Computational Toxicology: Volume I

607 Pages·2013·8.808 MB·English

by  Brad Reisfeld, Arthur N. Mayeno (auth.), Brad Reisfeld, Arthur N. Mayeno (eds.)

M M B TM
ETHODS IN OLECULAR IOLOGY
SeriesEditor
JohnM.Walker
School ofLife Sciences
University ofHertfordshire
Hatfield, Hertfordshire,AL109AB,UK
For further volumes:
http://www.springer.com/series/7651
.
Computational Toxicology
Volume I
Edited by
Brad Reisfeld
Chemical and Biological Engineering & School of Biomedical Engineering
Colorado State University, Colorado, USA
Arthur N. Mayeno
Chemical and Biological Engineering,
Colorado State University, Colorado, USA
Editors
BradReisfeld ArthurN.Mayeno
ChemicalandBiologicalEngineering ChemicalandBiologicalEngineering
&SchoolofBiomedicalEngineering ColoradoStateUniversity
ColoradoStateUniversity Colorado,USA
Colorado,USA
ISSN1064-3745 ISSN1940-6029(electronic)
ISBN978-1-62703-049-6 ISBN978-1-62703-050-2(eBook)
DOI10.1007/978-1-62703-050-2
SpringerNewYorkHeidelbergDordrechtLondon
LibraryofCongressControlNumber:2012947026
ªSpringerScience+BusinessMedia,LLC2012
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Preface
Rapidadvancesincomputerscience,biology,chemistry,andotherdisciplinesareenabling
powerful new computational tools and models for toxicology and pharmacology. These
computational tools hold tremendous promise for advancing applied and basic science,
fromstreamliningdrugefficacyandsafetytestingtoincreasingtheefficiencyandeffective-
ness of risk assessment for environmental chemicals. These approaches also offer the
potentialtoimproveexperimentaldesign,reducetheoverallnumberofexperimentaltrials
needed,anddecreasethenumberofanimalsusedinexperimentation.
Computationalapproachesareideallysuitedtoorganize,process,andanalyzethevast
libraries and databases of scientific information and to simulate complex biological phe-
nomena.Forinstance,theyallowresearchersto(1)investigatetoxicologicalandpharma-
cological phenomena across a wide range of scales of biological organization
(molecular $ cellular $ organism), (2) incorporate and analyze multiple biochemical
and biological interactions, (3) simulate biological processes and generate hypotheses
based on model predictions, which can be tested via targeted experimentation in vitro or
invivo,(4)exploretheconsequencesofinter-andintra-speciesdifferencesandpopulation
variability on the toxicology and pharmacology, and (5) extrapolate biological responses
acrossindividuals,species,andarangeofdoselevels.
Despitetheexceptionalpromiseofcomputationalapproaches,therearepresentlyvery
fewresourcesthatfocusonprovidingguidanceonthedevelopmentandpracticeofthese
tools to solve problems and perform analyses in this area. This volume was conceived as
part of the Methods in Molecular Biology series to meet this need and to provide both
biomedicalandquantitativescientistswithessentialbackground,context,examples,useful
tips, and an overview of current developments in the field. To this end, we present a
collectionofpracticaltechniquesandsoftwareincomputationaltoxicology,illustratedwith
relevant examples drawn principally from the fields of environmental and pharmaceutical
sciences.Thesecomputationaltechniquescanbeusedtoanalyzeandsimulateamyriadof
multi-scalebiochemicalandbiologicalphenomenaoccurringinhumansandotheranimals
followingexposuretoenvironmentaltoxicantsordosingwithdrugs.
This book (the first in a two-volume set) is organized into four parts each covering a
methodology or topic, subdivided into chapters that provide background, theory, and
illustrativeexamples.Eachpartisgenerallyself-contained,allowingthereadertostartwith
anypart,althoughsomeknowledge ofconceptsfromotherpartsmaybeassumed.PartI
introduces the field of computational toxicology and its current or potential applications.
PartIIoutlinestheprincipalelementsofmathematicalandcomputationalmodeling,and
accepted best practices and useful guidelines. Part III discusses the use of computational
techniques and databases to predict chemical properties and toxicity, as well as the use of
molecular dynamics. Part IV delineates the elements and approaches to pharmacokinetic
andpharmacodynamicmodeling,includingnon-compartmentalandcompartmentalmod-
eling, modeling of absorption, prediction of pharmacokinetic parameters, physiologically
based pharmacokinetic modeling, and mechanism-based pharmacodynamic modeling;
chemical mixture and population effects, as well as interspecies extrapolation, are also
describedandillustrated.
v
vi Preface
Althoughacompletepictureoftoxicologicalriskofteninvolvesananalysisofenviron-
mental transport,we believe that thisexpansive topic isbeyond the scope of thisvolume,
and it will not be covered here; overviews of computational techniques in this area are
containedinavarietyofexcellentreferences[1–4].
Computationaltechniquesareincreasinglyallowingscientiststogainnewinsightsinto
toxicological phenomena, integrate (and interpret) the results from a wide variety of
experiments, and develop more rigorous and quantitative means of assessing chemical
safetyandtoxicity.Moreover,thesetechniquescanprovidevaluableinsightsbeforeinitiat-
ing expensive laboratory experiments and into phenomena not easily amenable to experi-
mental analysis, e.g., detection of highly reactive, transient, or trace-level species in
biological milieu.Webelieve thatthe uniquecollection ofexplanatorymaterial,software,
and illustrative examples in Computational Toxicology will allow motivated readers to
participateinthisexcitingfieldandundertakeadiversityofrealisticproblemsofinterest.
We would like to express our sincere thanks to our authors whose enthusiasm and
diversecontributionshavemadethisprojectpossible.
Colorado,USA BradReisfeld
ArthurN.Mayeno
References
1. Clark,M.M.,Transportmodelingforenvironmentalengineersandscientists.2nded.2009,Hobo-
ken,N.J.:Wiley.
2. Hemond, H.F. and E.J. Fechner-Levy, Chemical fate and transport in the environment. 2nd ed.
2000,SanDiego:AcademicPress.xi,433p.
3. Logan,B.E.,Environmentaltransportprocesses.1999,NewYork:Wiley.xiii,654p.
4. Nirmalakhandan,N.,Modelingtoolsforenvironmentalengineersandscientists.2002,BocaRaton,
Fla.:CRCPress.xi,312p.
Contents
Preface.................................................................... v
Contributors............................................................... ix
PART I INTRODUCTION
1 WhatisComputationalToxicology?....................................... 3
BradReisfeldandArthurN.Mayeno
2 ComputationalToxicology:ApplicationinEnvironmentalChemicals........... 9
Yu-MeiTan,RoryConolly,DanielT.Chang,RogelioTornero-Velez,
MichaelR.Goldsmith,ShaneD.Peterson,andCurtisC.Dary
3 RoleofComputationalMethodsinPharmaceuticalSciences .................. 21
SandhyaKortagere,MarkusLill,andJohnKerrigan
PART II MATHEMATICAL AND COMPUTATIONAL MODELING
4 BestPracticesinMathematicalModeling................................... 51
LisetteG.dePillisandAmiE.Radunskaya
5 ToolsandTechniques................................................... 75
ArthurN.MayenoandBradReisfeld
PART III CHEMINFORMATICS AND CHEMICAL PROPERTY PREDICTION
6 PredictionofPhysicochemicalProperties................................... 93
JohnC.Dearden
7 InformingMechanisticToxicologywithComputationalMolecularModels...... 139
MichaelR.Goldsmith,ShaneD.Peterson,DanielT.Chang,
ThomasR.Transue,RogelioTornero-Velez,
Yu-MeiTan,andCurtisC.Dary
8 ChemicalStructureRepresentationsandApplications
inComputationalToxicity............................................... 167
MuthukumarasamyKarthikeyanandRenuVyas
9 AccessingandUsingChemicalPropertyDatabases .......................... 193
JannaHastings,ZaraJosephs,andChristophSteinbeck
10 Accessing,Using,andCreatingChemicalPropertyDatabases
forComputationalToxicologyModeling .................................. 221
AntonyJ.Williams,SeanEkins,OlaSpjuth,andEgonL.Willighagen
11 MolecularDynamics.................................................... 243
XiaolinChengandIvayloIvanov
vii
viii Contents
PART IV PHARMACOKINETIC AND PHARMACODYNAMIC MODELING
12 IntroductiontoPharmacokineticsinClinicalToxicology ..................... 289
PavanVajjah,GeoffreyK.Isbister,andStephenB.Duffull
13 ModelingofAbsorption................................................. 313
WalterS.Woltosz,MichaelB.Bolger,andVieraLukacova
14 PredictionofPharmacokineticParameters.................................. 337
A.K.MadanandHarishDureja
15 Ligand-andStructure-BasedPregnaneXReceptorModels ................... 359
SandhyaKortagere,MatthewD.Krasowski,andSeanEkins
16 Non-compartmentalAnalysis ............................................ 377
JohanGabrielssonandDanielWeiner
17 CompartmentalModelingintheAnalysisofBiologicalSystems ............... 391
JamesB.Bassingthwaighte,ErikButterworth,
BartholomewJardine,andGaryM.Raymond
18 PhysiologicallyBasedPharmacokinetic/ToxicokineticModeling............... 439
JerryL.Campbell,RebeccaA.Clewell,P.RobinanGentry,
MelvinE.Andersen,andHarveyJ.ClewellIII
19 InterspeciesExtrapolation ............................................... 501
ElainaM.Kenyon
20 PopulationEffectsandVariability......................................... 521
JeanLouDorne,BillyAmzal,Fre´de´ricBois,Ame´lieCre´pet,
JessicaTressou,andPhilippeVerger
21 Mechanism-BasedPharmacodynamicModeling............................. 583
MelanieA.Felmlee,MarilynE.Morris,andDonaldE.Mager
Index..................................................................... 601
List of Contributors
HERVE´ ABDI (cid:2) SchoolofBehavioralandBrainSciences,TheUniversityofTexas
atDallas,Richardson,TX,USA
BILLYAMZAL (cid:2) LA-SEREuropeLtd,London,UK
MELVIN E. ANDERSEN (cid:2) TheHamnerInstitutesforHealthSciences,
ResearchTrianglePark,NC,USA
JAMES B. BASSINGTHWAIGHTE (cid:2) DepartmentofBioengineering,University
ofWashington,Seattle,WA,USA
FRE´DE´RIC Y. BOIS (cid:2) RoyallieuResearchCenter,TechnologicalUniversity
ofCompiegne,Compiegne,France;INERIS,DRC/VIVA/METO,
VerneuilenHalatte,France
MICHAEL B. BOLGER (cid:2) SimulationsPlus,Inc.,Lancaster,CA,USA
ERIK BUTTERWORTH (cid:2) DepartmentofBioengineering,UniversityofWashington,Seattle,
WA,USA
(cid:2)
JERRY L. CAMPBELL JR. TheHamnerInstitutesforHealthSciences,
ResearchTrianglePark,NC,USA
DANIELT. CHANG (cid:2) NationalExposureResearchLaboratory,USEnvironmental
ProtectionAgency,ResearchTrianglePark,NC,USA
XIAOLIN CHENG (cid:2) OakRidgeNationalLaboratory,UT/ORNLCenter
forMolecularBiophysics,OakRidge,TN,USA;DepartmentofBiochemistry
andCellularandMolecularBiology,UniversityofTennessee,Knoxville,
TN,USA
(cid:2)
HARVEY J. CLEWELL III TheHamnerInstitutesforHealthSciences,ResearchTriangle
Park,NC,USA
REBECCA A. CLEWELL (cid:2) TheHamnerInstitutesforHealthSciences,
ResearchTrianglePark,NC,USA
JEAN PAUL COMET (cid:2) I3Slaboratory,UMR6070CNRS,UniversityofNice-Sophia
Antipolis,SophiaAntipolis,France
RORY CONOLLY (cid:2) NationalHealthandEnvironmentalEffectsResearchLaboratory,
U.S.EnvironmentalProtectionAgency,ResearchTrianglePark,NC,USA
AME´LIE CRE´PET (cid:2) FrenchAgencyforFood,EnvironmentandOccupationalHealthSafety
(ANSES),Maisons-Alfort,France
CURTIS C. DARY (cid:2) NationalExposureResearchlaboratory,USEnvironmentalProtection
Agency,ResearchTrianglePark,NC,USA
LISETTE G. DE PILLIS (cid:2) DepartmentofMathematics,HarveyMuddCollege,
Claremont,CA,USA
JEAN LOU DORNE (cid:2) EmergingRisksUnit,EuropeanFoodSafetyAuthority,
Parma,Italy
STEPHEN B. DUFFULL (cid:2) SchoolofPharmacy,UniversityofOtago,Otago,
NewZealand
HARISH DUREJA (cid:2) M.D.University,Rohtak,India
ix
x ListofContributors
SEAN EKINS (cid:2) CollaborationsinChemistry,FuquayVarina,NC,USA;Department
ofPharmaceuticalSciences,UniversityofMaryland,Baltimore,MD,USA;Department
ofPharmacology,UniversityofMedicine&Dentistry
ofNewJersey(UMDNJ)-RobertWoodJohnsonMedicalSchool,Piscataway,
NJ,USA
MELANIE A. FELMLEE (cid:2) DepartmentofPharmaceuticalSciences,
UniversityatBuffalo,StateUniversityofNewYork,Buffalo,NY,USA
JOHAN GABRIELSSON (cid:2) DivisionofPharmacologyandToxicology,
DepartmentofBiomedicalSciencesandVeterinaryPublicHealth,
SwedishUniversityofAgriculturalSciences,Uppsala,Sweden
P. ROBINAN GENTRY (cid:2) EnvironInternationalCorporation,Monroe,LA,USA
MICHAEL R. GOLDSMITH (cid:2) NationalExposureResearchLaboratory,
USEnvironmentalProtectionAgency,ResearchTrianglePark,NC,USA
JANNA HASTINGS (cid:2) EuropeanBioinformaticsInstitute,Hinxton,UK
GEOFFREY K. ISBISTER (cid:2) DepartmentofClinicalToxicologyandPharmacology,
CalvaryMaterNewcastle,UniversityofNewcastle,Newcastle,NSW,Australia;
DisciplineofClinicalPharmacology,UniversityofNewcastle,
Newcastle,NSW,Australia
IVAYLO IVANOV (cid:2) DepartmentofChemistry,GeorgiaStateUniversity,Atlanta,
GA,USA
BARTHOLOMEW JARDINE (cid:2) DepartmentofBioengineering,UniversityofWashington,
Seattle,WA,USA
ZARA JOSEPHS (cid:2) EuropeanBioinformatics Institute,Hinxton,UK
MUTHUKUMARASAMY KARTHIKEYAN (cid:2) NationalChemicalLaboratory,
DigitalInformationResourceCentre&CentreofExcellenceinScientificComputing,
Pune,India
ELAINA KENYON (cid:2) PharmacokineticsBranch,IntegratedSystemsToxicologyDivision,MD
B105-03,NationalHealthandEnvironmentalEffectsResearchLaboratory,Officeof
ResearchandDevelopment,U.S.EnvironmentalProtectionAgency,
ResearchTrianglePark,NC,USA
JOHN KERRIGAN (cid:2) CancerInstituteofNewJersey,RobertWoodJohnson
MedicalSchool,NewBrunswick,NJ,USA
SANDHYA KORTAGERE (cid:2) DepartmentofMicrobiologyandImmunology,DrexelUniversity
CollegeofMedicine,Philadelphia,PA,USA
MATTHEW D. KRASOWSKI (cid:2) DepartmentofPathology,UniversityofIowa
HospitalsandClinics,IowaCity,IA,USA
MARKUS LUKACOVA (cid:2) DepartmentofMedicinalChemistryandMolecularPharmacology,
PurdueUniversity,WestLafaytte,IN,USA
VIERA LUKACOVA (cid:2) SimulationsPlus,Inc.,Lancaster,CA,USA
A.K. MADAN (cid:2) Pt.B.D.SharmaUniversityofHealthSciences,Rohtak,India
DONALD E. MAGER (cid:2) DepartmentofPharmaceuticalSciences,University
atBuffalo,StateUniversityofNewYork,Buffalo,NY,USA
ARTHUR N. MAYENO (cid:2) DepartmentofChemicalandBiologicalEngineering,
ColoradoStateUniversity,FortCollins,CO,USA
MARILYN E. MORRIS (cid:2) DepartmentofPharmaceuticalSciences,
UniversityatBuffalo,StateUniversityofNewYork,Buffalo,NY,USA