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21st Annual Green Chemistry & Engineering ConferenceJune 2017, Reston, USA
Designing a sustainable toxicology undergraduate curriculum
Dalila Kovacs & Richard RediskeGrand Valley State University
Allendale, MI 49426
Toxicology for Chemists: an unique approaches for integrating toxicology into chemistry courses & programs
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WhoisGrandValley
• CarnegieClassification“Master’sLarge”publicinstitution
• ~25,000students,87%undergraduates
• ~45%first-generationcollegestudents
• ~20%ofthestudentstakeaservice-levelchemistrycourse(GeneralorGOB)
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Whytoxicology
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inundergraduatecurriculum?
• toprovidesbasicunderstandingofcontemporarytoxicology
• topreparestudentstobecomeandcontinuetoremaintheinformedandtheresponsiblecitizensthatoursocietyneeds.
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Rationaleforaddingthiscoursetothecurriculum
Wereadandhearmanyreportsofhealthissuesthatmaybeassociatedwithconsumerproductsandchemicals,butfewindividualshavethebackgroundtounderstandwhysomechemicalsaremoreharmfulthanothers.
Aninformedconsumerwouldbeabletomakesensibledecisionsregardinghishealthanwillbeabletoactaccordinglyinthepublicspace.
GCcommitmentSigninginstitutionsagreethatupongraduation,allchemistrymajorsshouldhaveproficiencyinthefollowingessentialgreenchemistrycompetencies:• Theory: workingknowledgeGreenChemistryprinciples• Toxicology:Haveanunderstandingofthemolecularmechanismsofhowchemicalsaffecthumanhealthandtheenvironment,andtheresourcestoidentifyandassessmolecularhazards
• LaboratorySkills:abilitytoassesschemicalproductsandprocessesanddesigngreeneralternativeswhenappropriate
• Application:Bepreparedtoservesocietyintheirprofessionalcapacityasscientistsandprofessionalsthroughthearticulation,evaluationandemploymentofmethodsandchemicalsthatarebenignforhumanhealthandtheenvironment
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GCcommitmentSigninginstitutionsagreethatupongraduation,allchemistrymajorsshouldhaveproficiencyinthefollowingessentialgreenchemistrycompetencies:Theory: workingknowledgeGreenChemistryprinciplesToxicology:Haveanunderstandingofthemolecularmechanismsofhowchemicalsaffecthumanhealthandtheenvironment,andtheresourcestoidentifyandassessmolecularhazardsLaboratorySkills:abilitytoassesschemicalproductsandprocessesanddesigngreeneralternativeswhenappropriateApplication:Bepreparedtoservesocietyintheirprofessionalcapacityasscientistsandprofessionalsthroughthearticulation,evaluationandemploymentofmethodsandchemicalsthatarebenignforhumanhealthandtheenvironment
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Toxicology:Haveanunderstandingofthemolecularmechanismsofhowchemicalsaffecthumanhealthandtheenvironment,andtheresourcestoidentifyandassessmolecularhazards
Amodelbothsustainable andadaptive
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Who:GVSUChemistryDepartmentandDowToxicologyandEnvironmentResearchandConsulting(TERC)team.
What:prepareanddeliverinnovativeteachingmaterialsinamoderncourseformat;providefundamentalprinciplesoftoxicologyalongwithcontemporaryadvancesinthefield;utilizeexperiencedprofessionalsindeliveringinformationdirectlytostudents.
How:activelyengagestudentsinlearningandapplyingtheprinciplesoftoxicologythroughthelensofgreenchemistry.
Introductiontocontemporarytoxicology
• UpperlevelGeneraleducation–Healththeme
• Hybrid
• (Dow-TERC)teambrings expertisein• toxicology• intraining(intoxicology)• trainingmaterials
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Introductiontocontemporarytoxicology
• Students• biomedicalscience• biology• chemistry• alliedhealth• nursing• industrialhygiene• environmentalstudies• andothers
• Familiaritywithtools andscientificevidencenecessarytoidentify:
• hazardousmaterials• meanstoreducehealthimpacts
• Possibledesignchangesforsustainablechemicalsandconsumerproducts
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• Amultidisciplinary overviewofthetoxiceffectsofchemicalsonhumanhealthandenvironment,publicpolicies,andthedevelopmentoflesshazardousalternativesthroughchemicaldesign.
• Thecoursefocusesonassessments,mechanisms,properties,healtheffects,andstrategiestoreduceriskandexposureineverydaylifeacrossdiversesocietalgroups.
Catalogdescription
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• Toxicologyisamultidisciplinaryexperimentalsciencethatcombineschemistry,biology,andphysiologytodeterminewhethersubstancesweareexposedtoinconsumerproductsandtheenvironmentarelikelytocauseharmfulhealtheffects.
• Withoutanunderstandingofthebasicprinciplesoftoxicology,onecannotmakeinformeddecisionsaboutthebenefitsandrisksassociatedwithchemicalsusedincurrentandfutureproducts
Rationaleforaddingthiscoursetothecurriculum
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Rationaleforaddingthiscoursetothecurriculum
• Bybridgingchemistrywithtoxicologyandtranslatinginformationfromthemacroscopichealtheffectstomoleculardesign,thiscoursewillprovideanoverviewofcontemporaryelementsoftoxicologyandallowstudentstoconnecttherelevanceofthesciencewiththeirindividuallivesandtheworld.
• Focusonthepracticalapplicationoftoxicologytorelevantcasestudiesofcommonchemicalsandmaterials.
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• Oneofthegrandchallengesforsustainability:defineproblemsmoreeffectively.
• Forchemists:thechallengeistodesignlesshazardouschemicals.
• Over100,000chemicalsinglobalcirculationand700+chemicalsareintroducedeachyeartotheUSmarketalone.
Sustainabilitychallenges
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• Knowledgechallenge:toxicologyevolvesrapidlyattheintersectionofchemistry,biology,healthandenvironmentalsciences.
• Instructiondeliverychallenge:availabilityofspecialists
Thesustainabilityofthiscourse dependsontheabilitytotakeadvantageof
• opensources• sharedknowledge• virtualcommunication,regardlessthelocationandtimeconstraintsimposedinaregularclassroom.
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Sustainabilityineducationundergraduatecourse
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• Allowsinformationandfeedbackflowfromspecialiststostudentsandbackwithoutthephysicalconstrainsoflocationandtimeimposedinaregularclassroom
• AccesstopeerreviewedandvalidatededucationmaterialssuchasthosefromNationalInstituteofHealth.SeeforexampleToxicologytutor(https://sis.nlm.nih.gov/enviro/toxtutor.html)andTOXNET(https://toxnet.nlm.nih.gov/).
Advantages ofhybridformat
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• Experientiallearningopportunities:studentsgainfamiliaritywithaccessing,andevaluatingpubliclyavailableresourcesande-governmentservices.
• GVSU&DowTERC:producesoundteachingmaterials,suchaspresentation/webcasts,casestudies,studentprojectsworkableon-line,etc.materialspreparedattheinceptionofthecoursewillremainavailableforfutureuseinthecourse.
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Advantagesofhybridformaton-line
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• Sitevisit(forexampleatDow)constitutestheculminatingexperienceofthecoursewithpossibleopeningsforstudentfutureresearchprojects.
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Advantagesofhybridformatinperson
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Metrics:assessmentsandevaluationofstudentlearning
• Exams
• Problemsets
• Quizzes
• WeeklyReflections:oneparagraphonwhatstudentslearnedduringtheweekandwhattheyfoundchallenging.Mayincludereflectionsontheworkoutsideofclasssuchasreadingsandotheronlinematerials,andonin-classactivities.
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Metrics:assessmentsandevaluationofstudentlearning
• Discussionforums:on-line
• Virtualandtraditional(Blended)groupwork:Synchronousandasynchronous.PostlectureactivitieswiththeDow-TERCteamwillbeconducedinvirtualworkgroupsoronanindividualbasis.
• StudentPresentations:preparedwithvoiceoverfeatureofpowerpoint,recorded,andposted.Peer,specialists,andinstructorviewing/grading.
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Syllabus
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Topics
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Topic Details
Introduction: toxicology&greenchemistry
Greenchemistryprinciples Hazardandriskassessment.BasicconceptsinRisk/ExposureassessmentRegulatoryoverview
Toxicology:historyandscope typesoftoxicology,toxicants
Currentandfuturetrends intoxicology Epidemiology/personalizedmedicine/linkinghumandata,animaldataandmodels. Globalview: naturalvs.manmadetoxicants
ToxicologyPrinciples:doseresponsefunction,bioassays,routesofexposure
OverviewofIRIS: listofchemicalsforprojects. REACH. SessiononusingREACHinRiskAssessment(RA).
Hazardvs.Risk; CaseStudyAnoverviewofLCA
Exposure. Precautionary.AvailableHazardtools
Toxicokinetics (TK) Metabolism,IVIVE,insilicoTKmodeling/GastroPlus CaseStudy
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Topic Details
Riskassessment differenttox.Endpoints,suchasDevelopment/Reproductive/Neurotox
Genotoxicityandchemicalcarcinogenesis
Genetox infoontransciptomics orepigenetics
Toxicity:Population&communityeffects Ecotoxicology andindirecttoxicity;roleofbiomarkers inpopulation/communities
DART– EDSPToxCast;DARTdecisiontree
Chemicalproperties/environmentalfatePredictiveToxicologyQSAR,DOW EpiSuite
Models &examples; power&limitationsmammalian/human+environmentalModelingProject
Bioprofiling: alternativemodelstoassesstoxicity
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Topics
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Topic DetailsConsumerProducts Regulatoryoverview;LCA
Toxicantcasestudies#1 Metals(MeHg,Fishconsumption)
Toxicantcasestudies#2 Metals(Pb;Flintwatercrisis);LCA
IRISProject potentialtopics– e.g.,microplastics
Toxicantcasestudies#3 PharmaceuticalsandPersonalCare
Toxicantcasestudies#4 FlameretardantsandPolymers(BPA,PVC,bioplastics–LCA
Topics
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SamplematerialsPrepared by Sue Mar ty, Ph .D. , D.A .B .T .
TERCScienceLeaderTheDowChemicalCompany
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1.Alternativetestingmethods
Dermalsensitization:testingapproaches
• Invitroapproaches• DirectPeptideReactivityAssay(DPRA)
• KeratinoSens assay(HaCaTcellswithstablyintegratedARE-luciferasereportergene)
• HumanCellLineActivationTest(hCLAT)
• SENS-IS(2017SRPproject)
DOW RESTRICTED
ActiveIngredients (AI)
Formulations w/ single AI
Formulations 2 or more AIs
N 20 16 9KeratinoSens 85% 100% 78%
DPRA 91% 87.5% 89% GHS Threshold - 87.5% 78%
WoE (2 of 3) 100% 100% 89%
Accuracy relative to in vivo data
DOW RESTRICTED
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1.Alternativetestingmethods
Conventionalmethod
Invitrocapabilities:bioaccumulation
BCF
Invitromethod
BCF0.0
1.0
2.0
3.0
4.0
BaP
C16E08
Decano
l
Delta
methrin
Diclofenac
17a-Estradiol
Fenthion
Zoxamide
logB
CF
invivo invitro
DOW RESTRICTED
• Bioaccumulation assessment is needed when log Kow > 4.5, most uncertain element in PBT assessment
• Rainbow trout hepatocytes/S9• Enhanced understanding of metabolic capabilities and refined
assessment for bioaccumulation• ILSI HESI Bioaccumulation Committee
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2.Predictivetoxicology
LD50 valuesadjusteddownwardby%available
ester group
AC50 Inhibition of Mitochondrial Membrane Potential (uM)
Rat
Ora
l LD
50(m
g/kg
)
AC50Inhibition of Mitochondrial Membrane Potential (
AC50 Inhibition of Mitochondrial Membrane Potential (
DOW RESTRICTED
PredictingHumanSystemicExposure● In Vitro Based Approach via GastroPlus PBPK modeling
Rat in vitro data• Metabolic stability• Permeability• Free fraction• Blood/plasma ratio
Rat in vivo data• Intravenous administration• Single oral doses• Repeat oral doses
Human in vitro dataEstimate of human ‘dose’
Humanin vivo prediction
(AUC)In vitro to in vivo
extrapolation (IVIVE)Build and validate a PBPK
model that uses in vitroinputs that can describe data
observed in vivo
Use TK knowledge (such as allometric scaling factor)
Duplicate in vitro data using human tissue
Hypothesis - if we can predict in vivo exposure from in vitro data in rat, using human in vitrodata and an informed PBPK model we can predict human in vivo exposure
DOW RESTRICTED
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Students’project
• Providealistofchemicals(candidates)forprojects;examples• Ethanolvs.Methanol,isopropanol,propyleneglycol,ethyleneglycol(dart,environmental
• Surfactants(biodegradable;saferchoices),apesvs.Ecosurf,othercasestudy
• Greenchemistry– canwecomparealternativesandhowthiscanimpactsafety?It’snotsimple:• (CHLOROFLUOROCARBONS,• JOHNSON&JOHNSONBABYSHAMPOO,• ORGANOCHLORINEINSECTICIDESTOops,• BPA– TKANDENVIRONMENTAL)
• LCA– recyclereadypackaging21st GC&E Reston, VA 2017 35
Overview:Projectdescription
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Overview:Projectdescription
• Abriefsummaryofwhyyouchosethischemical.Explainhow peoplearelikelytobeexposedtothechemical.Explainwhy isthisisachemicalofconcernorinterest.
• ThebasisoftheOralRfD,RfC,Carcinogenicityassessment,etc.–GeneralizeRFC/RFDAREEPA• criticaleffects• othertypesoftoxiceffects• basisofuncertaintyfactors• datagaps• ECOTOX?• PNECsandDNELs?
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• StatewhetheryouagreeordisagreewiththelevelofconfidencethattheEPAstatesintheirassessment.Explainyourposition.Suggestfurtherstudiesthatyoubelieveareimportanttoreduceuncertaintyandaddressdatagaps.
• Research,select,andpresentgreenchemistryalternativestochemicalofinterest.
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Overview:Projectdescription
Goal:Thefourstagesofcompetence
http://www.gordontraining.com/free-workplace-articles/learning-a-new-skill-is-easier-said-than-done/
Thegoalofthiscourseinteachingintroductorytoxicologyistobringallstudents fromlevel1 tolevel 2and aimforthemajorityofthemtoreachlevel3,consciouscompetency.
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Level You…1 Unconsciousincompetence don’tknowwhatyoudon’tknow
2 Consciousincompetence realizeyoudon’thaveadequateknowledge
3 Consciouscompetence areabletofunctionsafelyandeffectively
4 Unconsciouscompetence areveryknowledgeableandexperiencedregardingthesubjectathand
Coursedesignsustainable andadaptive
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Wearecurrentlyat:
§ submissionofcourseapproval
§ designingthecoursematerials
§ advertisingtostudents
Experiment-àWinter2018
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Thankyou!
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Since2008,thechemistrydepartmentat(GVSU)havecoursesdedicatedtogreenchemistry,bothfornon-majors,CHM111“Introductiontogreenchemistry”,andformajors,CHM311“GreenchemistryandIndustrialprocesses”,aswellasaGreenchemistrycertificationprogram(startedin2010).
Amajorchemistrycurriculumreform,ontheworksforabout3years,wasimplementedintheFallof2016.Thechangesareintendedtomaketheupperlevelcoursesevenlypopulatedandthelaboratorymoreinterdisciplinary.
Thegreenchemistrycourseswereincludedinthecurricularreform;thespecificchangesweretriggeredbydatacollectedintheyearssincethecourseswereimplemented.
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• PrinciplesandPracticeofToxicologyinPublicHealth.IraS.Richards
• Toxicology:TheBasicScienceofPoisons,SeventhEdition,Casarett &Doull's
• Anintroductiontotoxicology,PhilipBurcham (Springer)
Resources
CHM381
• Toxicology,thestudyofadverseeffectsofchemicalcontaminantsonlivingsystems. iscentraltoourabilitytopredictandpreventadversehumanandenvironmentalhealtheffects.
• Withoutanunderstandingofthebasicprinciplesoftoxicology,onecannotmakeinformeddecisionsaboutthebenefitsandrisksassociatedwithchemicalsusedincurrentandfutureproducts.
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