{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:17:14Z","timestamp":1789615034604,"version":"build-2803163510"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T00:00:00Z","timestamp":1581292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000139","name":"EPA","doi-asserted-by":"publisher","award":["STAR RD83561202"],"award-info":[{"award-number":["STAR RD83561202"]}],"id":[{"id":"10.13039\/100000139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P42 ES027704"],"award-info":[{"award-number":["P42 ES027704"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Academies of Sciences, Engineering, and Medicine\u2019s Gulf Research Program"},{"name":"Army Advanced Civil Schooling Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Determining the in vitro bioavailable concentration is a critical, yet unmet need to refine in vitro-to-in vivo extrapolation for unknown or variable composition, complex reaction product or biological material (UVCB) substances. UVCBs such as petroleum substances are commonly subjected to dimethyl sulfoxide (DMSO) extraction in order to retrieve the bioactive polycyclic aromatic compound (PAC) portion for in vitro testing. In addition to DMSO extraction, protein binding in cell culture media and dilution can all influence in vitro bioavailable concentrations of aliphatic and aromatic compounds in petroleum substances. However, these in vitro factors have not been fully characterized. In this study, we aimed to fill in these data gaps by characterizing the effects of these processes using both a defined mixture of analytical standards containing aliphatic and aromatic hydrocarbons, as well as 4 refined petroleum products as prototypical examples of UVCBs. Each substance was extracted with DMSO, and the protein binding in cell culture media was measured by using solid-phase microextraction. Semiquantitative analysis for aliphatic and aromatic compounds was achieved via gas chromatography-mass spectrometry. Our results showed that DMSO selectively extracted PACs from test substances, and that chemical profiles of PACs across molecular classes remained consistent after extraction. With respect to protein binding, chemical profiles were retained at a lower dilution (higher concentration), but a greater dilution factor (ie, lower concentration) resulted in higher protein binding in cell medium, which in turn altered the ultimate chemical profile of bioavailable PACs. Overall, this case study demonstrates that extraction procedures, protein binding in cell culture media, and dilution factors prior to in vitro testing can all contribute to determining the final bioavailable concentrations of bioactive constituents of UVCBs in vitro. Thus, in vitro-to-in vivo extrapolation for UVCBs may require greater attention to the concentration-dependent and compound-specific differences in recovery and bioavailability.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaa007","type":"journal-article","created":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T20:12:01Z","timestamp":1579032721000},"page":"168-177","source":"Crossref","is-referenced-by-count":12,"title":["<i>In Vitro<\/i> Bioavailability of the Hydrocarbon Fractions of Dimethyl Sulfoxide Extracts of Petroleum Substances"],"prefix":"10.1093","volume":"174","author":[{"given":"Yu-Syuan","family":"Luo","sequence":"first","affiliation":[{"name":"Interdisciplinary Faculty of Toxicology and Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle C","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Interdisciplinary Faculty of Toxicology and Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Rusyn","sequence":"additional","affiliation":[{"name":"Interdisciplinary Faculty of Toxicology and Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7575-2368","authenticated-orcid":false,"given":"Weihsueh A","family":"Chiu","sequence":"additional","affiliation":[{"name":"Interdisciplinary Faculty of Toxicology and Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,10]]},"reference":[{"key":"2021021001152026900_kfaa007-B1","year":"2000"},{"key":"2021021001152026900_kfaa007-B2","year":"2014"},{"key":"2021021001152026900_kfaa007-B3","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. 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