{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:05:53Z","timestamp":1791885953154,"version":"4.3.4"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,2,26]],"date-time":"2022-02-26T00:00:00Z","timestamp":1645833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BASF SE"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,26]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In this study, the ability of a new in vitro\/in silico quantitative in vitro\u2013in vivo extrapolation (QIVIVE) methodology was assessed to predict the in vivo neurotoxicity of tetrodotoxin (TTX) in rodents. In vitro concentration\u2013response data of TTX obtained in a multielectrode array assay with primary rat neonatal cortical cells and in an effect study with mouse neuro-2a cells were quantitatively extrapolated into in vivo dose\u2013response data, using newly developed physiologically based kinetic (PBK) models for TTX in rats and mice. Incorporating a kidney compartment accounting for active renal excretion in the PBK models proved to be essential for its performance. To evaluate the predictions, QIVIVE-derived dose\u2013response data were compared with in vivo data on neurotoxicity in rats and mice upon oral and parenteral dosing. The results revealed that for both rats and mice the predicted dose\u2013response data matched the data from available in vivo studies well. It is concluded that PBK modeling-based reserve dosimetry of in vitro TTX effect data can adequately predict the in vivo neurotoxicity of TTX in rodents, providing a novel proof-of-principle for this methodology.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac022","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T20:11:41Z","timestamp":1645819901000},"page":"127-138","source":"Crossref","is-referenced-by-count":15,"title":["Use of Physiologically Based Kinetic Modeling-Facilitated Reverse Dosimetry to Predict<i>In Vivo<\/i>Acute Toxicity of Tetrodotoxin in Rodents"],"prefix":"10.1093","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2700-9390","authenticated-orcid":false,"given":"Annelies","family":"Noorlander","sequence":"first","affiliation":[{"name":"Division of Toxicology, Wageningen University, 6708 WE Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-5842","authenticated-orcid":false,"given":"Mengying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Toxicology, Wageningen University, 6708 WE Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bennard","family":"van Ravenzwaay","sequence":"additional","affiliation":[{"name":"Division of Toxicology, Wageningen University, 6708 WE Wageningen, The Netherlands"},{"name":"Experimental Toxicology and Ecology, BASF SE, Ludwigshafen 67056, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne M C M","family":"Rietjens","sequence":"additional","affiliation":[{"name":"Division of Toxicology, Wageningen University, 6708 WE Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,26]]},"reference":[{"key":"2022042617174854300_kfac022-B1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3390\/toxins9030075","article-title":"Acute oral toxicity of tetrodotoxin in mice: Determination of lethal dose 50 (LD50) and no observed adverse effect level (NOAEL)","volume":"9","author":"Abal","year":"2017","journal-title":"Toxins (Basel)"},{"key":"2022042617174854300_kfac022-B2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.3390\/toxins6020693","article-title":"Tetrodotoxin: Chemistry, toxicity, source, distribution and detection","volume":"6","author":"Bane","year":"2014","journal-title":"Toxins"},{"key":"2022042617174854300_kfac022-B3","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1080\/19440049.2017.1368720","article-title":"Screening for the presence of lipophilic marine biotoxins in shellfish samples using the neuro-2a bioassay","volume":"35","author":"Bodero","year":"2018","journal-title":"Food Addit. 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