{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:59:04Z","timestamp":1790441944899,"version":"4.1.0"},"reference-count":0,"publisher":"ALTEX Edition","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ALTEX"],"abstract":"<jats:p>Brain development is highly dependent on hormonal signaling, hence developmental exposure to endocrine disrupting chemicals (EDCs) is of high concern. However, existing EDC hazard assessment methods lack the capacity to connect developmental neurotoxicity (DNT) to an endocrine mode of action, creating an urgent need for innovative tools addressing endocrine disruption (ED)-induced DNT. We have previously shown the applicability of the immortalized C17.2 murine neural progenitor cells for addressing ED-DNT. In this test sys-tem, the key neurodevelopmental processes (KNDPs) neurite outgrowth and branching were decreased by agonism of retinoic acid receptor (RAR), retinoic X receptor (RXR) and peroxisome proliferator-activated recep-tor (PPAR) \u03b2\/\u03b4. In the current study we further validate the use, and assess the added value, of the C17.2 test system for detection of ED-induced DNT by testing the effects of 17 chemicals on neuronal morphology and comparing the results to published DNT in vitro toxicity data. Out of the tested chemicals, endosulfan and cy-permethrin decreased neurite outgrowth and branching when tested alone. However, while permethrin, bi-sphenol F (BPF), benzyl butyl phthalate (BBzP) and its metabolite MBzP, perfluorooctanesulfonic acid (PFOS), and 3-phenoxybenzoic acid (3-PBA) did not independently reduce neurite outgrowth, they counteracted RAR, RXR or PPAR\u03b2\/\u03b4 agonist-induced decreases, indicating antagonistic activity. Compared to neurite morphology-related endpoints in ToxCast, C17.2 cells identified more chemicals as active, with increased sensitivity to this endpoint category. These findings confirm that the C17.2 test system is a valuable in vitro model for detecting ED-induced DNT, and that receptor agonist co-treatment enables identification of additional DNT compounds.\nPlain language summaryChemicals in our environment can interfere with the body\u2019s hormonal system and harm brain development, particularly in children. Identifying which chemicals pose this risk is challenging because current testing meth-ods are limited in their ability to connect hormone disruption to developmental brain damage. The current study demonstrated that a cell-based model, C17.2 cells, can reliably detect chemicals that disrupt hormonal path-ways linked to abnormal brain development. By observing the morphology of these cells, we can identify both chemicals that activate and those that block hormonal signals. The C17.2 model addresses a critical gap in current guidelines for assessing hormone-disrupting chemicals while reducing and replacing the need for ani-mal testing in line with the 3R principles, making it a valuable tool for improving chemical safety assessment and protecting public health.<\/jats:p>","DOI":"10.14573\/altex.2605181","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:28:54Z","timestamp":1790440134000},"source":"Crossref","is-referenced-by-count":0,"title":["Linking nuclear receptor antagonism with neuronal morphology improves detection of developmental neurotoxicants"],"prefix":"10.14573","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0237-3594","authenticated-orcid":true,"given":"Andrea","family":"Cediel-Ulloa","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"publisher"}],"name":"Uppsala University"},{"name":"Department of Organismal Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Guissard","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"publisher"}],"name":"Uppsala University"},{"name":"Department of Organismal Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Eriksson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"publisher"}],"name":"Uppsala University"},{"name":"Department of Organismal Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3414-7409","authenticated-orcid":true,"given":"Saga","family":"H\u00f6rling","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"publisher"}],"name":"Uppsala University"},{"name":"Department of Organismal Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6298-201X","authenticated-orcid":true,"given":"Anna","family":"Forsby","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f0yaq80","id-type":"ROR","asserted-by":"publisher"}],"name":"Stockholm University"},{"name":"Department of Biochemistry and Biophysics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6580-9201","authenticated-orcid":true,"given":"Jo\u00eblle","family":"R\u00fcegg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"publisher"}],"name":"Uppsala University"},{"name":"Department of Organismal Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"5675","published-online":{"date-parts":[[2026,9,25]]},"container-title":["ALTEX - Alternatives to Animal Experimentation"],"original-title":[],"link":[{"URL":"https:\/\/www.altex.org\/index.php\/altex\/article\/download\/3203\/3043","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.altex.org\/index.php\/altex\/article\/download\/3203\/3033","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.altex.org\/index.php\/altex\/article\/download\/3203\/3043","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:28:54Z","timestamp":1790440134000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.altex.org\/index.php\/altex\/article\/view\/3203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":0,"URL":"https:\/\/doi.org\/10.14573\/altex.2605181","relation":{},"ISSN":["1868-8551","1868-596X"],"issn-type":[{"value":"1868-8551","type":"electronic"},{"value":"1868-596X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9,25]]}}}