{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:38:07Z","timestamp":1790969887144,"version":"4.1.0"},"reference-count":57,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R43ES035657"],"award-info":[{"award-number":["R43ES035657"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.taap.2025.117435","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T02:46:53Z","timestamp":1749005213000},"page":"117435","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["In vitro and computational approaches to predict developmental toxicity: Integrating PBPK models with cell-based assays"],"prefix":"10.1016","volume":"502","author":[{"given":"Marjory","family":"Moreau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todor","family":"Antonijevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Carter","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.taap.2025.117435_bb0005","doi-asserted-by":"crossref","first-page":"365","DOI":"10.2165\/11597440-000000000-00000","article-title":"Anatomical, physiological and metabolic changes with gestational age during normal pregnancy: a database for parameters required in physiologically based pharmacokinetic modelling","volume":"51","author":"Abduljalil","year":"2012","journal-title":"Clin. Pharmacokinet."},{"key":"10.1016\/j.taap.2025.117435_bb0010","doi-asserted-by":"crossref","first-page":"9770","DOI":"10.1021\/es501955g","article-title":"Application of mass balance models and the chemical activity concept to facilitate the use of in vitro toxicity data for risk assessment","volume":"48","author":"Armitage","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"10.1016\/j.taap.2025.117435_bb0015","doi-asserted-by":"crossref","DOI":"10.3390\/toxics9110315","article-title":"Update and evaluation of a high-throughput in vitro mass balance distribution model: IV-MBM EQP v2.0","volume":"9","author":"Armitage","year":"2021","journal-title":"Toxics"},{"key":"10.1016\/j.taap.2025.117435_bb0020","first-page":"49","article-title":"Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use","volume":"34","author":"Aschner","year":"2017","journal-title":"ALTEX"},{"key":"10.1016\/j.taap.2025.117435_bb0025","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/bdrc.20175","article-title":"In vitro developmental toxicology assays: a review of the state of the science of rodent and zebrafish whole embryo culture and embryonic stem cell assays","volume":"90","author":"Augustine-Rauch","year":"2010","journal-title":"Birth Defects Res. C Embryo Today"},{"key":"10.1016\/j.taap.2025.117435_bib286","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.tiv.2017.11.016","article-title":"In vitro to in vivo extrapolation for high throughput prioritization and decision making","volume":"47","author":"Bell","year":"2018","journal-title":"Toxicol In Vitro"},{"key":"10.1016\/j.taap.2025.117435_bb0030","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2022.137035","article-title":"Establishment of a human cell-based in vitro battery to assess developmental neurotoxicity hazard of chemicals","volume":"311","author":"Blum","year":"2023","journal-title":"Chemosphere"},{"key":"10.1016\/j.taap.2025.117435_bb0035","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1159\/000071463","article-title":"Developmental neurotoxicity of toluene: in vivo and in vitro effects on astroglial cells","volume":"25","author":"Burry","year":"2003","journal-title":"Dev. Neurosci."},{"key":"10.1016\/j.taap.2025.117435_bb0040","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3389\/fphys.2018.00373","article-title":"Development of the human placenta and Fetal heart: synergic or independent?","volume":"9","author":"Burton","year":"2018","journal-title":"Front. Physiol."},{"key":"10.1016\/j.taap.2025.117435_bb0045","series-title":"Proposed re-Evaluation Decision: Carbaryl, (Agency PMR ed), Ottawa, Ontario","author":"Canada","year":"2009"},{"issue":"16","key":"10.1016\/j.taap.2025.117435_bb0050","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/bdr2.2019","article-title":"Quantitative in vitro to in vivo extrapolation for developmental toxicity potency of valproic acid analogues","volume":"114","author":"Chang","year":"2022","journal-title":"Birth Defects"},{"key":"10.1016\/j.taap.2025.117435_bb0055","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/bdrb.20115","article-title":"Evaluation of the developmental toxicity of lenalidomide in rabbits","volume":"80","author":"Christian","year":"2007","journal-title":"Birth Defects Res. B Dev. Reprod. Toxicol."},{"key":"10.1016\/j.taap.2025.117435_bb0060","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0048-9697(01)00730-6","article-title":"Comparison of cancer risk estimates for vinyl chloride using animal and human data with a PBPK model","volume":"274","author":"Clewell","year":"2001","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.taap.2025.117435_bb0065","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.yrtph.2007.10.012","article-title":"Development and specification of physiologically based pharmacokinetic models for use in risk assessment","volume":"50","author":"Clewell","year":"2008","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.taap.2025.117435_bb0070","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/0278-6915(83)90211-9","article-title":"A study of the teratogenic potential of caffeine ingested in drinking-water","volume":"21","author":"Collins","year":"1983","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.taap.2025.117435_bb0075","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/0278-6915(87)90098-6","article-title":"Potential reversibility of skeletal effects in rats exposed in utero to caffeine","volume":"25","author":"Collins","year":"1987","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.taap.2025.117435_bb0080","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1021\/acs.molpharmaceut.8b01276","article-title":"Physiologically based pharmacokinetic\/pharmacodynamic model for caffeine disposition in pregnancy","volume":"16","author":"Darakjian","year":"2019","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.taap.2025.117435_bb0085","unstructured":"ECHA Toxicological Information: Ethanol. n.d."},{"key":"10.1016\/j.taap.2025.117435_bb0090","first-page":"1","article-title":"Scientific opinion of the panel on panel on plant protection products and their residues (PPR) on a request from the European Commission on potential developmental neurotoxicity of deltamethrin","author":"EFSA","year":"2009","journal-title":"EFSA J."},{"key":"10.1016\/j.taap.2025.117435_bb0095","series-title":"Toxicological Review of Toluene, Washington D.C","author":"EPA","year":"2005"},{"key":"10.1016\/j.taap.2025.117435_bb0100","series-title":"Recommended Use of Body Weight3\/4 as the Default Method in Derivation of the Oral Reference Dose, (Advisor OotS ed), Washington, DC","author":"EPA","year":"2013"},{"key":"10.1016\/j.taap.2025.117435_bb0105","article-title":"FDA memorandum - table of NOAELS and LOAELS from bisphenol a toxicity studies in FMF 580","author":"FDA","year":"2007","journal-title":"Shackelford\/Twaroski."},{"key":"10.1016\/j.taap.2025.117435_bb0110","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1093\/toxsci\/kfx169","article-title":"From the cover: developmental neurotoxicants disrupt activity in cortical networks on microelectrode arrays: results of screening 86 compounds during neural network formation","volume":"160","author":"Frank","year":"2017","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.taap.2025.117435_bb0115","doi-asserted-by":"crossref","first-page":"311","DOI":"10.14573\/altex.1701171","article-title":"OECD\/EFSA workshop on developmental neurotoxicity (DNT): the use of non-animal test methods for regulatory purposes","volume":"34","author":"Fritsche","year":"2017","journal-title":"ALTEX"},{"key":"10.1016\/j.taap.2025.117435_bb0120","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.taap.2018.04.001","article-title":"Testing for developmental neurotoxicity using a battery of in vitro assays for key cellular events in neurodevelopment","volume":"354","author":"Harrill","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.taap.2025.117435_bb0125","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0892-0362(99)00013-6","article-title":"Developmental neurotoxicity after toluene inhalation exposure in rats","volume":"21","author":"Hass","year":"1999","journal-title":"Neurotoxicol. Teratol."},{"key":"10.1016\/j.taap.2025.117435_bb0130","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1124\/dmd.112.050245","article-title":"Drug metabolism and transport during pregnancy: how does drug disposition change during pregnancy and what are the mechanisms that cause such changes?","volume":"41","author":"Isoherranen","year":"2013","journal-title":"Drug Metab. Dispos."},{"issue":"19","key":"10.1016\/j.taap.2025.117435_bb0135","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1002\/bdr2.2001","article-title":"A novel human stem cell-based biomarker assay for in vitro assessment of developmental toxicity","volume":"114","author":"Jamalpoor","year":"2022","journal-title":"Birth Defects"},{"key":"10.1016\/j.taap.2025.117435_bb0140","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0215906","article-title":"Empirical models for anatomical and physiological changes in a human mother and fetus during pregnancy and gestation","volume":"14","author":"Kapraun","year":"2019","journal-title":"PLoS One"},{"key":"10.1016\/j.taap.2025.117435_bb0145","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/978-1-4614-3055-1_6","article-title":"Physiologically-based pharmacokinetic (PBPK) models in toxicity testing and risk assessment","volume":"745","author":"Lipscomb","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.taap.2025.117435_bb0150","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1093\/toxsci\/kfz211","article-title":"Development and application of a life-stage physiologically based pharmacokinetic (PBPK) model to the assessment of internal dose of pyrethroids in humans","volume":"173","author":"Mallick","year":"2020","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.taap.2025.117435_bb0155","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1093\/toxsci\/kfaa070","article-title":"Physiologically based pharmacokinetic modeling in risk assessment: case study with pyrethroids","volume":"176","author":"Mallick","year":"2020","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.taap.2025.117435_bb0160","doi-asserted-by":"crossref","DOI":"10.1016\/j.ntt.2022.107117","article-title":"An expert-driven literature review of \u201cnegative\u201d chemicals for developmental neurotoxicity (DNT) in vitro assay evaluation","volume":"93","author":"Martin","year":"2022","journal-title":"Neurotoxicol. Teratol."},{"key":"10.1016\/j.taap.2025.117435_bb0165","series-title":"Establishment of an a Priori Protocol for the Implementation and Interpretation of an In-Vitro Testing Battery for the as-SESSMENT of developmental Neurotoxicity, (2020:EN-1938. Esp ed)","first-page":"152","author":"Masjosthusmann","year":"2020"},{"key":"10.1016\/j.taap.2025.117435_bb0170","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fphar.2011.00031","article-title":"A workflow for global sensitivity analysis of PBPK models","volume":"2","author":"McNally","year":"2011","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.taap.2025.117435_bb0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.tox.2023.153684","article-title":"Animal-free assessment of developmental toxicity: combining PBPK modeling with the ReproTracker assay","volume":"500","author":"Moreau","year":"2023","journal-title":"Toxicology"},{"key":"10.1016\/j.taap.2025.117435_bb0180","series-title":"Data-Driven Evaluation of PBPK Models for Developmental Toxicity","author":"Moreau","year":"2025"},{"key":"10.1016\/j.taap.2025.117435_bb0185","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/0890-6238(93)90025-3","article-title":"Assessment of the effectiveness of animal developmental toxicity testing for human safety","volume":"7","author":"Newman","year":"1993","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.taap.2025.117435_bb0190","series-title":"Postnatal Evaluation of Behaviour and Cardiovascular Function in Rats Following Daily Oral Caffeine Dosing of Dams Throughout Gestation, Final Report, (Research NCfT ed)","author":"NTP","year":"1984"},{"key":"10.1016\/j.taap.2025.117435_bb0195","series-title":"Caffeine: SIDS Initial Assessment Report for SIAM 14, Paris, France","author":"OECD","year":"2002"},{"key":"10.1016\/j.taap.2025.117435_bb0200","series-title":"Initial Recommendations on Evaluation of Data from the Developmental Neurotoxicity (DNT) in-Vitro Testing Battery","author":"OECD","year":"2023"},{"key":"10.1016\/j.taap.2025.117435_bb0205","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/bdrb.21078","article-title":"Establishment and assessment of a new human embryonic stem cell-based biomarker assay for developmental toxicity screening","volume":"98","author":"Palmer","year":"2013","journal-title":"Birth Defects Res. B Dev. Reprod. Toxicol."},{"key":"10.1016\/j.taap.2025.117435_bb0210","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.reprotox.2017.07.011","article-title":"A human induced pluripotent stem cell-based in vitro assay predicts developmental toxicity through a retinoic acid receptor-mediated pathway for a series of related retinoid analogues","volume":"73","author":"Palmer","year":"2017","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.taap.2025.117435_bb0215","first-page":"350","article-title":"ReproTracker, a human stem cell-based reporter assay for in vitro dart assessment","volume":"73","author":"Racz","year":"2018","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.taap.2025.117435_bb0225","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.placenta.2020.07.009","article-title":"Differences in cytochrome p450 enzyme expression and activity in fetal and adult tissues","volume":"100","author":"Robinson","year":"2020","journal-title":"Placenta"},{"key":"10.1016\/j.taap.2025.117435_bb0230","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.envint.2016.11.030","article-title":"Quantitative bias analysis for epidemiological associations of perfluoroalkyl substance serum concentrations and early onset of menopause","volume":"99","author":"Ruark","year":"2017","journal-title":"Environ. Int."},{"key":"10.1016\/j.taap.2025.117435_bb0235","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3109\/10408448909037473","article-title":"Potential human developmental toxicants and the role of animal testing in their identification and characterization","volume":"19","author":"Schardein","year":"1989","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.taap.2025.117435_bb0240","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1007\/s00204-011-0767-1","article-title":"Developmental toxicity testing in the 21st century: the sword of Damocles shattered by embryonic stem cell assays?","volume":"85","author":"Seiler","year":"2011","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.taap.2025.117435_bb0245","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.envres.2016.07.004","article-title":"Pharmacokinetic bias analysis of the epidemiological associations between serum polybrominated diphenyl ether (BDE-47) and timing of menarche","volume":"150","author":"Song","year":"2016","journal-title":"Environ. Res."},{"key":"10.1016\/j.taap.2025.117435_bb0250","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/978-3-642-69928-3_95","article-title":"On the embryotoxic effects of benzene and its alkyl derivatives in mice, rats and rabbits","volume":"8","author":"Ungvary","year":"1985","journal-title":"Arch. Toxicol. Suppl."},{"key":"10.1016\/j.taap.2025.117435_bb0255","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.tox.2014.05.012","article-title":"Quantitative in vitro-to-in vivo extrapolation in a high-throughput environment","volume":"332","author":"Wetmore","year":"2015","journal-title":"Toxicology"},{"key":"10.1016\/j.taap.2025.117435_bb0260","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/toxsci\/kfr254","article-title":"Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment","volume":"125","author":"Wetmore","year":"2012","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.taap.2025.117435_bb0265","series-title":"Characterization and Application of Physiologically Based Pharmacokinetic Models in Risk Assessment, (Organization WH ed), Geneva, Switzerland","author":"WHO","year":"2010"},{"key":"10.1016\/j.taap.2025.117435_bb0270","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3390\/ijms10010037","article-title":"Developmental toxicity of ochratoxin a in rat embryo midbrain micromass cultures","volume":"10","author":"Wilk-Zasadna","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.taap.2025.117435_bb0275","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.envint.2015.05.006","article-title":"Can the observed association between serum perfluoroalkyl substances and delayed menarche be explained on the basis of puberty-related changes in physiology and pharmacokinetics?","volume":"82","author":"Wu","year":"2015","journal-title":"Environ. Int."},{"key":"10.1016\/j.taap.2025.117435_bb0280","doi-asserted-by":"crossref","first-page":"167","DOI":"10.14573\/altex.1601252","article-title":"Supporting read-across using biological data","volume":"33","author":"Zhu","year":"2016","journal-title":"ALTEX"},{"key":"10.1016\/j.taap.2025.117435_bb0285","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2020.590540","article-title":"Assessment of ethanol-induced toxicity on iPSC-derived human neurons using a novel high-throughput mitochondrial neuronal health (MNH) assay","volume":"8","author":"Zink","year":"2020","journal-title":"Front. Cell Dev. Biol."}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X2500211X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X2500211X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T17:27:34Z","timestamp":1753205254000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X2500211X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":57,"alternative-id":["S0041008X2500211X"],"URL":"https:\/\/doi.org\/10.1016\/j.taap.2025.117435","relation":{"is-supplemented-by":[{"id-type":"uri","id":"https:\/\/data.mendeley.com\/datasets\/mf5pg3zxh6\/1","asserted-by":"subject"}]},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"In vitro and computational approaches to predict developmental toxicity: Integrating PBPK models with cell-based assays","name":"articletitle","label":"Article Title"},{"value":"Toxicology and Applied Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.taap.2025.117435","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117435"}}