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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