Chemical Research in Toxicology最新文献

{"title":"Exploring Avenues of Predicting Drug-Induced Liver Injury","authors":"Don Pivithuru Liyanarachchi","doi":"10.1021/acs.chemrestox.6c00145","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.6c00145","url":null,"abstract":"<p>Drug induced liver injury prediction is advancing throughmechanisticmodeling, patient-derived systems, and emerging immune-based biomarkers.Integrating these approaches improves drug safety and reduces developmentfailures.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"39 9","pages":"1627–1629"},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetics of H2O2-Induced Hydroxyl Radical Release by Carcinogenic Mineral Fibers Crocidolite, Chrysotile, and Erionite","authors":"Elena Castellini,&nbsp;Alessandro F. Gualtieri","doi":"10.1021/acs.chemrestox.6c00003","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.6c00003","url":null,"abstract":"<p>Hydroxyl radicals(^•OH) display cyto-and genotoxicityand the ability to induce oxidative stress and chronic inflammationin vivo. In this work, we have monitored the kinetic profile of ^•OH radical release from the carcinogenic mineral fiberscrocidolite, chrysotile, and erionite at physiological pH (7.4). Thiswas achieved via fluorescence spectroscopy, using coumarin-3-carboxylicacid as a semiquantitative probe. A kinetic model was developed tointerpret the data. The formation of ^•OH radicalsis initiated by the binding of hydrogen peroxide (H₂O₂) to Fe²⁺ sites on the fibers, leading to oxidationto Fe³⁺ and release of ^•OH through theFenton reaction. ^•OH release was also detected atacidic pH (4.1) under conditions that mimic the intracellular environmentduring fiber phagocytosis. Although the experiments were conductedin a simplified chemical system, some hypotheses on the activity ofthe investigated fibers in the extracellular alveolar environmentcan be done. The results suggest that ^•OH generationis governed by a multistep mechanism that depends on the specificcrystal-chemical nature of the fiber. At pH 7.4, crocidolite exhibitsa radical production process which consists of a transition from arapid oxidation of pristine surface Fe²⁺ to a continuous,long-term redox cycling of Fe³⁺. A similar long-term activitywas observed for chrysotile, although masked at longer time scalesby probe adsorption. In contrast, erionite, which lacks structuraliron, releases ^•OH at a slower rate but with a long-lastingprocess, likely driven by the reduction of Fe³⁺ presentin nanoparticulate surface impurities. At long incubation times andalso at acidic pH 4.1, the kinetic model and experimental evidenceaddress the overlapping contribution of iron dissolution, indicatingthat homogeneous Fenton reactions complement the heterogeneous surfaceactivity. These findings highlight distinct, time-dependent oxidativepathways for these mineral fibers, providing deeper insights intotheir specific biochemical mechanisms.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"39 9","pages":"1659–1671"},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Mechanism of Lorlatinib-Induced Hepatotoxicity: Reactive Metabolites of Lorlatinib Activate Inflammasomes","authors":"Takumi Noda,&nbsp;Saori Tanaka,&nbsp;Chihiro Otsubo,&nbsp;Haruna Takagaki,&nbsp;Ayaka Kidani,&nbsp;Jina Suzuki,&nbsp;Mayuko Tamura-Takaori,&nbsp;Serina Mizuguchi,&nbsp;Ayumi Fujimoto,&nbsp;Kazuya Urashima,&nbsp;Yuka Kohda,&nbsp;Ryuji Kato","doi":"10.1021/acs.chemrestox.6c00327","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.6c00327","url":null,"abstract":"<p>Lorlatinib,a third-generation anaplastic lymphoma kinase (ALK)tyrosine kinase inhibitor, is widely used to treat ALK-positive nonsmallcell lung cancer. However, lorlatinib has occasionally been associatedwith severe liver injury. Immune-mediated adverse events are frequentlyprovoked by certain pharmacological agents or their reactive metabolites.However, the specific contribution of immune pathways to hepatotoxicitycaused by lorlatinib is yet to be fully elucidated. In the presentstudy, the potential for direct inflammasome stimulation by lorlatinibwas examined in differentiated THP-1 cells. This was accompanied byan evaluation of inflammasome-activating factors present in the culturesupernatants of FLC-4 cells treated with lorlatinib. Our results showedthat lorlatinib did not directly activate inflammasomes in differentiatedTHP-1 cells; however, the supernatants from FLC-4 cells activatedinflammasomes in differentiated THP-1 cells following treatment withlorlatinib. Detection of pyrido-pyrazole-containing metabolites inFLC-4 cells suggests that these reactive metabolites activate inflammasomes.Exposure of FLC-4 cells to lorlatinib resulted in elevated extracellularconcentrations of heat shock protein 90 (HSP90), a damage-associatedmolecular pattern (DAMP). These findings suggest that the reactivemetabolites of lorlatinib promote hepatocellular release of damage-associatedmolecular patterns, which in turn activate inflammasomes. Thus, inflammasomeactivation may be an important step in the activation of the immunesystem by lorlatinib and may cause immune-related adverse events insome patients.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"39 9","pages":"1878–1884"},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity Study of Therapeutically Active Copper Nitroprusside Analogue Nanoparticles: An In Vitro and In Vivo Approaches","authors":"Sanchita Tripathy,&nbsp;Swapnali Londhe,&nbsp;Sara Sangam,&nbsp;Madhusudana Kuncha,&nbsp;Yogesh Chandra,&nbsp;Chitta Ranjan Patra","doi":"10.1021/acs.chemrestox.6c00016","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.6c00016","url":null,"abstract":"<p>Copper-based nanomedicines have broader applicationsin the biomedicalsector because of their unique fundamental properties. Very recently,our group has designed and synthesized new copper nitroprusside analoguenanoparticles (CuNPANP <em>in vitro</em> and <em>in vivo</em>) anticancer therapy in both breast cancer and melanoma. The toxicitystudy of these therapeutically active nanomedicines in small and largeanimals is a prerequisite before their clinical translation. In thepresent manuscript, detailed toxicity studies of CuNPANP are demonstratedthrough various <em>in vitro</em> and <em>in vivo</em> studies. Initially, the biocompatible nature of the CuNPANP hasbeen established through several <em>in vitro</em> assays(cell viability assay, cell cycle study, apoptosis analysis, and determinationof reactive oxygen species using DCFDA) in RAW 264.7 cells. Further,the noninflammatory nature of the nanoparticles toward RAW 264.7 cellshas been investigated through immunocytochemistry (COX-2 staining)and Western blot analysis. The <em>in vivo</em> toxicity studiesof CuNPANP have been performed in a BALB/c mouse (male and female)model using therapeutic doses (1 and 5 mg kg^–1 bodyweight (b.w) in a time-dependent manner (30, 60, and 120 days). Therewere no significant changes observed in different body parameters(body weight, feed consumption, and relative organ weight) of themice and no major alterations were found in blood hematology and serumbiochemical measurements, while we compare the CuNPANP-treated groupswith the UT group. Furthermore, the histopathological examinationof male mice group upon 30, 60, and 120 days exposure reveals thebiocompatibility of CuNPANP. Further, the biodistribution study revealsthe distribution of copper in vital organs. Altogether, the resultsdemonstrate the nontoxicity and biocompatibility of the nanomaterials.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"39 9","pages":"1672–1688"},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIP13 Promotes Aflatoxin B1-Induced Hepatocellular Carcinoma Progression by Inhibiting Ferroptosis","authors":"Fanxin Zeng,&nbsp;Aoran Du,&nbsp;Yu Li,&nbsp;Hong Hu,&nbsp;Lijuan Hu,&nbsp;Rongbin Qiu","doi":"10.1021/acs.chemrestox.6c00310","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.6c00310","url":null,"abstract":"<p>Aflatoxin B1 (AFB1) is a potent foodborne hepatocarcinogenthatcontributes substantially to the global burden of hepatocellular carcinoma(HCC), yet the molecular mechanisms underlying AFB1-driven HCC progressionremain incompletely understood. In this study, we identified thyroidhormone receptor-interacting protein 13 (TRIP13) as an important contributorto AFB1-related HCC progression and investigated its involvement inferroptosis regulation. TCGA-LIHC, GSE25844, and single-cell RNA sequencingdata (GSE166635) revealed that TRIP13 was significantly upregulatedin AFB1-related HCC, enriched in malignant cell populations, and associatedwith poor clinical outcomes. In Huh7 cells, AFB1 treatment markedlyincreased TRIP13 expression, while TRIP13 knockdown significantlysuppressed AFB1-induced cell proliferation, colony formation, migration,and epithelial-mesenchymal transition (EMT). Bulk RNA sequencing andpathway enrichment analyses indicated that TRIP13 overexpression wasstrongly associated with ferroptosis-related signaling. Mechanistically,TRIP13 was associated with ferroptosis resistance through modulationof the KEAP1/NRF2/xCT/GPX4 pathway, thereby contributing to redoxhomeostasis during AFB1 exposure. Consistently, TRIP13 knockdown restoredferroptotic sensitivity, as evidenced by increased Fe²⁺ and malondialdehyde levels and altered glutathione metabolism. Importantly,ferroptosis induction with RSL3 effectively reversed the pro-tumoreffects of TRIP13 overexpression both in vitro and in vivo, includingenhanced proliferation, EMT, migration, and xenograft tumor growth.Collectively, these findings suggest that TRIP13 contributes to AFB1-associatedHCC progression through ferroptosis-related regulation and highlightthe AFB1/TRIP13/ferroptosis axis as a potential molecular mechanismand candidate target for further investigation in AFB1-related HCC.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"39 9","pages":"1867–1877"},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149010650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonsteroidal Anti-Inflammatory Drug Mefenamic Acid Induces Dysbiosis by Depleting Butyrogenic Gut Commensals","authors":"Nehal Batra,&nbsp;Prangya Ranjan Rout,&nbsp;Priyankar Dey","doi":"10.1021/acs.chemrestox.6c00394","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.6c00394","url":null,"abstract":"<p>Nonsteroidal anti-inflammatory drugs (NSAIDs) possesssevere sideeffects, including various types of gastrointestinal symptoms. Mefenamicacid is one of the most widely used NSAIDs globally. Using an anaerobic <em>in vitro</em> fermentation model, we showed that mefenamic acidreduced the abundance of gut commensals and increased the abundanceof pathobionts. Specifically, butyrate-producing commensals were reducedwith mefenamic acid treatment. These results corroborate the metabolomicsdata showing depletion of butyrate, propionate, and their derivatives.Therefore, NSAID consumption could lead to gut dysbiosis, which inturn could lead to gastrointestinal complications generally associatedwith long-term NSAID use.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"39 9","pages":"1642–1647"},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149010657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OBS Interferes with the Recovery of Intestinal Inflammation by Regulating the Gut Microbiota of Mice","authors":"Caiyun Wang,&nbsp;Yanan Gao,&nbsp;Ting Yang,&nbsp;Yanyan Li,&nbsp;Jing Sun,&nbsp;Xiaorong Chen,&nbsp;Yuanxiang Jin","doi":"10.1021/acs.chemrestox.6c00122","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.6c00122","url":null,"abstract":"<p>Per/polyfluoroalkylsubstances (PFASs) have been confirmed to havenegative health effects in animal models. As a novel alternative tolegacy PFASs, sodium ρ-perfluorous nonenoxybenzenesulfonate(OBS) raises growing concerns over environmental exposure and biologicaltoxicity. Herein, colitis models were constructed for exploring thetoxicity of OBS in intestinal homeostasis during the recovery period.The results verified the gut toxicity of OBS, which increased seruminterleukin-1β/6/17α/22 (IL-1β, IL-6, IL-17α,IL-22) levels, decreased colonic mucus secretion, and changed gutmicrobiota. During colitis recovery, no statistically significantdifference was observed in colonic mucus secretion and related geneexpression in dextran sulfate sodium-OBS (DSS-OBS) compared with theDSS; compared with the CON group, the unchanged mucus secretion andgene expression in DSS-OBS ghad still a statistically significantdifference. It indicated that the intestinal barrier disruption didnot worsen after the OBS exposure, but the recovery might be delayed.Moreover, OBS exposure significantly changed gut microbiota duringthe recovery period, suggesting that disrupted gut microbiota mightbe associated with the delay of OBS-mediated inhibition of intestinalbarrier repair. Additionally, network toxicology analysis identifiedthe action targets of OBS (including Nuclear Receptor Subfamily 1Group I Member 2 (NR1I2), Solute Carrier Family 22 Member 5 (SLC22A5),Glutathione S-Transferase Pi 1 (GSTP1), etc.), which mediate gut microbiotadisorder and intestinal barrier dysfunction, and serve as potentialbiomarkers for OBS-induced intestinal-related diseases. Collectively,OBS exhibits definitive gut toxicity. Although short-term OBS exposuredid not exacerbate the progression of colitis, it delayed the recoveryof intestinal function. Among, multiple target sites, coupled withthe gut microbiota, commonly mediate the gut toxicity of OBS. It suggestedthat the potential health risks of OBS cannot be overlooked, and therelevant departments should strengthen the management and developnext-generation alternatives.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"39 9","pages":"1702–1715"},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149010637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QSAR Modeling of Acute Aquatic Toxicity of Ethoxylated Alcohol Mixtures, and Estimation of Solubility Cut-Offs","authors":"David W. Roberts,&nbsp;M. Teresa García,&nbsp;Isabel Ribosa","doi":"10.1021/acs.chemrestox.5c00561","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.5c00561","url":null,"abstract":"<p>Commercial nonionicsurfactants are multicomponent mixtures, typicallyderived from ethoxylation of a primary alcohol that may be a mixtureof homologues and isomers with a range of degrees of ethoxylation. <em>Daphnia magna</em> and <em>Vibrio fischeri</em> toxicity data have been obtained for several nonionic surfactants,covering a wide range of average degrees of ethoxylation and parentalcohol structure, including both narrow-range and broad-range ethoxamerdistributions. These data are analyzed by means of a general narcosisquantitative structure–activity relationship (QSAR) based oncalculated log <em>P</em> values together with mixturetoxicity equations. In some cases not all components are sufficientlysoluble to make their full toxic contributions. An approach for identifyingsuch components and for taking their reduced toxic contributions intoaccount is derived from previously published structure-solubilityrelationships and validated against the experimental toxicity data.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"39 9","pages":"1648–1658"},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149010651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"To Flip or Not to Flip: Introducing the Universal Flippability Index (UFI) for Epigenetic and Damaged Nucleobases","authors":"Harikrishna Sekar Jayanthan","doi":"10.1021/acs.chemrestox.6c00181","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.6c00181","url":null,"abstract":"<p>The catalogue of chemical modificationson DNA and RNA─from5-methylcytosine (5mC) and its oxidized derivatives (5hmC, 5fC, 5caC),through oxidative damage lesions (8-oxoguanine, thymine glycol, FapyG,5-hydroxyuracil), to the RNA epitranscriptomic mark N6-methyladenosine(m⁶A)─has outpaced our mechanistic understandingof how proteins read, write and erase these marks. Structural biologyreveals a striking convergence: DNA glycosylases (UDG, hOGG1, TDG,AAG, MutY, NEIL, NTH1), methyltransferases (DNMT1, M.<em>Hha</em>I), TET dioxygenases and the m⁶A erasers FTO/ALKBH5 allemploy a shared base-flipping strategy. Yet static structural snapshotscannot explain why Thymine DNA Glycosylase rapidly excises 5fC and5caC from CpG sites while ignoring 5mC and 5hmC, nor why processingrates differ by orders of magnitude between substrates. We proposethe Universal Flippability Index (UFI), a computable thermodynamicmetric that quantifies the energetic cost of extrahelical base rotation.The UFI decomposes flippability into four physically interpretablecomponents ─ hydrogen-bond disruption (Δ<em>E</em>_HB), stacking loss (Δ<em>E</em>_Stack), steric/backbone-phosphate clash (Δ<em>E</em>_Steric), and solvent exposure (Δ<em>E</em>_Solv)─and reports a separate value for each paired conformer,e.g. <em>anti</em> vs <em>syn</em> 8-oxoG or m6A.A high UFI marks a “frustrated” base that breathes outof the helix; a low UFI marks a deeply locked nucleotide. Five casestudies illustrate the framework: (i) the TDG-selective epigeneticoxidation gradient (5mC → 5hmC → 5fC → 5caC);(ii) 8-oxoG as a steric “damage beacon”; (iii) NEIL/NTH1substrates Tg, FapyG and 5-OHU; (iv) etheno-adenine, processed byboth AAG (base excision) and ALKBH2 (direct reversal), showing thatUFI is necessary but not sufficient; and (v) m⁶A as a spring-loadedRNA switch. A computational roadmap parametrizes the UFI through quantum-mechanicalcalculations, molecular-dynamics free-energy simulations, and threeorthogonal experimental probes: imino-proton exchange, 19F NMR of2′-F-labeled substrates, and 31P NMR of the BI↔BII phosphate-backboneequilibrium.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"39 9","pages":"1630–1641"},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Biocompatibility and Toxicological Profile of Luminescent Calcium-Based Micro- and Nanomaterials","authors":"Guadalupe Genoveva Méndez Ramos,&nbsp;Yéssica Alejandra Linares González,&nbsp;Laura Morales,&nbsp;Abraham Nehemías Meza Rocha,&nbsp;Omar Soriano Romero,&nbsp;Rosendo Leovigildo Lozada Morales,&nbsp;Gilberto Alarcón Flores,&nbsp;Salvador Carmona Téllez","doi":"10.1021/acs.chemrestox.6c00080","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.6c00080","url":null,"abstract":"<p>Synthesis and characterization of calcium-based materials(CBMs)such as calcium pyrophosphate and hydroxyapatite activated with Er(III)–Yb(III)and Eu(III), respectively, are reported to establish their utilityas markers for dosimetry and biological imaging. Under 980 and 246nm excitation, these phosphors produce distinct emissions through ²H_11/2 to ⁴I_15/2 and ⁵D₀ to ⁷F₄ Er(III) and Eu(III)transitions, respectively. Despite the promising optical performanceof these materials, there is a notable lack of toxicological dataregarding lanthanides such as Er(III), Yb(III), and Eu(III) when utilizedas dopants. To address this knowledge gap, a chronic toxicity studywas performed by using the <em>Daphnia magna</em> model at 300 mg/L. The results indicate that although CBMs do notcause significant mortality, they can produce significant physiologicalchanges, such as delaying sexual maturity from 9.6 to 13 days andreducing the number of neonates per female (around 50%) in the Eu(III)-dopedsamples (the most critical case). Survival rates also showed a decrease,from 95% to near 70%, in doped hydroxyapatite. These findings suggestthat CBMs are suitable for biomedical applications because they cannotproduce either highly toxic or fatal effects at these levels. Nevertheless,their eventual implementation could require careful concentrationmanagement to protect the organism’s suitability. This workprovides an assessment of the environmental impact of these dopantsand supports their responsible integration into future device developmentand diagnostic biological imaging applications.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"39 9","pages":"1689–1701"},"PeriodicalIF":4.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}