{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:59:17Z","timestamp":1790441957604,"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>Cytochrome P450 (CYP) enzymes play a key role in the metabolism of both xenobiotics and endogenous com-pounds, and some CYP isoforms are susceptible to induction and\/or inhibition by certain chemicals. As CYP induction\/inhibition can significantly alter the in vivo fate of xenobiotics, i.e., levels of parent chemicals and\/or metabolites, and thus their toxicity, CYP induction\/inhibition data is needed for regulatory chemical toxicity hazard assessment. Utilizing available human in vivo pharmaceutical data, a successful validation was previ-ously conducted on the in vitro HepaRG\u2122 CYP induction test method for measurement of induction of the three key human CYP enzymes CYP1A1\/1A2, 2B6 and 3A4. However, further validation data was required to demonstrate applicability of the test method to also accurately detect CYP induction mediated by industrial and pesticidal chemicals. Here we report on a supplementary validation efforts to expand the chemical applicability domain beyond pharmaceutical chemicals for the HepaRG\u2122 CYP induction test method. This was first carried out in two laboratories under the auspices of the EU Horizon2020-funded project GOLIATH. Laboratory trans-fer was demonstrated and reproducibility assessed for the original 10 selected proficiency pharmaceuticals plus three reference inducers together with six additional non-pharmaceutical \u2018augmentation chemicals\u2019. For the proficiency pharmaceuticals, the method transferred well to one laboratory and was reasonably transfera-ble for the second laboratory. For the augmentation chemicals proposed as additional proficiency chemicals, the test method achieved reasonable but not optimum reproducibility. Recommendations are proposed to im-prove the test method\u2019s specificity regarding the uncertainty around borderline CYP inducing chemicals.\nPlain language summaryCytochrome P450 (CYP) enzymes help break down drugs and other chemicals in the body. Their activity can be increased or decreased by some chemicals, which can change how toxic the chemical is and when it is excreted. Because of this, CYP data is important for chemical safety assessments. A laboratory-based method using HepaRG\u2122 cells was previously validated to measure how pharmaceutical chemicals change the activity of three key CYP enzymes. This study aimed to show that it also works well for industrial and pesticidal chemi-cals. In the EU-funded GOLIATH project, two laboratories tested 10 pharmaceutical and 6 non-pharmaceutical chemicals. The method showed good reliability and reproducibility for pharmaceuticals overall. For non-pharmaceutical chemicals, results were acceptable but less consistent. The study concludes that the method is useful for CYP induction testing, but improvements are needs to increase accuracy and better handle chem-icals that show weak or borderline CYP induction effects.<\/jats:p>","DOI":"10.14573\/altex.2606131","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:25:46Z","timestamp":1790439946000},"source":"Crossref","is-referenced-by-count":0,"title":["HepaRG&lt;sup&gt;TM&lt;\/sup&gt; CYP induction test method augmentation part 1: The GOLIATH Study"],"prefix":"10.14573","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4858-0118","authenticated-orcid":false,"given":"Miriam N.","family":"Jacobs","sequence":"first","affiliation":[{"name":"UK Health Security Agency, Dept of Toxicology, Radiation, Chemical, Climate and Environmental Hazards (RCCE), Harwell Campus, Chilton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6527-0250","authenticated-orcid":false,"given":"Elodie","family":"Person","sequence":"additional","affiliation":[{"name":"University of Toulouse, EI PURPAN, ENVT, INRAE, TOXALIM, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5044-7180","authenticated-orcid":false,"given":"Barbara","family":"Kubickova","sequence":"additional","affiliation":[{"name":"UK Health Security Agency, Dept of Toxicology, Radiation, Chemical, Climate and Environmental Hazards (RCCE), Harwell Campus, Chilton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7984-0229","authenticated-orcid":false,"given":"Jorke H.","family":"Kamstra","sequence":"additional","affiliation":[{"name":"Utrecht University, Faculty of Veterinary Medicine, Department of Population Health Sciences, Institute for Risk Assessment Sciences, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6585-5569","authenticated-orcid":false,"given":"Nicolas","family":"Cabaton","sequence":"additional","affiliation":[{"name":"University of Toulouse, EI PURPAN, ENVT, INRAE, TOXALIM, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"seh consulting + services, Paderborn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6210-4046","authenticated-orcid":false,"given":"Agn\u00e8s","family":"Jamin","sequence":"additional","affiliation":[{"name":"Biopredic International, Parc d'activit\u00e9 de la Bret\u00e8che B\u00e2timent A4, Saint Gr\u00e9goire, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Lacroix","sequence":"additional","affiliation":[{"name":"University of Toulouse, ENVT, INRAE, INTHERES, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6321-1567","authenticated-orcid":false,"given":"Juliette","family":"Legler","sequence":"additional","affiliation":[{"name":"Utrecht University, Faculty of Veterinary Medicine, Department of Population Health Sciences, Institute for Risk Assessment Sciences, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Munic Kos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Nijmeijer","sequence":"additional","affiliation":[{"name":"Utrecht University, Faculty of Veterinary Medicine, Department of Population Health Sciences, Institute for Risk Assessment Sciences, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo L.","family":"Sinnige","sequence":"additional","affiliation":[{"name":"Utrecht University, Faculty of Veterinary Medicine, Department of Population Health Sciences, Institute for Risk Assessment Sciences, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Urien","sequence":"additional","affiliation":[{"name":"University of Toulouse, EI PURPAN, ENVT, INRAE, TOXALIM, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zalko","sequence":"additional","affiliation":[{"name":"University of Toulouse, EI PURPAN, ENVT, INRAE, TOXALIM, Toulouse, France"}],"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\/3219\/3040","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.altex.org\/index.php\/altex\/article\/download\/3219\/3039","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.altex.org\/index.php\/altex\/article\/download\/3219\/3040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:25:47Z","timestamp":1790439947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.altex.org\/index.php\/altex\/article\/view\/3219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":0,"URL":"https:\/\/doi.org\/10.14573\/altex.2606131","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]]}}}