NationalIndustrialChemicalsNotificationandA ssessmentScheme

Triglycidylisocyanurate (TGIC)

PriorityExistingChemicalSecondaryNotificationAssessmentReportNo.1S

CommonwealthofAustralia 2000ISBN0 642 455 236

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Preface

ThisassessmentwascarriedoutundertheNationalIndustrialChemicalsNotificationandAssessmentScheme(NICNAS).ThisSchemewasestablishedby theIndustrialChemicals(NotificationandAssessment)Act1989(theAct),whichcameintooperationon17July1990.

TheprincipalaimofNICNASistoaidintheprotectionofpeopleatwork,thepublicandtheenvironmentfromtheharmfuleffectsofindustrialchemicals,byassessingtherisksassociatedwiththemanufactureand useofsuchchemicals.

NICNASisadministered by theNationalOccupationalHealthSafetyCommission(NOHSC)andassessmentsarecarriedoutinconjunctionwithEnvironmentAustralia(EA)andtheTherapeuticGoodsAdministration(TGA),whocarryouttheenvironmentalandpublichealthassessments,respectively.NICNAShastwomajorprograms:onefocusingonrisksassociatedwithnewchemicals,priortoimportationormanufactureandtheotherfocusingon existingchemicalsalreadyin usein Australia.

AstherearemanythousandsofexistingindustrialchemicalsinuseinAustralia,NICNAShasanestablishedmechanismforprioritisingandassessingthesechemicals.Suchchemicalsarereferred toasPriorityExistingChemicals.

Thescopeofpriorityexistingchemicalassessmentspermitsrecommendationstobemadewhichwillassistinthemanagementoftheworkplace,publichealthandenvironmentalrisks.Recommendationsmaybedirectedtoindustry(employersandemployees)and/orotherFederalandState/Territoryregulatoryauthorities.NICNAScannotmakeregulatorydecisions,whichfallwithintheresponsibilityofotherregulatoryauthorities,andthereforerecommendations canonly begiveneffectthroughconsiderationofriskmanagementpracticesandprocessesbythoseagencies/authoritieschargedwithregulatorydecision-making.

WherefurtherinformationbecomesavailableafterpublicationofaPriorityExistingChemicalreportand/orwherecertainprescribedcircumstancesoccur,asstipulatedunderSection64(2)oftheAct,theDirector(ChemicalsNotificationand Assessment) mayrequireareassessmentofthehazardsofthechemicalunder‘secondarynotificationprovisions’(Division6)oftheAct.ThisFullPublicReporthasbeenpreparedinaccordancewiththeseprovisions.

UnderSection40oftheAct,apubliccommentprocessisalsoundertakenforsecondarynotificationassessmentreports.

ForthepurposesofSection78(1)oftheAct,copiesofFullPublicReportsforNewandExistingChemicalassessmentsmaybe inspected bythepublicatthelibraryof theNationalOccupationalHealthandSafetyCommission(NOHSC).SummaryReportsarepublishedin the CommonwealthChemicalGazette,which isalso available to thepublic at theNOHSC library.

CopiesofthisandotherpriorityexistingchemicalreportsareavailablefromNICNASeitherbyusingtheprescribedapplicationformatthebackofthisreport,ordirectlyfromthefollowingaddress:

GPOBox58
SydneyNSW2001
AUSTRALIA
InternationalTel:+61 (02)9577 9437
FreeCall: 1800 638 528
Fax:+61(02)9577 9465or +61 (02)9577 94659244

OtherinformationaboutNICNAS (alsoavailable onrequest)includes:

  • NICNASServiceCharter;
  • informationsheetsonNICNAS CompanyRegistration;
  • information sheets on Priority Existing Chemical and New Chemical assessmentprograms;
  • applicationforms for NewChemical andPriorityExistingChemicalassessments;
  • applicationformfor theAustralianInventoryof ChemicalSubstances(AICS)
  • subscriptiondetailsfortheCommonwealthChemicalGazette;and
  • subscriptiondetailsfortheNICNASHandbook for Notifiers.

Priority Existing Chemical and New Chemical Summary Reports together with otherinformationonNICNASactivitiescanbe found ontheNICNAS Web siteat:

Overview

Triglycidylisocyanurate(TGIC)wasthesubjectofanassessmentasaPriorityExistingChemicalandafullpublicreportwaspublishedinApril1994.Asaresultofnewdatabecomingavailable,thechemicalhasbeenreassessedunderthesecondarynotificationprovisionsoftheIndustrialChemicals(NotificationandAssessment)Act 1989(theAct).

Thisassessmenthasevaluatednewanimalstudiesincludingoraltoxicity/fertility,carcinogenicityandcontacthypersensitivitystudies,inadditiontohumancasereportsofrespiratorysensitisation.Anewbiodegradabilitystudywasalsoprovided.Theconsequencesofthenewdataonthehealthandenvironmentalhazardandriskassessmentswereevaluated.

TheoriginalTGICreport,(TGIC-1),concludedthatTGICisahazardoussubstance,beingtoxicby oralandinhalationalroutes(R23/25),askinsensitiser(R43),genotoxic(R46)andcapableofcausingseriouseyedamage(R41).

NewhumandataconfirmedthatTGICisaskinsensitiserandalsodemonstratedthatitisarespiratorysensitiser.RepeateddosetoxicitystudiesinanimalsindicatethatTGICcausessevereeffectsafterrepeatedexposure.Theprincipaleffectsweresignificantlylowerbodyweight,mastocytosisinlymphnodesanddepletionofspleenlymphoidcells.TGICwasnotcarcinogenicinmaleratsexposedtoTGICbygavage.However,thecarcinogenicpotentialof TGICin femaleratshasnotbeenstudied.

Inductionofchromosomalaberrationsandcytotoxicityinmousespermatogoniaraisedconcernsintheoriginalreport,regardingpotentialreproductiveeffectsofTGIC.ArecentfertilitystudyinmaleratsprovidessomeevidencethatTGICdoesnotaffectmalefertility.However,thepotentialforTGICtoaffectfemalefertilityandoffspringgrowthandfertilityhas notbeentested.

AsreportedinTGIC-1,TGICresiduesreleasedtotheenvironmentareexpectedtorapidlydegradeduetotheepoxidenatureofthecompound.ThereactivityofTGICprecludesanypossibilityofbioaccumulation.Intheaquaticenvironment,persistenceisexpectedtobelimited.

TheoccupationalriskassessmentinTGIC-1concludedthatTGICisunlikelytocauseadversehealtheffectsifappropriatecontrolmeasures,safeworkpracticesandatmosphericmonitoringstrategiesareimplemented.ThenewdatashowingthatTGICisarespiratorysensitiserconfirmstheneedtomaintainoccupationalexposurelevelstothelowestpracticablelevel.ThenewrepeateddosedatagoessomewaytowardspredictingthelongtermhealtheffectsofoccupationalexposuretoTGIC.However,thereremainseveraldatagaps, and thereforethe potentialforchronichealtheffectsis notfullyunderstood.

Thenew datadoesnotchange the publichealthandenvironmentconclusions oftheoriginalreport.TGICis unlikelyto presenta risktothepublicor the environment.

Recommendations

Furthertothenewdataprovidedunderthisassessment,andinaccordancewiththehealtheffectscriteriadetailedintheNationalOccupationalHealthandSafetyCommission’s(NOHSC) Approved Criteria for Classifying Hazardous Substances (NOHSC, 1999),

TGICshouldbeclassifiedwithadditionalriskphrases:‘maycausesensitisationbyinhalation’(R42)and‘dangerofseriousdamagetohealthbyprolongedexposureifswallowed’(R48).

Consistentwithgoodoccupationalhealthandsafetyprinciples,alloccupationalcontrolmeasuresincludingatmosphericmonitoring,asrecommendedintheTGIC-1reportshouldbe adheredto.

ItisrecommendedthatemployersconductanassessmentoftheriskstothehealthofemployeesfromexposuretoTGIC.Wherethereisalikelihoodofsensitisationoccurringin workers,then a healthsurveillanceprogramshouldbe provided.

Contents

PREFACEiii

OVERVIEWv

ACRONYMSANDABBREVIATIONSix

1.INTRODUCTION1

1.1DeclarationandassessmentasaPriorityExistingChemical1

1.2Secondarynotification1

1.3Objectives2

1.4Newdata2

1.5BackgroundonuseofTGICinAustralia2

1.6Reportformat2

1.7Peerreview3

2.APPLICANTS4

3.CHEMICALIDENTITYANDCOMPOSITION5

3.1ChemicalIdentity5

4.PHYSICALANDCHEMICALPROPERTIES6

5.EVALUATIONOFANIMALTOXICOLOGICALDATA7

5.1Skinsensitisation7

5.2Combined13-weektoxicityandfertilitystudy8

5.3Carcinogenicity9

6.HUMANHEALTHEFFECTS12

6.1Casereports12

6.2UKSWORDNotificationSystem13

7.HUMANHEALTHHAZARDASSESSMENTANDCLASSIFICATION14

7.1Skinsensitisation14

7.2Respiratorysensitisation15

7.3Repeateddosetoxicity16

7.4Fertility17

7.5Carcinogenicity

/

18

8.ENVIRONMENTALASSESSMENT / 19
8.1Environmentalexposure / 19
9.SUMMARYANDCONCLUSIONS / 20
10.RECOMMENDATIONS / 23
10.1Classificationandlabelling / 23
10.2Furtherstudies / 24
10.3HealthSurveillance / 25
10.4MaterialSafetyDataSheets / 25
10.5Atmosphericmonitoringandcontrolofoccupationalexposure / 25
11.SECONDARYNOTIFICATION / 26
APPENDIX1-SampleMaterialSafetyDataSheetforTriglycidylisocyanurate / 27
APPENDIX2-Recommendationsforatmosphericmonitoringandcontrolofoccupationalexposure(adaptedfromtheTgic-1Report) / 32
REFERENCES / 37
LISTOFTABLES
Table1-Resultsofskinsensitisationstudy / 8
Table2-ConcentrationlimitsandclassificationsforTGICasaningredientin
mixtures/preparations / 24

AcronymsandAbbreviations

CASChemicalAbstractsService

DNAdeoxyribonucleicacid

EAEnvironmentAustralia

FEV1forcedexpiratoryvolume in thefirstsecond

ggram

hhour

Llitre

LC50medianlethalconcentration

LD50medianlethaldose

LLNAlocallymph node assay

mgmilligram

MSDSMaterialSafetyDataSheet

NICNASNationalIndustrialChemicalsNotificationand AssessmentSchemeNOAEL no observed adverseeffectlevel

NOHSCNationalOccupationalHealthandSafetyCommissionOECDOrganisationforEconomicCooperationandDevelopmentPD15 provocative dosecausing15%depressionin FEV1

PEFpeakexpiratoryflow

ppmpartspermillion

S.I.stimulationindex

TGATherapeuticGoodsAdministration

TGICtriglycidylisocyanurate

TWAtime-weightedaverage

1.Introduction

1.1Declaration and assessment as aPriority Existing Chemical

Thechemicaltriglycidylisocyanurate(CASNumber2451-62-9),knownasTGIC,wasdeclaredaPriorityExistingChemical,undertheIndustrialChemicalsNotificationAssessment)Act1989(theAct) on5 November1991. TGICis usedinAustraliaasacross-linkingagentinpowdercoatingsinthemetalfinishingindustry.

Thereasonsforthedeclarationwere:(i)recentanimaltoxicitystudiesindicatedapotentialforTGICtocausegeneticdamage.ThestudiesraisedconcernthatTGICcouldbeahumancarcinogenandmutagenandcouldalsohaveadversereproductiveeffects;and (ii)there were a significantnumber of workers exposedtoTGIC.

AcomprehensiveevaluationoftheavailabletoxicityandexposuredatawasconductedandafullpublicreportwaspublishedinApril1994(NICNAS,1994).TheassessmentconcludedthatTGICshouldbeclassifiedastoxicbyoralandinhalationroutes,askinsensitiser,mutagenic(category2mutagen)andcapableofcausingseriouseyedamage.Thereportrecommendedaninterimoccupationalexposurelimitasguidanceforindustryuntilanationalexposurestandardhadbeenset.

ThereportalsodetailedanextensiveanalysisofcontrolmeasurestominimiseoccupationalexposuretoTGIC.ItconcludedthatTGICwasunlikelytocauseadversehumanhealtheffectsifappropriatecontrolmeasures(suchasfullprotectiveequipment)andatmosphericmonitoringstrategieswereinplace.However,itnotedthatthelongtermhealtheffectsinworkersexposedtoTGICweredifficulttopredictintheabsenceofchronicdata.TheoriginalassessmentreportalsoconcludedthatTGICwasunlikelytopresentarisktothepublicortheenvironment.

PublicationofthereportwasinitiallysubjecttodelayspendinganAdministrativeAppealsTribunal(AAT)decisionregardingtheclassificationofTGICintheareasofacutetoxicityandmutagenicity.AnapplicationhadbeenmadetotheAATforreviewoftheDirector’sdecisiontorefusetovarytheassessmentreport.AlldecisionsoftheDirectorconcerningclassificationwereupheld bythe AAT.

1.2Secondary notification

InaccordancewithSection62oftheAct,thepublicationofthefullpublicreportrevokedthedeclarationofTGICasaPriorityExistingChemical.However,underSection64(2)oftheAct,specificcircumstancesareprescribedwherereassessment(secondarynotification)ofaPriorityExistingChemical,maybewarranted.Thesecircumstancesincludeadditionalinformationastotheadversehealthorenvironmentaleffectsofthechemicalbecomingavailable.

In1998,onecompanynotifiedtheDirectorofnewinformationrelatingtotherespiratorysensitisingpotentialofTGIC.Asaconsequence,noticewasprovidedintheChemicalGazetteof5January1999requiringreassessmentofTGICunderSection65(2)oftheAct.AllpersonswhointroducedTGICintoAustralia,eitherbyimportormanufacture,wererequiredtoapplyforsecondarynotification,inorderforTGICtoproceedtoassessment.Secondarynotificationwasgivenbysixcompanies(seeSection 2),who alsosuppliedadditionaldata.

1.3Objectives

The objectives ofthisassessmentwere to reviewthenewdatamadeavailablesincethepublicationoftheoriginalassessmentreport(TGIC-1)andwhereappropriate,revisethe original assessmentwithregardto:

  • the characterisationofthepotentialhazardsof TGIC;
  • the characterisationoftherisksofadverseeffectstoworkers,thegeneralpublicandtheenvironment; and
  • therecommendationstocontrolexposuresand/orreducepotentialrisks.

1.4Newdata

New datasuppliedforthisassessmentwere:

i.13-weekoraltoxicity/fertilitystudyin malerats

ii.99-weekoral carcinogenicitystudyin malerats

iii.Contacthypersensitivitystudyin guineapigs

iv.2 human casereports ofskin and respiratorysensitisation

v.Biodegradabilitystudy

1.5Background onuseofTGIC in Australia

TGICisathree-dimensionalcross-linkingorcuringagentforpowdercoatingsorpolyesterresins.TGICisnotmanufacturedinAustralia.TheestimatedamountofTGICimportedastechnicalgradeandasacomponentofpowdercoatings,is100-1000tonnesperyear.ImportedtechnicalgradeTGICismixedwithresin,pigments,fillersandadditives,atbetweenfourandtenpercentbyweightofthefinalproduct.TGIC-containingpowdercoatingsaresprayedontometalobjects,usingan electrostaticprocess,prior tocuringin ovens.

1.6Report format

Foreasyreference,thegeneralformatofthisreportfollowsthatofTGIC-1.Onlysectionswherenewdataareavailableorrevisionshavebeenmadeareincludedinthisreport.ThefollowingsectionsintheTGIC-1reportremainunalteredandthereaderwillneed torefertotheoriginalreport:

  • Methodsofdetectionandanalysis
  • Use
  • Manufacture of TGICpowder coatings
  • Occupationalexposure
  • Publichealthassessment

1.7Peerreview

Duringallstagesofpreparation,thereporthasbeensubjecttointernalpeerreviewbyNICNAS,EnvironmentAustralia(EA)andtheTherapeuticGoodsAdministration(TGA).AssociateProfessorMalcolmSimmoftheUnitofOccupationalEnvironmentalHealthatMonashUniversityreviewedthehumancasereportsrelatingtoTGIC-inducedoccupationalasthma.

2.Applicants

Sixcompaniesappliedforsecondarynotificationassessmentofthechemical.Theapplicantssuppliedrelevantinformationforthisassessment,includinganimaltoxicitydata,humanhealthandenvironmentaldata.UnderSection36oftheAct,theapplicantswereprovidedwithadraftcopyofthereportforcorrectionoferrorsand variationofcontent.

Applicationswerereceivedfrom:

VanticoPty Limited

235 Settlement Road

ThomastownVIC3074

SumitomoAustraliaLimited

GPO Box 4241

SydneyNSW2001

DuluxAustralia
PowderIndustrialCoatings

51 Winterton Road

ClaytonVIC 3168

Jotun AustraliaPty Ltd

P.O.Box105

AltonaNth.VIC3025

Ameron Coatings

P.O.Box356

SevenHills NSW 2147

InterponPowderCoatingsAkzo NobelPty. Limited

P.O.Box26SunshineVIC3020

3.ChemicalIdentityandComposition

3.1Chemical Identity

ChemicalName:Triglycidylisocyanurate

CAS No.:2451-62-9

Synonyms:1,3,5-Triglycidylisocyanurate

TGIC

1,3,5-Triazine-2,4,6(1H,3H,5H)-trione1,3,5-tris(oxiranylmethyl)-1,3,5-Tris(oxiranylmethyl)1,3,5-triazine-2,4,6(1H,3H,5H)-trioneTris(2,3-epoxypropyl)isocyanurate

Trade Names:AralditePT810

TEPIC

TK10622

MolecularFormula:

C12H15N3O6

StructuralFormula:

MolecularWeight:

297.3

4.PhysicalandChemicalProperties

TGICismanufacturedandsuppliedasthetechnicalgradesTEPICandAralditePT810(alsoknownasTK10622).TGICtechnicalgradesarewhite,granularsolids(at20oCand101.3kPa)withnodiscernibleodour.TEPIChasameltingpointrangeof90to125oC,whileAralditePT810meltsat95oC.Densitiesare1420and1460 kg/m3respectively.

ThewatersolubilityandpartitioncoefficientforTEPICis9g/Lat25oCandlogPow-0.8, respectively.

ThereactivityofTGICin themoltenstateiswellcharacterisedandincludesreactionswiththefollowingfunctionalgroups:primaryandsecondaryamines,carboxylicacidsandanhydrides,thiols,phenols,andalcohols(athightemperatures).MoltenTGIC mayalso undergoautopolymerisation.

Theconversionfactorsfor TGIC(at 25oC) TGICare:

1mg/m3= 0.082 ppm, and

1 ppm=12.18 mg/m3

FurtherdetailsofthephysicalandchemicalpropertiesofTGICareprovidedinTGIC-1.

5.Evaluationofanimaltoxicologicaldata

Animaltoxicologicalstudiessubmittedforsecondarynotificationhavebeenevaluatedandarereportedbelow.Fullreportingofdataevaluatedintheoriginalassessment canbefoundinthe TGIC-1assessmentreport.

5.1Skin sensitisation

Guinea pig maximization study

TheskinsensitisationpotentialofTGIC(TK10622)wastestedinmaleAlbinoDunkinHartleyguineapigs(RCC,1997).ThestudywasconductedaccordingtoOECDGuidelineNo.406‘SkinSensitisation’(1992).

Basedonpretestdata,30%and25%TGICincornoilwereselected asthemaximumtolerateddoseandhighestnon-irritantdoseconcentrationssuitablefortheinductionandchallengephaserespectively.Thetestgroup(20animals),weresubjectedto twoinductionand challengephasescomprisingof:

InductionI:Intradermalinjections(0.1ml)ofadjuvantandof5%TGIC(equivalent to5 mg) in corn oilv/v(day1)

InductionII:Topicalapplication(approximately0.3ml)of 30% TGIC(equivalentto90mg)incornoilv/vunderocclusionfor48h(day8)

ChallengeI: Topicalapplication(0.2ml)of25%TGIC(equivalentto50mg)(leftflank)and corn oil only(rightflank),underocclusionfor 24h(day22)

ChallengeII: Topicalapplication(0.2ml)of25%TGIC(rightflank)andcornoil only(leftflank),underocclusionfor 24h(day29)

Guineapigsinthecontrolgroup(10animals)weretreatedwithvehicleonly,andwerenotsubjectedtoasecondchallenge.Allanimalswerepre-treatedwith10%Sodium-Lauryl-Sulfate(SLS) on day7,to enhancesensitisation.

Clinicalobservations,viability/mortality,bodyweightandmacroscopicfindingswererecorded.Skinreactionswererecordedat24and48hafterremovingthedressingfollowinginductionII,challengeIandchallengeII. Erythema andoedemawereassessedusingtheDraizenumericalgradingsystem.TheskinreactionsaresummarisedinTable1.Onlyveryslighterythema(Draizescore1)wasobservedinsomeoftheanimals.Nooedemawasobservedinanyoftheanimals. Oneanimalin thecontrolgroupdied onday7.

Ina positivecontrolgroup, 70% (7/10)of animalstestedpositive at challenge.Thepositivecontrolwasanon-irritatingconcentration(25%)ofalpha-hexylcinnamaldehyde.

InaccordancewithOECDGuidelineNo.406‘SkinSensitisation’(1992),TGICdid notinduceskinsensitisation inthisstudy.

Table 1-Resultsofskinsensitisationstudy

Number of animalspresentingwith erythema**

Phase / TreatmentGroup / 24h* / 48h*
InductionII / Control / 4/9 / 4/9
Test (30% TGIC) / 10/20 / 10/20
ChallengeI / Control / 0/9 / 0/9
Test (25% TGIC) / 4/20 / 1/20
ChallengeII / Test (25% TGIC) / 1/20 / 1/20
Positivecontrol / Alpha-hexylcinnamaldehyde / 7/10 / 7/10

*Time(h)aftertreatment

**Eachpositiveresponsereceived a Draizescoreof1forerythema.

LocalLymphNode Assay

ThemurineLocalLymphNodeAssay(LLNA),whichattributesastimulationindex(S.I.)asameasureoflymphocytestimulationderivedfromanimalauricularlymphnodes,hasbeenproposedasapredictivetestfortheidentificationofsensitisingagents,andinparticularasapredictorofskinsensitisationpotential(NIEHS,1999).

Lymphocyteproliferation,inducedinthelymphnodesoffemaleBALB/cmice(3pergroup,includingcontrol)exposedto0.2%to5%TGIC,(bytopicalapplicationtothedorsumofbothears),wasassessedandastimulationindex(S.I.)determined(Clottensetal,1996).TheLLNAisconsideredpositiveifaS.I.ofatleast3isobtained.ThemaximalS.I.forTGICwas2.0,witha2-foldincreaseinthelymphnodecellnumber(LNC)anda1.5foldincreaseinlymphnodeweight.Takentogether,thedatawereconsiderablylowerthanforthepositivecontrol,whichprovidedanS.I.of37witha6.4foldincreaseintotalLNC.Onlyanabstractforthisstudywasavailable.Inaddition,criticalinformationasdefinedbyNIEHS(1999), was notreported.

5.2Combined 13-week toxicity and fertility study

Acombinedoral13-weektoxicityandfertilitystudywasconductedinSpragueDawleyrats(CIT,1995).TheconductofthestudywassimilartoOECDGuidelineNo. 408,howeverfemales werenotexposedto TGICat anytime.

Toxicity study

Malerats(10pergroup)wereexposedtodoselevelsof0,10,30and100ppm(0,

0.73,2.08,7.32mg/kg/day)TGICfor94daysbydietaryadmixture(suppliedadlibitum).Examinationsforophthalmology(checkedbeforetreatmentandatweek13incontroland100ppmgroup),haematology,bloodbiochemistryandurinalysis(eachperformedatweek13)weremade.Bodyweightgainandfoodconsumptionwerecheckedweekly. Attheend ofthetreatmentperiodthemaleswerekilledand

apathologicalassessmentincludingorganweight,macroscopicandmicroscopicexaminationweremade.Microscopicexaminationwasperformedinlungs,liver,kidneys,prostate,seminalvesicles,testesandepididymisandlymphnodes(mandibularandmesenteric) ofallmales.

Notreatment-relatedclinicalsignsormortalitywereobservedatthe10or30ppmdose-level.At100ppm(7.32mg/kg/day),treatedanimalshadaconsistentlylowerbodyweightcomparedtocontrols,whichwassignificantthroughoutmostofthetreatmentperiod.Attheendofthestudy,treatedanimalshadan8%meanlowerbodyweightcomparedtocontrols.Inaddition,asignificantlylowerbodyweightgain(-16%)over the first6-weekperiod was observed.Thereafter, the bodyweightgainwassimilartothecontrols.Theonlyothereffectsobservedwerehemosiderosisand/orcongestionin themesentericlymph nodes of 4 animalsat100ppm.

Fertilitystudy

Aftertheinitial9-weekexposureperiodeachmalewasplacedovernightwith2unexposedfemalesuntilmatingoccurredoruptosevendaysmaximum. Onday

19ofpregnancy,thefemalesofeachgroupwereallocatedequallytotwosubgroups(hysterectomysubgroupordeliverysubgroup).Femalesinthehysterectomysubgroupwerekilledonday20,foetuseswereremovedbyCaesareansectionandexamined.Femalesinthedeliverygroupwereallowedtodeliverandreartheirprogenyuntilweaning.Betweenday22and25post-partum,thefemalesandpupswerekilledandexamined.Femalesreceivedonlyuntreateddietadlibitumthroughoutthestudy.

Noclinicalsigns,unscheduledmortality,abortions,differencesinbodyweightorrelevantmacroscopicfindings(atnecropsy)werenotedin the maternalanimals.Inthelitterofthehysterectomysubgroup,therewerenodifferencesincorporaluteaandimplantationsites,post-implantationlosses,livefoetusesandfatalexternalabnormalities.Inthelitterofthedeliverysubgroup,therewerenodifferencesinthelittersize, pup weightandviability,clinicalsignsorpup development.

Notreatment-relatedmaleinfertility,asmeasuredbythematingand fertilityindiceswasnoted.

Atreatment-relateddecreaseinmeannumberofspermatozoawasnotedinmalestreatedwith30and100ppmTGIC,however,furtherindependentstatisticalanalysisofthedata(ANOVA)revealedthatthiswasnotstatisticallysignificantwhencomparedto controls(p>0.5).Meanspermatozoaviabilitywasunaffected.

Undertheconditionsofthisstudy,thenoobservedadverseeffectlevel(NOAEL)is 7.32mg/kg/day(100 ppm).

5.3Carcinogenicity

The carcinogenicpotential of TGICwasexaminedin 50maleSprague-Dawley ratsperdoselevelovera99-weekexposure(CIT,1999).ThestudywasconductedaccordingtoOECDGuidelineNo.451(OECD,1981),withtheexceptionthatfemalerodentswerenotincludedinthestudy.

Animalsweregivenbydietaryadmixtureeither0,10,30,100or300ppmTGIC

(achieveddosesof 0,0.43,1.30,4.36and13.6mg/kg/day,respectively). In

addition,asatellitegroup(10malesperdoselevel)wereexposedfor26weeksto0, 100, and 300 ppmTGIC.

Microscopicexaminationwasperformedinalltissues,macroscopiclesionsandpalpablemassesfromcontrolandhigh-dose(300ppm)animalsattheendofthetreatmentperiodintheprincipalandsatellitegroups.Additionally,similarexaminationoftheintermediatedosed(100ppm)animalsoftheprincipalstudygroup was conductedattheend ofthetreatmentperiod.

a)Principal Group

Duetothehighlevelofmortalityand markedsigns of toxicityat 300ppm,treatment wasstoppedat week63 forthisgroup,andtheanimals weresacrificed.

The only positivetrend for neoplasticlesionswaspituitaryadenomas,howeverthiswas mainlydue toa higherincidenceat30 ppm.

At100ppm,terminalbodyweightwaslower(-9%)aswellasmeanfoodconsumptionintreatedanimalscomparedtocontrols,howeverthedifferenceswerenotstatisticallysignificant.A slightincrease inhepatocellularadenoma(6/50vs.4/50 forcontrols)and carcinomas(3/50vs.0/50forcontrols)was noted,howevertheincidencewasnotdose-relatedandwaswithintherangeofhistoricalcontrols.

Treatment-relatedeffectsobservedin the 300ppmgroupinclude:

  • Poorclinicalcondition(includingroundback,piloerectionandemaciation)was notedasearlyas week34.
  • Atweek52,ahighermeanneutrophilcount(+41%)andmeanmonocytecount(+50%)wasnoted, whileatweek 63,alowerlymphocytecount(-33%),andalowermeantotalleukocytecount(-23%)atweek63(P<0.01)was noted.
  • Asignificantlyhigherincidenceofmastocytosisinthemesentericlymphnodes, hemosiderosis,spleniclymphoiddepletion andsinusalhaemorrhage.
  • Ahighincidenceofdilatedlumenintheduodenum,jejunumandileum.Inaddition,ahigherincidenceofhyposecretionandsmalltubulo-alveolarunitsin theprostate.
  • Onsetofmortalityoccurredsignificantlyearlier(week45).
  • At52weeks,thesurvivalratewaslower(56%in300ppmgroupcomparedto 90%incontrols.)
  • Amarkeddecreaseinbodyweightgainpersistedthroughoutthe studyperiod,andbyweek62was68%lower(p<0.01)thancontrolsforthesameperiod.
  • Aconsistentlylowermeanfoodconsumption,whichwasstatisticallysignificant.

b)SatelliteToxicityGroup

Notreatment-relatedclinicalsignsormortalitywereobservedinthesatellitetoxicitygroup,andnoadverseeffectswereobservedat100ppm.Highdose(300ppm)treatedanimalsrevealedthefollowingchanges:

  • Bodyweightgainwasmarkedlylower(-77%)thancontrolsduringtheinitial8-weektreatmentperiodandlessmarked bythe end of the 16-weektreatmentperiod(-43%).
  • Significantlydecreasedmeanfoodconsumptionlevelthroughoutthe 16-weektreatmentperiod.
  • Slightlylowermeantotalleukocyte count(-35%,p<0.01),and a slightlyhigherthrombocytecount(+19%,p<0.05).
  • Slightlylowermeantotalproteinlevel(attributabletoa slightlylowerglobulinlevel)wasmostmarked atweek27 (-9%)whencomparedto controls.
  • Increasedrelativemesentericlymph nodes (88%,p<0.01),associatedwithhemosiderosis,plasmacytosis,mastocytosis andsinusalhaemorrhages.Statisticalsignificance asdetermined bytheKruskal-Wallistest,wasattributedto themesentericlymph node dataalone.
  • Lower absoluteweightsof thymus(-24%, p>0.05)andspleen(-37%,p>0.05),associatedwithlymphoiddepletion.
  • Lower absoluteweightsof prostate(-27%,p>0.05),andseminalvesicles(-36%,p>0.05),associatedwith moderatehyposecretion.

Conclusion

Inconclusion,therewerenoadverseeffectsinanimalstreatedupto100ppm.TGICfailed to induce an increase in tumours in a dose-dependentmanner in males,at dosesup to100 ppm.

Atthehighestdose(300ppm),theprincipaleffectsweredecreaseinbodyweight,mastocytosis inthe lymphnodesanddepletionofthespleenlymphoidcellsinbothstudygroups. Increasedmortalityresultedinthegroupbeingsacrificedatweek

63.Theauthorsconcludedthatmarkedmastocytosisinthemesentericlymphnode,togetherwithsinusalhaemorrhage,indicatethatahistamine-relatedhypotensionmighthavebeenthecauseofdeathinthisgroup.

TheNOAEL for non-neoplasticeffectsinthisstudyis100 ppm(4.36 mg/kg/day).

6.HumanHealthEffects

6.1Case reports

Tworecentcasereportswereavailableforassessment.

Thefirstpublishedcasereport(Piirilaetal.,1997)describesamalespraypainterexposedtopowderpaintscontainingTGIC(4%v/v),forperiodsextending5–8hdailyover7years.Theworkersufferedfromeczemaonhishands,faceandbody,symptomsofdyspnoea,particularlyduringandafterworkdays,andfromdyspnoea,coughingandwheezingatnightandduringexercise.Theauthorsstatethat‘noatopictendencyhadbeenverified’priortoworkingasaspraypainter.Protectiveclothingandamotorisedbreathingprotectorwereusedduringpainting.TGIC-inducedcontactdermatitiswasdiagnosed,followingpositivepatchtestingwithpolyesterpaintcontaining10%and3.2%TGIC,or1%,0.32%or0.1%TGICin petroleum.

Skinprick teststoTGICandtests forIgEspecific to TGICwerenegative,howevertotalserumIgEwaselevated.Peakflowfollow-uprevealedaregular20%diurnalvariation,reducingtolessthan10%followinga3monthbudesonidetreatment,and significantbronchodilatationresponsesof17 –20%.Thelactose-controlchallengetestwasnegative.Moderatebronchialhypersensitivity(PD150.33mg),asmeasuredbytheprovocativedosecausing15%depressioninFEV1,wasobservedfollowingahistaminechallengetest.Achallengetestwithpaintcontaining 4%TGIC,induceda15% fallinpeak expiratoryflow(PEF)30minutesafterexposure,togetherwithtightnessinthechest.Additionally,therewasalatefallof23%intheforcedexpiratoryvolumeinthefirstsecond(FEV1)and17%inPEF, at 11h and16h afterchallenge,respectively.

When challengedwith 4% TGIC containinglactose(1:1), animmediate17%fallinPEF(within15minutes)wasobserved.Inaddition,alate16%fallinPEFand19%inFEV1(both6hpostexposure),anda16%fallinPEFand15%inFEV1(both13hpostexposure)wasobserved.Whenthehistaminechallengetestwasrepeatedpostchallenge,moderatebronchialhyper-reactivitywasobserved,withthe PD15significantlylower.

Thesecondpublishedcasereport(Meulemanetal.,1999)describesaspraypainter(withoutpre-existingatopicdisease)exposedtopolyesterpowderpigments,containing1–7%w/wTGIC,overathree-yearperiod.Althoughheworeaprotectivemask,butnotprotectivegloves,hedevelopedsustainederythematous,papular,andplaque-likelesionsonhisarmsandlegs,aswellastheaxillaeandupperpartoftheback.Respiratorysymptomsincluding,rhinitis,dyspnoea,coughandwheezing,appearedshortlyaftertheskinlesions.Adecreaseinsymptomsduring weekendsprovided aclearassociationwith hisoccupationalactivities.Positivepatchtestresults,toTGIC(0.5%and5%inpetroleum)andoneofthepigment powder samples,were observed 2to 3dayspostexposure.

Specificbronchialprovocationtestsinvolvinginhalationofaerosolised 0.05%TGIC(inlactose)inducedaprogressivedecreaseinFEV1to–22%by6h.Thefollowingday,asecondchallengetestusing0.1%TGIC(inlactose)wasmounted,theresponsewasclearlypositivewithamaximaldecreaseinFEV1of–31%at4hafterexposure.Theworkerexperiencedcoughing,wheezing,dyspnoea and itchingduringthenightfollowingtheprovocationtest.SkinpricktestswithTGICwereinconclusive.SerumIgElevelsweremeasuredbeforethebronchialprovocationtestsandfoundto beelevated.

Takentogether,thedataprovideevidenceofallergiccontactdermatitisandoccupationalasthma as aresultofexposureto TGIC.

6.2UKSWORD Notification System

TheUKSurveillanceofWork-RelatedOccupationalRespiratoryDisease(SWORD)isanationalschemeforthereportingofnewcasesofoccupationalrespiratorydiseases(includingasthma)bythoracicandoccupationalphysicians.SincetheSchemebeganin1989,elevencasesofasthmahavebeenattributedtoTGICexposure(approximately2casesperyearfrom1994-2000)(McDonaldJC(2000),personalcommunication).

7.HumanHealthHazardAssessmentandClassification

ThissectionintegratesdataonanimaltoxicityandhumanhealtheffectsinordertocharacterisepotentialhumanhealthhazardsfromexposuretoTGICandclassifythesehazards.Theclassificationcriteriausedthroughoutarethe NOHSCApprovedCriteriaforClassifyingHazardousSubstances(theApprovedCriteria)(NOHSC,1999).

Onlythosetoxicityendpointswherenewdatawereavailableforthisassessmentareconsidered.Thehazardassessmentoftheseendpointstakesintoaccountthenewdata(describedandevaluatedinSection6)andrelevantdatafromtheTGIC-1report.

7.1Skin sensitisation

InTGIC-1,animalandhumanhealthdataconcerningtheskinsensitisationpotentialof TGICwere available.A summaryof the datais asfollows:

Animal studies

In2studies,theskinsensitisationpotentialofTGICwasassessedinmaleandfemaleguineapigs(Ciba-GeigyLtd,1988,SafepharmLaboratoriesLtd,1988).Inthestudies,atwo-stageinductionprocesswasfollowedby 1or2challengephases.ThedurationofexposuretoTGICduringthechallengephasewaslimitedto24h.ThechallengephaseconcentrationsofTGICwere20mg(CibaGeigyLtd,1988a)or50-100mg(SafepharmLaboratoriesLtd,1988).TGICtestedpositiveforsensitisationinbothstudies.

Humanstudies

ThreecasestudiesreportedTGIC-inducedcontactdermatitis.IneachcasetheworkerhadbeenexposedtoTGICorTGICpowdercoatings,andcomplainedofdermatitis.Theworkerswerepatch-testedwithTGICandtheresultswerepositive.ICIDuluxalsoprovidedasummaryofthehealthstatusofemployeesatanAustralianpowdercoatingmanufacturingplant,whereby,twoemployeeshadallergicdermatitis(confirmedpositive byTGIC patch-testanalysis).

Newanimalandhumandata,concerningtheskinsensitisationpotentialofTGICare summarisedas follows:

Animal studies

Anegativestudywasreported,examiningtheskinsensitisationpotentialofTGICinagroupof20maleguineapigs.AmurineLLNAwasnegativehoweveronly anabstractwasavailableforassessment, and essentialinformationwas notreported.

Humanstudies

Tworecentlypublishedcasereportswereavailableforthisassessment.Inbothstudies,spraypaintersusingTGICpowdercoatingsforextendedperiodsoftimereporteddermatitis.Clinicalexaminationrevealedeczemainbothworkers,andreturnedpositivepatch-tests to TGICand TGICpowder coatings.

Insummary,therearenow5humancasereportsofskinsensitisation,2positiveand1negativeguineapigmaximisastionstudiesand1negativemurineLLNA(abstractonly).Therecentsensitisationstudyinguineapigswasnegative,whichisincontrastwiththefindingsof2similarstudiesreportedinTGIC-1.Althoughtherearesmalldifferencesindoseatinductionandchallengeintheseanimalstudies,theyareunlikelytoaccountforthedifferencesinresults.Infact,themethodologyadoptedbySafepharmLaboratoriesLtd(1991)isthesameasthelateststudy(Ciba-GeigyLtd,1997),withtheexceptionoftheslightlylowerdosesatthesecondinduction(90mgintheCibastudyc.f.100-150mgintheSafepharmstudy).

Classificationstatus

Based upon availableanimal and humandata,TGICsatisfiestheApprovedCriteriafor classification asa substancecausingsensitisationbyskincontact.

7.2Respiratory sensitisation

TGIC-1reportedthatICIDuluxhadprovidedasummaryofthehealthstatusofemployeesatanAustralianpowdercoatingsplant.In1991,twoseparateincidentsofTGIC-aggravatedintrinsicasthmawerereported(nofurtherdetailsprovided).Shortlyafter,twenty-eightemployeesweregivenmedicalexaminations,andrespiratoryirritation was present or reportedin fiveemployees. No TGIC exposuremonitoringdatawasprovided(thisdatawasnotusedforclassificationbecauseofthelackofreportingdetail).

Newrespiratorysensitisationdataislimitedtotwohumancasereports(Piirilaetal.,1997;Meulemanetal.,1999),eachdemonstratingpositivebronchialprovocationtestdata.The studiesreportontwospraypainters,who,afterworkingwithTGICpowdercoatings(1-7%w/w)forextendedperiodsoftime,reportedrespiratorysymptomsincludingrhinitis,dyspnoea, cough and wheeze.

Inbothcases,occupationalasthmawasdiagnosedfollowingbronchialprovocationtests,involvingchallengestoaerosolisedTGIC.Thetimetakentoreachagreaterthan20%reductioninFEV1wasconsiderablylongerinthePiirilareport(11hvs6h)andtheconcentrationofTGICusedduringbronchialprovicationwasmuchhigher(4%vs0.05%).Theseclinicaldifferencesmayreflectpatient-specificdifferencesandareconsiderednottoweakentheevidenceforthepositivecausalrelationshipbetweenTGICandoccupationalasthma.SkinprickteststounconjugatedTGIChowever,werenegativeinone(Piirilaetal.,1997),andinconclusive intheother(Meuleman et al.,1999).

Astherearecurrentlynoknownpublishedepidemiologicalstudies,ratesofoccupationalasthmainTGIC-exposedpopulationsremain unclear. However,undertheUKSWORDnotificationsystem,elevencasesofasthmahavebeenattributed toTGICsince 1989.

Classificationstatus

The classificationsystem prescribedintheApprovedCriteriastatesthat achemicalmeetsthesecriteriaifthereisevidencethatthesubstancecaninducespecificrespiratoryhypersensitivity.AsisthecasewithTGIC,thisevidenceisusuallyhumandata.InconsideringthehumanevidenceforTGIC,theexplanatorynotesregardingthe use ofR42 have been takenintoaccountas follows:

  • Twocasereportsshowpositivebronchialchallenge onexposureto TGICandthus providesufficientevidenceforclassification ontheirown. (paragraph

4.63 ofthe ApprovedCriteria)

  • In the twocasestudies,exposureto TGIC resultedinrespiratoryhypersensitivity,thatis,theclinicalconditionofasthma(inadditiontodyspnoea andrhinitis).Thereis nodatato showthattheasthmaelicited byTGICis a resultofrespiratoryirritationin bronchialhyper-reactiveindividuals.Therewas noevidencethatthe asthma was caused byirritation inhyper-reactiveindividuals.Similartootherlow molecularweightsubstancesknownto causerespiratorysensitisation, noimmunologicalmechanismhas beendemonstrated.(paragraphs4.59 and4.64)
  • Both casestudiesproviderelevantclinicalhistory(medicalandoccupationalinformation)tosupporta relationshipbetweenexposure to TGICand thedevelopment ofrespiratoryhypersensitivity. Lungfunctiontests,includingserialpeakflowmeasurementsand assaysforbronchialhyper-responsivenessto histamine,provide furtherevidence.(paragraph4.62)

Supportingevidence

  • Case reportsdo notgive anindicationoftheincidenceof respiratorysensitisationamongstTGIC workers andno epidemiologicalstudieshave beenconducted.Becauseoftheotherknownadversehealtheffectsof TGIC, thewearingof personalprotectiveequipment(includingrespiratoryprotection)isrecommended by manufacturers anddistributorsof TGICand TGIC productsand iscommonpracticeinworkplaces.Therefore,thenumber of casesreported asa functionof populationsizewouldbeexpectedto be low.However, in addition tothe2 casestudieddiscussed inthereportin detail,underthe UKSWORDnotificationscheme 11 casesofoccupationalasthmahave been attributedtoTGIC exposure.(paragraph4.60)
  • TGICis structurallyrelatedto isocyanatesand hasreactiveepoxidesidegroups,whichsuggests TGICmayhave the potentialforsensitisation.(paragraph4.61)

7.3Repeated dose toxicity

Nolong-termrepeateddosestudieswereavailableforassessmentforTGIC-1.Onlyshort-termrepeateddose(5or7day)studiesinrodentswereavailable.Resultsoftheseshort-termstudiesaredescribedbelow.

Maleratswereadministered0,54or216mg/kg/dayTGIC,andfemalesadministered0,43and172mg/kg/daybygavagefor7days(ShellResearchLtd,1971). No abnormal clinical signs or symptoms were observed. Minor

cytoplasmicvacuolationofdistalconvolutedtubuleepitheliawereobservedinmalesinthelowdosegroup.Inthehighdosegroups,renaltubulardamage,andhaemorrhagicanddegenerativechangesofthegastricandduodenalmucosawereobserved.

Malemicewereadministered0,10,40or140mg/m3TGICforfivedays(SafepharmLaboratoriesLtd,1991).Noadverseeffectswereobservedinmiceexposedto10mg/m3TGIC.However,adverseclinicalsigns,increasedbodyweightlossesandhighermortalityoccurredatinhaleddoselevelsof40and140mg/m3TGIC.

Malemicewereexposednose-onlyto7.8mg/m3ororallyto115mg/kg/day,TGIC,forfivedays(SafepharmLaboratoriesLtd,1992).Noadverseclinicalsignsor deaths wereobservedandbodyweightgain was unaffected.

Inthisreport,a13-weektoxicitystudywasassessed(CIT,1995).Exposureto0,10,30or100ppm(0,0.72,2.08or7.32mg/kg/day)TGICbydietaryadmixtureinmaleratswaswelltolerated.Atthehighestdose,treatedanimalsexhibitedastatisticallysignificantlower bodyweight,theonlyeffectobserved.

Additionally,dataonthenon-neoplasticeffectsofTGICcanbeobtainedfromthenew99-weekcarcinogenicitystudyinmaleratsexposedto0,10,30,100or300

ppm(0,0.43,1.30or4.36 and13.6mg/kg/day)(CIT,1999).Principaleffectsseenatthehighestdosestudied(300ppm)included,decreaseinbodyweight,mastocytosisinthelymphnodesanddepletionofthespleenlymphoidcells.However,increasedmortalitywithinthegroupmeanttheseanimalsweresacrificedatweek63.Therewerenotreatment-relatednon-neoplasticchangesobservedinlowerdosedgroups.

Classificationstatus

Reduced body weightwasobserved in the 13-weektoxicitystudy at100ppm(7.32mg/kg/day)andinacarcinogenicitystudy(CIT,1999)arapidonsetofmortalityandothersevereeffectswereobservedat300ppm(13.6mg/kg/day)TGIC.TGICis classified as‘Harmful’forsevereeffectsafterrepeated or prolongedexposure.

7.4Fertility

Whilenostandardfertility studieswereavailable forassessmentfor TGIC-1,genotoxicitystudiesindicatedthatTGICinducedchromosomalaberrationsandcytotoxicityinmousespermatogoniaandreducedfertilityinmalesinadominantlethaltest.ThesefindingsraisedthepossibilityofreproductiveeffectsofTGIC.StudiesinmalemiceincludedexposureofTGICbynose-onlyinhalation(SafepharmLaboratoriesLtd,1992),andoraladministration(Ciba-Geigy Ltd,1986; HazletonLaboratoriesAmericaInc, 1989;and HazletonMicrotest,1991).

Thenose-onlyinhalationstudyestablishedthatexposureofmiceto7.8mg/m3TGIC(onlydosetested)over5daysdidnotinducechromosomalaberrationsorcytotoxicityin spermatogonialcells, or adverseclinicaleffects.In the oral studies,chromosomalaberrationswereseenatthelowestdosetested,28.5mg/kg/dayandcytotoxicityat 57.5mg/kg/dayand above.

InadominantlethalstudyinwhichTGICdidnotinducemutations,reducedfertilitywasobservedinmalesatthehighestdose,50mg/m3. Thereductionsin

fertilitywereconsistentwitheffectsonmaturesperm,maturingspermatidsandType-B spermatogonia.

Inthisreport,acombined,13-weekfertilitystudywasassessed(CIT1995).Exposureto0,10,30or100ppm(0,0.72,2.08or7.32mg/kg/day)TGICbydietaryadmixtureinmaleratswaswelltolerated.Aslighttreatment-relateddecreaseinthemeannumberofspermatozoawasnotedatthe30and100ppmdoses;however,thiswasnotstatisticallysignificantwhencomparedto controls.

Therewasnotreatment-relatedinfertilityinmalesorchangesinembryonicandpupdevelopment.However,femaleswerenotexposed in this study. TheNOAEL is consideredto be 7.32 mg/kg/d.

Classificationstatus

Thepotentialeffectsofchromosomaldamageinspermatogoniainmicewerenotdemonstratedasinfertilityinmalerats,ordevelopmentaleffectswhenmaleswereexposedtorepeated,lowerdosesofTGIC.TheeffectsofTGIConfemalefertilityanddevelopmentaleffectsasaresultofmaternalexposuretoTGIChavenotbeeninvestigated.

ThereisinsufficientdatatoclassifyTGICwithrespecttoeffectsonfertilityordevelopmentaltoxicity.

7.5Carcinogenicity

AlthoughnocarcinogenicitystudieswereavailableforassessmentforTGIC-1,themutagenicpotentialofTGICwasassessed,andcategorisedasa‘Category2mutagen’accordingly.TGICwaspositiveinanumberofshort-terminvivoandinvitrogenotoxicitystudiesandshowntocovalentlybindtoDNA.Theresultsraisethe questionof potentialcarcinogeniceffectsof TGIC.

Inthisreport,thecarcinogenicpotentialofTGICwasexaminedinmaleSprague-Dawleyratsovera99-weekexposureperiod.Animalsweregivenbydietaryadmixtureeither0,10,30,100or300ppm(0,0.43,1.30,4.36and13.6mg/kg/day)TGIC.The300ppmdosedgroupwassacrificedatweek63duetohighmortalityand adverseclinicalsigns.

TheNOAELfornon-neoplasticeffectsis4.36mg/kg/d.ThisNOAELisapproximatelyequivalenttoaninhalationexposurelevelof23.2mg/m3over6-hours(assumingaratbodyweightof0.215kgandinhalationrateof0.161m3/d).TGICfailedtoinduceanincreaseintheincidenceoftumoursatdosesupto100ppmin malerats.

Non-neoplasticeffectswerenotobservedat100ppmandfemaleswerenotinvestigated.NotwithstandingthepositivemutagenicitypotentialofTGICreportedinTGIC-1,additionaldataisrequiredbeforeclassificationforthecarcinogenicpotentialof TGIC can be made.

Classificationstatus

Thereisinsufficientdatatoclassifythecarcinogenicpotentialof TGIC.

8.EnvironmentalAssessment

8.1Environmental exposure

AshighlightedintheinitialassessmentofTGIC,thechemicalisanepoxidewhereanyresiduesreleasedtotheenvironmentareexpectedtoberapidlydegraded,eitherthroughmicrobalactionorabiotichydrolysis.Intheaquaticenvironment,persistenceisexpectedtobelimited(half-lifeexpectedtobelessthan10daysinfreshwater)withhydrolysisproceedingmorerapidlyinthemarineenvironment.StudiesprovidedshowedTGICisnotreadilybiodegradableusingthemodifiedSturmtest,with48%degradationfromasolutioncontainingTGICat20ppmafter28days.However,inamodifiedZahn-Wellenstest,thecompoundwasinherentlydegradable.

SincetheoriginalTGIC-1assessment,thereadybiodegradabilityofTGIChasbeenfurtherassessedinaCO2evolution(28dayModifiedSturm)TestinaccordancewithEECDirective92/69andOECDGuidelineNo.301B(Grutzner,1997).Exposurewasprolongedto43daysbecausethechemicalshowednosignofbiodegradationbyexposureday28.Theinoculumwasactivatedsludgefromadomesticwastewatertreatmentplant.Concentrationsinthetestsolutionappearedtobearound33ppm,with100mgofTGICaddedtotestflaskscontaining3litresofmedium.Onlyoneconcentrationwastestedforbiodegradability.Todeterminewhetherthecompoundhadanytoxiceffectonthemicroorganisms,atoxicitycontrolwasestablishedwhere51mgofTGICwasaddedalongwith39mgofthereferencecompound,aniline,toaflaskcontaining3litresoftestmedium,givingaconcentrationofaround17ppm.Thisconcentrationwasaroundhalfofthatusedtotestbiodegradability,andthereasonforthisisnotmadeclearinthestudy.TheoutcomesofthisstudyshowedTGICtobenonbiodegradableandnondegradable(intheabsenceofactivatedsludge)overthe43daysexposurewithzerodegradationrecorded.Likewise,theabioticcontrolcontainingTGICandsteriletestmediumshowednoabioticdegradation.Whilethetoxicitycontrolshowednoinhibitoryeffect(around44%degradedafter28days,althoughitisnotclearwhetherthiswassolelydueto theaniline),theeffectiveconcentrationof TGICwasaroundhalfthatusedinthedegradationstrudy.However,asanearliertestshowed48%degradationfromasolutioncontainingTGICat20ppmafter28days(seeabove), aninhibitoryeffectat 33 ppmmust be considered.

9.SummaryandConclusions

Triglycidylisocyanurate(TGIC)isatriepoxycompoundusedasacross-linkingorcuringagentforpolyesterresins.InAustralia,TGICisonlyimported,andisusedprincipallyasaningredientinpolyesterpowdercoatingsinthemetalfinishingindustry.TGICiseitherimportedastechnicalgradeTGICforthemanufactureofpowdercoatingsorimportedinpowdercoatingsformulatedoverseas.Anelectrostaticprocessisusedtospraypowdercoatingsontometalobjects,suchassteelfurniture,carparts,metalfencing, window anddoorframes.

TGICwasassessedbyNICNASasapriorityexistingchemicalin1994.Theavailabilityofsignificantnewdatahasledthechemicaltobereassessed(secondarynotification).Newdatasuppliedforsecondarynotificationassessmentincludedcontacthypersensitivity,repeateddosetoxicity,fertilityandcarcinogenicityanimaldata,humanhealtheffectsdataandanenvironmentalbiodegradabilitystudy.

The new data was assessedand consideredtogetherwith the healthassessmentdatainoriginalTGICreport.Themajorimpactofthenewdatarelatestorespiratorysensitisation,andeffectsduetoprolongedexposure.Thedata,consideredasawhole,aresummarisedbelow.

Thehumanhealtheffectsreportedintheliteratureareskinandrespiratorysensitisation.Severalcasereportsofallergicdermatitisand occupationalasthmainworkersexposedtoTGICorTGICpowdercoatingshavebeenpublished.PatchtestswithTGIC,toconfirmskinsensitisationoftheseworkers,werepositive.Positivebronchialchallengetestsconfirmedrespiratorysensitisation.OtherhealtheffectsreportedamongstworkersinAustraliaincludenasal,eyeandthroatirritation,skinrashandnosebleeds.

Inanimals,TGICisacutelytoxicbytheoralandinhalationalroutesbuthaslowacutedermaltoxicity.TGICcausesseriouseyeeffects,isaskinsensitiserandisnot a skinirritant.The majoreffectsin short-termrepeateddosestudieswereatthesite ofapplication,includingrenal,lungand gastric/duodenaldamage.

TGICisgenotoxic,invitroandinvivoinmice.TGICinducedchromosomalaberrationsinmousespermatogoniafollowingoraladministration.TGICwasalsopositiveininvivonucleusanomalyassaysandinducedsisterchromatidexchangesinanumberofinvitrogenotoxicitystudies.Theevidenceforinduction ofdominantlethalmutationsbyTGICisequivocal.TGICwasshowntobindtoratliverDNAinvivofollowingoralandintraperitonealadministration.GenotoxicitystudiesindicatedthatinhalationofTGICresultedincytotoxicityandchromosomalaberrationsinspermatogonialcellsofmice.Inadominantlethalstudy,TGICshowedreducedfertilityfollowinginhalationinsomebutnotallcasesstudied.ThisdataraisedconcernsthattheremaybeariskofreproductiveeffectsfromexposuretoTGIC.Inarecentstudy,effectsonmalefertilityanddevelopmentaleffectswerenotobservedwhenmaleratswereexposedtoTGICuptothemaximumdosetested(100ppm).However,evenatthehighestdose,apartfromaslightly lowerbody weightgain,noothereffectswere observed. Effectsonfemale

fertilityanddevelopmentaleffectsasaresultofmaternalexposure,havenotbeentested.

TheonlyavailablechronicdataindicatethattheNOAELinmaleratsis100ppm,withsevereeffectsoccurringat300ppm.TGICdidnotinduceanincreaseintumoursupto100ppmintheseanimals.Principaleffectsat300ppmincludeddecreaseinbodyweight,mastocytosisinthelymphnodes,depletionofthespleenlymphoidcells anddeath.Females werenottested.

ThesourcesofoccupationalexposureduringmanufactureofTGICpowdercoatingsincludeweighingoutofTGIC,fillinghoppers,mixing,transferofpowdermixesinopenvessels,extrusion,milling,bagging,cleaningupspills,andcleaningequipment.Sourcesofoccupationalexposureduring useof TGICpowdercoatingsincludefillinghoppers,spraying,cleaningupspills,cleaningequipmentandcleaningspraybooths.

Baseduponalltheavailabledata,andinaccordancewithNOHSCApprovedCriteria, TGICshould beclassifiedas:

  • toxic byinhalation andifswallowed.
  • maycause sensitisationbyinhalation.
  • riskofseriousdamage to eyes.
  • maycause sensitisationbyskincontact.
  • ‘harmful’forsevereeffectsafterrepeatedorprolongedexposure.
  • maycause heritablegenetic damage(Category2 mutagen).

Asaresultoftheoriginaltoxicityassessment,TGIC-1notedthattherewereanumberofcriticaldatagapsandrecommendedstudiestoexaminethechronictoxicity,carcinogenicityandreproductivetoxicityofTGIC.

Theimpactofnewdataontherecommendationsforfurthertoxicitytesting,asoutlined in TGIC-1, is summarisedaccordingly:

  • Theoralcarcinogenicityinmaleratsprovidessomeevidenceforlackoftumourdevelopment(up to4.36 mg/kg/day). However,femaleswerenottested. Additionaldataisrequiredbeforeclassification forthecarcinogenicpotentialof TGICcan be made.
  • Thecombined13-weektoxicity/fertilitystudyprovidessomeinformationonreproductivetoxicity. Thestudyestablished aNOAEL(7.32mg/kg/day)formalerats (includingfertility),reportingno treatment-relatedinfertilityinmales or change inembryonicand pupdevelopmentfollowingexposureofmales to TGIC.However,femaleswerenotexposedtoTGICand potentialeffects onthe nextgeneration werenotstudied.Therefore,thestudydidnotadequatelyaddresspotentialeffectson theoffspring(as a resultofmale orfemalereproductivetoxicity) or femalefertility.

AtthetimeofwritingtheTGIC-1report,nonationaloccupationalexposurestandardforTGIChadbeenadopted.TGIC-1acknowledgedthatanationaloccupationalexposurestandardshouldbepredicatedonchronicdata,butinitsabsenceconcludedthegenotoxicpotentialofTGICasthecriticaldeterminantinestablishing an occupational exposure standard. Accordingly, TGIC-1

recommendedthatNOHSCsetanexposurestandard.Subsequently,atime-weightedaverageexposurestandardforTGICof0.08mg/m3wassetbyNOHSC(adoptedDecember,1995).TheexposurestandardwasbasedontheSafepharm6-hourinhalationstudy(SafepharmLaboratoriesLtd,1992),wherethelowestnoeffectlevelwas 7.8 mg/m3.

TheNOAELfornon-neoplasticeffectsinarecent99-weekoralstudyinmaleratswas100ppm(4.36mg/kg/d).ThisNOAELisapproximatelyequivalenttoa6-hourexposurelevelof23mg/m3(basedonaratbodyweightof215gandaninhalationrateof0.161m3/d).Basedonthechronicdata,reviewoftheoccupationalexposurestandardis notwarranted.

ThenewdatademonstratesthatTGICisarespiratorysensitiserandlikeallsensitisers,exposurelevelsshouldbekepttoaminimum.ThisisconsistentwiththeconclusioninTGIC-1;thatis,TGICisasensitiserandisgenotoxic,andtherefore,occupationalexposurelevelsshouldbemaintainedatthelowestlevelspracticable.Experiencehasshownthatexposurelevelsof0.08mg/m3canbeachievedandmaintainedinpowdercoatingmanufacturingplantsandspraypaintworkshops.

Theconclusionsoftheearlierreportstillstand,thatTGICisunlikelytocauseadversehumanhealtheffectsifappropriatecontrolmeasures(includingpersonalprotectiveequipmentwherenecessary),safeworkpracticesandatmosphericmonitoringandhealthsurveillancestrategies(whennecessary)areimplemented.

AdditionalbiodegradabilitydataforTGICconfirmsthefindingsoftheTGIC-1assessment,that is, TGICisnotexpected toaccumulateinsoilor sedimentbecauseofhighmobility andlimitedpersistence.Persistence intheaquaticenvironment isalsoexpectedtobelimited.ThereactivityofTGICprecludesanypossibilityofbioaccumulation.

Finally,TGICisunlikelytopresentarisktothepublicortheenvironmentunderthe current useconditions.

10.Recommendations

10.1Classification andlabelling

IntheTGIC-1report,TGICwasclassifiedastoxicbyoralandinhalationroutes,capableofcausingseriouseyedamage,askinsensitiser,andaCategory2mutagen,inaccordancewiththehealtheffectscriteriadetailedintheNationalCommission’sApprovedCriteriaforClassifyingHarzardousSubstances(NOHSC,1999).

ThissecondarynotificationassessmenthasshownnodatatochangeTGIC-1recommendationsandinaddition,newdataindicatethatTGICshouldalsobeclassifiedasarespiratorysensitiserand‘harmful’forsevereeffectsfollowingrepeatedexposure.

BasedontheclassificationofitshealtheffectsandinaccordancewiththeApprovedCriteria(NOHSC,1999),TGICisconsideredtobeahazardoussubstance.

The completerequirements forthelabelling ofhazardoussubstancesaredetailedintheNationalCodeofPracticefortheLabellingofWorkplaceHazardousSubstances(NOHSC,1994a).ThefollowingriskphrasesandappropriatesafetyphrasesapplytothepresentreportandhavebeendeterminedbyapplicationofthecriteriagiveninthelabellingguidancenoteandwillensurethatthelabellingrequirementsoftheNationalCommission’sNationalModelRegulationsfortheControlofWorkplaceHazardousSubstances(NOHSC,1994b) havebeenmet.

Riskphrases

  • R23/25Toxic byinhalationandifswallowed.
  • R41Riskof seriousdamage to eyes.
  • R42Maycausesensitisationbyinhalation.
  • R43Maycausesensitisationbyskincontact.
  • R46Maycauseheritablegeneticdamage.
  • R48/22Danger of seriousdamage to health byprolongedexposureifswallowed.

Appropriatesafetyphrasesinclude:

  • S22Do not breathedust.
  • S24/25Avoidcontactwithskinandeyes.
  • S26Incaseofcontactwitheyes,rinseimmediatelywithplentyofwaterandcontact a doctoror PoisonsInformationCentre.
  • S28Aftercontactwithskin,washimmediatelywithplentyof…[material tobe specified by manufacturer].
  • S36Wearsuitableprotectiveclothing.
  • S37Wearsuitablegloves.
  • S38In case of insufficient ventilation wear suitable respiratoryequipment.
  • S39Weareye/faceprotection.
  • S44IfyoufeelunwellcontactadoctororPoisonsInformationCentre(showlabelwherepossible).

WhereTGICisaningredientinamixture/preparation,asinpowdercoatings,thefollowingconcentrationlimitsapply:

Table 2- Concentrationlimits andclassificationsfor TGIC as aningredientinmixtures/preparations

ConcentrationlimitClassification

25%CToxic;R23/25, R48/22, R41, R42/43, R46

10%C25%Harmful;R20/22,R41,R42/43,R46,R48/22

5%C10%Harmful;R20/22,R41,R42/43,R46

3%C5%Harmful;R20/22, R42/43,R36, R46

1%C3%Harmful;R42/43, R36, R46

0.5%C1%

0.1%C0.5%

Harmful;R36, R46

Harmful;R46

C0.1%Not a hazardoussubstance

CconcentrationofTGICinpowdercoatings

TheabovedatarepresentclassificationsforpreparationscontainingTGICatconcentrationsbetweentherangesshown.However,shouldtherebeotherhazardousingredientspresentinthepreparation,theoverallclassificationforthepreparationneedstobedetermined.InthiscaseusersshouldrefertotheNationalCommission’sApprovedCriteriaforClassifyingHazardousSubstances(NOHSC,1999)forfurtherguidance.

10.2Further studies

The datagaps and recommendedfurtherstudiesnoted in TGIC-1 stillapplyand areas follows:

  • Chronictoxicityandcarcinogenicitydata(such asa combinedchronicinhalation/carconogenicitystudyina mammalianspecies).
  • Reproductive and developmentaltoxicity(suchas amultigenerationreproductionstudy).

10.3Health Surveillance

AworkplaceassessmentisrequiredbytheNationalModelRegulationsfortheControlofWorkplaceHazardousSubstances(NOHSC,1994b)oftheriskstohealthconsequentuponexposuretoahazardoussubstance.AccordingtotheNOHSCGuidelinesforHealthSurveillance(NOHSC,1995)anemployermustconsiderifuse of ahazardoussubstanceintheworkplacepresentsa significantriskto healthand,ifso,establish an appropriatehealthsurveillanceprogram.

AsTGICisarespiratoryandskinsensitiser,particularattentionshouldbepaidtoworkerexposureviaskincontactandinhalationofTGICpowdercoatings.Amedicalpractitionerappointedbytheemployercanassistindecidingifthehealthsurveillanceisrequired,and ifso, design anappropriate a program.

10.4Material Safety Data Sheets

TheNOHSCNationalCodeofPracticeforthePreparationofMaterialSafetyData Sheets(NOHSC,1994c)providesguidanceforthepreparation ofMSDS.

ItisrecommendedthatsuppliersamendtheirMSDS,takingintoaccountthenewhealtheffectsdataand theclassification and cut-offlevelsrecommendedin Section

11.1.Inparticular, the MSDSshouldreflectthenewinformationon chronichealtheffectsandrespiratorysensitisation.Somesuggestedwordingisprovidedinthesample MSDS atAppendix1.

10.5Atmosphericmonitoring and control ofoccupational exposure

RecommendationsinTGIC-1inrelationtoatmosphericmonitoringandoccupationalcontrolmeasuresareconsideredtobeappropriate.Forinformation, acopyof therelevantsectionsfromTGIC-1 is providedin Appendix2.

11.SecondaryNotification

UnderSection65oftheAct,thesecondarynotificationofTGICmayberequired,whereanapplicantorotherintroducer(importer)ofTGIC,becomesawareofanycircumstanceswhichmaywarrantareassessmentofitshazardsandrisks.Specificcircumstancesinclude:

a)Thefunctionoruse of TGIChas changed, orislikelytochange, significantly;

b)TheamountofTGICintroducedintoAustraliahasincreased,orislikelytoincreasesignificantly;

c)Manufacture ofTGIChas begun in Australia;or

d)Additionalinformationhas becomeavailable totheapplicant/notifieras totheadversehealthand/orenvironmentaleffects of TGIC.

TheDirectormustbenotifiedwithin28daysoftheintroducerbecomingawareofanyof theabovecircumstances.

Appendix 1

SampleMaterialSafetyDataSheetforTriglycidylisocyanurate

Appendix 2

RECOMMENDATIONSFOR ATMOSPHERIC MONITORINGAND

CONTROL OF OCCUPATIONAL EXPOSURE (adaptedfromtheTGIC-1report)

A2.1 Atmosphericmonitoring

Atmosphericmonitoringinbothpowdercoatingmanufacturingplantsandspray-paintingestablishmentsshouldbecarriedoutroutinely.Thefrequencyofmonitoringshouldensurethattheoccupationalexposurelimitof0.08mg/m3for TGICisnotbeingexceededand thatthehealthofworkersisthereforebeingprotected.Atmosphericmonitoringprovidesaquantitativeestimateofworkerexposure,identifiesareaswherehighlevelsofatmosphericTGICoccur andprovides abasisfor measuringtheeffectivenessof controlimprovements.

Asmanufacturersofpowdercoatingshandle'pure'(technicalgrade)TGIC,routineairmonitoringoftotaldustandTGICshouldbecarriedout.Airmonitoringintheseplantsshouldbecarriedoutwhereexposureislikelytooccur,suchaswherethefillingofhoppers,milling,extrusionand baggingtakesplace.

Routineairmonitoring ofspray-paintingworkshopsshouldbecarriedout toensurethattheexposurelimitof0.08mg/m3forTGICisnotbeingexceeded.ThemostaccuratemethodistomeasureatmosphericlevelsofTGIC,butitisrecognisedthatthismethodmaynotbepractical.Routinemonitoringfortotaldustmaybemorepractical.However,whenmeasuringtotaldustitmustbeassumedthatallTGICinthepowdercoatingsisbioavailable.Forexample,inworkplacesusingfivepercentTGICpowdercoating,thetotaldustlevelshouldnotexceed1.6mg/m3.MonitoringshouldbecarriedoutwhereworkerexposuretoTGICinspraypaintingworkshopsislikelytooccur,suchasduringfillinghoppers,sprayingandclean-upoperations.

MethodsusedforairmonitoringanddeterminationofTGICcontenthavebeenreceivedfromNissanChemicalIndustriesLtd,Japan,andCiba-GeigyPtyLtd,Switzerland,andareprovidedasAttachment1andAttachment2*.Thevalidityandsuitabilityofthesemonitoringtechniqueshavenot beenassessedinthisreport.

Foradviceandassistanceinmonitoringcontact,stateandterritoryoccupationalhealthandsafetyauthorities.

A2.2 Controlofoccupationalexposure

Consistentwithgoodoccupationalhygieneprinciples,allworkerexposureshouldbeminimisedandspraypaintersandmanufacturersofpowdercoatingsshouldaimforthelowestpracticablelevelsofatmosphericTGICandTGICpowdercoating.Inanycase,thelevelsshouldnotexceedtheexposurelimit of 0.08mg/m3for TGIC.

*Attachments1and2arenotreproducedinthisappendix–refertoTGIC-1report.

Experiencehasshownthatthislevelcanbeachievedandmaintainedinpowdercoatingmanufacturingplantswheretherearehazardcontrolmeasures,safeworkpracticesand,wherenecessary,personalprotectiveequipmentisworn.

Dataindicatethatalthoughtheexposurelimitcanbeachievedinspraypaintworkshops,itwasoftenexceededwherecontrolmeasures,workpracticesandpersonalprotectiveequipmentvaryand oftenareinadequate.

Thesettingofanoccupationalexposurelimitdoesnotprecludeeffortstofurtherreduceexposure.TominimiseworkerexposuretoTGIC,thecontrolmeasureslistedbelowshouldbefollowed.Thecontrolmeasuresshouldbeseenasahierarchy,thatis,implemented inthesequence in whichtheyare presented.

A2.2.1 Applicationofpowdercoating

Substitution

TGICisusedinpowdercoatingsasacuringagent,primarilybecauseitgivesultravioletstabilitytothepaintfilm.TGIC-freepowdercoatingsareavailablewhichmeetthespecificationsoftheendusers.ReviewofthehazardsandefficacyoftheseTGIC-freepowdercoatingswasoutsidethescopeofthisassessment.SubstitutionwithTGIC-freepowdercoatingsshouldbeconsidered.However,substitutionshouldonlybewithlesshazardoussubstancesandthehealthhazardsofanypotentialsubstituteshouldbeknowntoemployers and employees.

Isolation

Thespraypaintingprocessshouldbeseparatefromotherworkplaceactivities,suchasbydistance orinanotherbuilding.

Engineeringcontrols

Themosteffectiveengineeringcontrolsforreducingworkerexposureareenclosure,localexhaustventilationandautomationofthesprayprocess.Inparticular,thisassessmentrecommendsthat:

  • spraypaintingof TGICpowder coatingsshould beperformed in a booth;
  • spraypaintingbooths andequipmentshouldbe inaccordancewithAustralianStandardAS3754-1990- SafeApplicationof PowderCoatings byElectrostaticSpraying. Inparticular,thedesign oftheboothshould besuchthatairbornepowderdoesnotescapefromthe boothintotheworkplace.Forallinstallations,localexhaustventilationshouldbe provided andtheaverageair velocitythrough each boothopeningshouldbe notlessthan 0.4 m/sec;
  • localexhaustventilationshouldbeused whenspraying,duringfillingofhoppers, whenreclaimingpowder andduringclean-up;
  • automaticsprayguns, feedlinesandfeedequipmentshouldbeused;
  • spraygun airpressureshould be minimisedto preventover sprayasthiscouldresultin unnecessarypowderbuild-upwithinthe spraybooth;
  • the powersupplyandpowdercoatingfeedlinesshouldbe interlocked withtheairextractionsystemso thatifafaultdevelopsinthe ventilationsystem, thepowder coatingand powersuppliesarecutoff;
  • the spreadofdustwithinthe powdercoatingbuildingshouldbeminimised.Circumstancesleadingtodraughtsand airturbulenceshouldbeevaluated andcontrolsimplemented;
  • operationsofopeningpowdercoatingpackages,loadingof hoppersandreclaimingpowdershouldbe containedto preventor minimise the generationof dusts;
  • thelayoutoftheworkstation and thesize ofthehopperopeningshouldbe suchthatgeneration ofdustisminimisedinfillingthe hopper;and
  • othermethodsin theuseof hoppersshouldbe considered,namely:

largehoppersshouldbeusedtoavoidfrequentrefillingofsmallerunits,and

preferenceshould be given to the useof powdercoatingssupplied indrumswhich allowmechanicaltransferofthepowder tohoppers.

Safework practices

Safeworkpracticesarenecessarytosupplementtheengineeringcontrolmeasuresinorderto minimiseworkerexposure.

Safe workpracticesshouldinclude:

  • workpracticesdesignedtoavoid the generation ofdust;
  • restrictingaccessto spraypaintingareas;
  • designinga safeworkplace so thatthespraypainterisneverbetweenthe objectto besprayed andthe airflow of contaminatedair;
  • situatingthearticlesto be sprayedsufficientlywithintheboothtoavoidricochet;
  • implementinggoodpersonalhygienepractices,forexample, powder coatingdustshouldnot beallowedto collecton theface,exposed bodyareasshould bethoroughlywashed andoverallsshould beregularlycleaned;
  • storingpowdercoatingandwastepowderina designatedareaandaccessrestricted;
  • cleaningboothsandsurroundingareas ona regularbasis;
  • promptlycleaning-upspillsof powdercoatings toreducethespread of TGIC;
  • not usingcompressed-air ordrysweepingduringclean-upoperations;
  • usinga spark-proofsqueegee whena wetclean-up is required;
  • emptyingvacuumcleanersin theboothandunderexhaustventilation;
  • takingcaretoavoidthegenerationof dustduringdisposalofwastepowder.
  • wastepowderbeingbakedin the originalboxfordisposaltolandfillas asolid;
  • vacuumingprimarydecontaminationof workclothing;
  • checkingregularlythecleaningand maintenance ofplantequipment,includingventilationandsprayequipment and filters;and
  • properinductiontrainingandgeneraltrainingof workersaboutthepotentialhazardsofsprayingwithTGIC powder coatingsandin thesafe workpracticesnecessaryto minimiseexposure.

Electrostaticspraypaintingbringswithitelectricalhazardsandadditionalrequirementsforsafeworkpracticesarerequired.Forexample,allequipment,includingspraygunsandbooth,shouldbeearthed.Allhooksusedtosuspendobjectstobesprayedshouldbecleanedpriortore-useinordertomaintaineffectivemetalcontact.Earthingofequipment,objectsbeingcoatedandpersonnelensuresmaximumcoatingefficiency,reducesfreedustand preventsbuild-up of staticchargescapable ofcausingignition.

Personalprotectiveequipment

Controlofworkerexposureshouldbeachievedasfarasispracticablebymeansotherthantheuseofpersonalprotectiveequipment.However,whenothercontrolmeasures,suchasengineeringcontrolsandsafeworkpractices,donotadequatelyprotecttheworker,thenpersonalprotectiveequipmentshould be worn.

Personalprotectiveequipmentshouldincludefullprotectiveclothingincludingoveralls,gloves,headandeyeprotectionandrespiratoryprotection,selectedandused incompliancewithrelevantAustralianStandards.Inparticular:

  • a full-faceair-suppliedparticulaterespiratorshouldbe worn,whichcomplieswithAS1716 -1991-RespiratoryProtectiveDevices, and usedinaccordancewithAS17151991-Selection, Use andMaintenanceofRespiratoryProtectiveDevices;
  • therespiratoryprotectiveequipmentshouldprovideheadcoveringtoavoid dust build-up aroundthe edges of thefacemasks. A ventilatedfull-headcoveringmayalso be morecomfortablein ahotenvironment;
  • duringmanualspraying,thegun-handmust not beinsulatedfromthe gun.Eitherthe gunhandshouldbe cowled bya coversleeve orthe palmof aninsulatingglovemaybe cutout. Operatorsstandingoutsidea boothandsprayinginsidea booththrough an apertureshouldwearthistype ofprotectiveequipment;and
  • anti-static andconductivefootwearshouldbe provided.

Workerswhomaycomeintodirectcontactwith TGICpowder coatingsincludepersons:

  • fillinghoppers;
  • manuallysprayingpowdercoatings,including'touch-up'spraying;
  • reclaimingpowder;
  • emptyingor cleaningindustrialvacuumcleaners;
  • cleaningspraybooths,filters and otherequipment;and
  • cleaningup majorspills ofpowder coating.

A2.2.2 Manufactureofpowdercoating

Whereapplicable,thecontrolsmeasuresoutlinedaboveforspraypaintingshouldbeimplementedinthepowdercoatingmanufacturingplant.Thesemeasuresincludeisolationof theformulationprocess,enclosure,automation,localexhaustventilationandthewearingofpersonalprotectiveequipmentwhennecessary.Anyopenprocessorleakagewillincreaseworkerexposure.Any manualprocesswillalsoincreaseworkerexposure.

Localexhaustventilationshouldbeprovidedwhenfillingthehoppers,whenaddingtothemixer,duringmixing,extrusionand bagging, and atopentransferpoints.