File No: NA/503Date:April 1997
NATIONALINDUSTRIALCHEMICALSNOTIFICATIONANDASSESSMENTSCHEME
FULLPUBLICREPORT
2,6-Naphthalenedicarboxylicacid
ThisAssessmenthasbeencompiledinaccordancewiththeprovisions oftheIndustrialChemicals(NotificationandAssessment)Act1989(theAct),andRegulations.ThislegislationisanActoftheCommonwealthofAustralia.TheNationalIndustrialChemicalsNotificationandAssessmentScheme(NICNAS)isadministeredbyWorksafeAustraliawhichalsoconductstheoccupationalhealthsafetyassessment.TheassessmentofenvironmentalhazardisconductedbytheDepartmentoftheEnvironment,Sport,andTerritoriesandtheassessmentofpublichealthisconductedbytheDepartmentofHealthandFamilyServices.
Forthepurposesofsubsection78(1)oftheAct,copiesofthisfullpublicreportmaybeinspectedbythepublicattheLibrary,WorksafeAustralia,92-94ParramattaRoad,Camperdown NSW2050,betweenthefollowinghours:
Monday-Wednesday8.30am-5.00pmThursday8.30am-8.00pm
Friday8.30am-5.00pm
ForEnquiriespleasecontacttheAdministrationCoordinatorat:
StreetAddress: 92Parramatta RdCamperdown, NSW 2050,AUSTRALIA
PostalAddress:GPOBox58,Sydney2001,AUSTRALIA
Telephone:(61)(02)9577-9466 FAX (61)(02) 9577-9465
Director
ChemicalsNotificationandAssessment
NA/503
2,6-Naphthalenedicarboxylicacid
1.APPLICANT
AmocoChemicals PtyLtd of28-34 OrangeGrove RoadLIVERPOOLNSW 2170hassubmittedastandardnotificationstatementinsupportoftheirapplicationforanassessmentcertificatefor2,6-naphthalenedicarboxylicacid. Noapplicationforexemptinformationwasmade,hencetheFullPublicReportispublishedinitsentirety.
2.IDENTITYOFTHECHEMICAL
ChemicalName:2,6-naphthalenedicarboxylicacid
ChemicalAbstracts Service
(CAS)RegistryNo.:1141-38-4
OtherNames:2,6-napthalicacid
Trade Name:AmocoPNDA
MolecularFormula:C12H8O4
StructuralFormula:
MolecularWeight:216.2
MethodofDetectionandDetermination:
infrared(IR),nuclearmagneticresonance(NMR)spectroscopies
Spectral Data:IRspectrumcharacteristicpeaks 478,585,755,
778,831,915,951,1104,1144,1180cm-1
3.PHYSICALANDCHEMICALPROPERTIES
Appearanceat 20°Cand101.3kPa:
whitecrystallineorflakesolid,nocharacteristicodour
MeltingPoint:decomposesbeforemeltingpointisreached;onsetofdecompositionat300°C
Density:1.5g.mL-1
VapourPressure:notdetermined
WaterSolubility:1.03mg.L-1@20oC(seecommentsbelow)
PartitionCo-efficient
(n-octanol/water):logPow=-1.77@pH7(seecommentsbelow)
HydrolysisasaFunction
ofpH:notdetermined
Adsorption/Desorption:notdetermined
DissociationConstant:pKa1= 3.8,pKa2=4.7(estimated,seebelow)
FlashPoint:200°C
Particle size:90%offlakes0.6mm
FlammabilityLimits:notflammableAutoignitionTemperature:notavailableExplosiveProperties: stable
Reactivity/Stability:consideredinertunderatmosphericconditions;
noincompatibilitiesdetermined;stable;notpronetospontaneousdecomposition;ifinvolvedinfire,unpredictabledecompositionproductsmaybegenerated
CommentsonPhysico-ChemicalProperties
Thewatersolubilityofthenotifiedchemicalwasdeterminedbyextrapolatingalinearregressionofhightemperaturedata(320-150°C). Theregressionlinehadan r2valueof0.999.ThechemicalcontainscarboxylicacidfunctionalitiesandthewatersolubilityofthechemicalisexpectedtodependonthepHofthemedium.AtlowpHvalues,atwhichthechemicalexistspredominantlyinthefreecarboxylicacid form,thesolubility inwateris expectedtobe verylow. However,athigherpHthecarboxylicacidgroupswillbedeprotonatedandtheresultingwatersolubilityof
thecarboxylateformofthechemicalwillbehigher.
Nodataonthehydrolyticbehaviourofthechemicalwasprovidedbythe notifier.Thechemicalcontainsnofunctionalgroupswhichwouldbeexpectedtohydrolyseunderenvironmentalconditions.
ThepartitioncoefficientofthenotifiedchemicalwasdeterminedatpH7.AtthispHthechemicalwillbecompletelyionised,consequentlythepartitioncoefficientmeasuredisthatofthecarboxylateformratherthantheacidform.AnestimatedlogKOW=2.93wasestimatedfortheacidformusingtheatom/fragmentcontributionmethoddevelopedbySyracuseResearchCorporation{SyracuseResearchCorporation,1997#39}.
BasedonthemeasuredpartitioncoefficientthechemicalwouldnotbeexpectedtostronglyadsorbtosoilorsedimentatpH7(i.e.inthecarboxylateform). However,adsorptivityalsohasastrongnegativecorrelationwithsolubilityandthelowsolubilityofthecarboxylicacidformofthechemicalsuggeststhatitwilladsorbmorestrongly.ThenotifierhasprovidedanestimateoflogKOC=2.67basedonthemethodofLymanet al.{Lyman,1982#40}. ItappearsthisestimateisbasedestimatedonanestimatedlogKOWfortheacidformratherthanthemeasuredvalueof-1.77forthecarboxylateform.
ThepKavaluesforthechemicalwereestimatedbyreferencetotheliteratureandhavean uncertaintyof ± 0.2pKaunits.
4.PURITYOFTHECHEMICALDegreeofPurity:Impurities: / 99.5%
0.5%
ChemicalName / CASNo. / Weight%
dicarboxy tetralin / - / 0.08
formylnaphthoicacid / - / 0.015
trimelliticacid / 528-44-9 / 0.001
naphthoicacid+methyl (NA) / - / 0.005
allothers / - / 0.02
noneoftheabovearelistedashavingtoxicorhazardouspropertiesinToxline
{ToxlineSilverPlatter,1996#27}.
Additives/Adjuvants:none
5.USE,VOLUMEANDFORMULATION
ThenotifiedchemicalwillnotbemanufacturedinAustralia. Itwillonlybeimportedinlimitedquantitiesfortrialdevelopmentstudies. Thenotifiedchemicalisamonomerusedtomanufacturepolyethylenenaphthalate(PEN)andpolyethylenephthalate(PET)polymersandcopolymers. PENandPET polymersareusedforpackagingofpharmaceuticalandcosmeticproducts,beverageandfoodcontainers,filmsforvariouspurposessuchassailing,photographicandelectricalapplications. Themaximumproportionofthenotifiedmonomerusedinthepolymersandcopolymerswillbelessthan8%. Thelevelofresidualmonomersincludingthenotifiedchemicalislow;theaverageislessthan210ppm.
Theestimatedimportvolumewillbenilforthefirstthreeyears,followedby0.4tonneforthefourthyear and1.3tonnesforthefifthyear.
6.OCCUPATIONALEXPOSURE
Thenotifiedchemicalwillbeimportedin22.7kgpolyethylenelinedfibredrums,tobesuppliedtoplasticmanufacturersfortrialproductruns.Waterside,warehouseandtransportworkerswillnotcomeintocontactwiththenotifiedmonomer,exceptintheeventofaccidentorleakingpackaging.
Dermalexposuremayoccurwhenworkerstransferthenotifiedchemicaltoaprocessvessel. Accidentaleyecontactmayalsooccuratthisstage.
Thenotifierstatesthatinhalational,dermalandocularexposuretothenotifiedchemicalwillbeminimisedduringpolymermanufacturesincetheseprocessesessentiallyoccurincontinuous,enclosedautomatedplants. Inaddition,theseprocesseswillbecarriedoutunderlocalexhaustandgeneralventilation.
Workersmayalsocomeintocontactwithplasticproductscontainingthenotifiedchemicalaftermanufacture. Dermalcontactwouldbeexpectedtobethemainrouteofexposure,forexamplewhentransferringrawpolymerforfurtherprocessingorloadingpolymerproductsintopackagesfordelivery. Sincethemonomerwillalmostentirelybeinthepolymerform,exposuretothenotifiedchemicalatthistimewouldbenegligible.
7.PUBLICEXPOSURE
Nopublicexposuretothenotifiedchemicalisexpectedtooccurduringitsdistributionorstorageatmanufacturingsites.
Disposalofanywastenotifiedchemicalbyincinerationortolandfillisnotexpectedtoresultinsignificantpublicexposure. Ifspillageofthenotifiedchemicalweretooccuritwouldbesweptupandplacedinsealedcontainersforre-useordisposal.
Thepublicisexpectedtohaveextensivecontactwithsomepolymerproductscontainingthenotifiedchemicalsuchasfoodandbeveragecontainers,andthe
packingmaterialusedforpharmaceuticalsandcosmetics. Howeverthepublicisunlikelytohavesignificantcontactwithotherproductscontainingthenotifiedchemical.
MigrationofthenotifiedchemicalfromPENplastictofourfoodsimulatingsolventshasbeenshowntooccur(completereferencetobeprovidedbynotifier).Water,oliveoiland15%and3%w/vaqueoussolutionsofethanolandaceticacid,respectivelywereusedassolventsundertestconditionsoftendaysat40oC (allsimulants)andtwohoursat70oC(aqueoussimulantsonly). Onlylowlevelsofthenotifiedchemicalweredetectedineachofthefoodsimulantstested(<0.05mgofthenotifiedchemicalperlitreofeachfoodsimulant1). Themeanlevelof notifiedchemicalinthePENplasticwasdeterminedtobe0.21mg.g-1.Giventhatmigrationofthenotifiedchemicalisnotsignificant,publicexposure,ifitweretooccur,wouldbeextremelylow. AlthoughnoinformationwasprovidedontheresiduallevelofthenotifiedchemicalinPEN/PETpolymersoritspotentialtomigratefromsuchpolymers,thenotifiedchemicalwillbeusedatalowerconcentrationandtherefore,thelevelofresidualnotifiedchemicalanditspotentialtomigratefromsuchplasticsisexpectedtobelower.
8.ENVIRONMENTALEXPOSURERelease
Nomanufacturingofthepolymerfromthenotifiedchemicalisenvisagedintheforeseeablefuture.Hence,itisanticipatedthatreleaseofthenotifiedchemicalwillbeminimal.Toprovideaworstcaseestimate,thefollowingreleasesofthenotifiedchemicalweregeneratedassumingallthenotifiedchemicalwaspolymerisedandusedintheproductionofarticlesfromthepolymer.
Residuesremaininginthedrumswillbedisposedofwithdrumstolandfill.Thenotifierhasestimatedthattheresidueremainingineachdrumwillbelessthan227g(<1%).Atthemaximumrateofimport,thiscorrespondstoamaximumof13kgperannumofchemical,whichwillbedisposedoftolandfillwithpackaging.
Releasetotheenvironmentofthepolymercontainingthenotifiedchemicalasaresultofmanufacturingintoarticlesisexpectedtobeminimal.Manufacturingtakesplaceinaclosedsystem.Thepolymerwillbefedautomaticallyintoextrusionandmouldingmachineryfromahopper.Scrapwillberegroundandreused.
Contaminatedpolymerscrapswillbedepositedintomunicipallandfillsorincinerated.Overall,suchwastestreamswouldaccountforatmost0.5%oftheannualimportofthechemical(i.e.amaximumof6.5kgofpolymerisedwastechemicalmaybedepositedinlandfillatthemaximumrateofimport).
Usedarticlescontainingthepolymerwillalsoeventuallybedepositedinlandfillsorrecycled.Theseaspectshavebeenaddressedinotherseparatenotifications(PLC/52andPLC/54).
Fate
Nodatafromstandardreadybiodegradationtestshavebeenprovidedbythenotifier.Thenotifierhasprovidedstudieswhichindicatethatthechemicalundergoesbiodegradationinwastewatertreatment.Measurementofthetotalorganiccarbon(TOC)oftheeffluentfromareactorsystemwhichwasdosedatratesupto500ppmperday,indicatedthatvirtuallyallthenotifiedchemicalwasremovedfromtheeffluent. Thetrialwasconductedoveratleasta3monthperiod.Thenotifierhaspresentedresultsofa"Neely100-DayPartitionPattern"whichpredictsthat94%wouldpartitiontowater,withsmallfractionstogroundandhydrosoil(~3%each),andvirtuallynonepresentinair.Thiswascalculatedfromchemicalpropertieswhichwereestimatedusingquantitativestructureactivityrelationship (QSAR)calculations {Montana StateUniversityInstitute for ProgramAnalysis, #41}includingawatersolubilityof1.3g.L-1whichisgreaterthan1000-foldthewatersolubilityestimatedfrommeasurement(~1.03mg.L-1at 20°C likelytobethefullyionisedform).
Shouldthepolymerisationofthenotifiedchemicaloccur,themajorityofthechemicalwouldnotbeexpectedtobereleasedtotheenvironmentuntilithasbeenpolymerisedandmouldedintofilms,sheetingorcontainers.Theenduse productswilleitherbedepositedinlandfillorrecycledattheendoftheirusefullife.Biodegradationofthepolymerscontainingthenotifiedchemicalisunlikely.
PolymerisationofthenotifiedchemicalwouldproducepolymerswhichareanalogoustoPET,andtherefore,wouldbeexpectedtoreplacePETin someapplications.Assuch,itisanticipatedthatitwillbecomepartofthePETwastestreamwhichaccountsforapproximately0.6%ofthedomesticwastestream
{PlanetArk,1997#42}. ThecompanyhasestimatedthatthecurrentrateofrecyclingofPETis30%Australiawidereaching50%incapitalcities.ThisisinaccordwithfigurespublishedbyPlanetArk.In199530%ofthePETwastestreamwasrecycledAustraliawide(~15000tonnesofPET).ThefigurewashigherinSydney whereit reached 53% {Planet Ark,1997 #42}. Itisanticipated that therecyclingratesofthepolymerscontainingthenotifiedchemicalwillbesimilartothatofPET.
9.EVALUATIONOFTOXICOLOGICALDATA
9.1AcuteToxicity
Summaryoftheacutetoxicityof2,6-naphthalenedicarboxylicacid
TestSpeciesOutcomeReference
acute oral toxicityratLD505000mg.kg-1{Johnson,
1991#67}
acutedermaltoxicity
rabbitLD502000mg.kg-1{Johnson,
1991#69}
inhalation toxicityrat4h LC50 1.23 mg.L-1{Ledbetter,
1988#46}
skinirritationrabbitslightirritant*{Johnson,
1991#68}
eye irritationrabbitslightirritant{Johnson,
1991#70}
skinsensitisationguineapignotasensitiser{Edgar,1997
#78}
*summaryonly
9.1.1OralToxicity{Johnson,1991#67}Species/strain:rat/unknownNumber/sexofanimals: 5 per sexObservationperiod: unknown
Methodofadministration:gavage,doseof5g.kg-1,preparedasa33%
(w/v)aqueoussuspension
Clinicalobservations:none
Mortality:nil
Morphologicalfindings:none
Testmethod:inaccordancewithUSFoodandDrugAdministration(FDA)Good LaboratoryPractice (GLP),protocol not identified
LD50:5000mg.kg-1`
Result:thenotifiedchemicalwasoflowacuteoraltoxicitytoratsinalimittest
9.1.2DermalToxicity{Johnson,1991#69}
Species/strain:rabbit/NewZealandWhite
Number/sexofanimals:5male/sex
Observationperiod:14 days
Methodofadministration:2g.kg-1appliedtomoistenedshavedbacks
for24hours(occluded)thenremovedandsitewashedwith0.9%salinesolution
Clinicalobservations:mildtransientdermalirritation(erythema)in
tworabbitsfollowingunwrapping
Mortality:nil
Morphologicalfindings:onefemalerabbithadredareasonlungsat
necropsy,allothersnormal
Testmethod:inaccordancewithUSFoodandDrugAdministration(FDA)Good LaboratoryPractice (GLP),protocol not identified
LD50:2000mg.kg-1
Result:thenotifiedchemicalwasoflowacutedermaltoxicityinrabbits
9.1.3InhalationToxicity{Ledbetter,1988#46}Species/strain:rat/Sprague-DawleyNumber/sexofanimals: 5males/sexObservationperiod: 14 days
Methodofadministration:ratsexposedtoaparticulateaerosolfor4
hourswithnoseonlyexposure;timeweightedaverage(TWA)was2.25mg.L-1with54.6%ofparticles10m,thereforeactualrespirableconcentrationwas1.23mg.L-1
Clinicalobservations:inguinalareawassoiled,animalswerecold
tothe touch for approximately2 hours afterexposure,rednessaroundnose;meanbodyweightsincreasedduringstudy
Mortality:nil
Morphologicalfindings:atnecropsy2malesandonefemalerathad
focionlungsandonemalehadredfocionthethymus
Testmethod:notstated
LC50:1.23mg.L-1
Result:thenotifiedchemicalwasoflowacuteinhalationaltoxicityin rats
9.1.4SkinIrritation{Johnson,1991#68}
Species/strain:rabbit/NewZealandWhiteNumber/sexofanimals: 3/sexnotspecifiedObservationperiod: 72hours
Methodofadministration:0.5 g.kg-1appliedtomoistenedshavedbacks
for24hours(occluded)thenremovedandsitewashedwithsalinesolution
Draizescores{Draize,1959
#4}:
rangedfrom0-8.0at48hours,primarydermalirritationscorewas0.2
Testmethod:notspecified
Result:slightskinirritantinrabbits
9.1.5EyeIrritation{Johnson,1991#70}
Species/strain:rabbitstrainnotspecifiedNumber/sexofanimals: 3/sexnotspecifiedObservationperiod: 72hours
Methodofadministration:0.1gintotherightconjunctivalsacofone eyeofeachanimal
Draizescores{Draize,1959#4}ofunirrigatedeyes:
TimeafterinstillationAnimal1day2 days3 days
Conjunctiva
rccdderccdderccdde
1 / 1 / 1 / 0 / 0 / 0 / 0 / 0 / 0 / 02 / 2 / 3 / 1 / 1 / 1 / 0 / 0 / 0 / 0
3 / 1 / 1 / 0 / 1 / 0 / 0 / 1 / 0 / 0
1seeAttachment1forDraizescales
c rednessd chemosise discharge
alliridalandcornealscoreswerezero
Testmethod:notspecified
Result:slighteyeirritantinrabbits
9.1.6SkinSensitisation{Edgar,1997#78}
Species/strain:guineapig/Dunkin-Hartley
Numberofanimals:10controls/20testanimals
Inductionprocedure:day1-eachanimalwastreatedwith0.5mL
of75%(topicalapplicationtotheleftflank) ofthenotifiedchemicalinsteriledistilledwater;patchesweresecuredunderanocclusivewrapforsixhours,andthenremovedandcleanedwithsteriliseddistilledwater;
theprocedurewasrepeatedonceeachweekforthreeconsecutiveweeks.
Challengeprocedure:thirteendaysafterthefinal induction
application,0.5mLofa75%solutionofthenotifiedchemicalwasappliedtotherightflank,andheldwithocclusivewrap. Patcheswereremovedaftersixhoursandcleanedwithsteriliseddistilledwater.
Challengeoutcome:
Challengeconcentration
TestanimalsControlanimals
24hours*48hours*24hours48hours
75%0/200/200/100/10
* timeafterpatchremoval
** numberofanimalsexhibitingpositiveresponse
Testmethod:similartoOECDguidelines{OrganisationforEconomicCo-operationandDevelopment,1995-1996#15}
Result:thenotifiedchemicalwasnotaskinsensitiseringuineapigs
9.2RepeatedDoseToxicity{Johnson,1994#51}Species/strain:rat/Sprague-DawleyNumber/sexofanimals: 20/sex/group
Methodofadministration:administeredorally,admixedtothediet
Dose/Studyduration::2000,10000and50000ppmfor90days
Clinicalobservations:transientdiarrhoeainhighdoseanimals;
increasedfoodconsumptioninmiddleandhighdosemales
Clinicalchemistry/Haematology
no toxicologically significant effectswereobservedonclinicalchemistryorhaematologyparameters.
Histopathology:meanliverweightsweredecreasedinhighdosemaleshowevernomicroscopicchangeswereobserved;dilationofcaecumand/orcoloninmanyhighdoseanimals,insignificantdilationofthelumenofthecoloninsomeoftheseanimals
Testmethod:inaccordancewithUSFoodandDrugAdministration(FDA),GoodLaboratoryPractice (GLP),protocol not identified
Result:notarget organidentified;lowtoxicityfollowingrepeatdoses
9.3Genotoxicity
9.3.1SalmonellatyphimuriumReverseMutationAssay{San,1991#53}Strains: TA98,TA100,TA1535,TA1537,TA1538Concentrationrange: 667-10000g/platewithorwithoutratliver
S9fraction,dosepreparedinsolutionof
dimethylsulphoxide(DMSO)
Testmethod:similartoOECDguidelines{OrganisationforEconomicCo-operationandDevelopment,1995-1996#15}
Result:thenotifiedchemicalwasnotmutagenicinthissystemwithorwithoutmetabolicactivation
9.3.2.1Hypoxanthine-GuaninePhosphoribosylTransferase(HGPRT)MutationAssaywithChineseHamsterOvary(CHO)Cells{Jacobson-Kram,1991
#77}
Cellline:CHO-K1-BH4
Doses:685,342.5,171.3,85.7,42.9g/ml withorwithoutratliverS9fraction;positivecontrols-ethylmethanesulphonateinnon-activatedtests andbenzo(a)pyreneinactivated tests
Testmethod:inaccordancewithOECDguidelines
{OrganisationforEconomicCo-operationandDevelopment,1995-1996#15}
Result:thenotifiedchemicalwasnotmutagenicinthistestsystem;untreatedandpositivecontrolsgaveappropriateresponses
9.3.2.2CHOChromosomalAberrationAssayinvitro{Leddy, 1995#55}
Cellline:ChineseHamster Ovary
Doses:2000,1000,500,250,125g/mlwithorwithout ratliverS9fraction; vehicle controls,positivecontrols-cyclophosphamideandmethylmethanesulphonate
Testmethod:inaccordancewithOECDguidelines
{OrganisationforEconomicCo-operationandDevelopment,1995-1996#15}
Result:slightprecipitationwasobservedat1000and2000g.mL-1;somecytotoxicity at thesedoses;moderateincreaseinpolyploidyat
2 000g.mL-1withmetabolicactivation,someindicationthatthiswasdoserelated;the
1 000g/mL-1sampleindicatedalevelofclastogenesisthatishigherthancontrolsbutnotatthelevelofsignificancedemonstratedinthe2000g.mL-1test;thereforethechemicalisweaklyclastogenicinthissystem;“weakly”indicating5-10%aberrantcellsexcludinggaps;positivecontrolsgaveappropriateresponse;vehiclecontrolshadlevelsofaberrationswithinthe95%confidencelimitsofthehistoricalnegativecontroldata
9.3.2.3CHOChromosomalAberrationAssayinvitro{Putman,1991 #57}
Cellline:ChineseHamster Ovary
Doses:714,357,179,89.5g.mL-1with orwithout ratliverS9fraction;doseselectiondictatedbysolventsolubility;solventDMSO; positivecontrols-cyclophosphamideandmethylmethanesulphonate
Testmethod:inaccordancewithOECDguidelines
{OrganisationforEconomicCo-operationandDevelopment,1995-1996#15}
Result:statisticallysignificantincrease(p<0.05)inchromosomalstructuralaberrationsat714and89.5g.mL-1in thenon-activatedtestsystem;noapparentdose-responserelationship(usingCochran-Armitagetest);positiveandnegativecontrolresultsacceptable;someevidenceofclastogenesis,howeverresultsinconclusive
9.4OverallAssessmentofToxicologicalData
ThenotifiedchemicalwasoflowacuteoraltoxicityintheratwithanLD50inexcessof5000mg.kg-1. A dermaltoxicity study in rabbits alsoindicatedlowtoxicity withanLD50inexcessof2000mg.kg-1.Arat inhalational toxicitystudy didnot result inanymortalityatdosesofupto1.23mg.L-1. Onautopsy,30%ofanimalsshowedlungfoci. Inarepeatdosestudyfeedingof90daysdurationtherewasno
significant evidenceofadverseeffectsatdosesupto50000ppm;the only effectswereminorandincludeddilationofthecaecumandcolon,andareductioninmeanliverweight.
Thenotifiedchemicalhassomepotentialforbothskinandeyeirritation. Studiesusingrabbitsgaveslighterythemainaskinstudyandslightconjunctivalrednessinaneyeirritationstudy. Inbothstudiesthelevelofirritationwasbelow thatrequiringahazardousclassificationaccordingtotheNationalOccupationalHealthandSafetyCommission’sCriteriaforClassifyingHazardousSubstances{NationalOccupationalHealthandSafetyCommission,1994#9}. Thenotifiedchemicalproducednoresponseinanon-adjuvantskinsensitisationstudyinguineapigsatchallengeconcentrationsupto75%..
AmutagenicitystudyusingSalmonellatyphimuriumwasnegativebothwithorwithoutmetabolicactivationusingDMSOasasolvent. AChineseHamsterovary(CHO)assay(HGPRTlocus)wasnegative,withorwithoutmetabolicactivation. ACHOcellstudytoassessclastogenicpotentialindicatedthatclastogenesiswasdosedependent;however,therewereproblemsevidentwithprecipitationofthetestchemical. Asecondstudygavesignificantlevelsofchromosomalaberrationswithoutmetabolicactivation,howeverthelevelofaberrationswerenotclearlydosedependent. Insummary,thenotifiedchemicalintwotestsystemsinvitrowasnotmutagenic,however,itwasweaklyclastogenicinonein vitrostudyandpossiblyclastogenicinanother.
10.ASSESSMENTOFENVIRONMENTALEFFECTS
Thenotifierhasprovidedestimatesofthe96hourLC50foraquaticspeciesbasedontheprimarymodeofaction(nonpolarnarcosis)andstructure-toxicityrelationshipswhicharebasedonquantitativestructure-activityrelationship(QSAR)calculationsdeveloped by Montana State University {Montana State UniversityInstituteforProgramAnalysis, #41}.Theseresultsaresummarisedbelow:
Test / Species / LC50(mg.L-1)acutetoxicity / bluegillsunfish / 55
acutetoxicity / fatheadminnow / 61
acutetoxicity / catfish / 52
acutetoxicity / rainbowtrout / 53
acutetoxicity / mosquitofish / 64
acutetoxicity / goldfish / 73
acutetoxicity / Daphniamagna / 52
Thesevaluesarestatedtohaveonlyafactor-of-tworeliabilityandwerecalculatedbasedonanestimatedwatersolubilityof1.3g.L-1.Additionally, according tothesuppliedoutputfromtheQSARSystem,thenotifiedchemicaldoesnotcontainstructuralfeatureswhicharecurrentlyregardedashighlytoxictoalgae.
ECOSAR {USEPA ECOSAR,1994 #43} estimatesthe fishacute 96 hourtoxicityas19mg.L-1anddaphnia48hourtoxicityas67mg.L-1. Italsopredictsachronicvalueforalgaeof1.5mg.L-1. Resultswerecalculatedonestimatedwatersolubilitiesof2.9g.L-1andusingstructureactivityrelationshipsdevelopedforesters.
Theabovedatasuggeststhatthenotifiedchemicalhasslighttoxicitytofishanddaphnia andmayhavemoderatetoxicityto algae.
11.ASSESSMENTOFENVIRONMENTALHAZARD
Disposalofthenotifiedchemicaltolandfillisunlikelytopresentahazardtotheenvironmentduetothelimitedrelease.Thenotifierhaspresentedaworstcaselandfillleachingconcentrationofthechemicalintheleachateof0.5mg.L-1(basedonthedissolutionof13kgwastechemicalinaleachatevolumeof2.529x107L inoneyear{Miller,1980#44}.Theestimatedconcentrationofthechemicalintheleachateisbelowtheestimatedwatersolubilityofthechemical.Incinerationofthenotifiedchemicalwillresultinitsdestruction,producingoxidesofcarbonandwater.
Shouldlocalpolymerisationofthenotifiedchemicaloccur,thechemicalwillbetrappedinthepolymermatrixoftheendusearticlesandcontaminatedpolymerscrapswhichwillultimatelybedisposedoftolandfill.Biodegradationofthearticlesisalsoconsideredunlikely.
Thelowenvironmentalexposureofthechemicalasaresultoftheproposeduse,togetherwithitsexpectednegligibleenvironmentaltoxicityoncepolymerised,indicatethattheoverallenvironmentalhazardshouldbenegligible.
12.ASSESSMENTOFPUBLICANDOCCUPATIONALHEALTHANDSAFETYEFFECTS
Thenotifiedchemicalisastable,non-volatile,whitecrystallinesolidwhichisoflowsolubilityinwater. Ithasamolecularweightof216.2whichindicatesthattransmissionacrossbiologicalmembranesispossible.Theoctanol-waterpartitioncoefficientdoesnotprecludebioaccumulation.
ThenotifiedchemicalwillnotbemanufacturedinAustraliabutwillbeimportedforplasticpolymerformulation. Transportworkerswouldonlybeexposedtothenotifiedchemicalintheunlikelyeventofanaccidentwhichcouldleadtoacutedermal,eyeandinhalationexposure. Workerexposureduringplasticproductionismostlikelytotakeplaceviainhalation.Basedonapossibilityofrelationshiptonaphthalene(showntohavesomelong-termlungtoxicityinanimals),chronicinhalationofthenotifiedchemicalmayhaveeffectsonthelungsofworkers.Thenotifierexpectsplasticmanufacturetoinvolveanautomatedplantwithlittleornodirectcontactofworkerswiththenotifiedchemical. Hencetheriskistoworkersislow.
ThenotifiedchemicalwillbepresentatlowlevelsinPENandPEN/PETpolymersandnosignificantmigrationofthenotifiedchemicalfromsuchpolymersisexpectedtooccur. TheuseofPENandPEN/PETplasticsinproductssuchasfoodandbeveragecontainersandaspackagingmaterialforpharmaceuticalsandcosmeticsisthereforenotexpectedtoresultinsignificantpublicexposuretothenotifiedchemical. Thereforetheproposeduseofthenotifiedchemicalpresentsnegligiblerisktopublicsafety.
Basedonthedescribedusepatternforthenotifiedchemical,andtheavailabletoxicologicalandphysico-chemicaldata,itisnotconsideredthatthenotifiedchemicalwillposeasignificantrisktoworkersexposedtothechemicalandisnotclassifiedashazardousaccordingtoWorksafeAustraliacriteria{NationalOccupationalHealthandSafetyCommission,1994#9}.
13.RECOMMENDATIONS
Tominimiseoccupationalexposureto2,6-naphthalenedicarboxylicacidthefollowingguidelinesandprecautionsshouldbeobserved:
- ItisgoodpracticetowearindustrialclothingwhichconformstothespecificationsdetailedinAustralianStandard(AS)2919{StandardsAustralia,1987#18}andoccupationalfootwearwhichconformstoAustralian andNewZealandStandard(AS/NZS)2210{StandardsAustralia/StandardsNewZealand,1994#24};
- Spillageofthenotifiedchemicalshouldbeavoided,spillagesshouldbecleaneduppromptlywithabsorbentswhichshouldthenbeputintocontainersfordisposal;
- Goodpersonalhygieneshouldbepractisedtominimisethepotentialforingestion;
- AcopyoftheMSDSshouldbeeasilyaccessibletoemployees.
- theoccupationalatmosphericlevelfordimethyl2,6-naphthalenedicarboxylicacidwouldbeadvisedtobemaintainedbelowthetimeweightedaverage(TWA)atmosphericexposurestandardassetfornaphthaleneof10ppm
{NationalOccupationalHealthandSafetyCommission,1995#14}
- Althoughthechemicalisnotclassifiedasflammable,andisnotnormallydust-generating,careshouldalsobetakentolimitatmosphericlevelsandpossiblestaticelectricitydischargesourcesintheworkenvironment. Allcarbonbasedpowderedsubstanceshavethepotentialforcombustionandexplosionandattentiontothispossibilityisadvisableintheworkenvironment.
Giventhattheproductscontainingthenotifiedpolymerwillbeusedaspackingmaterialforfoodandbeverages,thenotifiermayneedtocontacttheindividual
AustralianStatejurisdictions,asStatefoodlawsrequirethatmanufacturersmustensurethatmaterilasusedinfoodpackagingarefitforthatpurpose. Inaddition,giventhatthenotifiedpolymerwillalsobeusedtomanufacturepackagingmaterialforpharmaceuticals,thenotifiershouldsubmitanappropriateapplicationtotheMedicalDevicesSectionoftheConformityAssessmentBranchoftheTherapeuticGoodsAdministration.
14.MATERIALSAFETYDATASHEET
TheMSDSforthenotifiedchemicalwasprovidedinaccordancewiththeNationalCode of Practice for the Preparationof Material Safety Data Sheets{NationalOccupationalHealthandSafetyCommission,1994#13}.
ThisMSDSwasprovidedbytheapplicantaspartofthenotificationstatement. It isreproducedhereasamatterofpublicrecord. Theaccuracyofthis informationremainstheresponsibilityoftheapplicant.
15.REQUIREMENTSFORSECONDARYNOTIFICATION
SecondarynotificationunderSection64oftheActwillberequiredifthemethodofusechangesinsuchawayastogreatlyincreasetheenvironmentalexposureofthenotifiedchemical,orifadditionalinformationbecomesavailableonadverseenvironmentaleffectsofthechemical. Ecotoxicityresultsforfish,daphnia andalgaewouldberequiredtoconfirmtheQSARestimatesshouldmoresignificantexposureoftheaquaticcompartmentbe expected. Alternatively, QSAR estimatesusingthecorrectwatersolubilityfortheacidshouldbeprovided.
16.REFERENCES
1.SyracuseResearchCorporation1997,LogKowProgram,Internetaddress;
2.Lyman, W., Potts, RG, Magil,GC 1982, User's Guide Chemest- A ProgramforChemical PropertyEstimation, ,Arthur D.Little Inc,Aciorn ParkCambridgeMA.
3.ToxlineSilverPlatter 1996,ToxlineSilverPlatterCD-ROMdatabase:January1994-June1996,SilverPlatterInternational,N.V.
4.MontanaStateUniversityInstituteforProgramAnalysis,QSARSystem;AStructure-ActivityBasedChemicalModellingandInformationSystem,TDSNumericaTM, TechnicalDatabaseServicesIncorporated, New York.
5.PlanetArk 1997,TheplanetArkRecyclingReport,
6.Johnson,W.1991, Acuteoraltoxicitystudyof2,6-napthalenedicarboxylicacid(2,6-NDA)inrats, Projectno.,1659,Amoco Corporation,Chicago, Il,USA.
7.Johnson,W.1991, Acutedermaltoxicitystudyof2,6-napthalenedicarboxylicacid(2,6-NDA)inrabbits,Project no.,1660, IITResearchInstitute,Chicago,Il,USA.
8.Ledbetter, A. 1988,Acuteinhalationtoxicitystudyof 2,6-naphthalenedicarboxylicacidinrats,Projectno., 1227,IITResearch Institute,Chicago,Il,USA.
9.Johnson,W.1991, Abbreviatedacutedermalirritancy/corrosivitystudyof2,6-naphthalenedicarboxylicacid(2,6-NDA)inrabbits,Projectno.,1658,IITResearchInstitute,Chicago,Il,USA.
10.Johnson,W.1991, Abbreviatedprimaryeyeirritationstudyof2,6-naphthalenedicarboxylicacid(2,6-NDA)inrabbits,Projectno.,1657,IITResearchInstitute,Chicago,Il,USA.
11.Edgar,F. 1997,2,6-NapthaleneDicarboxylicAcidBuehlerSensitisationTest in Guinea Pigs,Project no., 15070, Inveresk Research, Tranet.
12.Draize,J.H.1959,'AppraisaloftheSafetyofChemicalsinFoods,DrugsandCosmetics',AssociationofFoodandDrugOfficials oftheUS,vol.49,pp.2-56.
13.OrganisationforEconomicCo-operationandDevelopment1995-1996,
OECDGuidelinesfortheTestingofChemicalsonCD-Rom,OECD,Paris.
14.Johnson,W.1994,90-dayoral(diet)toxicitystudyof2,6-naphthalenedicarboxylicacid(2,6-NDA)inrats,Projectno.,ProjectNo. L08518,IITResearchInstitute,Chicago,Il,USA.
15.San,R.H.C.,Wagner,V.O.1991,Salmonella/mammalianmicrosomeplateincorporationmutagenicityassay(Amestest)withaconfirmatoryassay,Project no., T9571.501014,Microbiological Associates, Inc., Rockville, USA.
16.Jacobson-Kram,D.1991, CHO/HGPRTmutationassaywithconfirmation,Projectno.,T9571.332001, MicrobiologicalAssociatesInc.,Rockville,MD,USA.
17.Leddy,I.A.,Innes,D.C.1995,2,6-napthalenedicarboxylicacidchromosommalaberrationassaywithChinesehamsterovarycellsinvitro.,Projectno.,10934,InvereskResearchInternational,Tranent, Scotland.
18.Putman,D.L.,Morris,M.J.1991,ChromosomeaberrationsinChineseHamsterOvary(CHO)cells, Projectno.,T9571.337,MicrobiologicalAssociates,Inc.,Rockville,USA.
19.NationalOccupationalHealthandSafetyCommission1994,ApprovedCriteriaforClassifyingHazardousSubstances[NOHSC:1008(1994)],AustralianGovernmentPublishingService,Canberra.
20.USEPAECOSAR1994,AComputerProgramfoEstimatingtheEcotoxicityofIndustrialChemicalsBasedonStructureActivityRelationships,United States Environment Protection Agency. EPA/748/R93/002, Washington DC.
21.Miller,D.W.1980,WasteDisposalEffectsonGroundwater:AComprehensiveSurveyoftheOccurrence andControlofGroundwaterContaminationResultingfromWasteDisposalPractices,PremierPressBerkleyCalifornia.
22.StandardsAustralia1987,AustralianStandard2919-1987,IndustrialClothing,StandardsAssociationofAustralia, Sydney.
23.StandardsAustralia/StandardsNewZealand1994,Australian/NewZealandStandard2210-1994,OccupationalProtectiveFootwear,StandardsAssociationofAustralia/StandardsAssociationofNewZealand,Sydney/Wellington.
24.NationalOccupationalHealthandSafetyCommission1995,'AdoptedNationalExposureStandardsforAtmosphericContaminantsintheOccupationalEnvironment,[NOHSC:1003(1995)]',inExposureStandardsforAtmosphericContaminantsintheOccupationalEnvironment:GuidanceNoteandNationalExposureStandards,AustralianGovernmentPublishingService, Canberra.
25.NationalOccupationalHealthandSafetyCommission1994,NationalCodeofPracticeforthePreparationofMaterialSafetyDataSheets[NOHSC:2011(1994)],AustralianGovernmentPublishingService,Canberra.
Attachment 1
TheDraizeScaleforevaluationofskinreactionsisasfollows:
ErythemaFormationRatingOedemaFormationRating
No erythema0Nooedema0
Veryslighterythema(barelyperceptible)
1Veryslightoedema(barely1
perceptible)
Well-definederythema2Slightoedema(edgesofareawell-2
definedbydefiniteraising
Moderatetosevereerythema3Moderateoedema(raisedapprox.13
mm)
Severeerythema(beetredness)4Severeoedema(raisedmorethan14
mmand extendingbeyondareaofexposure)
TheDraizescaleforevaluationofeyereactionsisasfollows:
CORNEA
OpacityRatingArea of CorneainvolvedRating
Noopacity0 none25%orless(notzero)1
Diffusearea,detailsof irisclearlyvisible
Easilyvisibletranslucentareas,detailsofirisslightlyobscure
1slight25%to50%2
2mild50%to75%3
Opalescentareas,nodetailsofirisvisible,sizeofpupilbarelydiscernible
3
moderate
Greaterthan75%4
Opaque,irisinvisible4severe
CONJUNCTIVAERedness / Rating / Chemosis / Rating / Discharge / Rating
Vesselsnormal / 0 none / No swelling / 0 none / No discharge / 0 none
Vesselsdefinitely / 1 / Anyswellingabove / 1slight / Anyamountdifferent / 1slight
injectedabovenormal / slight / normal / fromnormal
Morediffuse,deeper / 2mod. / Obviousswelling / 2mild / Discharge with / 2mod.
crimsonredwith / withpartialeversion / moisteningoflids
individualvesselsnot / oflids / andadjacenthairs
easilydiscernible / Swellingwithlids / 3mod. / Discharge with / 3
Diffusebeefyred / 3 / half-closed / moisteningoflids / severe
severe / Swellingwithlids / 4 / andhairsandconsiderablearea
half-closedto
completelyclosed / severe / around eye
IRIS
ValuesRating
Normal0 none
Foldsabovenormal,congestion,swelling,circumcornealinjection,irisreactstolight1slightNoreactiontolight,haemorrhage,grossdestruction 2severe