{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:52:03Z","timestamp":1770749523564,"version":"3.50.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Conseil Europ\u00e9en des F\u00e9d\u00e9rations de l'Industrie Chimique"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The purpose of this study was to use chemical similarity evaluations, transcriptional profiling, in vitro toxicokinetic data, and physiologically based pharmacokinetic (PBPK) models to support read-across for a series of branched carboxylic acids using valproic acid (VPA), a known developmental toxicant, as a comparator. The chemicals included 2-propylpentanoic acid (VPA), 2-ethylbutanoic acid, 2-ethylhexanoic acid (EHA), 2-methylnonanoic acid, 2-hexyldecanoic acid, 2-propylnonanoic acid (PNA), dipentyl acetic acid or 2-pentylheptanoic acid, octanoic acid (a straight chain alkyl acid), and 2-ethylhexanol. Transcriptomics was evaluated in 4 cell types (A549, HepG2, MCF7, and iCell cardiomyocytes) 6\u2009h after exposure to 3 concentrations of the compounds, using the L1000 platform. The transcriptional profiling data indicate that 2- or 3-carbon alkyl substituents at the alpha position of the carboxylic acid (EHA and PNA) elicit a transcriptional profile similar to the one elicited by VPA. The transcriptional profile is different for the other chemicals tested, which provides support for limiting read-across from VPA to much shorter and longer acids. Molecular docking models for histone deacetylases, the putative target of VPA, provide a possible mechanistic explanation for the activity cliff elucidated by transcriptomics. In vitro toxicokinetic data were utilized in a PBPK model to estimate internal dosimetry. The PBPK modeling data show that as the branched chain increases, predicted plasma Cmax decreases. This work demonstrates how transcriptomics and other mode of action-based methods can improve read-across.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac139","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:30:51Z","timestamp":1672360251000},"page":"343-356","source":"Crossref","is-referenced-by-count":10,"title":["Structure-activity relationship read-across and transcriptomics for branched carboxylic acids"],"prefix":"10.1093","volume":"191","author":[{"given":"Shengde","family":"Wu","sequence":"first","affiliation":[{"name":"Global Product Stewardship, The Procter and Gamble Company , Mason, Ohio 45040, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corie","family":"Ellison","sequence":"additional","affiliation":[{"name":"Global Product Stewardship, The Procter and Gamble Company , Mason, Ohio 45040, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Naciff","sequence":"additional","affiliation":[{"name":"Global Product Stewardship, The Procter and Gamble Company , Mason, Ohio 45040, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Karb","sequence":"additional","affiliation":[{"name":"Global Product Stewardship, The Procter and Gamble Company , Mason, Ohio 45040, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy","family":"Obringer","sequence":"additional","affiliation":[{"name":"Global Product Stewardship, The Procter and Gamble Company , Mason, Ohio 45040, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5648-7653","authenticated-orcid":false,"given":"Gang","family":"Yan","sequence":"additional","affiliation":[{"name":"Global Product Stewardship, The Procter and Gamble Company , Mason, Ohio 45040, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Shan","sequence":"additional","affiliation":[{"name":"Global Product Stewardship, The Procter and Gamble Company , Mason, Ohio 45040, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Smith","sequence":"additional","affiliation":[{"name":"Global Product Stewardship, The Procter and Gamble Company , Mason, Ohio 45040, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Wang","sequence":"additional","affiliation":[{"name":"Global Product Stewardship, The Procter and Gamble Company , Mason, Ohio 45040, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George P","family":"Daston","sequence":"additional","affiliation":[{"name":"Global Product Stewardship, The Procter and Gamble Company , Mason, Ohio 45040, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"2023021707594307100_","first-page":"183","article-title":"Computational characteristics of valproic acid binding to histone deacetylase","volume":"15","author":"Abouzeid","year":"2007","journal-title":"Saudi Pharm. J."},{"key":"2023021707594307100_","first-page":"732","article-title":"Influence of a single dose of ethanol on the kinetics of valproic acid in rats","volume":"18","author":"Alonso","year":"1990","journal-title":"Drug Metab. Dispos"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/(SICI)1096-9926(199606)54:2<93::AID-TERA5>3.0.CO;2-5","article-title":"Valproic acid-induced somite teratogenesis in the chick embryo: Relationship with Pax-1 gene expression","volume":"54","author":"Barnes","year":"1996","journal-title":"Teratology"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2174\/138920007779315053","article-title":"Scaling factors for the extrapolation of in vivo metabolic drug clearance from in vitro data: Reaching a consensus on values of human microsomal protein and hepatocellularity per gram of liver","volume":"8","author":"Barter","year":"2007","journal-title":"Curr. Drug Metab"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1007\/s00894-011-1240-z","article-title":"Exploration of the valproic acid binding site on histone deacetylase 8 using docking and molecular dynamic simulations","volume":"18","author":"Berm\u00fadez-Lugo","year":"2012","journal-title":"J. Mol. Model"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.yrtph.2011.03.002","article-title":"Case studies to test: A framework for using structural, reactivity, metabolic and physicochemical similarity to evaluate the suitability of analogs for SAR-based toxicological assessments","volume":"60","author":"Blackburn","year":"2011","journal-title":"Regul. Toxicol. Pharmcol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.yrtph.2014.01.004","article-title":"A framework to facilitate consistent characterization of read across uncertainty","volume":"68","author":"Blackburn","year":"2014","journal-title":"Regul. Toxicol. Pharmcol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0014-2999(98)00462-2","article-title":"Studies on the teratogen pharmacophore of valproic acid analogues: Evidence of interactions at a hydrophobic center","volume":"354","author":"Bojic","year":"1998","journal-title":"Eur. J. Pharmacol"},{"key":"2023021707594307100_","author":"Chang","year":"2021"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/toxsci\/kfw058","article-title":"Grouping 34 chemicals based on mode of action using connectivity mapping","volume":"151","author":"De Abrew","year":"2016","journal-title":"Toxicol. Sci"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.tox.2019.05.008","article-title":"Use of connectivity mapping to support read across: A deeper dive using data from 186 chemicals, 19 cell lines and 2 case studies","volume":"423","author":"De Abrew","year":"2019","journal-title":"Toxicology"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.tox.2014.11.008","article-title":"A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action","volume":"328","author":"De Abrew","year":"2015","journal-title":"Toxicology"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3109\/03602538608998290","article-title":"Structure metabolism relationships (SMR) for the prediction of health hazards by the environmental protection agency. II. Application to teratogenicity and other toxic effects caused by aliphatic acids","volume":"17","author":"Di Carlo","year":"1986","journal-title":"Drug Metab. Rev"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1021\/tx0502241","article-title":"Teratogenic effects mediated by inhibition of histone deacetylases: Evidence from quantitative structure activity relationships of 20 valproic acid derivatives","volume":"19","author":"Eikel","year":"2006","journal-title":"Chem. Res. Toxicol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"104667","DOI":"10.1016\/j.yrtph.2020.104667","article-title":"Application of structural and functional pharmacokinetic analogs for physiologically based pharmacokinetic model development and evaluation","volume":"114","author":"Ellison","year":"2020","journal-title":"Regul. Toxicol. Pharmacol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1080\/004982598239272","article-title":"Metabolism of 2-ethylhexanoic acid administered orally or dermally to the female Fischer 344 rat","volume":"28","author":"English","year":"1998","journal-title":"Xenobiotica"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1423-0127-18-48","article-title":"Valproic acid inhibits neural progenitor cell death by activation of NF-\u03baB signaling pathway and up-regulation of Bcl-XL","volume":"18","author":"Go","year":"2011","journal-title":"J. Biomed. Sci"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"6969","DOI":"10.1093\/emboj\/20.24.6969","article-title":"Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells","volume":"20","author":"G\u00f6ttlicher","year":"2001","journal-title":"EMBO J"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1006\/taap.1995.1066","article-title":"In vitro glucuronidation of peroxisomal proliferators: 2-ethylhexanoic acid enantiomers and their structural analogs","volume":"131","author":"Hamdoune","year":"1995","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/toxsci\/kfab009","article-title":"High-throughput transcriptomics platform for screening environmental chemicals","volume":"181","author":"Harrill","year":"2021","journal-title":"Toxicol. Sci"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3389\/fgene.2017.00168","article-title":"A pipeline for high-throughput concentration response modeling of gene expression for toxicogenomics","volume":"8","author":"House","year":"2017","journal-title":"Front. Genet"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1006\/faat.1993.1027","article-title":"Assessment of the developmental toxicity of 2-ethylhexanoic acid in rats and rabbits","volume":"20","author":"Hendrickx","year":"1993","journal-title":"Fundam. Appl. Toxicol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1211\/jpp.59.3.0007","article-title":"Investigation of low levels of plasma valproic acid concentration following simultaneous administration of sodium valproate and rizatriptan benzoate","volume":"59","author":"Hokama","year":"2007","journal-title":"J. Pharm. Pharmacol"},{"key":"2023021707594307100_","volume-title":"Characterization and Application of Physiologically Based Pharmacokinetic Models in Risk Assessment World Health Organization.","author":"International Programme on Chemical Safety (IPCS)","year":"2010"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/toxsci\/kfr070","article-title":"Short-time gene expression response to valproic acid and valproic acid analogs in mouse embryonic stem cells","volume":"121","author":"Jergil","year":"2011","journal-title":"Toxicol. Sci"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1527-3458.2003.tb00249.x","article-title":"Valproate: Past, present, and future","volume":"9","author":"Johannessen","year":"2003","journal-title":"CNS Drug Rev"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1002\/jat.1608","article-title":"Dose-dependent pharmacokinetics of toxic metabolites is not related to increased toxicity following high-dose valproic acid in rats","volume":"30","author":"Jung","year":"2010","journal-title":"J. Appl. Toxicol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2220\/biomedres.30.101","article-title":"Effects of a dopamine receptor agonist and atropine sulfate on absorption of valproic acid in rats","volume":"30","author":"Kameya","year":"2009","journal-title":"Biomed. Res"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1248\/bpb1978.13.533","article-title":"Effect of pregnancy on the disposition of valproate in rats","volume":"13","author":"Kobayashi","year":"1990","journal-title":"J. Pharmacobiodyn"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1093\/emboj\/cdg315","article-title":"The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2","volume":"22","author":"Kr\u00e4mer","year":"2003","journal-title":"EMBO J"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1126\/science.1132939","article-title":"The Connectivity Map: Using gene-expression signatures to connect small molecules, genes, and disease","volume":"313","author":"Lamb","year":"2006","journal-title":"Science"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/tera.1420350319","article-title":"Teratogen update: Valproic acid","volume":"35","author":"Lammer","year":"1987","journal-title":"Teratology"},{"key":"2023021707594307100_","first-page":"255","article-title":"Serum protein binding and pharmacokinetics of valproate in man, dog, rat and mouse","volume":"204","author":"L\u00f6scher","year":"1978","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1080\/00498250701704819","article-title":"Intestinal permeability and its relevance for absorption and elimination","volume":"37","author":"Lennern\u00e4s","year":"2007","journal-title":"Xenobiotica"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1097\/01.fpc.0000170914.11898.3a","article-title":"Valproic acid-induced skeletal malformations: Associated gene expression cascades","volume":"15","author":"Massa","year":"2005","journal-title":"Pharmacogenet. Genomics"},{"key":"2023021707594307100_","first-page":"CD003196","article-title":"Valproic acid, valproate and divalproex in the maintenance treatment of bipolar disorder","volume":"3","author":"Macritchie","year":"2001","journal-title":"Cochrane Database Syst. Rev"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/(SICI)1520-6866(1996)16:2<97::AID-TCM4>3.0.CO;2-A","article-title":"Teratogenic effects of sodium valproate in mice and rats at midgestation and at term","volume":"16","author":"Menegola","year":"1996","journal-title":"Teratog. Carcinog. Mutagen"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"111303","DOI":"10.1016\/j.fct.2020.111303","article-title":"Development of an adverse outcome pathway for cranio-facial malformations: A contribution from in silico simulations and in vitro data","volume":"140","author":"Metruccio","year":"2020","journal-title":"Food Chem. Toxicol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.cbi.2010.09.022","article-title":"Cytotoxicity and gene array analysis of alveolar epithelial A549 cells exposed to paraquat","volume":"188","author":"Mitsopoulos","year":"2010","journal-title":"Chem. Biol. Interact"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1006\/faat.1994.1029","article-title":"Developmental toxicity and structure-activity relationships of aliphatic acids, including dose\u2013response assessment of valproic acid in mice and rats","volume":"22","author":"Narotsky","year":"1994","journal-title":"Fundam. Appl. Toxicol"},{"key":"2023021707594307100_","volume-title":"Risk Assessment of Prenatally-Induced Adverse Health Effects","author":"Nau","year":"1992"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/323276a0","article-title":"Weak acids may act as teratogens by accumulating in the basic milieu of the early mammalian embryo","volume":"323","author":"Nau","year":"1986","journal-title":"Nature"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1289\/ehp.8670113","article-title":"Species differences in pharmacokinetics and drug teratogenesis","volume":"70","author":"Nau","year":"1986","journal-title":"Environ. Health Perspect"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S0022-3476(84)80567-3","article-title":"Valproic acid in the perinatal period: Decreased maternal serum protein binding results in fetal accumulation and neonatal displacement of the drug and some metabolites","volume":"104","author":"Nau","year":"1984","journal-title":"J. Pediatr"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/(SICI)1098-2744(199903)24:3<153::AID-MC1>3.0.CO;2-P","article-title":"Microarrays and toxicology: The advent of toxicogenomics","volume":"24","author":"Nuwaysir","year":"1999","journal-title":"Mol. Carcinog"},{"key":"2023021707594307100_","first-page":"1350","article-title":"Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes","volume":"27","author":"Obach","year":"1999","journal-title":"Drug Metab. Dispos"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1248\/cpb.34.2950","article-title":"Disposition and pharmacokinetics of valproic acid in rats","volume":"34","author":"Ogiso","year":"1986","journal-title":"Chem. Pharm. Bull. (Tokyo)"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1248\/bpb1978.12.255","article-title":"Effects of anticonvulsants on plasma levels and entero-hepatic circulation of valproic acid and on hepatic drug metabolizing enzyme activities in rats","volume":"12","author":"Ogiso","year":"1989","journal-title":"J. Pharmacobiodyn"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.reprotox.2009.02.014","article-title":"Valproic acid in pregnancy: How much are we endangering the embryo and fetus?","volume":"28","author":"Ornoy","year":"2009","journal-title":"Reprod. Toxicol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1124\/dmd.112.045500","article-title":"Influence of enterohepatic recycling on the time course of brain-to-blood partitioning of valproic acid in rats","volume":"40","author":"Padowski","year":"2012","journal-title":"Drug Metab. Dispos"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1093\/toxsci\/kfv174","article-title":"The effects of class-specific histone deacetylase inhibitors on the development of limbs during organogenesis","volume":"148","author":"Paradis","year":"2015","journal-title":"Toxicol. Sci"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"654467","DOI":"10.3389\/fcell.2021.654467","article-title":"Chromatin imbalance as the vertex between fetal valproate syndrome and chromatinopathies","volume":"9","author":"Parodi","year":"2021","journal-title":"Front. Cell Dev. Biol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/0272-0590(92)90088-Y","article-title":"The developmental toxicity of 2-ethylhexanoic acid in Wistar rats","volume":"19","author":"Pennanen","year":"1992","journal-title":"Fundam. Appl. Toxicol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/BF01073869","article-title":"Physiologic and metabolic influences on enterohepatic recirculation: Simulations based upon the disposition of valproic acid in the rat","volume":"19","author":"Pollack","year":"1991","journal-title":"J. Pharmacokinet. Biopharm"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"100136","DOI":"10.1016\/j.comtox.2020.100136","article-title":"Using chemical structure information to develop predictive models for in vitro toxicokinetic parameters to inform high-throughput risk-assessment","volume":"16","author":"Pradeep","year":"2020","journal-title":"Comput. Toxicol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/S0140-6736(84)92079-8","article-title":"Valproate and spina bifida","volume":"324","author":"Robert","year":"1984","journal-title":"Lancet"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.3389\/fgene.2019.01233","article-title":"Assessing chemical-induced liver injury in vivo from in vitro gene expression data in the rat: The case of thioacetamide toxicity","volume":"26","author":"Schyman","year":"2019","journal-title":"Front Genet"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1289\/ehp.94102s1197","article-title":"Pharmacokinetic determinants of embryotoxicity in rats associated with organic acids","volume":"102","author":"Scott","year":"1994","journal-title":"Environ. Health Perspect"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.cell.2017.10.049","article-title":"A next generation connectivity map: L1000 platform and the first 1,000,000 profiles","volume":"171","author":"Subramanian","year":"2017","journal-title":"Cell"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1211\/0022357011776171","article-title":"Inhibition by carbapenem antibiotic imipenem of intestinal absorption of valproic acid in rats","volume":"53","author":"Torii","year":"2001","journal-title":"J. Pharm. Pharmacol"},{"key":"2023021707594307100_","first-page":"1433","article-title":"Probenecid-associated alterations in valproic acid pharmacokinetics in rats: Can in vivo disposition of valproate glucuronide be predicted from in vitro formation data?","volume":"28","author":"Ward","year":"2000","journal-title":"Drug Metab. Dispos"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1080\/10408440591007403","article-title":"Mode of action: Inhibition of histone deacetylase, altering WNT-dependent gene expression, and regulation of beta-catenin\u2013developmental effects of valproic acid","volume":"35","author":"Wiltse","year":"2005","journal-title":"Crit. Rev. Toxicol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.yrtph.2009.09.006","article-title":"A framework for using structural, reactivity, metabolic and physicochemical similarity to evaluate the suitability of analogs for SAR-based toxicological assessments","volume":"56","author":"Wu","year":"2010","journal-title":"Regul. Toxicol. Pharmcol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1021\/tx400226u","article-title":"Framework for identifying chemicals with structural features associated with the potential to act as developmental or reproductive toxicants","volume":"26","author":"Wu","year":"2013","journal-title":"Chem. Res. Toxicol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1211\/0022357001773986","article-title":"Effects of lithium on the pharmacokinetics of valproate in rats","volume":"52","author":"Yoshioka","year":"2000","journal-title":"J. Pharm. Pharmacol"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/toxsci\/kfp198","article-title":"Evaluating placental transfer and tissue concentrations of manganese in the pregnant rat and fetuses after inhalation exposures with a PBPK model","volume":"112","author":"Yoon","year":"2009","journal-title":"Toxicol. Sci"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jchromb.2018.02.040","article-title":"Fast quantification of short chain fatty acids and ketone bodies by liquid chromatography-tandem mass spectrometry after facile derivatization coupled with liquid-liquid extraction","volume":"1083","author":"Zeng","year":"2018","journal-title":"J. Chromatogr. B"},{"key":"2023021707594307100_","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/tpj.2013.39","article-title":"Data mining reveals a network of early-response genes as a consensus signature of drug-induced in vitro and in vivo toxicity","volume":"14","author":"Zhang","year":"2014","journal-title":"Pharmacogenomics J"}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxsci\/advance-article-pdf\/doi\/10.1093\/toxsci\/kfac139\/48758942\/kfac139.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/191\/2\/343\/49199056\/kfac139.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/191\/2\/343\/49199056\/kfac139.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T12:12:22Z","timestamp":1679227942000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/191\/2\/343\/6965632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,30]]},"references-count":69,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,12,30]]},"published-print":{"date-parts":[[2023,2,17]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfac139","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,2,1]]},"published":{"date-parts":[[2022,12,30]]}}}