File No: NA/635October 1999
NATIONALINDUSTRIALCHEMICALSNOTIFICATIONAND ASSESSMENTSCHEME
FULLPUBLICREPORT
2-cyclohexyl propanal
ThisAssessmenthasbeencompiledinaccordancewiththeprovisionsoftheIndustrialChemicals(NotificationandAssessment)Act1989(theAct)andRegulations.ThislegislationisanActoftheCommonwealthofAustralia.TheNationalIndustrialChemicalsNotificationandAssessmentScheme(NICNAS)isadministeredbytheNationalOccupationalHealthandSafetyCommissionwhichalsoconductstheoccupationalhealthsafetyassessment.TheassessmentofenvironmentalhazardisconductedbytheDepartmentoftheEnvironmentandtheassessmentofpublichealthisconducted bythe Department of Health and Aged Care.
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Chemicals Notification and Assessment
FULL PUBLIC REPORT
27 October, 2000
NA/635Page 1 of 24
NA/635
FULLPUBLICREPORT
2-cyclohexyl propanal
1.APPLICANT
Kao(Australia)MarketingPtyLtdof103YerrickRoadLAKEMBANSW2195hassubmittedastandardnotificationstatementinsupportoftheirapplicationforanassessmentcertificate for 2-cyclohexylpropanal.
2.IDENTITY OFTHE CHEMICAL
ChemicalName:2-cyclohexyl propanal
ChemicalAbstracts Service
(CAS) Registry No.:2109-22-00
Other Names:PollenalII
Trade Name:PollenalII
Molecular Formula:StructuralFormula:
C9H16O
Molecular Weight:
140.2
MethodofDetection
and Determination:ultraviolet-visible (UV/Vis), infrared (IR), nuclear
magnetic resonance (NMR) and mass spectroscopy;gasliquid chromatography(GLC)
SpectralData:UV/Vis: the notified chemical in ethanol exhibited anabsorbance peak at 220 nm
IR: the 10 strongest peaks were 2 926, 2 853, 2 697,
1 725, 1 449, 1 399, 1 375, 1 001, 889 and 401 cm-1;
the peak at 2 926 was ascribed to CH, that at 2 697 toCH(C=O) and that at 1 725 to C=O
NMR:1H-NMR was provided
Comments on Chemical Identity
The notified chemical is a well defined simple aldehyde containingacyclohexylmoiety. Thenewchemicalalsocontains up to 4%of unidentifiedimpurities.
The notifier provided comprehensive spectroscopic data -IR, UV/Vis, NMR and massspectroscopy- on the new chemical which maybe used to identifythe material.AGLC alsoaccompanied the notification.
3.PHYSICALAND CHEMICALPROPERTIESAppearance at 20°C
and 101.3 kPa:clear colourless, non-viscous liquid
Boiling Point:196.5-200.0°C at 1025 mbar
Specific Gravity:0.915
Vapour Pressure:0.0817 0.0065 kPa at 25°C
Water Solubility:423 mg/Lat 20°C
Henry’s Law Constant:27.04 Pa/m3/mole - see notes below.
PartitionCo-efficient
(n-octanol/water):logPow= 2.95 at 20C - see notes below
Hydrolysis as a Function
ofpH:no significanthydrolysis at pH 4 and 7, some hydrolysisat pH 9- see notes below.
Adsorption/Desorption:logKoc= 2.49 byQSAR calculations – see notes below
DissociationConstant:no data provided - see notes below
Surface Tension:notsurface active - see notes below.
Fat Solubility:totallymiscible - see notesbelow.
FlashPoint:91°C (closed cup)
Flammability:not flammableAutoignitionTemperature:188°CExplosive Properties: not explosive
Comments on Physico-ChemicalProperties
Watersolubilitywasdeterminedbystirringanexcessofthetestsubstancewith100mLofdistilledwater at 30 oCfor 1, 2 and 3 days,equilibratingfor1dayat20C,thenseparating theaqueousandnonaqueouslayersbycentrifugation.Thecontentofthenewchemicalintheaqueousphasewasthendetermined bygaschromatography.Therewaslittledifferencebetweentheresultsforthosesolutionspreparedbystirringfor1,2or3dayspriortoequilibration(solubilityat20oCwasdeterminedas432,432and405mg/L,respectively),whichindicate that the reported solubilityis reliable.
TheHenry’sLawconstantwasdeterminedfromthemolecularweight,measuredvapourpressureandwatersolubilityusingtheequation-H=MW(g/mole)xVapourPressure(Pa)/Water solubility(g/L).
Thedegreeofhydrolysiswasdeterminedat50oCatpH4,7and9overa5daytestperiod.After2.4hoursthedegreeofhydrolysiswasrespectively0.7%,1.8%,and10.9%,andafter5days9.5%,10.5%and61.9%.AlthoughhydrolysisisslowatpH4and7,itissignificantlyhigheratpH9.However,theresultsindicateahalf-lifeofbetweenonedayandoneyearforthechemicalat25oCandpH9,andgreaterthanoneyearatpH4and7.Consequentlythecompoundisnotexpectedtoexhibitsignificanthydrolysisunderambientenvironmentalconditions.
Then-octanol/waterpartitioncoefficientwasdeterminedusingtheshakeflaskmethod,withanalysesofboththeaqueousandorganicphasesperformedbygaschromatography.ThedeterminedvalueofLogPowindicatesthenewchemicalhashighaffinityforhydrocarbon-likeenvironments.Massbalancecalculationsonthequantitiesofnewchemicalpartitionedintothen-octanolandwaterphasesgaverecoveriesinexcessof96.8%,whichindicatesthatthe method used was appropriate for this determination, and the overall result is reliable.
LogKocwascalculatedfrom the value ofLogPowusingtherelationshipLogKoc=0.81xLogPow+0.10.Thisrelationshipisappropriateforpredominantlyhydrophobiccompounds.ThevalueforLogKocof2.49indicatesthatthechemicalmaypartitionintotheorganiccomponentofsoilsandsediments,andbecomeassociatedwiththesematerials.However,this tendencymaybe reduced because of the highwater solubility.
Thecompoundcontainsnofunctionalitiescapableofreadilydissociatinginaqueousmedia.The notifier indicated that dissociation constant data were not applicable.
Thenewchemicaliscompletelymiscibleinfatat37C(experimentalreportsubmitted),whichisinaccordwiththepredominantlyhydrocarbonnatureofthematerialandthehighvalue for LogPow.
Thematerialismarginallysurfaceactive,withthesurfacetension(Method84/449/EEC(A5)ofanaqueoussolutioncontainingapproximately90%ofthetestsubstancesaturationof60.6mN/m at 20.5oC (water = 72.66 mN/m).
Calculationsbasedonthemolecularstructureusingthequantitativestructureactivityrelationships(QSAR)oftheUSEnvironmentProtectionAgencyASTERdatabase(reference
2)furnishedthefollowingestimatesforenvironmentallyrelevantphysico-chemicalparameters.Wherecomparisonwithdatasuppliedbythenotifierispossible,theagreementisreasonable.
ASTER DATA (all calculatedusing QSAR)
PropertyQSAR estimate
Boiling Point:185C
Vapour Pressure:0.728 mm of Hg(90.05 Pa)
Water Solubility:374 mg/L
Henry’sConstant:35.9 Pa/m3/mole
log Kow:2.73
log Koc:2.82
Hydrolytic degradation halflife:hydrolysis is unlikely
4.PURITY OFTHE CHEMICAL
Degree ofPurity:Toxic or Hazardous / 98.6% (range: 95.0 – 99.9%)
Impurities:
Chemical Name / CAS No. / Weight %
2-cyclohexyl propionic acid / not provided / 1.0%
unknown / 4.0%
Additives/Adjuvants:
Chemical NameCAS No.Weight %
2,6-ditertiarybutyl4-hydroxytoluene128-37-0 0.05%
5.USE,VOLUMEAND FORMULATION
Thenotifiedchemicalisto be used as a fragrance enhancer in household, toiletryand
cosmetic products.Itwillbeimportedatarateof0.5tonnesinthefirstyearincreasingto1.7tonnes/year bythe year 2002.
Thenotifiedchemicalwillbeimportedinsealed,unbreakablelacqueredsteeldrumsof32or200 Lcapacitymixed with other ingredients.
Thenotifiedchemicalisblendedintoaformulatedperfume,whichisthenincorporatedintohousehold products at a level of approximately0.1%.
6.OCCUPATIONALEXPOSURE
Thenotifierstatesthatitwillneedonlyonewatersideworker,forklifttruckdriverandtruckdrivertohandleclosedcontainersofthenotifiedchemical.Duringtransportorstorageofdrumscontainingthenotifiedchemicaloccupationalexposuremayoccurintheeventofaccidental spillage.
Thechemical,inliquidform,iseithermanuallyorautomaticallychargedtoamixertobeblendedintoaformulatedperfumeataconcentrationof0.1–5%whichisthenautomaticallyfilledintocontainers.Thebatchsizeswerestatedtobe25kg,50kg,100kg,500kgor1tonne.Thenotifierstatesthatqualitycontroltesting(sampling,analysisandodourevaluation)takes2to3minutes/day/personoronepersonatotalof6to9minutes/day.Compounding(blending)whichiseitherautomatedormanual,involvesasingleworkerfor2to3minutes/day.Discharge(fillingofcontainers)isanautomatedprocesssaidtoinvolveoneworkerfor5minutesperday.Duringadditionofthenotifiedchemicaltothemixerforproductionoftheperfumeformulation,exposuretospillsispossible.Someexposuretotheformulationcouldoccurduringqualitycontroltesting.Thenotifierstatesthatcuffedbutylrubber gloves, goggles, plastic face shields, aprons and bootsarewornduringtheseprocesses.Thenotifieralsostatesthatthereshouldbelocalexhaustventilationinplaceandsplashprooffillingdevicestopreventcontactwiththenotifiedchemical.Themixingvesselsarestatedtoretain0.05%oftheformulation(maximum0.5kgperbatch)sothatexposuretosmallamounts of the chemical duringsolvent washingis possible.
Exposuretospillsispossibleduringadditionoftheperfumeformulationtootheringredientsfollowedbyblendingintohouseholdproductsanddispensingsuchproductsintocontainers.Localexhaustventilationisinplaceoverthemixingvessels.Theperfumeformulationisaddedtothemixingvesseleithermanuallyorautomaticallybyasingleworker.Fillingofcontainers,suchascartons,plasticbottles,plasticfilmisanautomaticormanualprocess.Thisisdoneatanumberofcustomersitesalthoughthedetailsarenotavailable.Theperfume in incorporated into household products at approximately0.1%.
7.PUBLIC EXPOSURE
Thenotifiedchemicalwillenterthepublicdomainashouseholdproduct(egdetergents,toiletries,cosmetics)containingthenotifiedchemicalatalowconcentration(approximately0.1%).Althoughthepublicwillmakedermalandinhalationalcontact,andpossiblyeyecontact(eg.whileusingshampooscontainingthenotifiedchemical)withthenotifiedchemical,exposureislikelytobenegligiblebecauseofthelowconcentrationofthenotified
chemicalintheproducts.Thepotentialforpublicexposuretothenotifiedchemicalduringtransport, reformulation and use or from disposal is assessed as negligible.
8.ENVIRONMENTALEXPOSURERelease
Thenewproductisusedtoprepareperfumeblends,whicharesubsequentlyincorporatedinto
soaps,detergents,fabricsoftenersandotherhouseholdproducts,andmaycontainbetween
0.04and0.23%ofthechemical.Thenotifierindicatedthattheseproductionactivitieswouldbeperformedbyanumberofdifferentcompanies.However,itisexpectedthatproductionwilltakeplaceinpurposeconstructedfacilities,andthenotifiermadethefollowingestimatesinrespectofreleasetotheenvironmentduringperfumeblendingandmanufactureofthefinalproducts.
Thenotifierindicatesthatduringblendingoftheperfumemixture,0.05%ofthe newchemicalislostthroughwashingoutthemixingvessels,andonanannualbasisthisamountstoamaximumlossof0.85kg.Itwasalsostatedthatmaterialreleasedintheformulatingplantsas a result of equipmentwashing(andpresumablyanyspillage) is sent with other wastetoon-sitetreatmentfacilitieswhichmayincludeunitoperationssuchasdissolvedairflotationandgranulatedcarbonfilters.Itisstatedinthesubmissionthat94%(annuallyaround0.80kg)ofthenewchemicalwouldberemovedfromthewastewaterbythistreatmentandbecomeincorporatedintothesolidwastestreamandincinerated.Thetreatedwastewater,containingtheremaining6%(annuallyaround50g)ofchemicalispresumablydischarged to the sewer systems.
Itwasindicatedinthesubmissionthatnoliquidwastestreamsareproducedduringproductionofthesoap,detergentandotherconsumerproductsintowhichtheperfumeblendisadded,butthataround0.01%ofthenewchemical(annually170g)maybelostasaconsequenceofsteamcleaningthemixingvesselsatproductchangeover.Presumablythiswouldalsobesenttothewatertreatmentplantwhere94%(annually160g)wouldbecomeincorporated in solid residuals and be incinerated.
Noreferencetothequantitiesofchemicallikelyto belost andreleasedas aresult ofaccidentalspillagewasmadeinthesubmission.However,thisassessmentestimatesthat1%oftotalimportquantitycouldbelostthroughaccident,whichamountstoanannualreleaseofaround 17 kg.If these spills arecleanedupwithwateranddivertedtowastewatertreatmentatthemanufacturingsitewhere94%ofthechemicalisremovedandincinerated,anestimated
1.0 kgof chemical could be released from the manufacturingsites to sewage.
Thenotifierstatedthattheemptysteeldrumsoftheimportedchemicalwouldbesentforrecycling.However, it is possible that the emptycontainerswouldbeplacedintolandfill,andalthoughnoestimatesoftheamountofresidualchemicalleftinthedrumswaspresentedintheapplication,thisassessmentestimatesthisat0.05%oftheimportquantity,oraround0.85kgper annum.
However,thenewchemicalisafragranceenhancerforuseindomesticcleaningproducts,andconsequentlyallwillbeeventuallyreleasedintotheenvironmentasaconsequenceof
normalproductusage.Itisexpectedthatthisreleasewouldbeprimarilytotheseweragesystem,althoughbecauseofthemeasuredvapourpressureof81.7Paat25oC,muchwouldbe expected to volatilise andenter the atmosphere.
Emptycontainersoftheconsumerproductsarelikelytocontainsomeresidualunusedproduct;thesepackageswouldbediscardedwithdomesticgarbageandbedisposedoftolandfill.
Fate
ThenotifierprovidedalaboratoryreportontheassessmentofthebiodegradationofthenotifiedchemicalconductedinaccordancewiththeOECDTestGuidelineTG301D(ClosedBottleTest).Theresultsofthistestindicated11%lossofinitialchemicaloxygendemand(COD)ofthetestmaterialafter28days,andaccordinglythenotifiedchemicalcannotbeclassed as readilybiodegradable.
Allthenewchemicalwilleventuallybereleasedintotheenvironment,andthemajoritycouldbeexpectedtobedischargedintoseweragesystems.However,oncereleasedinthismanner,the relativelyhighvapour pressure indicatesthatasignificantfractionwouldpartitionintotheatmosphere.TheSimpleTreatModel(EuropeanCommission1996Part2)maybeusedtoestimatepartitioningintodifferentcompartments,fortheproportionofchemicalwhichreaches the sewage treatment plant (ie is notvolatilisedorotherwisedestroyedduringpassagetotheplant).BasedonaHenry’sLawConstantof27.04Pa/m3/mole,aLogKowof2.95andthecompoundnotbeingbiodegradable,themodelindicatesthatthechemicalisexpectedtopartition into the air,water andsewer sludge compartmentsasfollows -
AIRWATERSEWERPLANT
SLUDGE 44%50% 6%
MackayLevel1calculationsfromtheASTERdatabase(USEnvironmetalProtectionAgency1998)indicatethatwhenreleasedtotheenvironmentthechemicalwouldpartitionintothevarious compartments as listed below –
Atmospheric compartment92.08%
Water compartment7.31%
Soil compartment0.31% Aquatic biota compartment0%
TheMackaymodelassumesanequilibriumisestablishedbetweenallphases.Intheenvironmentanequilibriumstatewillnotbereachedaschemicalwhichreachestheatmospherewillbeeffectivelyremovedfromthesystem(bydiffusionintotheatmosphereorblownawaybywind).Consideringtheassumptionsandapproximationsinherentinboththesemodels,particularlyinrespectofthesignificantlydifferentHenry’sLawConstantandpartitioncoefficientusedineachmodel,thedifferencebetweenthetwosetsofresultsisnotsurprising. Both methodologies indicate significant partitioningto the atmosphere.
Oncereleasedtotheatmosphereitisconsideredthatthechemicalwouldbequicklydecomposedthroughphotolyticallypromotedfreeradicalreactions.Hence,overtimethesediment/water andwater/airpartitioning willbedriventowardthelossofthechemicaltotheatmosphere.Intheatmosphereitislikelythatthesubstancewillberapidlydegradedthroughreactionwithhydroxylradicals(throughhydrogenabstractionmechanisms).AcalculationbasedonthemethodsdescribedinOECDEnvironmentalMonographsNo61indicatesthatinthetropospherethenewchemicalwouldreactwithinthismanner,witharateconstantestimatedas22.74x10-12cm3/molecule/sec.Rateconstantsofthisorderareindicativeoffastdegradation(OECDEnvironmentalMonographNo61),andthecompoundisnotexpected to persist in the atmosphere.
ThenewchemicalishydrophobicincharacterwithLogPow=2.95,andestimatedLogKoc=
2.49.Consequentlywhenreleasedintothesewersystemsomewouldbeexpected toassociatewiththeorganiccomponentoftheparticulatematterpresentintherawsewage,andeventuallybecomeincorporatedintosediments.Hereitwouldbeslowlydegradedthroughbiological and abiotic processes to water, carbon dioxide and methane.
Theresidualchemical,whichisdisposedoftolandfillwithinemptydrums,discardedconsumerpackagingorwithresidualsolidsderivedfromwatertreatmentattheproductionfacilities,wouldalsobeexpectedtovolatiliseandentertheatmosphere.However,somechemicalmayremainadsorbedtosoilparticles,andinthissituationwouldbeexpectedtobeslowlydestroyedbysimilarmechanismstothoseoperatinginsediments.Any wastematerialcontainingthenotifiedchemicalplacedintocompostfacilitiescouldalsobeexpectedtobedestroyedthrough aerobic and anaerobicbiologicaldegradationprocesses.Incinerationofthematerial would produce water vapour and oxides of carbon.
TheASTERcalculationsmentionedabovealsoestimateabioaccumulationfactorof58forthecompoundinfish(fatheadminnow).Thisisalowvalueforthisparameterindicatinglittlepotentialforbioaccumulation.Althoughthenewchemicalishydrophobic,itisvolatileandisconsequentlynotexpectedtohaveprolongedresidencetimesintheaquaticcompartmentor to bioaccumulate.
9.EVALUATION OFTOXICOLOGICALDATA
9.1Acute Toxicity
Summary ofthe acute toxicity of2-cyclohexyl propanal
TestSpeciesOutcomeReference
acute oral toxicityratLD505 000 mg/kgfor
males
LD502 000 mg/kgforfemales
(Allan, 1992a)
acute dermal toxicityratLD502 000 mg/kg(Allan, 1992b)
acute inhalationtoxicity
ratLC50 5.32 mg/L(Jackson, 1994)
skin irritationrabbitslight to moderate irritant(Liggett, 1992a)
eye irritationrabbitslight irritant(Liggett, 1992b)
skin sensitisationguinea pigsensitiser(Parcell, 1992)
9.1.1Oral Toxicity (Allan, 1992a)
Species/strain:rat/Sprague-Dawley
Number/sex of animals:5/sex(group 1)
5 females (group 2)
Dose:
5 000 mg/kg(group 1)
2 000 mg/kg(group 2)
Observation period:14 days
Method of administration:gavage
Clinical observations:piloerectionwasobservedinallratsandincreased
salivationinratstreatedwith5000mg/kgwithinfiveminutesofdosing;afterday1abnormalgaitwasobservedinallrats;hunchedposture,lethargy,decreasedrespiratoryrate,ptosisandpalloroftheextermitieswereobservedinratsdosedwith5000mg/kg;prostrationwasobservedinonedeadfemale;recoveryofrats,asjudgedbyexternalappearanceandbehaviour,wascomplete:byday2forratsdosedwith2000mg/kg;byday3forallbut one rat dosed at5000mg/kg;andday4foronefemaledosedat5000mg/kg;bodyweightgainwas not affected bytreatment
Mortality:2 females from group1
Morphological findings:none
Test method:Directive84/449/EEC(OJNo.L251)PartBMethodB.1(EuropeanEconomicCommunity,1984)
LD50:5 000 mg/kgfor males
2 000 mg/kgfor females
Result:thenotifiedchemicalwasofverylowacuteoraltoxicityin rats
9.1.2Dermal Toxicity (Allan, 1992b)
Species/strain:rat/Sprague-Dawley
Number/sex of animals:5/sex
Observation period:14 days
Method of administration:thenotifiedchemical,aviscousliquid,wasspread
evenlyoveranareaofapproximately25cm2andcovered with an occlusive dressingfor 24 hours
Clinical observations:nosigns of systemic reaction to treatment; well
definederythemainninerats,slighterythemainoneratandslightoedemainmaleratswereobserved on day2; all animals recovered byday5
Mortality:none
Morphological findings:none
Test method:Directive84/449/EEC(OJNo.L251)PartBMethodB.3(EuropeanEconomicCommunity,1984)
LD50:2 000 mg/kg
Result:the notified chemical was of low acute dermaltoxicityin rats
9.1.3Inhalation Toxicity (Jackson, 1994)
Species/strain:rat/Sprague-DawleyNumber/sex of animals:5/sex(test and control groups)Observation period: 14 days
Dose(Exposure Concentration)5.32 mg/L
Method of administration:snout onlyexposure to (liquid) aerosol (87%within
respirable range) for 4 hours
Clinical observations:asoiledappearanceofthefurwasnotedonday0
fortestandcontrolanimals;exaggeratedrespiratorymovements,staggeringgaitandpoorgroomingnoteduptoday3;brownstainingaroundthesnout,jawsandaroundtheeyeswerepersistentafterday3;foodconsumptionofthetestgroupslightlyreduced on day1
Mortality:none
Morphological findings:Test method: / none
OECDguidelineTG403(Organisationfor
EconomicCo-operationandDevelopment,1995-
1996)
LC50: / > 5.32 mg/L
Result: / the notified chemical was of very low acuteinhalation toxicityin rats
9.1.4 / Skin Irritation (Liggett, 1992a)
Species/strain: / rabbit/New Zealand White
Number/sex of animals: / 3/females
Observation period: / 12 days
Method of administration: / 0.5mLofthenotifiedchemicalappliedundera
625mm2 gauzepadunderocclusivedressingfor4 hours
Draize scores:(Draize, 1959)of unirrigated eyes
Timeaftertreatment(days)
Animal#
Erythema
*123456789
111222221a0a0a
21122222a1a0a0a
31122222a1a1a0a
Oedema
11111111100
21122221100
31122221110
seeAttachment1forDraizescalesa=sloughingofepidermis *=approximately30minutesafterremovalofthedressing
Test method:Directive84/449/EEC(OJNo.L251)PartBMethodB.4(EuropeanEconomicCommunity,1984)
Result:veryslighterythemawasobservedinallthreeanimals30minutesafterremovalofthedressing;well-definederythema wasseen in allthree animalsfromday2to6andcontinuedasveryslighterythemauptoday7andinoneanimaluptoday
8;veryslightoedemawasobservedinallthreeanimals30minutesafterremovalofthedressingwhichpersisteduptoday7inoneanimal;slightoedemawasobservedintwoanimalsfromday2to5andcontinuedasveryslightoedemauptoday7andday8(oneanimal);desquamationofthestratumcorneum(sloughing)wasseenin2animalsfromday6andinallthreeanimalsfromday7today10
thenotifiedchemicalwasamoderateskinirritantin rabbits
9.1.5Eye Irritation (Liggett, 1992b)
Species/strain:rabbit/New Zealand WhiteNumber/sex of animals: one male and two femalesObservation period: 7days
Method of administration:0.1 mL of the notified chemical into the
conjunctival sac of one eye
Test method:Directive84/449/EEC(OJNo.L251)PartBMethodB.5(EuropeanEconomicCommunity,1984)
Result:dullingofthecorneawasobservedin2animalsonehourafterinstillation;scatteredanddiffuseareasofcornealopacitywasobservedin2animalsonday1andpersisteduptoday3inoneanimal;noiridaleffectswereobserved;allrabbitsexhibitedmildtomoderaterednessandchemosisoftheconjunctiva1hrpost-instillationwhichpersistedtoday1or2;noothereffectswereseenup to 7 dayspost-instillation
the notified chemical was slight eye irritant inrabbits
9.1.6Skin Sensitisation(Parcell, 1992)
Species/strain:guinea pig/Dunkin-Hartley
Number of animals:20 test; 10 controls
Induction procedure:3pairsofintradermalinjectionsinthescapularregion as follows:
-Freund’s Complete Adjuvant (FCA)diluted 1:1 with water;
-notifiedchemical,10%(v/v)inAlembicol D
-notified chemical, 10% (v/v) in FCAand Alembicol D 1:1
sevendaysaftertheabovetreatment,topicalinductionwasperformedbyapplyinga8cm2filterpapersoakedwith0.4mLofthenotifiedchemicaltothesamescapularregionunderocclusivedressingfor48hours;controlanimalsweresimilarlytreated but without the notified chemical
Challenge procedure:14 days after topical induction, test and control
animalswerechallengedusingnotifiedchemical,at 75% and 40% (v/v) in Alembicol D
anteriorsiteontheflankofeachtestanimalwastreatedwith0.2mLofthenotifiedchemical,75%(v/v)inAlembicolDandtheposteriorsitewastreatedwith0.2mLofthenotifiedchemical,40%(v/v)solutioninAlembicolDunderocclusivedressingfor24hours;controlanimalsweresimilarlytreated but without the notified chemical
Challenge outcome:
Challenge
Test animalsControl animals
concentration24 hours*48 hours*24 hours48 hours
75% (v/v) inAlembicol
40% (v/v) inAlembicol
**20/2020/200/100/10
20/2019/200/100/10
* timeafterpatchremoval
**numberofanimalsexhibitingpositiveresponse
Challenge outcome:marked persistent erythema and oedema were
observedinalltestanimalonthechallengesitesat24 and 48 hours after patch removal
Test method:Directive84/449/EEC(OJNo.L251)PartBMethodB.6(EuropeanEconomicCommunity,1984)
Result:the notified chemical was a skin sensitiser in
guinea pigs
9.2Repeated Dose Toxicity (Edwards, 1992)
Species/strain:rat/Sprague-DawleyCrl:CD(SD)
Number/sex of animals:5/sex/group
Method of administration:thenotifiedchemicalincornoilwasadministered
bygavage
Dose/Study duration::control:0mg/kg/dayfor 28 days
low dose: / 15 / / mid dose: / 150 / /
highdose: / 1 000 / /
Water consumption:a relative increase in water consumption was
observedinhighdosegroupmales(12.6%)andfemales(24.5%);atlowerdosegroupsthiseffectwas not remarkable
Clinical observations:occasional salivation (with greater frequency in
males)inmiddoserats;salivationinhighdoseratswaspersistentfromday2;waddlinggaitwasobservedinhighdoseratsaccompaniedbyaslightlethargy;occasionalpilo-erectionandthinappearance observed in highdose females
Clinical
chemistry/Haematologyclinicalchemistry:statisticallysignificantincreases
inglobulinlevelsaccompaniedbyanincreaseintotalproteinlevelsinmales;adecreaseinglutamicoxaloacetictransaminase(GOT)inhigh dosegroup;relativeincreaseinglucoseinhighdosefemales;alltheabovechangesincomparisontohistoricalrangewasconsideredtobeincidental;athighdoseadecreaseinchloride(p<0.01)inbothmaleandfemales,whichinfemales,wasaccompaniedbyincreasedphosphorousions;two(2/5)individualchlorideionvaluesamongfemalesandone(1/5)amongmaleswereslightlybelowthebackgroundrangeandmayindicatetreatmentrelatedeffects
haematology:statisticallysignificantincreaseinthrombotesttimeandvariationinmean cellvolumewereobservedinhighdosemalesbutwerenotdosedependent;decreasedeosinophillevelsobservedinhighdosefemaleswerewithinthehistorical range
Body/Organ weights:statisticallysignificantreductioninmean
bodyweightgaininhighdosemales;infemalesastatisticallyincrease was observed atweek 2only;
significantlylowerabsolutespleenweightsobservedinhighdosemalesandsignificantlyincreasedabsoluteandrelativekidneyweightsobservedinhighdosefemales;itwasarguedthatthemajorityofindividualvalueswerewithinthehistorical backgroundrange
Macroscopic findings:smallprostatesandminimalcontentsin seminal
vesicles in highdose males
Histopathology:focaltubularbasophiliaand/orcorticalscarringofthekidneyisthehighdosegroupwereconsideredbackground events
Test method:Directive84/449/EEC(OJNo.L251)PartBMethodB.7(EuropeanEconomicCommunity,1984)
Result:thetargetorganwasidentifiedastheblood,withchangesjudgedtobeofminorimportanceandadaptiveinnature;thenoobservableeffectlevel(NOEL)wasjudgedtobe15 mg/kg/dayonthebasis of salivation in rats at mid and highdose.
9.3Genotoxicity
9.3.1Salmonella typhimuriumReverse Mutation Assay (Jones Kitching, 1992)Strains: TA 1535, TA 1537, TA 1538, TA 98 and TA 100Concentration range: 0, 1.5, 5, 15, 50 and 150 g/plate
Test method:OECD guideline TG 471 (Organisation for
EconomicCo-operationandDevelopment,1995-1996)
Result:toxicityofthenotifiedchemicalwasnotedat500and5000g/platesothetopdoseinthemaintestwasreducedto150g/plate;noincreaseinthenumberofprototrophic(histidine-independent)backmutantswasobserveduptothetopdoseinthepresenceorabsenceofmetabolicactivationprovidedbyAroclor-inducedratlivermicrosomalpreparations(S9fraction);negativeandpositivecontrols gave the expected responses.
9.3.2Chromosomal Aberrations inHumanLympocytes in vitro(Jones et al., 1992)
Cells:lymphocytesfromhealthyhumanmaledonors,stimulatedto dividewith phytohaemagglutinin(PHA)
Treatmentregime:Aroclor1254-inducedratlivermicrosomal
preparations(S9fraction)wereaddedtoculturestreated for 16 hours with 0, 78.1, 321.5 and
425 g/mL orfor24hourswith0,19.5,312.5,625and5000g/mLofthenotifiedchemical;cultureswithout S9 fraction were treated at 0, 39.1, 156.3or
312.5 g/mLfor16hours;100cellswereexamined per dose level
Test method:OECDguidelineTG473(OrganisationforEconomicCo-operationandDevelopment,1995-1996)
Result:noincreaseinthenumberofchromosomalaberrations(eitherincludingorexcludinggaps)occurredinculturestreatedfor16hours(withorwithoutS9fraction)withthenotifiedchemicalrelativetocontrols;therewasastatisticallysignificantand reproducable increase in thenumberchromosomalaberrationsinculturestreatedat625
µg/mlfor24hoursinthepresenceofS9mix;inarepeattestof625µg/mlto5000µg/ml,therewasastatisticallysignificantincreaseinaberrantcellsatalldoses;positiveandnegativecontrolsgavetheexpected responses
thenotifiedchemicalwasclastogenicinhumanlymphocytes in the presence of S9 mix
9.3.3Micronucleus Assay in the Bone MarrowCells ofthe Mouse (Proudlock, 1992)
Species/strain:mice/CD-1
Number and sex of animals: 40/sex; 3groups
Doses:1920mg/kg;mitomycinC(12mg/kg)aspositivecontrolandaqueous1%methylcelluloseasnegative control
Method of administration:intragastric gavage;
Test method:similartoOECDguidelines474andEECannexVcommittee No. L251B
Result:noreductionintheratioofpolychromaticerythrocytesorsignificantincreaseinpolychromaticerythrocyteswereobservedatanydoselevelwhenobservedat24,48and72hourtimepoints
thenotifiedchemicalhasnotshownanyevidenceof causingchromosome damage
9.4Overall Assessment ofToxicological Data
Thenotifiedchemicalwasofverylowacuteoraltoxicity(males)andinhalationtoxicity(LD505 000mg/kgfororaltoxicity;LC505.32mg/Lforinhalationtoxicity)andoflowacuteoraltoxicity(females)anddermaltoxicity(LD502000mg/kg)inrats.Itwasaslighttomoderateskinirritantandaslighteyeirritantinrabbits. Itwas askin sensitiser in guinea pigs.
Clinical signs of persistent salivationwereobservedina28-dayoralrepeatdosestudyin rats at mid and highdoses.The NOELwas 15 mg/kg/day.
ThenotifiedchemicalwasclastogenicinhumanlymphocytesinthepresenceofS-9mixbutwasnotmutagenicinbacteriainvitroorinvivointhemousemicronucleusassay.Basedonthesetestresultsthenotifiedchemicalisconsideredtobeweaklygenotoxic.
Thenotifiedchemicalwouldbedeterminedtobeahazardoussubstanceaccordingtothe NOHSCApproved Criteria forClassifyingHazardousSubstancesintermsofskinsensitisationandpersistentskinirritation(NationalOccupationalHealthandSafetyCommission, 1994a).
10.ASSESSMENT OFENVIRONMENTALEFFECTS
Thenotifierprovidedthefollowingecotoxicitydatainsupportoftheirapplication.Theecotoxicitytests were performed in accordance withOECD TestGuidelines.
TestSpeciesResults(Measured)
AcuteToxicity[OECD 203]
Oncorhynchus mykiss
(Rainbow trout)
LC50(96 h) = 3.2 mg/LNOEC (96 h) = 1.5 mg/L
AcuteImmobilisation[OECD 202 Part 1]
Daphnia magnaEC50(48 h) = 1.2 mg/LNOEC(48 h) = 0.6 mg/L
Thetestsonrainbowtroutwereperformedusingsolutionsofthetestmaterialmadeupindechlorinatedwater.Stocksolutionsofthetestwereautomaticallydispensedintothe20Ltestvesselsatarateof0.35mL/h,whilethemediumitselfwascontinuouslyrenewedatapproximately118mL/min.Thetestswereconductedovera96hourperiodatacontrolledtemperatureof14oC.Fivesolutionsofthechemicalwithmeanmeasuredconcentrationsof0.8,1.5,2.8,4.8and9.0mg/Lweretested,togetherwithonecontrol.Solutionanalysiswasconductedbyextractionwithdichloromethanefollowedbygaschromatographicdeterminationoftheextractedtestchemicalonwatersamplestakenat0,24and96hoursaftercommencementofthetests.Themeasuredresultswere(withoneexception)alwayswithin 25% of the nominal concentrations.
Tenfishweretestedateachconcentration,andduringtheseteststhepHofthetestsolutionswasalwaysbetween7.1and7.2,whiledissolvedoxygenconcentrations(DOC)werealwaysbetween 10.1 and 10.3 mg/L.
Thetestsresultsindicatethatthenotifiedchemicalismoderatelytoxictotherainbowtroutwith a 96 hourLC50of3.2mg/LdeterminedusingthemethodofThompsonandWeil(1952).TheresponseslistedintherawdataweresuchthatProbitanalysiswasnotpossible,butthisassessment places the 96 hour LC50 between 2.8 and 4.8 mg/L.
Theacuteimmobilisationtestsondaphniawereperformedusingsolutionsofthetestmaterialmadeupindechlorinatedwater.Astocksolutionofthetestmaterial(containingTween80detergentandacetonetoassistsolubility)wasseriallydilutedandusedinastaticnonrenewalsystemovera48hourperiodatacontrolledtemperatureof21oC.Ninesolutionsofthechemicalwithnominalconcentrationsof0.32,0.58,1.0,1.8,3.2,5.8,10,18and32mg/Lweretested,togetherwithonecontrol.Solutionanalysiswasconductedonmediumsamplestaken at 0 and 48 hours, byextraction with dichloromethane followedbygaschromatographicdeterminationoftheextractedtestchemical.Therelevantmeasuredconcentrationswere0.6,2.1, 4.4 and 7.6 mg/L.
Tendaphniaweretestedinduplicateateachconcentration.DuringtheseteststhepHofthetestsolutionswasalwaysbetween7.1and7.2,whileDOClevels(measuredforthecontrolonly)werealwaysbetween8.0and8.9mg/L.Thecriterionfordecidingonimmobilisationwasiftheanimalswereunabletoswimaftergentleagitationofthetestvessel.Thetestsresultsindicatethatthenotifiedchemicalismoderatelytoxictodaphniawitha48hourEC50of 1.2 mg/Ldetermined usingthe method of Thompson and Weil (1952). Theresponseslistedin the raw data were such that Probit analysis wasnotpossible,butthisassessmentplacesthe48 hour EC50between 0.6 and 2.1 mg/L.
Thenotifierdidnotprovidelaboratoryreportsontheeffectofthechemicalondaphniareproductionoralgalgrowth,sincethesestudieshadnotbeenconducted.However,thisdeficiency was acknowledged and some calculated estimates comparing the Predicted
EnvironmentalConcentration(worstcasescenario)withPredictedNoEffectConcentration(taken as 1/1000 of the daphnia EC50) were presented.
TheQASRcalculationsoftheASTERdatabase(USEnvironmetalProtectionAgency1998)also furnished a predicted LC50= 8.7 mg/Lfor acute toxicityto Fathead minnow.
11.ASSESSMENT OFENVIRONMENTALHAZARD
Themajorityofthenewchemicalisaningredientofdomesticcleaningproductsandmostofthematerialwouldeventuallybereleasedintodomesticseweragesystemsasaconsequenceofproductuse.However,duetothevolatilityofthematerial,ahighproportionisexpectedtoenter the atmosphere.
Theecotoxicitydataindicatesthatthenewchemicalismoderatelytoxictotheaquatictestspecies.However,basedonmaximumestimatedannualimportsof1.7tonne,allofwhichiseventuallyreleasedtosewer,thedailyreleaseonanationwidebasisis8.2kg/day. Assuminganationalpopulationof18,000,000andthateachpersoncontributesanaverage150L/daytooverallsewageflows,thepredictedconcentrationinsewageeffluentonanationwidebasisisestimatedas1.7g/L.Whenreleasedtoreceivingwaterstheconcentrationisgenerallyunderstoodtobereducedbyafurtherfactorofatleast10,sothePredictedEnvironmentalConcentrationisaround0.17g/L.Thisisnearlyfourordersofmagnitudelessthanthedemonstratedchronictoxicitytothedaphnia(EC50=1.2mg/L),themostsensitivespeciesagainstwhich the new chemicalwas tested.
ThechemicalishydrophobicwithLogPow=2.95,indicatingsignificantaffinityfortheorganiccomponentofsoilsandsediments.TheSimpleTreatandMackayLevel1calculationsmentionedabovealsoindicatethatduetotherelativelyhighvapourpressuremuchofthechemicalwouldpartitionintotheatmosphereandbedestroyedby reactionswithhydroxyfreeradicals.Nevertheless,itislikelythatsomeofthechemicalwouldbecomeboundtosoilsandsediments,andhereisexpectedtobeslowlydegradedtowater,carbondioxideandmethanethroughbiologicalprocesses.Thesemechanismswouldoperatetocontinuouslyremovethechemicalfromtheaqueouscompartment,sooverallenvironmentalconcentrations would be unlikelyto increase with prolonged release of the chemical.
The above considerations indicate minimal hazardtotheenvironmentwhenthenewchemicalisusedasacomponentofdomesticproductsinthemannerindicatedbythenotifier.However,itshouldbeappreciatedthatthenewcompoundwillbeusedinperfumeformulationswithtwosimilarchemicals(NICNASsubmissionsNA/633andNA/634),whichwillbepresentintheproductsatsimilarlevels.Consequentlythesafetymarginforenvironmentalhazardwillbereducedbyafactorofapproximately10.AlgaeandchronicdaphniatestsareonlyavailableforthechemicaladdressedinthereportonNA/634,wherethechronictestshowsthatchemicalNA/634islesstoxicthantheacuteresultforeitherthepresent chemical or NA/633.
12.ASSESSMENTOFPUBLICANDOCCUPATIONALHEALTHANDSAFETYEFFECTS
Onthebasisofthesubmittedtoxicologicaldatathenotifiedchemicalisunlikelytoexhibitacuteorsubacutesystemictoxicity.However,itmaybeaslighttomoderateskinirritantandslighteyeirritant.Itisastrongskinsensitiserandisweaklygenotoxic.ThenotifiedchemicalwouldbeclassifiedashazardousaccordingtotheNOHSCApprovedCriteriaforClassifyingHazardousSubstancesintermsofskinsensitisationandpersistentskinirritation.ItwouldwarranttheriskphrasesR38IrritatingtoskinandR43Maycausesensitisationbyskin contact.The number and type of genotoxic studies conducted are insufficienttoconsidera hazardous substances classification for genetic effects.
Theriskofadversehealtheffectstoworkersinvolvedintransportandstorageisconsideredto be minimal except in thecaseofaccidentalspillage,wheretheremaybeaslightriskofeyeorskinirritationandastrongchanceofskinsensitisationifexposureisrepeated.Thereisariskofeyeorskinirritancyorskinsensitisationduringmanualadditionofthenotifiedchemical to vessels used for formulatingperfume for household products, duringsamplingforqualitycontrolpurposesandduringsystemmaintenance.Theriskoftheseeffectsislikely tobehighestduringhandlingoftheundilutedchemicalforexamplewhenaddingtomixingvessels.Theriskofirritationismuchreduced,buttherealpossibilityofskinsensitisation(andrespiratorysensitisation)remainsforworkershandlingtheformulatedperfume.Thenotifierstatesthattheconcentrationofthechemicalintheformulatedperfumeisupto5%,whichwouldbeahazardoussubstancebasedonskinsensitisation,wherethecutoffconcentrationis1%.Theriskofeyeorskinirritationduringautomaticpackagingislikelytobenegligiblehowever,giventhatthematerialisastrongsensitisersensitisingreactionsmaydevelopiftheexposuretothechemicaloccurs.Thenotifierstatesthatworkerswilluseorganicsolventresistantgloves,suchasbutylrubbergloves,andsafetyglasses;processeswilloccurunderlocalexhaustventilation.Itiscriticalthatallfeasiblestepsaretakentoreduce dermal and inhalation exposure to the notified chemical.
Thereisaslightriskofeyeorskinirritationandarealriskofsensitisationforworkersinvolvedinmanualadditionoftheperfumeformulationtovesselsusedtoblendhouseholdproducts.Oncetheenduseproductsaremixed,theriskofirritationandsensitisationresultingfromexposuretothenotifiedchemicalisverylowasitispresentinverysmallamounts (0.1%).
Workersconductingqualitycontroltesting,machinemaintenanceandpackagefillingwillbeatan equivalentrisk and need to take precautions to avoid contamination with the chemical.
Given thestrongsensitisingeffectsseeninexperimentalanimals,thisassessmentrecommendsthatworkerswhohavebecomesensitisedshouldnotcontinuetohandlethechemical in the workplace.
Althoughmembersofthepublicwillmakedermalandinhalationalcontactandpossibleeyecontactwiththenotifiedchemical,exposureislikelytobenegligiblebecauseofthelowconcentration of the notified chemicalinconsumerproducts(approximately0.1%).Althoughthenotifiedchemicalisaslighttomoderateskinirritant,aslighteyeirritant,askinsensitiserandisweaklygenotoxic,thesehazardsareunlikelytobesignificantbecauseofthelowconcentration of the notified chemical in the products.
13.MATERIALSAFETY DATA SHEET
TheMSDSforthenotifiedchemicalwasprovidedinaccordancewiththeNationalCodeofPracticeforthePreparationofMaterialSafetyDataSheets(NationalOccupationalHealthand SafetyCommission, 1994b).
ThisMSDSwasprovidedbytheapplicantaspartofthenotificationstatement.Itisreproducedhereasamatterofpublicrecord.Theaccuracyofthisinformationremainstheresponsibilityof the applicant.
14.RECOMMENDATIONS
Tominimiseoccupationalexposuretothenotifiedchemicalthefollowingguidelinesandprecautions should be observed:
- SafetygogglesshouldbeselectedandfittedinaccordancewithAustralianStandard(AS)1336(StandardsAustralia,1994)tocomplywithAustralian/NewZealandStandard (AS/NZS) 1337 (Standards Australia/Standards New Zealand, 1992);
- IndustrialclothingshouldconformtothespecificationsdetailedinAS2919(Standards Australia, 1987);
- ImpermeableglovesshouldconformtoAS/NZS2161.2(StandardsAustralia/Standards New Zealand, 1998);
- AlloccupationalfootwearshouldconformtoAS/NZS2210(StandardsAustralia/Standards New Zealand, 1994);
- Spillageofthenotifiedchemicalshouldbeavoided.Spillageshouldbecleaneduppromptlywith absorbents which should then be put into containers for disposal;
- Good personal hygiene should be practised to minimise the potential for ingestion;
- A copyof the MSDSshould be easilyaccessible to employees.
- Sensitised workers should not continue to handle the chemical in the workplace.
- ThenotifiedchemicalmayberecommendedtotheNationalOccupationalHealthandSafetyCommissionforconsiderationforinclusionintheNOHSCListofDesignatedHazardous Substances.
15.REQUIREMENTSFOR SECONDARY NOTIFICATION
UndertheAct,secondarynotificationofthenotifiedchemicalshallberequiredifanyofthecircumstancesstipulatedundersubsection64(2)oftheActarise.Also,ifannualimportsofthenewmaterialexceed7tonnes(fourtimesthepresentestimates),wewillrequirefulltestresultsandreportsontheeffectsofthechemicalondaphniareproductionandtheinhibitionof algalgrowth.
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