2019
Development and Application of a Life-Stage Physiologically Based Pharmacokinetic (PBPK) Model to the Assessment of Internal Dose of Pyrethroids in Humans
Mallick P, Moreau M, Song G, Efremenko A, Pendse S, Creek M, Osimitz T, Hines R, Hinderliter P, Clewell H, Lake B, Yoon M. Development and Application of a Life-Stage Physiologically Based Pharmacokinetic (PBPK) Model to the Assessment of Internal Dose of Pyrethroids in Humans. Toxicological Sciences 2019, 173: 86-99. PMID: 31593217, PMCID: PMC6944222, DOI: 10.1093/toxsci/kfz211.Peer-Reviewed Original ResearchMeSH KeywordsCarboxylesteraseCytochrome P-450 Enzyme SystemDose-Response Relationship, DrugHumansKineticsLiverMicrosomes, LiverModels, BiologicalNitrilesPermethrinPharmacokineticsPyrethrinsConceptsTarget tissue exposureTissue exposurePharmacokinetic modelLiver blood flowLow internal exposureAge-related sensitivityAge-dependent changesEfficient metabolic clearanceIndividual cytochrome P450Human hepatic metabolismAge-related differencesCis-permethrinHepatic metabolismBlood flowMetabolic clearanceCES enzymesHepatic CLintInternal doseIntrinsic clearanceTarget tissuesInternal exposureClearanceCarboxylesterase enzymesCytochrome P450Vivo extrapolation
2016
Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards
El-Masri H, Kleinstreuer N, Hines R, Adams L, Tal T, Isaacs K, Wetmore B, Tan Y. Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards. Toxicological Sciences 2016, 152: 230-243. PMID: 27208077, PMCID: PMC5009469, DOI: 10.1093/toxsci/kfw082.Peer-Reviewed Original ResearchConceptsPutative adverse outcome pathwayExposure levelsPharmacokinetic modelAdverse outcome pathwaysPotential exposure levelsFetal blood levelsExternal exposure levelsMaternal exposureBlood levelsExposure modelHigh-throughput toxicity screeningVasculogenesis/angiogenesisOutcome pathwaysPBPK modelExposure estimatesChemical dispositionDevelopmental toxicityPotential exposureVivo extrapolationExposureAdulthood stagesToxicityAssaysEnvironmental exposure modelsPregnancy
2014
Tolerance to Acetaminophen Hepatotoxicity in the Mouse Model of Autoprotection Is Associated with Induction of Flavin-Containing Monooxygenase-3 (FMO3) in Hepatocytes
Rudraiah S, Rohrer P, Gurevich I, Goedken M, Rasmussen T, Hines R, Manautou J. Tolerance to Acetaminophen Hepatotoxicity in the Mouse Model of Autoprotection Is Associated with Induction of Flavin-Containing Monooxygenase-3 (FMO3) in Hepatocytes. Toxicological Sciences 2014, 141: 263-277. PMID: 24973094, PMCID: PMC4271123, DOI: 10.1093/toxsci/kfu124.Peer-Reviewed Original ResearchConceptsMale C57BL/6J miceAPAP hepatotoxicityFlavin-Containing Monooxygenase 3Protein expressionC57BL/6J miceFemale miceMouse modelMRNA levelsFirst time inductionNovel protective functionSingle doseAPAP treatmentMale miceAPAP cytotoxicityAcetaminophen pretreatmentHepatotoxic doseHigh doseAcetaminophen hepatotoxicityHepatotoxicityMice resultsCell line clonesMRNA expressionFMO3 expressionMiceAPAP
2009
Approaches for Assessing Risks to Sensitive Populations: Lessons Learned from Evaluating Risks in the Pediatric Population
Hines R, Sargent D, Autrup H, Birnbaum L, Brent R, Doerrer N, Hubal E, Juberg D, Laurent C, Luebke R, Olejniczak K, Portier C, Slikker W. Approaches for Assessing Risks to Sensitive Populations: Lessons Learned from Evaluating Risks in the Pediatric Population. Toxicological Sciences 2009, 113: 4-26. PMID: 19770482, PMCID: PMC3469276, DOI: 10.1093/toxsci/kfp217.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsBiomarkersChildChild, PreschoolDose-Response Relationship, DrugEnvironmental ExposureEnvironmental MonitoringGenetic Predisposition to DiseaseGovernment RegulationHealth PolicyHumansInfantInfant, NewbornModels, BiologicalPharmacokineticsPublic HealthRisk AssessmentRisk FactorsToxicity Tests
2003
CYP2C9exon 4 mutations and warfarin dose phenotype in Asians
Rettie A, Tai G, Veenstra D, Farin F, Srinouanprachan S, Lin Y, Thummel K, Hines R. CYP2C9exon 4 mutations and warfarin dose phenotype in Asians. Blood 2003, 101: 2896-2897. PMID: 12642346, DOI: 10.1182/blood-2002-11-3452.Peer-Reviewed Original ResearchAryl Hydrocarbon HydroxylasesAsian PeopleCytochrome P-450 CYP2C9Dose-Response Relationship, DrugExonsHumansMutationPhenotypeWarfarin