{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:01:25Z","timestamp":1790892085684,"version":"4.1.0"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Clariant Produkte (Deutschland) GmbH","award":["Clariant Produkte (Deutschland) GmbH"],"award-info":[{"award-number":["Clariant Produkte (Deutschland) GmbH"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1007\/s00204-025-04260-4","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:55:04Z","timestamp":1769619304000},"page":"2111-2134","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reassessing the carcinogenic potential of dibutyl hydrogen phosphate: new insight from repeated-dose toxicity studies"],"prefix":"10.1007","volume":"100","author":[{"given":"Susann","family":"Fayyaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0352-2985","authenticated-orcid":false,"given":"Ursula G.","family":"Sauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Guthmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Lichtblau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Hufnagel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1112-2922","authenticated-orcid":false,"given":"Fabian A.","family":"Grimm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"4260_CR1","unstructured":"Note: All websites were accessed in September 2025"},{"issue":"1","key":"4260_CR2","doi-asserted-by":"publisher","first-page":"18330","DOI":"10.1038\/s41598-024-69157-1","volume":"14","author":"MA Aljallal","year":"2024","unstructured":"Aljallal MA, Chaudhry Q, Price NR (2024) Assessment of performance of the profilers provided in the OECD QSAR toolbox for category formation of chemicals. Sci Rep 14(1):18330. https:\/\/doi.org\/10.1038\/s41598-024-69157-1","journal-title":"Sci Rep"},{"issue":"2","key":"4260_CR3","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/0027-5107(91)90061-r","volume":"248","author":"RL Anderson","year":"1991","unstructured":"Anderson RL (1991) Early indicators of bladder carcinogenesis produced by non-genotoxic agents. Mutat Res 248(2):261\u2013270. https:\/\/doi.org\/10.1016\/0027-5107(91)90061-r","journal-title":"Mutat Res"},{"key":"4260_CR5","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1006\/faat.1997.2391","volume":"40","author":"LL Arnold","year":"1997","unstructured":"Arnold LL, Christenson WR, Cano M, John MK, Wahle BS, Cohen SM (1997) Tributyl phosphate effects on urine and bladder epithelium in male Sprague-Dawley rats. Fundam Appl Toxicol 40:247\u2013255. https:\/\/doi.org\/10.1006\/faat.1997.2391","journal-title":"Fundam Appl Toxicol"},{"issue":"4","key":"4260_CR4","doi-asserted-by":"publisher","first-page":"266","DOI":"10.3139\/113.110570","volume":"55","author":"P Arora","year":"2018","unstructured":"Arora P, Singh R, Seshadri G, Kumar Tyagi A (2018) Synthesis, properties and applications of anionic phosphate ester surfactants: a review. Tenside Surf Det 55(4):266\u2013272. https:\/\/doi.org\/10.3139\/113.110570","journal-title":"Tenside Surf Det"},{"key":"4260_CR6","unstructured":"ATSDR (2012) Agency for Toxic Substances and Disease Registry. Toxicological profiles for phosphate ester flame retardants. US Department of Health and Human Services. Public Health Service, September 2012. https:\/\/www.atsdr.cdc.gov\/ToxProfiles\/tp202.pdf"},{"key":"4260_CR7","unstructured":"Auletta CS, Wooding WL, Kotkoskie LA (1997) Sub-chronic dietary toxicity study with tributyl phosphate in the mouse. Abstract no. 882 of the 36th Annual Meeting of the Society of Toxicology, 9\u201313 March 1997, Cincinnati, OH, Toxicologist (36):173\u2013174"},{"key":"4260_CR8","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/s0300-483x(98)00057-2","volume":"128","author":"CS Auletta","year":"1998","unstructured":"Auletta CS, Weiner ML, Richter WR (1998a) A dietary toxicity\/oncogenicity study of tributyl phosphate in the rat. Toxicology 128:125\u2013134. https:\/\/doi.org\/10.1016\/s0300-483x(98)00057-2","journal-title":"Toxicology"},{"key":"4260_CR9","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/s0300-483x(98)00056-0","volume":"128","author":"CS Auletta","year":"1998","unstructured":"Auletta CS, Kotkoskie LA, Saulog T, Richter WR (1998b) A dietary oncogenicity study of tributyl phosphate in the CD-1 mouse. Toxicology 128:135\u2013141. https:\/\/doi.org\/10.1016\/s0300-483x(98)00056-0","journal-title":"Toxicology"},{"key":"4260_CR10","unstructured":"BG RCI (2000) Institution for Statutory Accident Insurance and Prevention Raw Materials and Chemical Industry. Toxicological evaluations No. 170. Tributyl phosphate CAS No. 126-73-8, last updated 11\/2000; https:\/\/www.bgrci.de\/fileadmin\/BGRCI\/Downloads\/DL_Praevention\/Fachwissen\/Gefahrstoffe\/TOXIKOLOGISCHE_BEWERTUNGEN\/Bewertungen\/ToxBew170-E.pdf"},{"key":"4260_CR11","unstructured":"Charit\u00e9 (2024) ProTox 3.0\u2014prediction of toxicity of chemicals, Charit\u00e9 University of Medicine, Berlin, Germany. https:\/\/tox.charite.de\/protox3\/index.php?site=home"},{"issue":"147","key":"4260_CR12","first-page":"175","volume":"1999","author":"SM Cohen","year":"1999","unstructured":"Cohen SM (1999) Calcium phosphate-containing urinary precipitate in rat urinary bladder carcinogenesis. IARC Sci Publ 1999(147):175\u2013189","journal-title":"IARC Sci Publ"},{"issue":"4","key":"4260_CR15","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1039\/c7tx00294g","volume":"7","author":"SM Cohen","year":"2018","unstructured":"Cohen SM (2018) Screening for human urinary bladder carcinogens: two-year bioassay is unnecessary. Toxicol Res (Camb) 7(4):565\u2013575. https:\/\/doi.org\/10.1039\/c7tx00294g","journal-title":"Toxicol Res (Camb)"},{"issue":"24","key":"4260_CR13","first-page":"6493","volume":"51","author":"SM Cohen","year":"1991","unstructured":"Cohen SM, Ellwein LB (1991) Genetic errors, cell proliferation, and carcinogenesis. Cancer Res 51(24):6493\u20136505","journal-title":"Cancer Res"},{"key":"4260_CR14","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1021\/tx00030a002","volume":"5","author":"SM Cohen","year":"1992","unstructured":"Cohen SM, Ellwein LB (1992) Risk assessment based on high-dose animal exposure experiments. Chem Res Toxicol 5:742\u2013748. https:\/\/doi.org\/10.1021\/tx00030a002","journal-title":"Chem Res Toxicol"},{"issue":"3","key":"4260_CR16","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1080\/01926230701197115","volume":"35","author":"SM Cohen","year":"2007","unstructured":"Cohen SM, Ohnishi T, Clark NM, He J, Arnold LL (2007) Investigations of rodent urinary bladder carcinogens: collection, processing, and evaluation of urine and bladders. Toxicol Pathol 35(3):337\u2013347. https:\/\/doi.org\/10.1080\/01926230701197115","journal-title":"Toxicol Pathol"},{"key":"4260_CR17","first-page":"257","volume":"35","author":"CPCSEA","year":"2003","unstructured":"CPCSEA (2003) Committee for the Purpose of Control and Supervision of Experiments on Animals. Guidelines for laboratory animal facility. J Pharmacol Clin Res 35:257\u2013274","journal-title":"J Pharmacol Clin Res"},{"issue":"7","key":"4260_CR18","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1080\/01926230601072327","volume":"34","author":"MA Dominick","year":"2006","unstructured":"Dominick MA, White MR, Sanderson TP, Van Vleet T, Cohen SM, Arnold LE, Cano M, Tannehill-Gregg S, Moehlenkamp JD, Waites CR, Schilling BE (2006) Urothelial carcinogenesis in the urinary bladder of male rats treated with muraglitazar, a PPAR alpha\/gamma agonist: evidence for urolithiasis as the inciting event in the mode of action. Toxicol Pathol 34(7):903\u2013920. https:\/\/doi.org\/10.1080\/01926230601072327","journal-title":"Toxicol Pathol"},{"key":"4260_CR19","unstructured":"DTU (2024) Danish Technical University; Danish (Q)SAR database; developed by the DTU National Food Institute with support from the Danish EPA, the Nordic Council of Ministers and ECHA; https:\/\/qsardb.food.dtu.dk\/database\/index.html"},{"key":"4260_CR23","unstructured":"ECHA (2024a) European Chemicals Agency. Registered substance factsheet; dibutyl hydrogen phosphate, EC number 203-509-8, CAS no. 107-66-4; https:\/\/www.echa.europa.eu\/web\/guest\/registration-dossier\/-\/registered-dossier\/12811"},{"key":"4260_CR24","unstructured":"ECHA (2024b) European Chemicals Agency. Registered substance factsheet; tributyl phosphate, EC number 204-800-2, CAS no. 126-73-8; https:\/\/echa.europa.eu\/registration-dossier\/-\/registered-dossier\/13548\/7\/2\/2"},{"key":"4260_CR20","unstructured":"ECHA (2012) European Chemicals Agency. Substance identity \u2013 multiconstituent substances. Lead registrant workshop, 2nd February 2012. Sanna Airaksinen, Unit C2 \u2013 substance identification and data sharing; https:\/\/echa.europa.eu\/documents\/10162\/22816103\/09_sa_sidmulti_d1_lrws_20120203_en.pdf\/cedb1b08-5dcd-4470-8dee-014822a49c11"},{"key":"4260_CR21","unstructured":"ECHA (2013) European Chemicals Agency. Substance evaluation report, version 1. Tributyl phosphate, EC number 204-800-2, CAS No. 126-73-8; https:\/\/echa.europa.eu\/documents\/10162\/dc15fbc5-f1c0-bef1-050a-eb97926c6aeb"},{"key":"4260_CR22","unstructured":"ECHA (2017) European Chemicals Agency. Read-Across Assessment Framework (RAAF). ECHA-17-R-01-EN. March 2017"},{"key":"4260_CR25","unstructured":"ECHA (2024c) European Chemicals Agency. Substance Infocard; butyl dihydrogen phosphate, EC No. 204-800-2, CAS No. 1623-15-0; https:\/\/echa.europa.eu\/substance-information\/-\/substanceinfo\/100.015.096"},{"key":"4260_CR26","unstructured":"ECHA (2024d) European Chemicals Agency. Guidance on the application of the CLP criteria. Part 3: Health hazards. Version 5. ECHA-24-G-06-EN. https:\/\/echa.europa.eu\/guidance-documents\/guidance-on-clp"},{"issue":"8","key":"4260_CR27","doi-asserted-by":"publisher","first-page":"4971","DOI":"10.2903\/j.efsa.2017.4971","volume":"15","author":"A Hardy","year":"2017","unstructured":"EFSA Scientific Committee. European Food Safety Authority Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V, Solecki R, Turck D, Benfenati E, Chaudhry QM, Craig P, Frampton G, Greiner M, Hart A, Hogstrand C, Lambre C, Luttik R, Makowski D, Siani A, Wahlstroem H, Aguilera J, Dorne J-L, Fernandez Dumont A, Hempen M, Valtuena Martinez S, Martino L, Smeraldi C, Terron A, Georgiadis N, Younes M (2017) Scientific opinion on the guidance on the use of the weight of evidence approach in scientific assessments. EFSA J 15(8):4971. https:\/\/doi.org\/10.2903\/j.efsa.2017.4971 https:\/\/doi.org\/10.2903\/j.efsa.2017.4971","journal-title":"EFSA J"},{"key":"4260_CR29","unstructured":"European Parliament and Council (2006) Regulation (EC) 1907\/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999\/45\/EC and repealing Council Regulation (EEC) 793\/93 and Commission Regulation (EC) 1488\/94 as well as Council Directive 76\/769\/EEC and Commission Directives 91\/155\/EEC, 93\/67\/EEC, 93\/105\/EC and 2000\/21\/EC. OJ L 396:1, 30\u2013December 2006"},{"key":"4260_CR28","first-page":"1","volume":"353","author":"European Parliament and Council","year":"2008","unstructured":"European Parliament and Council (2008) Regulation (EC) 1272\/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67\/548\/EEC and 1999\/45\/EC, and amending Regulation (EC) 1907\/2006. OJ L 353:1\u20131355, 31 December 2008","journal-title":"OJ L"},{"key":"4260_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.yrtph.2017.11.003","volume":"92","author":"SP Felter","year":"2018","unstructured":"Felter SP, Foreman JE, Boobis A, Corton JC, Doi AM, Flowers L, Goodman J, Haber LT, Jacobs A, Klaunig JE, Lynch AM, Moggs J, Pandiri A (2018) Human relevance of rodent liver tumors: key insights from a Toxicology Forum workshop on nongenotoxic modes of action. Regul Toxicol Pharmacol 92:1\u20137. https:\/\/doi.org\/10.1016\/j.yrtph.2017.11.003","journal-title":"Regul Toxicol Pharmacol"},{"issue":"8","key":"4260_CR31","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1080\/10408444.2021.2003295","volume":"51","author":"SP Felter","year":"2021","unstructured":"Felter SP, Bhat VS, Botham PA, Bussard DA, Casey W, Hayes AW, Hilton GM, Magurany KA, Sauer UG, Ohanian EV (2021) Assessing chemical carcinogenicity: hazard identification, classification, and risk assessment. Insight from a Toxicology Forum state-of-the-science workshop. Crit Rev Toxicol 51(8):653\u2013694. https:\/\/doi.org\/10.1080\/10408444.2021.2003295","journal-title":"Crit Rev Toxicol"},{"key":"4260_CR32","unstructured":"FMC Corporation (1985) Thirteen-week feeding study of tributyl phosphate in rats. FMC study No. I82-705. Final Report, April 1985. US National Technical Reports Information Service No. OTS 0510254"},{"issue":"6","key":"4260_CR33","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1007\/s00204-020-02733-2","volume":"94","author":"A Hartwig","year":"2020","unstructured":"Hartwig A, Arand M, Epe B, Guth S, Jahnke G, Lampen A, Martus HJ, Monien B, Rietjens IMCM, Schmitz-Spanke S, Schriever-Schwemmer G, Steinberg P, Eisenbrand G (2020) Mode of action-based risk assessment of genotoxic carcinogens. Arch Toxicol 94(6):1787\u20131877. Erratum in: Arch Toxicol 2020, 94(9):3347 https:\/\/doi.org\/10.1007\/s00204-020-02733-2","journal-title":"Arch Toxicol"},{"key":"4260_CR34","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1080\/15428119591016962","volume":"56","author":"CE Healy","year":"1995","unstructured":"Healy CE, Beyrouty PC, Broxup BR (1995) Acute and subchronic neurotoxicity studies with tri-n-butyl phosphate in adult Sprague-Dawley rats. Am Ind Hyg Assoc J 56:349\u2013355. https:\/\/doi.org\/10.1080\/15428119591016962","journal-title":"Am Ind Hyg Assoc J"},{"key":"4260_CR48","unstructured":"ILAR (1996) Institute of Laboratory Animal Resources. Guide for the care and use of laboratory animals. Commission on Life Sciences, National Research Council. National Academy, Washington DC"},{"key":"4260_CR35","unstructured":"Indian Government (1960) The prevention of cruelty to animals act, 1960; https:\/\/www.indiacode.nic.in\/bitstream\/123456789\/11237\/1\/the_prevention_of_cruelty_to_animals_act%2C_1960.pdf"},{"key":"4260_CR36","unstructured":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS. VEGA, IRCCS, IRCCS, Milan (2024) Italy; https:\/\/www.vegahub.eu\/portfolio-item\/vega-qsar\/"},{"key":"4260_CR37","doi-asserted-by":"publisher","first-page":"3526","DOI":"10.1039\/c4ob00478g","volume":"12","author":"HJ Jessen","year":"2014","unstructured":"Jessen HJ, Ahmed N, Hofer A (2014) Phosphate esters and anhydrides \u2013 recent strategies targeting nature\u2019s favoured modifications. Org Biomol Chem 12:3526\u20133530. https:\/\/doi.org\/10.1039\/c4ob00478g","journal-title":"Org Biomol Chem"},{"key":"4260_CR38","unstructured":"Laboratory of Mathematical Chemistry (undated) OECD QSAR Toolbox, Version 3.1. Strategies for grouping chemicals to fill data gaps to assess genetic toxicity and genotoxic carcinogenicity (where covalent DNA binding is the molecular initiating event); http:\/\/oasis-lmc.org\/media\/63585\/Guidance-for-genotoxicity-profiling-QSAR%20TB%20V3%201.pdf"},{"key":"4260_CR39","unstructured":"Laboratory of Mathematical Chemistry (2024) OASIS QSAR Toolbox v. 4.5. Laboratory of Mathematical Chemistry, Burgas, Bulgaria; https:\/\/oasis-lmc.org\/"},{"key":"4260_CR40","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1080\/00039896.1985.10545937","volume":"40","author":"S Laham","year":"1985","unstructured":"Laham S, Long G, Broxup B (1985) Induction of urinary bladder hyperplasia in Sprague-Dawley rats orally administered tri-n-butyl phosphate. Arch Environ Health 40:301\u2013306. https:\/\/doi.org\/10.1080\/00039896.1985.10545937","journal-title":"Arch Environ Health"},{"key":"4260_CR41","unstructured":"Lhasa Ltd (2024a) Derek Nexus. Version 6.3.0. Expert knowledge-based toxicity prediction software. Lhasa Ltd., Leeds, United Kingdom. https:\/\/www.lhasalimited.org\/solutions\/in-silico-mutagenicity-assessment\/"},{"key":"4260_CR42","unstructured":"Lhasa Ltd (2024b) Meteor Nexus. Version 3.2.0. Expert decision support software for predicting the metabolic fate of chemicals in mammals. Lhasa Ltd., Leeds, United Kingdom. https:\/\/www.lhasalimited.org\/solutions\/metabolite-identification-and-analysis\/"},{"key":"4260_CR43","unstructured":"LibreTexts Chemistry\u2122 (2024) sp3 hybridization. Contributor: Nguyen QN; https:\/\/chem.libretexts.org\/Bookshelves\/Inorganic_Chemistry\/Map%3A_Inorganic_Chemistry_(Housecroft)\/05%3A_Bonding_in_Polyatomic_Molecules\/5.02%3A_Valence_Bond_Theory_-_Hybridization_of_Atomic_Orbitals\/5.2D%3A_sp3_Hybridization"},{"key":"4260_CR44","doi-asserted-by":"publisher","unstructured":"MAK Commission (2002) German Research Foundation, Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area. Tributyl phosphate. MAK value documentation. In: the MAK [Maximum concentration at the workplace] collection for occupational health and safety. Wiley-VCH Verlag GmbH & Co. KGaA. https:\/\/doi.org\/10.1002\/3527600418.mb12673e0017","DOI":"10.1002\/3527600418.mb12673e0017"},{"key":"4260_CR45","doi-asserted-by":"publisher","unstructured":"MAK Commission (2014) German Research Foundation, Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area. Di-n-butyl phosphate and its technical mixtures. MAK value documentation. In: the MAK [Maximum concentration at the workplace] collection for occupational health and safety. Wiley-VCH Verlag GmbH & Co. KGaA. https:\/\/doi.org\/10.1002\/3527600418.mb10766kske4714","DOI":"10.1002\/3527600418.mb10766kske4714"},{"issue":"1","key":"4260_CR47","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.toxlet.2010.07.013","volume":"199","author":"M Neerathilingam","year":"2010","unstructured":"Neerathilingam M, Volk DE, Sarkar S, Alam TM, Alam MK, Ansari GA, Luxon BA (2010) 1H NMR-based metabonomic investigation of tributyl phosphate exposure in rats. Toxicol Lett 199(1):10\u201316 https:\/\/doi.org\/10.1016\/j.toxlet.2010.07.013","journal-title":"Toxicol Lett"},{"key":"4260_CR46","unstructured":"NICNAS (2020) Australian National Industrial Chemicals Notification and Assessment Scheme. Monobutyl phosphate: human health tier II assessment. NICNAS Inventory Multi-tiered Assessment and Prioritisation (IMAP) framework; https:\/\/cdnservices.industrialchemicals.gov.au\/statements\/IMAP_14796%20-%20IMAP%20Assessment%20-%2012%20December%202019.pdf"},{"key":"4260_CR49","unstructured":"OECD (1994) Organisation for Economic Co-operation and Development. Screening Information Dataset (SIDS). Dibutyl phosphate. CAS No.: 107-66-4. SIDS Initial Assessment Report for SIAM 2, Paris, 4\u20136 July 1994. https:\/\/hpvchemicals.oecd.org\/UI\/handler.axd?id=ab370623-2a3e-49b4-b26a-61e4e033b12a"},{"key":"4260_CR50","unstructured":"OECD (1998) Organisation for Economic Co-operation and Development. Series on principles of good laboratory practice and compliance monitoring. Principles on good laboratory practice (as revised in 1997). ENV\/MC\/CHEM(98)17. OECD, Paris. distributed 26 January 1998"},{"key":"4260_CR51","volume-title":"Series on testing and assessment no. 19. Guidance document on the recognition, assessment and use of clinical signs as human endpoints for experimental animals used in safety evaluation. ENV\/JM\/MONO(2000)7","author":"OECD","year":"2000","unstructured":"OECD 2000. Organisation for Economic Co-operation and Development. Series on testing and assessment no. 19. Guidance document on the recognition, assessment and use of clinical signs as humane endpoints for experimental animals used in safety evaluation. ENV\/JM\/MONO(2000)7. OECD, Paris, distributed 21 December 2000"},{"key":"4260_CR52","unstructured":"OECD (2008) Organisation for Economic Co-operation and Development. Guidelines for the testing of chemicals No. 407. Repeated dose 28-day oral toxicity study in rodents. OECD, Paris. adopted 3 October 2008"},{"key":"4260_CR53","unstructured":"OECD (2016) Organisation for Economic Co-operation and Development. Guidelines for the testing of chemicals No. 422. Combined repeated dose toxicity study with the reproduction\/developmental toxicity screening test. OECD, Paris. adopted 29 July 2016"},{"key":"4260_CR54","unstructured":"OECD (2018) Organisation for Economic Co-operation and Development. Guidelines for the testing of chemicals No. 408. Repeated dose 90-day oral toxicity study in rodents. OECD, Paris. adopted 25 June 2018"},{"key":"4260_CR55","unstructured":"OECD (2024) Organisation for Economic Co-operation and Development. QSAR toolbox for grouping chemicals into categories. Version 4.6. Organisation for Economic Co-operation and Development & European Chemicals Agency. https:\/\/qsartoolbox.org\/"},{"key":"4260_CR56","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/0378-4274(80)90172-1","volume":"6","author":"H Oishi","year":"1980","unstructured":"Oishi H, Oishi S, Hiraga K (1980) Toxicity of tri-n-butyl phosphate, with special reference to organ weights, serum components and cholinesterase activity in male rats. Toxicol Lett 6:81\u201385. https:\/\/doi.org\/10.1016\/0378-4274(80)90172-1","journal-title":"Toxicol Lett"},{"key":"4260_CR57","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/0378-4274(82)90135-7","volume":"13","author":"H Oishi","year":"1982","unstructured":"Oishi H, Oishi S, Hiraga K (1982) Toxicity of several phosphoric acid esters in rats. Toxicol Lett 13:29\u201334. https:\/\/doi.org\/10.1016\/0378-4274(82)90135-7","journal-title":"Toxicol Lett"},{"key":"4260_CR58","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.yrtph.2018.04.016","volume":"96","author":"DM Proctor","year":"2018","unstructured":"Proctor DM, Suh M, Chappell G, Borghoff SJ, Thompson CM, Wiench K, Finch L, Ellis-Hutchings R (2018) An adverse outcome pathway (AOP) for forestomach tumors induced by non-genotoxic initiating events. Regul Toxicol Pharmacol 96:30\u201340. https:\/\/doi.org\/10.1016\/j.yrtph.2018.04.016","journal-title":"Regul Toxicol Pharmacol"},{"key":"4260_CR59","unstructured":"PubChem (2024) Butyl 3-hydroxybutyl hydrogen phosphate. Natl Libr Med, PubChem; https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Butyl-3-hydroxybutyl-hydrogen-phosphate"},{"key":"4260_CR60","doi-asserted-by":"publisher","first-page":"104583","DOI":"10.1016\/j.yrtph.2020.104583","volume":"111","author":"UG Sauer","year":"2020","unstructured":"Sauer UG, Barter RA, Becker RA, Benfenati E, Berggren E, Hubesch B, Hollnagel HM, Inawaka K, Keene AM, Mayer P, Plotzke K, Skoglund R, Albert O (2020) 21st century approaches for evaluating exposures, biological activity, and risks of complex substances: workshop highlights. Regul Toxicol Pharmacol 111:104583. https:\/\/doi.org\/10.1016\/j.yrtph.2020.104583","journal-title":"Regul Toxicol Pharmacol"},{"key":"4260_CR61","unstructured":"SOCMA (1991) Synthetic Organic Chemical Manufacturers Association Inc. \u2013 Bio\/dynamics Inc. Final report for a 90-day dietary study of tributyl phosphate in the mouse. Project No. 89-3531. US National Technical Reports Information Service No. OTS 0534083"},{"key":"4260_CR62","unstructured":"SOCMA (1992a) Synthetic Organic Chemical Manufacturers Association Inc. Tributyl phosphate\u2014a special subchronic dietary study to examine the mechanism of urinary bladder carcinogenesis in the rat. Final report. US National Technical Reports Information Service No. OTS 0572980"},{"key":"4260_CR63","unstructured":"SOCMA (1992b) Synthetic Organic Chemical Manufacturers Association Inc. Two-generation reproductive toxicity study of tributyl phosphate administered in the feed to CD\u00ae (Sprague-Dawley) rats. Final report, volume I of IV. US National Technical Reports Information Service No. OTS 0558679"},{"key":"4260_CR64","unstructured":"SOCMA (1996) Synthetic Organic Chemical Manufacturers Association Inc. Pharmacokinetics of TBP in rats: Section I \u2013 distribution, metabolism, and excretion of 14C-tributyl phosphate. Final report. US National Technical Reports Information Service No. OTS 0558698"},{"key":"4260_CR65","unstructured":"Soderberg T (2024) Overview of phosphate groups. Chapter 9.2 in: organic chemistry with a biological emphasis. Univ Minn Morris. LibreTexts\u2122; https:\/\/chem.libretexts.org\/Bookshelves\/Organic_Chemistry\/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_v2.0_(Soderberg)"},{"issue":"3","key":"4260_CR66","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1021\/jf00123a046","volume":"32","author":"T Suzuki","year":"1984","unstructured":"Suzuki T, Sasaki K, Takeda M, Uchiyama M (1984a) Metabolism of tributyl phosphate in male rats. J Agric Food Chem 32(3):603\u2013610. https:\/\/doi.org\/10.1021\/jf00123a046","journal-title":"J Agric Food Chem"},{"issue":"6","key":"4260_CR67","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1021\/jf00126a017","volume":"32","author":"T Suzuki","year":"1984","unstructured":"Suzuki T, Sasaki K, Takeda M, Uchiyama M (1984b) Some sulfur-containing metabolites of tributyl phosphate in the rat. J Agric Food Chem 32(6):1278\u20131283. https:\/\/doi.org\/10.1021\/jf00126a017","journal-title":"J Agric Food Chem"},{"issue":"1","key":"4260_CR68","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1093\/toxsci\/kfm083","volume":"98","author":"SH Tannehill-Gregg","year":"2007","unstructured":"Tannehill-Gregg SH, Sanderson TP, Minnema D, Voelker R, Ulland B, Cohen SM, Arnold LL, Schilling BE, Waites CR, Dominick MA (2007) Rodent carcinogenicity profile of the antidiabetic dual PPAR alpha and gamma agonist Muraglitazar. Toxicol Sci 98(1):258\u2013270. https:\/\/doi.org\/10.1093\/toxsci\/kfm083","journal-title":"Toxicol Sci"},{"issue":"3","key":"4260_CR69","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1177\/0192623309332990","volume":"37","author":"SH Tannehill-Gregg","year":"2009","unstructured":"Tannehill-Gregg SH, Dominick MA, Reisinger AJ, Moehlenkamp JD, Waites CR, Stock DA, Sanderson TP, Cohen SM, Arnold LL, Schilling BE (2009) Strain-related differences in urine composition of male rats of potential relevance to urolithiasis. Toxicol Pathol 37(3):293\u2013305. https:\/\/doi.org\/10.1177\/0192623309332990","journal-title":"Toxicol Pathol"},{"key":"4260_CR70","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.yrtph.2018.05.006","volume":"96","author":"CM Thompson","year":"2018","unstructured":"Thompson CM, Suh M, Proctor DM, Chappell G, Borghoff S, Ellis-Hutchings R, Wiench K, Finch L (2018) Assessment of the mode of action underlying development of forestomach tumors in rodents following oral exposure to Ethyl acrylate and relevance to humans. Regul Toxicol Pharmacol 96:178\u2013189. https:\/\/doi.org\/10.1016\/j.yrtph.2018.05.006","journal-title":"Regul Toxicol Pharmacol"},{"issue":"1","key":"4260_CR71","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1006\/faat.1997.2373","volume":"40","author":"RW Tyl","year":"1997","unstructured":"Tyl RW, Gerhart JM, Myers CB, Marr MC, Brine DR, Seely JC, Henrich RT (1997) Two-generation reproductive toxicity study of dietary tributyl phosphate in CD rats. Fundam Appl Toxicol 40(1):90\u2013100. https:\/\/doi.org\/10.1006\/faat.1997.2373","journal-title":"Fundam Appl Toxicol"},{"key":"4260_CR73","unstructured":"US EPA (2024) United States Environmental Protection Agency. Toxicity Estimation Software Tool (TEST); US EPA Research, Durham NC, USA; https:\/\/www.epa.gov\/comptox-tools\/toxicity-estimation-software-tool-test"},{"key":"4260_CR72","unstructured":"US EPA (2010) United States Environmental Protection Agency. Provisional peer-reviewed toxicity values for tributyl phosphate (CASRN 126-73-8). Superfund Health Risk Technical Support Center. National Center for Environmental Assessment. Office of Research and Development US EPA. EPA\/690\/R-10\/024F, final version of 11 August 2010; https:\/\/cfpub.epa.gov\/ncea\/pprtv\/documents\/TributylPhosphate.pdf?msclkid=2338690acf6711ec8aebcc388d7a3df9"},{"key":"4260_CR74","unstructured":"US FDA (2005) United States Food and Drug Administration. Advisory Committee Briefing Document. Preclinical Pharmacology and Toxicology Summary. Pargluva\u00ae (muraglitazar, BMS-298,585). Anim Toxicol Summary NDA 21\u2013865"},{"key":"4260_CR75","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.yrtph.2019.01.021","volume":"103","author":"DC Wolf","year":"2019","unstructured":"Wolf DC, Cohen SM, Boobis AR, Dellarco VL, Fenner-Crisp PA, Moretto A, Pastoor TP, Schoeny RS, Seed JG, Doe JE (2019) Chemical carcinogenicity revisited 1: A unified theory of carcinogenicity based on contemporary knowledge. Regul Toxicol Pharmacol 103:86\u201392. https:\/\/doi.org\/10.1016\/j.yrtph.2019.01.021","journal-title":"Regul Toxicol Pharmacol"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-025-04260-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00204-025-04260-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-025-04260-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T08:09:40Z","timestamp":1776326980000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00204-025-04260-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":75,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["4260"],"URL":"https:\/\/doi.org\/10.1007\/s00204-025-04260-4","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]},"assertion":[{"value":"19 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}