Biomarkers in Toxicology

1170 Pages·2019·50.908 MB·English

by  Ramesh C. Gupta (editor)

BIOMARKERS IN
TOXICOLOGY
SECOND EDITION
Edited by
R C. G , DVM, MVS , P D, DABT, FACT, FACN, FATS
AMESH UPTA C H
Professor andHead, Toxicology Department
Breathitt Veterinary Centre
Murray StateUniversity
Hopkinsville, Kentucky
UnitedStates
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This book is dedicated to my daughter Rekha, wife Denise,
and parents the late Chandra and Triveni Gupta.
Contributors
ArturoAnado´n Department ofPharmacology and SubashChandraGupta DepartmentofBiochemistry,
Toxicology,FacultyofVeterinary Medicine,Universidad InstituteofScience, BanarasHinduUniversity,Varanasi,
ComplutensedeMadrid,Madrid,Spain India
VellareddyAnantharam Parkinson’sDisorderResearch SaurabhChatterjee Department ofEnvironmentalHealth
Laboratory,Iowa CenterforAdvancedNeurotoxicology, Sciences,ArnoldSchoolofPublicHealth,University of
DepartmentofBiomedicalSciences, IowaState University, SouthCarolina, Columbia,SC,UnitedStates
Ames,IA,UnitedStates CatheryneChiang DepartmentofComparativeBiosciences,
AnthonyE.Archibong DepartmentofMicrobiology, UniversityofIllinoisat Urbana-Champaign,Urbana,IL,
Immunology&Physiology,Meharry MedicalCollege, UnitedStates
Nashville,TN,UnitedStates AnirudhJ.Chintalapati St.John’sUniversity,Collegeof
IrmaAres DepartmentofPharmacology andToxicology, PharmacyandHealthSciences, Departmentof
FacultyofVeterinaryMedicine, UniversidadComplutense PharmaceuticalSciences,ToxicologyDivision,NewYork,
deMadrid,Madrid,Spain UnitedStates
AdamD.Aulbach CharlesRiverLaboratories,Mattawan, P.Cohn NewJerseyDepartmentofHealth(retired),Trenton,
MI,UnitedStates NJ,UnitedStates
NikeeAwasthee DepartmentofBiochemistry,Instituteof RobertW.Coppock Toxicologist andAssociates, Ltd,
Science,BanarasHinduUniversity,Varanasi,India Vegreville,AB,Canada
AryamitraBanerjee StudyDirector,ToxicologyResearch LucioG.Costa DepartmentofEnvironmental and
Laboratory,University ofIllinois atChicago,Chicago,IL, OccupationalHealth Sciences,UniversityofWashington,
UnitedStates Seattle,WA,UnitedStates;DepartmentofMedicine&
LeahD.Banks DepartmentofBiochemistry,CancerBiology, Surgery,UniversityofParma,Parma,Italy
Neuroscience&Pharmacology,MeharryMedical College, TirupapuliyurV.Damodaran DepartmentofBiologicaland
Nashville,TN,UnitedStates BiomedicalSciences,North CarolinaCentralUniversity,
FrankA.Barile St. John’sUniversity,CollegeofPharmacy Durham,NC,UnitedStates
andHealthSciences, DepartmentofPharmaceutical ClintonD’Souza Division ofEnvironmentalHealthand
Sciences,ToxicologyDivision,NewYork,UnitedStates Toxicology,NitteUniversityCenterforScienceEducation
SudheerR.Beedanagari BristolMyers Squibb,New andResearch(NUCSER),Deralakatte, India
Brunswick,NJ, UnitedStates Wolf-D.Dettbarn Vanderbilt University,Nashville, TN,
CharalamposBelantis DepartmentofUrology,University UnitedStates
GeneralHospitalofHeraklion,UniversityofCrete,Medical AmyA.Devlin USFoodandDrugAdministration,Silver
School,Heraklion,Crete,Greece Spring,MD,UnitedStates
EnricoBergamaschi Laboratory ofToxicologyand RobinB.Doss ToxicologyDepartment, BreathittVeterinary
OccupationalEpidemiology,Department ofPublicHealth Center,MurrayState University,Hopkinsville,Kentucky,
ScienceandPediatrics, UniversityofTurin,Italy UnitedStates
SadikshyaBhandari MolecularandCellBiology,University ShiwangiDwivedi Division ofEnvironmentalHealthand
ofConnecticut, Storrs, CT,UnitedStates Toxicology,NitteUniversityCenterforScienceEducation
SnehaP.Bhatia ResearchInstitute forFragranceMaterials, andResearch(NUCSER),Deralakatte, India
NJ,UnitedStates MargittaM.Dziwenka FacultyofMedicine&Dentistry,
KarynBischoff Cornell University,DiagnosticToxicologist, DivisionofHealthSciences LaboratoryAnimal Services,
NewYorkStateAnimal HealthDiagnosticCenter,Ithaca Edmonton,AB,Canada
NY,UnitedStates JorgeEste´vez Institutode Bioingenier´ıa,Universidad
DavidJ.Borts DepartmentofVeterinary Diagnosticand MiguelHerna´ndezde Elche,Spain
ProductionAnimal Medicine,CollegeofVeterinary DanielS.Fabricant PresidentandCEO,NaturalProducts
Medicine,Iowa StateUniversity,Ames,IA,UnitedStates Association,WashingtonD.C.,UnitedStates
EmilyBrehm DepartmentofComparativeBiosciences, A.M.Fan CaliforniaEnvironmentalProtection
UniversityofIllinois at Urbana-Champaign,Urbana,IL, Agency(retired),Oakland/Sacramento,CA,
UnitedStates UnitedStates
xix
xx
CONTRIBUTORS
VanessaA.Fitsanakis DepartmentofPharmaceutical HollyE.Hatfield Department of Biochemistry, University
Sciences,NortheastOhioMedicalUniversity,Rootstown, of Cincinnati Medical School, Cincinnati, OH,
OH,UnitedStates UnitedStates
JohnFlaskos Laboratory ofBiochemistryandToxicology, WallaceA.Hayes University ofSouthFlorida Collegeof
FacultyofVeterinary Medicine,Aristotle Universityof PublicHealth,Tampa,FL,UnitedStates; MichiganState
Thessaloniki,Thessaloniki, Greece University,EastLansing, MI,UnitedStates
JodiA.Flaws DepartmentofComparativeBiosciences, IoannisHeretis DepartmentofUrology,UniversityGeneral
UniversityofIllinois atUrbana-Champaign,Urbana,IL, HospitalofHeraklion,UniversityofCrete,MedicalSchool,
UnitedStates Heraklion,Crete,Greece
SwaranJ.S.Flora NationalInstituteofPharmaceutical AntonioF.Herna´ndez DepartmentofLegalMedicineand
EducationandResearch,Raebareli,U.P.,India Toxicology,University ofGranadaSchoolofMedicine,
SueM.Ford DepartmentofPharmaceuticalSciences, Granada,Spain
CollegeofPharmacy&HealthSciences,St.John’s CoreyJ.Hilmas SeniorVicePresidentofScientificand
University,Jamaica,NY,UnitedStates RegulatoryAffairs,Natural ProductsAssociation,
JessicaS.Fortin CollegeofVeterinary Medicine,Michigan Washington D.C.,UnitedStates
StateUniversity,EastLansing,MI, UnitedStates DarrylB.Hood CollegeofPublicHealth,OhioState
DomnikiFragou LaboratoryofForensicMedicine& University,Columbus, OH,UnitedStates
Toxicology,SchoolofMedicine,Aristotle Universityof PasiHuuskonen SchoolofPharmacy/Toxicology,Facultyof
Thessaloniki,Greece HealthSciences,University ofEasternFinland,Kuopio,
ShayneC.Gad Principal ofGadConsultingServices, Finland
Raleigh,NC,UnitedStates StewartB.Jacobson ShinNipponBiomedical Laboratories
BiancaGalateanu DepartmentofBiochemistryandMolecular USA,Ltd,Everett,WA,UnitedStates
Biology,UniversityofBucharest,Bucharest,Romania SandraA.James-Yi Associate PrincipleScientist, Product
DaleR.Gardner UnitedStatesDepartmentofAgriculture, Safety/Nutritional Toxicology,MaryKayInc.,Addison,
AgriculturalResearchService,Poisonous PlantResearch Texas,UnitedStates
Laboratory,Logan, UT,UnitedStates HuajunJin Parkinson’sDisorderResearchLaboratory,Iowa
GeorgeGeorgiadis DepartmentofUrology,University CenterforAdvancedNeurotoxicology,Departmentof
GeneralHospitalofHeraklion,UniversityofCrete,Medical BiomedicalSciences,Iowa StateUniversity,Ames,IA,
School,Heraklion, Crete,Greece UnitedStates
FernandoGil DepartmentofLegalMedicine and JunKanno JapanBioassayResearch Center,Japan
Toxicology,UniversityofGranadaSchoolofMedicine, Organization ofOccupational HealthandSafety,Hadano,
Granada,Spain Japan
SaryuGoel NonclinicalExpert,Leesburg,VA,UnitedStates ArthiKanthasamy Parkinson’sDisorderResearch
Laboratory,IowaCenterforAdvancedNeurotoxicology,
MaryGulumian ToxicologyResearchProjectsNIOH,School
DepartmentofBiomedicalSciences,IowaState University,
ofPathology,UniversityoftheWitwatersrandSouthAfrica
Ames,IA,United States
P.K.Gupta Director ToxicologyConsultingGroup,Former
AnumanthaG.Kanthasamy Parkinson’sDisorderResearch
PrincipalScientistandChiefDivisionofPharmacologyand
Laboratory,IowaCenterforAdvancedNeurotoxicology,
Toxicology,IVRI,Advisor,WorldHealthOrganization
DepartmentofBiomedicalSciences,IowaState University,
(Geneva),Bareilly,India
Ames,IA,United States
RameshC.Gupta ToxicologyDepartment, Breathitt
ShilpaN.Kaore Raipur InstituteofMedicalSciences,
Veterinary Center,MurrayState University,Hopkinsville,
Raipur,India
Kentucky,UnitedStates
NavinchandraM.Kaore Raipur InstituteofMedical
RekhaK.Gupta SchoolofMedicine,University of
Sciences,Raipur,India
Louisville, Louisville,KY,UnitedStates
BhupendraS.Kaphalia DepartmentofPathology,
SharonGwaltney-Brant Veterinary InformationNetwork,
UniversityofTexasMedicalBranch,Galveston,TX,United
Mahomet,IL,UnitedStates
States
AlanJ.Hargreaves SchoolofScienceandTechnology,
VesaKarttunen SchoolofPharmacy/Toxicology,Faculty of
NottinghamTrentUniversity,Nottingham,UnitedKingdom
HealthSciences,University ofEasternFinland,Kuopio,
KellyL.Harris DepartmentofBiochemistry,CancerBiology, Finland
Neuroscience &Pharmacology,Meharry MedicalCollege,
GurjotKaur HumanandEnvironmentalToxicology,
Nashville,TN,UnitedStates
DepartmentofBiology,University ofKonstanz,Konstanz,
KennethJ.Harris DepartmentofBiochemistry,Cancer Germany
Biology,Neuroscience&Pharmacology,MeharryMedical
RavneetKaur Aveley,WesternAustralia
College,Nashville, TN,UnitedStates
xxi
CONTRIBUTORS
PrasadaRaoS.Kodavanti NeurotoxicologyBranch,Toxicity CharalamposMavridis Department ofUrology,University
AssessmentDivision, NationalHealthandEnvironmental GeneralHospitalofHeraklion,UniversityofCrete,Medical
Effects Research Laboratory,OfficeofResearchand School,Heraklion, Crete,Greece
Development,U.S.Environmental Protection Agency, RogerO.McClellan IndependentAdvisor,Toxicologyand
ResearchTriangle Park,NC,UnitedStates RiskAnalysis,Albuquerque,NewMexico,UnitedStates
UrmilaP.Kodavanti EnvironmentalPublicHealthDivision, VincentP.Meador CovanceLaboratories, Inc.,Global
NationalHealthandEnvironmentalEffectsResearch Pathology,Madison,WI,UnitedStates
Laboratory,OfficeofResearchandDevelopment,United
LarsFriisMikkelsen EllegaardGo¨ttingenMinipigsA/S,
StatesEnvironmentalProtectionAgency,Durham,North
Dalmose,Denmark
Carolina,United States
DejanMilatovic Charlottesville, VA,UnitedStates
GeorgeA.Kontadakis LaboratoryofOpticsandVisionand
IdaR.MillerMukherjee InstituteofPsychiatryandHuman
OphthalmologyDepartment,University ofCrete,
Behavior,Bambolim, Goa,India
Heraklion,Greece
AnupamaMukherjee OralPathology,Microbiologyand
GopalaKrishna NonclinicalConsultants, EllicottCity,MD,
ForensicOdontology,GoaDental CollegeandHospital,
UnitedStates
Panaji,India
PriyaA.Krishna NonclinicalConsultants,EllicottCity,MD,
PushpinderKaurMultani Johnson&Johnson,Janssen
UnitedStates
Research&Development, Malvern,PA, UnitedStates
KavyaA.Krishna NonclinicalConsultants, EllicottCity,
Pa¨iviMyllynen NordLab,Oulu,Finland
MD,UnitedStates
KirsiMyo¨ha¨nen EuropeanChemicalsAgency,Helsinki,
MariaKummu ResearchUnitofBiomedicine,
Finland
PharmacologyandToxicology,FacultyofMedicine,
RekekNegga DepartmentofBiology,King University,
UniversityofOulu,Oulu,Finland
Bristol,TN,UnitedStates
GeorgeD.Kymionis JulesGoninEyeHospital, Facultyof
CarolinaNegrei DepartamentofToxicology,Facultyof
BiologyandMedicine,University ofLausanne, Lausanne,
Switzerland Pharmacy,“Carol Davila”UniversityofMedicineand
Pharmacy,Bucharest,Romania
RajivLall VetsPlusInc.,Menomonie,WI,UnitedStates
MelitonN.Novilla ShinNipponBiomedicalLaboratories
P.Lin National InstituteofEnvironmentalHealth Sciences,
USA,Ltd,Everett,WA, UnitedStates;SchoolofVeterinary
NationalHealthResearchInstitutes,Taiwan
Medicine,PurdueUniversity,WestLafayette,IN,United
BommannaG.Loganathan DepartmentofChemistryand States
Watershed StudiesInstitute,Murray StateUniversity,
StephaniePadilla IntegratedSystemsToxicologyDivision,
Murray,KY,UnitedStates
OfficeofResearch andDevelopment, U.S.Environmental
JarkkoLoikkanen EuropeanChemicalsAgency,Helsinki, Protection Agency,Research TrianglePark,NC,United
Finland States
MarcelloLotti DipartimentodiScienzeCardio-Toraco- CarlosM.Palmeira Centerfor NeurosciencesandCell
VascolarieSanita` Pubblica, Universita` degliStudiPadova, BiologyoftheUniversityofCoimbraandDepartmentof
Padova,Italy LifeSciencesoftheUniversityofCoimbraLargoMarqueˆs
MichaelA.Lynes MolecularandCellBiology,Universityof dePombal,Coimbra, Portugal
Connecticut, Storrs,CT,United States KipE.Panter UnitedStatesDepartment ofAgriculture,
BrindaMahadevan MedicalSafety &Surveillance, Abbott AgriculturalResearchService,Poisonous PlantResearch
Laboratories,Columbus,OH,UnitedStates Laboratory,Logan, UT,United States
JitendraK.Malik DivisionofPharmacologyandToxicology, MarkkuPasanen SchoolofPharmacy/Toxicology,Faculty
IndianVeterinary ResearchInstitute, Izatnagar,Bareilly, ofHealthSciences, UniversityofEasternFinland,Kuopio,
UttarPradesh,India Finland
CharalamposMamoulakis DepartmentofUrology, DanielJ.Patrick CharlesRiverLaboratories,Mattawan,MI,
UniversityGeneralHospitalofHeraklion,Universityof UnitedStates
Crete, MedicalSchool, Heraklion,Crete,Greece SofiaPavanello DipartimentodiScienzeCardio-Toraco-
JaneA.Mantey DepartmentofBiochemistry,Cancer VascolarieSanita` Pubblica, Universita` degliStudiPadova,
Biology,Neuroscience&Pharmacology,Meharry Medical Padova,Italy
College,Nashville,TN,UnitedStates HenrikDuelundPedersen EllegaardGo¨ttingenMinipigs
Mar´ıaRosaMartı´nez-Larran˜aga Departmentof A/S,Dalmose,Denmark
PharmacologyandToxicology,FacultyofVeterinary OlaviPelkonen Research UnitofBiomedicine,
Medicine,Universidad ComplutensedeMadrid,Madrid, PharmacologyandToxicology,FacultyofMedicine,
Spain UniversityofOulu,Oulu,Finland
Mar´ıaAra´nzazuMartı´nez DepartmentofPharmacology MichaelA.Pellizzon ResearchDiets, Inc.,NewBrunswick,
andToxicology,Faculty ofVeterinaryMedicine, NJ,UnitedStates
UniversidadComplutensede Madrid,Madrid,Spain JasonPitt University ofEvansville, Evansville, IN
xxii
CONTRIBUTORS
ArgyroPlaka Laboratory ofOpticsandVisionand MiguelA.Sogorb InstitutodeBioingenier´ıa,Universidad
OphthalmologyDepartment, UniversityofCrete, MiguelHerna´ndezdeElche,Spain
Heraklion,Greece AjaySrivastava VetsPlusInc.,Menomonie,WI,United
AramandlaRamesh DepartmentofBiochemistry,Cancer States
Biology,Neuroscience&Pharmacology,MeharryMedical SzabinaA.Stice Division ofBiotechnologyandGRAS
College,Nashville, TN,UnitedStates NoticeReview,CenterforFoodSafety andApplied
SaniyaRattan DepartmentofComparativeBiosciences, Nutrition,USFoodandDrugAdministration,CollegePark,
UniversityofIllinois atUrbana-Champaign,Urbana,IL, MD,United States
UnitedStates MarkusStorvik SchoolofPharmacy/Toxicology,Faculty of
JenniRepo SchoolofPharmacy/Toxicology,Facultyof HealthSciences,University ofEasternFinland,Kuopio,
HealthSciences,University ofEasternFinland,Kuopio, Finland
Finland DavidT.Szabo PPGIndustries Incorporated,Pittsburgh,
MatthewR.Ricci ResearchDiets,Inc., NewBrunswick,NJ, PA, UnitedStates
UnitedStates Joa˜oS.Teodoro CenterforNeurosciencesandCellBiology
AnabelaP.Rolo Centerfor NeurosciencesandCellBiology ofthe UniversityofCoimbraandDepartmentofLife
ofthe UniversityofCoimbraandDepartmentofLife Sciences oftheUniversity ofCoimbraLargoMarqueˆsde
SciencesoftheUniversity ofCoimbraLargoMarqueˆsde Pombal,Coimbra, Portugal
Pombal,Coimbra, Portugal AristidisM.Tsatsakis CenterofToxicologyScience&
MagdaliniSachana OrganizationforEconomicCooperation Research,MedicalSchool, UniversityofCrete,Heraklion,
andDevelopment(OECD),Paris,France Greece
HeidiSahlman School ofPharmacy/Toxicology,Faculty of JohnTsiaoussis LaboratoryofAnatomy-Histology-
HealthSciences,University ofEasternFinland,Kuopio, Embryology,MedicalSchool,University ofCrete,
Finland Heraklion,Crete,Greece
NitinSaini Johnson&Johnson,JanssenResearch& KirsiVa¨ha¨kangas SchoolofPharmacy/Toxicology,Faculty
Development,Malvern, PA,UnitedStates ofHealth Sciences,UniversityofEasternFinland,Kuopio,
VandanaSaini Washington,United States Finland
KaiSavolainen NanosafetyResearchCentre,Finnish SumitSinghVerma DepartmentofBiochemistry,Instituteof
Science, BanarasHindu University,Varanasi, India
InstituteofOccupationalHealth,Helsinki,Finland
RataneshKumarSeth DepartmentofEnvironmentalHealth EugenioVilanova Institutode Bioingenier´ıa,Universidad
Sciences,ArnoldSchoolofPublicHealth,University of MiguelHerna´ndezdeElche,Spain
SouthCarolina, Columbia,SC,UnitedStates SuryanarayanaV.Vulimiri National Centerfor
AbhaSharma NationalInstitute ofPharmaceutical Environmental Assessment,Environmental Protection
EducationandResearch,Raebareli,U.P.,India Agency(EPA),Washington DC,United States
AnuragSharma Division ofEnvironmentalHealth and GenoaR.Warner DepartmentofComparativeBiosciences,
Toxicology,NitteUniversityCenterforScienceEducation UniversityofIllinois atUrbana-Champaign,Urbana,IL,
andResearch(NUCSER), Deralakatte,India UnitedStates
ElinaSieppi ResearchUnitofBiomedicine, Pharmacology KevinD.Welch UnitedStatesDepartmentofAgriculture,
andToxicology,FacultyofMedicine,University ofOulu, Agricultural ResearchService,Poisonous PlantResearch
Oulu,Finland Laboratory,Logan,UT,UnitedStates
RuiSilva CenterforNeurosciencesandCellBiology ofthe ChristinaWilson-Frank PurdueUniversity,Collegeof
UniversityofCoimbraandDepartment ofLifeSciences of Veterinary Medicine,Animal DiseaseDiagnostic
theUniversityofCoimbraLargoMarqueˆsdePombal, Laboratory,DepartmentofComparativePathobiology,West
Coimbra,Portugal Lafayette,IN,UnitedStates
AnitaSinha VetsPlusInc.,Menomonie,WI,United States S.H.You InstituteofFoodSafetyandRiskManagement,
NationalTaiwanOceanUniversity,Keelung,Taiwan
IordanisSkamagkas DepartmentofUrology,University
GeneralHospitalofHeraklion,UniversityofCrete,Medical SnjezanaZaja-Milatovic PAREXELInternational,
School,Heraklion, Crete,Greece Alexandria, VA,UnitedStates
SamanthaJ.Snow EnvironmentalPublicHealthDivision, IoannisE.Zisis DepartmentofUrology,UniversityGeneral
NationalHealthandEnvironmental EffectsResearch HospitalofHeraklion,UniversityofCrete,MedicalSchool,
Laboratory,OfficeofResearchandDevelopment, United Heraklion,Crete,Greece
StatesEnvironmental Protection Agency,Durham,North CsabaK.Zoltani EmeritusUSArmyResearch Lab,
Carolina, UnitedStates Aberdeen Proving Ground,MD,UnitedStates
Foreword
The first edition of BiomarkersinToxicology,editedbyRameshGupta,waspublishedin2014.Thewholeareaof
biomarkers, notonlyintoxicology,israpidly developing,partlybecauseoftheavailability ofhighlysophisticated
analytical equipment, and so the second edition of this book is greatly welcomed. The second edition contains 12
new chapters,and most of theresthave been updated.
Merriam Webster defines a biomarker as a distinctive biological or biologically derived indicator (as a metab-
olite)ofaprocess,event,orcondition(as,forexample,aging,disease,oroilformation).Thereareotherdefinitions,
for example, in Environmental Health Criteria 222 Biomarkers. In Risk Assessment http://www.inchem.org/
documents/ehc/ehc/ehc222.htm#1.0 biomarkers are defined thus “A biomarker is any substance, structure or
process that can be measured in the body or its products and influence or predict the incidence of outcome or
disease.”Thesubjectofthepresentbookisbiomarkersintoxicology,butitshouldberememberedthatbiomarkers
includesubstancesusedinthedetectionofnumerousdiseases,includingtheautoimmunediseases,whicharenot
generallythoughttobetoxicologicalinorigin.However,biomarkersarecrucialtotoxicologyandallieddisciplines
such as epidemiology andrisk assessment.
The earliest toxicological biomarkers of exposure date from beforeprecise analytical techniques wereavailable
andincludetheKaysereFleischerring(described1902/3),usuallyindicativeofcopperaccumulationinthecornea
in cases of Wilson’s disease, as well as lead lines in the gums associated with lead toxicity. The cherry red color
noted as a (rather unreliable) clinical sign in carbon monoxide poisoning may also be described as a biomarker.
Oneoftheearliestbiomarkersrelyingonbiochemicalanalyticaltechniqueswasmeasurementofcholinesterase
activity,initiallywholebloodcholinesteraseandlaterplasmapseudocholinesterase(butyrylcholinesterase)andred
blood cell acetylcholinesterase. Cholinesterase measurements were introduced at defense laboratories after World
WarIIasascreeningtestforexcessiveexposuretoorganophosphatecompounds:a20%depressioninactivitywas
consideredtomandatecessationofexposureofindividualstoorganophosphatenerveagents(thebasisofthe20%
figure is obscure, but seemed protective). Pseudocholinesterase and red blood cell acetylcholinesterase measure-
mentsnowhavenumeroususesinworkerprotection,clinicaldiagnosisofpoisoning,andhumanandexperimental
animal studies (including regulatory ones) in relation to the use of organophosphate and other anticholinesterase
pesticides. Since World War II biomarkers of toxicity have ballooned in importance and number in worker and
consumerprotectionandclinicalandexperimentaltoxicologyandarealsowidelyusedinregulationofchemicals
in animal and, less commonly, human experimental studies. Toxicological biomarkers are also used in allied
disciplines, for example, epidemiology, and may be used to estimate loads of exposure in populations being
investigated.
Intoxicology,biomarkersareoftendividedintobiomarkersofexposure,ofeffect,andofsusceptibility,andallof
these are dealt with in this book, which is extremely wide-ranging. The book has an initial introductory part,
including discussion of rodent, nonhuman primate, and zebrafish and Caenorhabditis elegans models for toxico-
logical testing. There are two new chapters in this part: firstly, Drosophila melanogaster, Eisenia fetida, and Daphnia
magna for toxicity testing and biomarkers and secondly, adverse outcome pathways and biomarkers.
Part II, systems toxicity biomarkers, comprises chapters on biomarkers of toxicity in relation to all important
organsandorgansystems.Thereisanadditionalchapteronreproductiveanddevelopmentaltoxicitybiomarkers,
andanotheronototoxicitybiomarkers. Part III, renamedchemical agents, solvents,andgasestoxicity biomarkers,
deals with biomarkers in relation to the toxicity of specific groups of compounds and comprises chapters on
pesticides, as well as polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), brominated flame re-
tardants,polycyclicaromatichydrocarbons(PAHs),bisphenolA,melamineandcyanuricacid,andmetals;thereis
averyusefulchapteronbiomarkersofchemicalmixturetoxicity.PartIV(biotoxinsbiomarkers)hasthreechapters
on, respectively, freshwater cyanotoxins, mycotoxins, and poisonous plants: biomarkers for diagnosis (of
poisoning). Part V covers pharmaceuticals and nutraceuticals, with chapters on drug toxicity biomarkers and
nutriphenomicbiomarkerstogetherwithanewchapteronbiomarkersoftoxicityfordietaryingredientscontained
in dietary supplements. Part VI covers nanomaterials and radiation, with two chapters, one on biomarkers of
exposureandeffectofengineerednanomaterialsandtheotheronbiomarkersofexposureandeffectsofradiation.
xxiii
xxiv
FOREWORD
Part VII is entitled carcinogens biomonitoring and cancer biomarkers and contains six chapters. These are on
biomonitoring exposures to carcinogens, genotoxicity biomarkers, epigenetic biomarkers in toxicology, breast
cancer biomarkers, pancreatic and ovarian cancer biomarkers, and prostate cancer biomarkers. Part VIII is called
disease biomarkers and deals with biomarkers of Alzheimer’s disease, biomarkers of Parkinson’s disease, bio-
markers for drugs of abuse and neuropsychiatric disorders: models and mechanisms, osteoarthritis biomarkers,
pathological biomarkers in toxicology and oral pathology biomarkers. Of these, the chapters on osteoarthritis and
oral pathology are new. Part IX is called special topics. This part of the book contains chapters on biomarkers of
mitochondrial dysfunction and toxicity, biomarkers of blood-brain barrier dysfunction, biomarkers of oxidative/
nitrosative stress and neurotoxicity, cytoskeletal disruption as a biomarker of developmental neurotoxicity, mem-
brane transporters and transporter substrates as biomarkers for drug pharmacokinetics, pharmacodynamics, and
toxicity/adverse events, and citrulline: pharmacological perspectives and role as a biomarker in diseases and
toxicity. Of these chapters, that on the blood-brain barrier dysfunction is new and is particularly welcome as the
blood-brainbarrierisveryimportantinprotectingthecentralnervoussystemagainsttoxicants.Thelastpartofthe
bookisonapplicationsofbiomarkers.Itcontainsthreenewchapters:biomarkersdetectionfortoxicitytestingusing
microarray technology, metabolomics, and proteomics. Also there are chapters on transcriptomic biomarkers,
percellome toxicogenomics, biomarkers in computational toxicology, biomarkers in biomonitoring of xenobiotics
and biomarkers in toxicology, risk assessment, and environmental chemical regulations.
The 67-chapter book has an outstanding array of authors from the United States, Canada, Denmark, Finland,
Greece, India, Italy, Japan, Portugal, Romania, and Spain. Professor Gupta deserves our gratitude for assembling
such a distinguished group of experts to produce so comprehensive a book on this rapidly growing and very
important field.
Timothy C Marrs
Edenbridge
UnitedKingdom