{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:45:00Z","timestamp":1770079500392,"version":"3.49.0"},"reference-count":29,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>Higher olefins are a class of alkenes widely used as intermediates in the production of essential consumer and industrial products. This radiolabel disposition and partial mass balance study investigated the distribution and excretion of four 14C-radiolabelled alpha higher olefins (i.e., 1-octene, 1-decene, 1-hexadecene, and 1-eicosene) in male Wistar rats following a single oral dose (100 mg\/kg). Blood, liver, kidney, adipose tissue, urine, and faeces were collected and analysed for total 14C-derived radioactivity. Urinary elimination was rapid, with approximately 70% and 90% of total radioactivity recovered in urinary excreted within 24 and 48 h, respectively. Excretion patterns showed a clear chain-length-dependent trend: shorter-chain olefins (C8, C10) exhibited higher urinary excretion, indicating greater systemic absorption, while longer-chain olefins (C16, C20) were primarily eliminated via faeces, suggesting limited intestinal uptake. Tissue distribution was minimal in blood, liver, and kidney, but adipose tissue retention increased with chain length. Total recovery of administered radioactivity in the analysed matrices was low, ranging from 17% to 60%. Importantly, because exhaled 14CO2 and volatile parent compounds were not captured, the missing fraction cannot be quantified and the balance cannot be considered closed. All in all, the current study describes the partial disposition of higher olefins and highlights the influence of molecular size and lipophilicity on the biological fat, though further studies are required to fully characterise their metabolic profile and total elimination kinetics.<\/jats:p>","DOI":"10.3390\/jox16010026","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:00:47Z","timestamp":1770033647000},"page":"26","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toxicokinetic and Partial Mass Balance Assessment of 14C-Alpha Olefins in Rats"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8491-9548","authenticated-orcid":false,"given":"Quan","family":"Shi","sequence":"first","affiliation":[{"name":"Shell Global Solutions International B.V., Carel van Bylandtlaan 16, 2596 HR The Hague, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Dunn","sequence":"additional","affiliation":[{"name":"Penman Consulting BVBA, Avenue des Arts 10, 1210 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan-Carlos","family":"Carrillo","sequence":"additional","affiliation":[{"name":"Shell Global Solutions International B.V., Carel van Bylandtlaan 16, 2596 HR The Hague, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael G.","family":"Penman","sequence":"additional","affiliation":[{"name":"Penman Consulting BVBA, Avenue des Arts 10, 1210 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H.","family":"Powrie","sequence":"additional","affiliation":[{"name":"CXR Biosciences Ltd., 2 James Lindsay Place, Dundee Technopole, Dundee DD1 5JJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5913-3907","authenticated-orcid":false,"given":"Corinne","family":"Haines","sequence":"additional","affiliation":[{"name":"Penman Consulting BVBA, Avenue des Arts 10, 1210 Brussels, Belgium"},{"name":"CXR Biosciences Ltd., 2 James Lindsay Place, Dundee Technopole, Dundee DD1 5JJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Shen","sequence":"additional","affiliation":[{"name":"Shell Oil Company, 150 N. Dairy Ashford Rd., Houston, TX 77079, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Tian","sequence":"additional","affiliation":[{"name":"Faculty of Brain Sciences, University College London, 11-43 Bath St., London EC1V 9EL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Jia","sequence":"additional","affiliation":[{"name":"Chevron Phillips Chemical Company, 9500 Lakeside Blvd., Houston, TX 77381, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2607-321X","authenticated-orcid":false,"given":"Fabienne","family":"Hubert","sequence":"additional","affiliation":[{"name":"INEOS Oligomers, Hawkslease, Chapel Lane, Hampshire SO43 7FG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6964-6681","authenticated-orcid":false,"given":"Peter J.","family":"Boogaard","sequence":"additional","affiliation":[{"name":"Division of Toxicology, Wageningen University and Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1021\/acs.chemrestox.2c00089","article-title":"Assessment of the Intestinal Absorption of Higher Olefins by the Everted Gut Sac Model in Combination with In Silico New Approach Methodologies","volume":"35","author":"Shi","year":"2022","journal-title":"Chem. Res. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/0009-2509(81)80161-3","article-title":"Thermal cracking for olefins production. Fundamentals and their application to industrial problems","volume":"36","author":"Froment","year":"1981","journal-title":"Chem. Eng. Sci."},{"key":"ref_3","unstructured":"Klaus, W., and Hans-J\u00fcrgen, A. (2008). Industrial Organic Chemistry, John Wiley & Sons."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1177\/10915818231210856","article-title":"Toxicological Assessment of Higher Olefins in OECD TG 422 Repeated Dose and Reproductive\/Developmental Toxicity Screening Tests in Han Wistar Rats","volume":"43","author":"Shi","year":"2024","journal-title":"Int. J. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Shi, Q., Penman, M.G., Carrillo, J.-C., Rompay, A.R.V., Kamelia, L., Rooseboom, M., Shen, H., Jia, S., Tian, Y., and Dunn, J. (2024). The subchronic toxicity of higher olefins in Han Wistar rats. BMC Pharmacol. Toxicol., 25.","DOI":"10.1186\/s40360-024-00786-y"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105070","DOI":"10.1016\/j.yrtph.2021.105070","article-title":"Opportunities and challenges related to saturation of toxicokinetic processes: Implications for risk assessment","volume":"127","author":"Tan","year":"2021","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5234","DOI":"10.1016\/S0021-9258(18)62746-2","article-title":"Epoxides as Obligatory Intermediates in the Metabolism of Olefins to Glycols","volume":"245","author":"Maynert","year":"1970","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3109\/00498257309151525","article-title":"Mammalian Epoxide Hydrases: Inducible Enzymes Catalysing the Inactivation of Carcinogenic and Cytotoxic Metabolites Derived from Aromatic and Olefinic Compounds","volume":"3","author":"Franz","year":"1973","journal-title":"Xenobiotica"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1021\/tx00042a006","article-title":"The oxidation of tetrasubstituted alkenes by cytochrome P450","volume":"7","author":"Gorycki","year":"1994","journal-title":"Chem. Res. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/S0026-895X(25)14207-7","article-title":"Destruction of cytochrome P-450 by ethylene and other olefins","volume":"18","author":"Mico","year":"1980","journal-title":"Mol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8686","DOI":"10.1021\/ja00180a008","article-title":"Theoretical investigations of terminal alkenes as putative suicide substrates of cytochrome P-450","volume":"112","author":"Luke","year":"1990","journal-title":"J. Am. Chem. Soc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/0006-2952(75)90445-1","article-title":"The biotransformation of 1-hexadecene to carcinogenic 1,2-epoxyhexadecane by hepatic microsomes","volume":"24","author":"Watabe","year":"1975","journal-title":"Biochem. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/0006-2952(86)90126-7","article-title":"Metabolic activation of olefins. Conversion of 1-octene to a putative reactive intermediate 1-octen-3-one: An alternative pathway to epoxidation","volume":"35","author":"White","year":"1986","journal-title":"Biochem. Pharmacol."},{"key":"ref_14","unstructured":"Klaassen, C.D. (2008). Casarett and Doull\u2019s Toxicology: The Basic Science of Poisons [Internet], McGraw-Hill. [7th ed.]."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1600-0773.1993.tb01557.x","article-title":"Inhalation kinetics of C8 to C10 1-alkenes and iso-alkanes in the rat after repeated exposures","volume":"73","author":"Zahlsen","year":"1993","journal-title":"Pharmacol. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1021\/jacsau.2c00030","article-title":"Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges","volume":"2","author":"Babin","year":"2022","journal-title":"JACS Au"},{"key":"ref_17","first-page":"1101","article-title":"Metabolic disposition of the new fluoroquinolone antibacterial agent DW116 in rats","volume":"25","author":"Park","year":"1997","journal-title":"Drug Metab. Dispos."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"711","DOI":"10.3109\/00498254.2015.1016475","article-title":"Metabolic disposition of the anti-cancer agent [(14)C]laromustine in male rats","volume":"45","author":"Nassar","year":"2015","journal-title":"Xenobiotica"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108756","DOI":"10.1016\/j.reprotox.2024.108756","article-title":"Prenatal developmental toxicity evaluation of higher olefins in Sprague-Dawley rats","volume":"132","author":"Shi","year":"2025","journal-title":"Reprod. Toxicol."},{"key":"ref_20","unstructured":"OECD (2010). Test No. 417: Toxicokinetics [Internet]. OECD Guidelines for the Testing of Chemicals, OECD."},{"key":"ref_21","unstructured":"(2025, May 13). ECHA REACH-Registration, Evaluation, Authorisation and Restriction of Chemicals Regulation-Oct-1-ene (CAS Number: 111-66-0) Acute Toxicity Endpoint Summary [Internet]. Available online: https:\/\/echa.europa.eu\/registration-dossier\/-\/registered-dossier\/15355\/7\/3\/1."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Faber, K. (2018). Biotransformations in Organic Chemistry, Springer.","DOI":"10.1007\/978-3-319-61590-5"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Boji\u0107, M., Debeljak, \u017d., and Guengerich, F.P. (2023). Principles of Xenobiotic Metabolism (Biotransformation). Pharmacogenomics in Clinical Practice, Springer International Publishing.","DOI":"10.1007\/978-3-031-45903-0_2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"a040576","DOI":"10.1101\/cshperspect.a040576","article-title":"Lipid Metabolism","volume":"13","author":"Chandel","year":"2021","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10545-010-9061-2","article-title":"A general introduction to the biochemistry of mitochondrial fatty acid \u03b2-oxidation","volume":"33","author":"Houten","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-chain fatty acids: Linking diet, the microbiome and immunity","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","first-page":"11","article-title":"Nutrient Utilization in Humans: Metabolism Pathways","volume":"3","author":"Poian","year":"2010","journal-title":"Nat. Educ."},{"key":"ref_28","unstructured":"EPA (2011). Screening-level hazard characterization of high production volume chemicals\u2014Higher Olefins Category. U.S. Environmental Protection Agency Hazard Characterization Document, U.S. Environmental Protection Agency."},{"key":"ref_29","first-page":"820","article-title":"Standard Water Generating Vials for Lipophilic Compounds","volume":"95","author":"Dincel","year":"2023","journal-title":"Anal. Chem."}],"container-title":["Journal of Xenobiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4713\/16\/1\/26\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:37:06Z","timestamp":1770035826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4713\/16\/1\/26"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jox16010026"],"URL":"https:\/\/doi.org\/10.3390\/jox16010026","relation":{},"ISSN":["2039-4713"],"issn-type":[{"value":"2039-4713","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]}}}