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However, meeting toxicological evaluation requirements remains challenging, particularly with respect to controlled flow dynamics, usability, and biological replicates. We present a modular, tubing-free liver-on-a-chip platform with a clamping cartridge and software-controlled recirculation that enables 12 parallel channels and reproducible recirculating concentrations. Using the hepatotoxic chemical triphenyl phosphate, the platform enhanced hepatic function compared with static culture, showing higher cytochrome P450 1A2, 3A4, and 2E1 mRNA expression and increased metabolite formation. Exposure to 10 \u03bcM triphenyl phosphate altered urea, lactate dehydrogenase, and aspartate aminotransferase levels with responses occurring at lower measured concentrations on-chip than in plate-based cultures. RNA sequencing revealed pathway-level perturbations consistent with triphenyl phosphate-induced hepatotoxicity, including spliceosome and inflammatory signaling pathways. These results demonstrate advances in the toxicological application of organ-on-a-chip platforms, improving toxicity assessment through enhanced flow fidelity and parallel biological replicates.<\/jats:p>","DOI":"10.1021\/acs.est.6c03280","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:50:38Z","timestamp":1788292238000},"page":"25243-25252","source":"Crossref","is-referenced-by-count":0,"title":["Modular Liver-on-a-Chip\nPlatform for Accelerating\nToxicological Applications: A Case Study of Triphenyl Phosphate Hepatotoxicity"],"prefix":"10.1021","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0145-3581","authenticated-orcid":true,"given":"Jiyun","family":"Kang","sequence":"first","affiliation":[{"name":"Seoul National University of Science and Technology , , ,","place":["Seoul, Republic of Korea, 01811"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hohyun","family":"Jin","sequence":"additional","affiliation":[{"name":"Seoul National University of Science and Technology , , ,","place":["Seoul, Republic of Korea, 01811"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"BioSpero, Inc. , ,","place":["Jeju, Republic of Korea, 63309"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6608-5031","authenticated-orcid":true,"given":"Mangong","family":"Shin","sequence":"additional","affiliation":[{"name":"Hanyang University , , ,","place":["Ansan, Republic of Korea, 15588"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-Seop","family":"Shin","sequence":"additional","affiliation":[{"name":"Korea Research Institute of Chemical Technology , , ,","place":["Daejeon, Republic of Korea, 34114"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6618-2036","authenticated-orcid":true,"given":"Hyo-Bang","family":"Moon","sequence":"additional","affiliation":[{"name":"Hanyang University , , ,","place":["Ansan, Republic of Korea, 15588"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1130-8698","authenticated-orcid":true,"given":"Ki-Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University of Science and Technology , , ,","place":["Seoul, Republic of Korea, 01811"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"issue":"1","key":"2026091511120909200_cit1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1093\/toxsci\/kfab134","article-title":"The future of uncertainty factors with in vitro studies\nusing human cells","volume":"186","author":"Dourson","year":"2022","journal-title":"Toxicol. 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In  CompTox Chemicals Dashboard; 2025; https:\/\/comptox.epa.gov\/dashboard\/chemical\/executive-summary\/DTXSID1021952 (accessed 2025 July 10)."},{"key":"2026091511120909200_cit17","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2022.158093","article-title":"Potential adverse outcome\npathways with hazard identification of organophosphate esters","volume":"851","author":"Wang","year":"2022","journal-title":"Sci. Total Environ."},{"key":"2026091511120909200_cit18","unstructured":"Tran, C. M.\n          \n          Thyroid and\nneurological disruption of several organophosphate esters, degradation\nproducts, and mixtures in embryo-larval zebrafish and their potential\ncrosstalk. 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Saf."},{"key":"2026091511120909200_cit28","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2025.111735","article-title":"Challenges and solutions in measuring commonly used\nbiomarkers for drug-induced liver injury in a liver-on-a-chip platform","volume":"413","author":"Shi","year":"2025","journal-title":"Toxicol. Lett."},{"key":"2026091511120909200_cit29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2024.116748","article-title":"Species-specific\nmetabolism of triphenyl phosphate and its mono-hydroxylated product\nby human and rat CYP2E1 and the carp ortholog","volume":"283","author":"Hu","year":"2024","journal-title":"Ecotoxicol. Environ. 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