity in\nan Estuarine Clam under Various Salinities Modeled in a Toxicokinetic-Toxicodynamic\nFramework","volume":"53","author":"Tan","year":"2019","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit34","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.aquatox.2015.03.016","article-title":"Analyzing\nthe effectiveness of using branchial NKA activity as a biomarker for\nassessing waterborne copper toxicity in tilapia (Oreochromis mossambicus):\nA damage-based modeling approach","volume":"163","author":"Wu","year":"2015","journal-title":"Aquat. Toxicol."},{"key":"2026081710283376500_cit35","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17111941","article-title":"Zebrafish: A Model for the Study\nof Toxicants Affecting Muscle Development and Function","volume":"17","author":"Dubin\u0301ska-Magiera","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"2026081710283376500_cit36","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.aquatox.2015.01.011","article-title":"Subcellular partitioning\nof non-essential\ntrace metals (Ag, As, Cd, Ni, Pb, and Tl) in livers of American (Anguilla\nrostrata) and European (Anguilla anguilla) yellow eels","volume":"160","author":"Rosabal","year":"2015","journal-title":"Aquat. Toxicol."},{"key":"2026081710283376500_cit37","doi-asserted-by":"publisher","first-page":"183","DOI":"10.3354\/meps249183","article-title":"Subcellular\ncompartmentalization\nof Cd and Zn in two bivalves. I. Significance of metal-sensitive fractions\n(MSF) and biologically detoxified metal (BDM)","volume":"249","author":"Wallace","year":"2003","journal-title":"Mar. Ecol.: Prog. Ser."},{"key":"2026081710283376500_cit38","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1016\/j.chemosphere.2018.10.212","article-title":"Metal subcellular partitioning determines\nexcretion pathways and sensitivity to cadmium toxicity in two marine\nfish species","volume":"217","author":"Le\nCroizier","year":"2019","journal-title":"Chemosphere"},{"key":"2026081710283376500_cit39","doi-asserted-by":"publisher","first-page":"12654","DOI":"10.1021\/es503133g","article-title":"Uptake and subcellular\ndistributions of cadmium and selenium in transplanted aquatic insect\nlarvae","volume":"48","author":"Rosabal","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit40","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.aquatox.2008.07.014","article-title":"Trophic transfer of Cd from larval\nchironomids (Chironomus riparius) exposed via sediment or waterborne\nroutes, to zebrafish (Danio rerio): tissue-specific and subcellular\ncomparisons","volume":"90","author":"Be\u0301chard","year":"2008","journal-title":"Aquat. Toxicol."},{"key":"2026081710283376500_cit41","doi-asserted-by":"publisher","first-page":"9709","DOI":"10.1021\/es301987u","article-title":"Two-compartment toxicokinetic-toxicodynamic\nmodel to\npredict metal toxicity in Daphnia magna","volume":"46","author":"Tan","year":"2012","journal-title":"Environ.\nSci. Technol."},{"key":"2026081710283376500_cit42","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.envpol.2018.06.077","article-title":"Subcellular\ndistributions of trace elements (Cd, Pb, As, Hg, Se) in the livers\nof Alaskan yelloweye rockfish (Sebastes ruberrimus)","volume":"242","author":"Barst","year":"2018","journal-title":"Environ. Pollut."},{"key":"2026081710283376500_cit43","doi-asserted-by":"publisher","first-page":"8912","DOI":"10.1021\/acs.est.8b02600","article-title":"Waterborne\nand Dietborne Toxicity of Inorganic Arsenic to the Freshwater Zooplankton\nDaphnia magna","volume":"52","author":"Wang","year":"2018","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit44","doi-asserted-by":"publisher","first-page":"2365","DOI":"10.1897\/04-637R.1","article-title":"Dynamics of metal subcellular distribution\nand its\nrelationship with metal uptake in marine mussels","volume":"24","author":"Ng","year":"2005","journal-title":"Environ. Toxicol. Chem."},{"key":"2026081710283376500_cit45","doi-asserted-by":"publisher","first-page":"5946","DOI":"10.1021\/es5005126","article-title":"Importance\nof toxicokinetics for\ninterspecies variation in sensitivity to chemicals","volume":"48","author":"Nyman","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit46","doi-asserted-by":"publisher","first-page":"17407","DOI":"10.1007\/s11356-017-9421-7","article-title":"Evaluation on subcellular\npartitioning and biodynamics\nof pulse copper toxicity in tilapia reveals impacts of a major environmental\ndisturbance","volume":"24","author":"Ju","year":"2017","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"2026081710283376500_cit47","doi-asserted-by":"publisher","first-page":"3131","DOI":"10.1021\/es011201l","article-title":"Prediction\nof time-dependent PAH\ntoxicity in Hyalella azteca using a damage assessment model","volume":"36","author":"Lee","year":"2002","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit48","doi-asserted-by":"publisher","DOI":"10.2903\/j.efsa.2018.5377","article-title":"Scientific Opinion on the state of\nthe art of Toxicokinetic\/Toxicodynamic (TKTD) effect models for regulatory\nrisk assessment of pesticides for aquatic organisms","volume":"16","author":"Ockleford","year":"2018","journal-title":"EFSA J."},{"key":"2026081710283376500_cit49","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2019.134004","article-title":"Biokinetics and\nsubcellular distribution of metals\nin Daphnia magna following Zn exposure: Implication for metal regulation","volume":"696","author":"Zhao","year":"2019","journal-title":"Sci. Total Environ."},{"key":"2026081710283376500_cit50","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.aquatox.2018.07.001","article-title":"Subcellular\npartitioning\nof metals and metalloids (As, Cd, Cu, Se and Zn) in liver and gonads\nof wild white suckers (Catostomus commersonii) collected downstream\nfrom a mining operation","volume":"202","author":"Urien","year":"2018","journal-title":"Aquat. Toxicol."},{"key":"2026081710283376500_cit51","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1002\/etc.3998","article-title":"Binding\nof trace elements (Ag, Cd, Co, Cu, Ni, and Tl) to cytosolic biomolecules\nin livers of juvenile yellow perch (Perca flavescens) collected from\nlakes representing metal contamination gradients","volume":"37","author":"Caron","year":"2018","journal-title":"Environ. Toxicol. Chem."},{"key":"2026081710283376500_cit52","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.aquatox.2008.01.003","article-title":"Trophic transfer\nand dietary toxicity of Cd from the\noligochaete to the rainbow trout","volume":"87","author":"Ng","year":"2008","journal-title":"Aquat. Toxicol."},{"key":"2026081710283376500_cit53","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.aquatox.2012.03.019","article-title":"Subcellular\ndifferences in handling\nCu excess in three freshwater fish species contributes greatly to\ntheir differences in sensitivity to Cu","volume":"118\u2013119","author":"Eyckmans","year":"2012","journal-title":"Aquat.\nToxicol."},{"key":"2026081710283376500_cit54","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.aquatox.2008.10.007","article-title":"Bioaccumulation and\nsubcellular partitioning of zinc in rainbow trout (Oncorhynchus mykiss):\ncross-talk between waterborne and dietary uptake","volume":"91","author":"Sappal","year":"2009","journal-title":"Aquat. Toxicol."},{"key":"2026081710283376500_cit55","doi-asserted-by":"publisher","first-page":"5687","DOI":"10.1021\/acs.est.0c00189","article-title":"Linking Morphology,\nToxicokinetic, and Toxicodynamic\nTraits of Aquatic Invertebrates to Pyrethroid Sensitivity","volume":"54","author":"Dalhoff","year":"2020","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit56","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.envpol.2019.05.003","article-title":"Toxicokinetic-toxicodynamic\nmodeling of cadmium and lead toxicity to larvae and adult zebrafish","volume":"251","author":"Gao","year":"2019","journal-title":"Environ. Pollut."},{"key":"2026081710283376500_cit57","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.etap.2007.08.007","article-title":"Responses of metallothionein\nand reduced glutathione in a freshwater\nfish Oreochromis niloticus following metal exposures","volume":"25","author":"Atli","year":"2008","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"2026081710283376500_cit58","doi-asserted-by":"publisher","first-page":"13147","DOI":"10.1021\/acs.est.0c03794","article-title":"De Novo\nDevelopment of a Quantitative\nAdverse Outcome Pathway (qAOP) Network for Ultraviolet B (UVB) Radiation\nUsing Targeted Laboratory Tests and Automated Data Mining","volume":"54","author":"Song","year":"2020","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit59","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1039\/C8EM00069G","article-title":"Trace metals in oysters: molecular\nand cellular mechanisms and ecotoxicological impacts","volume":"20","author":"Wang","year":"2018","journal-title":"Environ. Sci.: Processes Impacts"},{"key":"2026081710283376500_cit60","doi-asserted-by":"publisher","first-page":"14670","DOI":"10.1021\/acs.est.9b05006","article-title":"Dynamics of Cadmium Acclimation in Daphnia pulex: Linking\nFitness Costs, Cross-Tolerance, and Hyper-Induction of Metallothionein","volume":"53","author":"Shaw","year":"2019","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit61","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.ecoenv.2006.10.005","article-title":"The determination of earthworm species\nsensitivity differences to cadmium genotoxicity using the comet assay","volume":"67","author":"Fourie","year":"2007","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2026081710283376500_cit62","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2019.104692","article-title":"Vision of\na near future: Bridging the human health-environment divide. Toward\nan integrated strategy to understand mechanisms across species for\nchemical safety assessment","volume":"62","author":"Rivetti","year":"2020","journal-title":"Toxicol. in Vitro"},{"key":"2026081710283376500_cit63","doi-asserted-by":"publisher","first-page":"14058","DOI":"10.1007\/s11356-020-07958-3","article-title":"Evaluation\nof bioconcentration and toxicity of five metals in the freshwater\nrotifer Euchlanis dilatata Ehrenberg, 1832","volume":"27","author":"Herna\u0301ndez-Flores","year":"2020","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"2026081710283376500_cit64","doi-asserted-by":"publisher","first-page":"3898","DOI":"10.1021\/acs.est.8b07188","article-title":"Toxicokinetics\nof 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."},{"key":"2026081710283376500_cit65","doi-asserted-by":"publisher","first-page":"2088","DOI":"10.1007\/s10646-012-0962-8","article-title":"Species\ntraits as predictors for intrinsic sensitivity\nof aquatic invertebrates to the insecticide chlorpyrifos","volume":"21","author":"Rubach","year":"2012","journal-title":"Ecotoxicology"},{"key":"2026081710283376500_cit66","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2020.111043","article-title":"A biological characteristic\nextrapolation of compound toxicity for different developmental stage\nspecies with toxicokinetic-toxicodynamic model","volume":"203","author":"Gao","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2026081710283376500_cit67","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.envpol.2016.07.022","article-title":"Sensitivity of the\nearly-life stages of freshwater mollusks to neonicotinoid and butenolide\ninsecticides","volume":"218","author":"Prosser","year":"2016","journal-title":"Environ. Pollut."},{"key":"2026081710283376500_cit68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.envint.2018.01.011","article-title":"Comparing the toxic\npotency in vivo of long-chain perfluoroalkyl acids and fluorinated\nalternatives","volume":"113","author":"Gomis","year":"2018","journal-title":"Environ. Int."},{"key":"2026081710283376500_cit69","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1016\/j.chemosphere.2012.01.018","article-title":"Use of\nwhole-body\nand subcellular Cu residues of Lumbriculus variegatus to predict waterborne\nCu toxicity to both L. variegatus and Chironomus riparius in fresh\nwater","volume":"87","author":"Ng","year":"2012","journal-title":"Chemosphere"},{"key":"2026081710283376500_cit70","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.aquatox.2012.05.001","article-title":"Subcellular\nmetal partitioning in\nlarvae of the insect Chaoborus collected along an environmental metal\nexposure gradient (Cd, Cu, Ni and Zn)","volume":"120\u2013121","author":"Rosabal","year":"2012","journal-title":"Aquat.\nToxicol."},{"key":"2026081710283376500_cit71","doi-asserted-by":"publisher","first-page":"6247","DOI":"10.1021\/es049844z","article-title":"Time-dependent\ntoxicity of fluoranthene\nto freshwater invertebrates and the role of biotransformation on lethal\nbody residues","volume":"38","author":"Schuler","year":"2004","journal-title":"Environ. Sci. Technol."},{"key":"2026081710283376500_cit72","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1016\/j.scitotenv.2018.01.068","article-title":"Predicting cadmium and lead toxicities\nin zebrafish (Danio rerio) larvae by using a toxicokinetic-toxicodynamic\nmodel that considers the effects of cations","volume":"625","author":"Feng","year":"2018","journal-title":"Sci. Total Environ."},{"key":"2026081710283376500_cit73","doi-asserted-by":"publisher","first-page":"13899","DOI":"10.1021\/acs.est.0c06644","article-title":"Predicting Risks\nof Cadmium Toxicity in Salinity-Fluctuating Estuarine Waters Using\nthe Toxicokinetic-Toxicodynamic Model","volume":"54","author":"Zhong","year":"2020","journal-title":"Environ.\nSci. Technol."},{"key":"2026081710283376500_cit74","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecolmodel.2019.108904","article-title":"Revisiting\nsimplified DEBtox models for analysing ecotoxicity data","volume":"416","author":"Jager","year":"2020","journal-title":"Ecol. Model."},{"key":"2026081710283376500_cit75","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2020.141027","article-title":"Sublethal\neffect modelling for environmental\nrisk assessment of chemicals: Problem definition, model variants,\napplication and challenges","volume":"745","author":"Sherborne","year":"2020","journal-title":"Sci. Total Environ."}],"container-title":["Environmental Science &amp; Technology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.est.0c08725","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/55\/13\/8965\/3700284\/es0c08725.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/55\/13\/8965\/3700284\/es0c08725.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:11:35Z","timestamp":1786979495000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/esthag\/article\/55\/13\/8965\/383413\/Role-of-Toxicokinetic-and-Toxicodynamic-Parameters"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,15]]},"references-count":75,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,6,15]]},"published-print":{"date-parts":[[2021,7,6]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.est.0c08725","relation":{},"ISSN":["0013-936X","1520-5851"],"issn-type":[{"value":"0013-936X","type":"print"},{"value":"1520-5851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,15]]}}}