Acetaldehyde - C2H4O - PubChem

17/3/2015
NIH
acetaldehyde|C2H4OPubChem
U.S.NationalLibraryofMedicine
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SearchCompounds
CHEMISTRY
D A T A B A S E
acetaldehyde
Vendors
Pharmacology
Literature
Patents
Bioactivities
Alsoknownas:ethanal,aceticaldehyde,ethylaldehyde,aldehyde,Acetaldehyd,75070
Molecular
MolecularWeight:
Formula:C2H4O 44.05256g/mol
InChIKey:
FDAUNII:
IKHGUXGNUITLKFUHFFFAOYSANGO1N1ZPR3B
Acolorless,flammableliquidusedinthemanufactureofaceticacid,perfumes,andflavors.Itis
alsoanintermediateinthemetabolismofalcohol.Ithasageneralnarcoticactionandalso
causesirritationofmucousmembranes.Largedosesmaycausedeathfromrespiratoryparalysis.
fromMeSH[10]
http://pubchem.ncbi.nlm.nih.gov/compound/acetaldehyde#section=ChemicalandPhysicalProperties
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Contents
1 2DStructure
2 3DConformer
3 Identification
4 ChemicalandPhysicalProperties
5 RelatedRecords
6 ChemicalVendors
7 PharmacologyandBiochemistry
8 UseandManufacturing
9 SafetyandHazards
10 Toxicity
11 Literature
12 Patents
13 BiomolecularInteractionsandPathways
14 BiologicalTestResults
15 Classification
16 InformationSources
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1 2DStructure
Search
Download
GetImage
fromPubChem[9]http://pubchem.ncbi.nlm.nih.gov
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2 3DConformer
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Search
ShowHydrogens
ShowAtoms
Animate
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3 Identification
3.1 ComputedDescriptors
3.1.1 IUPACName
acetaldehyde
3.1.2 InChI
InChI=1S/C2H4O/c123/h2H,1H3
3.1.3 InChIKey
IKHGUXGNUITLKFUHFFFAOYSAN
3.1.4 CanonicalSMILES
CC=O
3.2 OtherIdentifiers
3.2.1 CAS
75070
fromEPAChemicalDataReport[2]http://www.epa.gov/cdr/
75070
fromNIOSHPocketGuide[4]http://www.cdc.gov/niosh/npg/npgd0001.html
75070
fromOSHAOccupationalChemicalDB[5]http://www.osha.gov/chemicaldata/chemResult.html?RecNo=570
3.2.2 ECNumber
2008368
fromILOICSC[3]http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=0009
2008368
fromECHA[6]http://echa.europa.eu/
3.2.3 ICSCNumber
0009
3.2.4 RTECSNumber
AB1925000
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AB1925000
3.2.5 UNNumber
1089
1089 fromOSHAOccupationalChemicalDB[5]http://www.osha.gov/chemicaldata/chemResult.html?RecNo=570
3.2.6 UNII
GO1N1ZPR3B
fromFDA/SPLIndexingdata[8]
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm377913.htm
3.2.7 Wikipedia
Acetaldehyde
fromWiki[7]http://en.wikipedia.org/wiki/Acetaldehyde
3.3 Synonyms
3.3.1 MeSHSynonyms
1. Acetaldehyde
2. Ethanal
fromMeSH[10]http://www.ncbi.nlm.nih.gov/mesh/68000079
3.3.2 DepositorSuppliedSynonyms
1. acetaldehyde
11. Aceticethanol
21. Acetaldehyd[German]
31. RCRAwasteno.U001
2. ethanal
12. acetaldehydes
22. ACETYLGROUP
32. Aldehydeacetique[French]
3. aceticaldehyde
13. ethaldehyde
23. CHEBI:15343
33. 1oxapropylene
4. ethylaldehyde
14. Acetaldehyde(natural)
24. Acetaldehydepolymerized
34. AI331167
5. aldehyde
15. Aldeideacetica
25. NCIC56326
35. FEMANo.2003
6. Acetaldehyd
16. Octowyaldehyd
26. NSC7594
36. Acetaldehyded4
7. 75070
17. Aldehydeacetique
27. Octowyaldehyd[Polish]
37. EINECS2008368
8. Acetylaldehyde
18. RCRAwastenumberU001
28. UNIIGO1N1ZPR3B
38. Acetaldehydesolution
9. ethanone
19. CCRIS1396
29. UN1089
39. acetoaldehyde
20. HSDB230
30. Aldeideacetica[Italian]
40. Acetaldeyde
10. Azetaldehyd
3.4 CreateDate
20040916
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4 ChemicalandPhysicalProperties
4.1 ComputedProperties
MolecularWeight
44.05256g/mol
MolecularFormula
C2H4O
XLogP3
0.3
HydrogenBondDonorCount
HydrogenBondAcceptorCount
RotatableBondCount
ExactMass
44.026215g/mol
MonoisotopicMass
44.026215g/mol
TopologicalPolarSurfaceArea
17.1A^2
HeavyAtomCount
FormalCharge
Complexity
10.3
IsotopeAtomCount
DefinedAtomStereocenterCount
UndefinedAtomStereocenterCount
DefinedBondStereocenterCount
UndefinedBondStereocenterCount
CovalentlyBondedUnitCount
1
4.2 ExperimentalProperties
4.2.1 PhysicalDescription
LiquidGasVapor
fromEPAChemicalDataReport[2]http://www.epa.gov/cdr/
GASORCOLOURLESSLIQUIDWITHPUNGENTODOUR.
Colorlessliquidorgas(above69F)withapungent,fruityodor.
Colorlessliquidorgas(above69F)withapungent,fruityodor.
4.2.2 Color
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Volatileliquidorgas
Lide,D.R.CRCHandbookofChemistryandPhysics88THEdition20072008.CRCPress,Taylor&Francis,BocaRaton,FL
2007,p.34
fromHSDB[1]http://toxnet.nlm.nih.gov/cgibin/sis/search/r?dbs+hsdb:@term+@rn+@rel+75070
Colorlessliquidorgas(above69degreesF)
NIOSH.NIOSHPocketGuidetoChemicalHazards&OtherDatabasesCDROM.DepartmentofHealth&HumanServices,
CentersforDiseasePrevention&Control.NationalInstituteforOccupationalSafety&Health.DHHS(NIOSH)PublicationNo.
2005151(2005)
4.2.3 Odor
Pungent,fruityodor
Lewis,R.J.Sr.Hawley'sCondensedChemicalDictionary15thEdition.JohnWiley&Sons,Inc.NewYork,NY2007.,p.5
4.2.4 BoilingPoint
20.1degC
2007,p.34
20.2C
69F
69F
4.2.5 MeltingPoint
123.37degC
2007,p.34
123C
190F
190F
4.2.6 FlashPoint
38.89degC(Closedcup)40degC(Opencup)
AmericanConferenceofGovernmentalIndustrialHygienists.DocumentationoftheTLV'sandBEI'swithOtherWorldWide
OccupationalExposureValues.CDROMCincinnati,OH4524016342007.
38C
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36F
36F
4.2.7 Solubility
Misciblewithethanol,ether,benzeneslightlysolubleinchloroform
2007,p.34
Misciblewithgasoline,solventnaphtha,toluene,xylene,turpentine,andacetone
Riddick,J.A.,W.B.Bunger,SakanoT.K.TechniquesofChemistry4thed.,VolumeII.OrganicSolvents.NewYork,NY:John
WileyandSons.,1985.,p.327
Misciblewithwater/1X10+6mg/Lat25degC/
Solubilityinwater:miscible
Miscible
4.2.8 Density
0.7834g/cucmat18degC
2007,p.34
Relativedensity(water=1):0.78 fromILOICSC[3]http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=0009
0.79
0.79 fromOSHAOccupationalChemicalDB[5]http://www.osha.gov/chemicaldata/chemResult.html?RecNo=570
4.2.9 VaporDensity
1.52(Air=1)
Gerhartz,W.(execed.).Ullmann'sEncyclopediaofIndustrialChemistry.5thed.VolA1:DeerfieldBeach,FL:VCHPublishers,
1985toPresent.,p.VA1:32(1985)
Relativevapourdensity(air=1):1.5
4.2.10 VaporPressure
902mmHgat25degC
Boublik,T.,Fried,V.,andHala,E.,TheVapourPressuresofPureSubstances.SecondRevisedEdition.Amsterdam:
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Elsevier,1984.,p.125
Vapourpressure,kPaat20C:101
740mmHg
740mmHg
4.2.11 LogP
logKow=0.34
TSCATS.ToxicSubstancesControlActTestSubmissionsDatabase.Manufacturersubmissions(4,8d,8e,FYI)tothe
USEPA.
0.63
4.2.12 AutoIgnition
347degF175degC
FireProtectionGuidetoHazardousMaterials.13ed.Quincy,MA:NationalFireProtectionAssociation,2002.,p.3259
185C
4.2.13 Decomposition
Decomposesabove400degCtoform...methane&carbonmonoxide.
IARC.MonographsontheEvaluationoftheCarcinogenicRiskofChemicalstoMan.Geneva:WorldHealthOrganization,
InternationalAgencyforResearchonCancer,1972PRESENT.(Multivolumework).Availableat:
http://monographs.iarc.fr/index.php,p.V36102(1985)
Whenheatedtodecompositionitemitsacridsmokeandfumes.
Lewis,R.J.Sr.(ed)Sax'sDangerousPropertiesofIndustrialMaterials.11thEdition.WileyInterscience,Wiley&Sons,Inc.
Hoboken,NJ.2004.,p.5
4.2.14 Viscosity
0.2456mPa.secat15degC(1.0mPa.sec=1.0cP)
4.2.15 HeatofCombustion
1166.37kJ/molat25degC(liquid)
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4.2.16 HeatofVaporization
26.11kJ/molat25degC
4.2.17 SurfaceTension
21.2mN/mat20degC(1.0mN/m=1.0dyn/cm)
KirkOthmerEncyclopediaofChemicalTechnology.4thed.Volumes1:NewYork,NY.JohnWileyandSons,1991Present.,
p.V1:95(1991)
4.2.18 Ionicity
10.22eV
10.22eV
4.2.19 Polymerization
Polymerizationmayoccurinpresenceofacidtracescausingexothermicreaction,increasedvesselpressure,fire,&
explosion.
InternationalLabourOffice.EncyclopediaofOccupationalHealthandSafety.VolumesIandII.NewYork:McGrawHillBook
Co.,1971.,p.23
Impurematerialwillpolymerizereadilyinpresenceoftracemetals(iron)oracids...Acetaldenydeispolymerized
violentlybyconc.sulfuricacid.
Bretherick,L.HandbookofReactiveChemicalHazards.4thed.Boston,MA:ButterworthHeinemannLtd.,1990,p.271
Hazardouspolymerizationmayoccur.
4.2.20 OdorThreshold
Recognitioninair=2.1x101ppm(chemicallypure)
Fazzalari,F.A.(ed.).CompilationofOdorandTasteThresholdValuesData.ASTMDataSeriesDS48A(CommitteeE18).
Philadelphia,PA:AmericanSocietyforTestingandMaterials,1978.,p.59
Odorlow:0.0002mg/cumOdorhigh:4.14mg/cum
RuthJHAmIndHygAssocJ47:A14251(1986)
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4.2.21 DissociationConstants
Ka=0.7X1014at0degC
pKa=13.57at25degC
Serjeant,E.P.,DempseyB.IonisationConstantsofOrganicAcidsinAqueousSolution.InternationalUnionofPureand
AppliedChemistry(IUPAC).IUPACChemicalDataSeriesNo.23,1979.NewYork,NewYork:PergamonPress,Inc.,p.989
4.2.22 OtherExperimentalProperties
Coefficientofexpansion,0.00169/degC(0to30degC)latentheatoffusion,3.24kJ/molheatofsolutionin
water,6.82kJ/molat25degCdipolemoment,8.97X103degC.m
p.V1:95(1991)
Heatcapacityofliquid:1.38J/gdegKat20degCheatcapacityofvapor:1.24J/gdegKat25degC,101.3kPa
Henry'sLawconstant=6.67X105atmcum/molat25degC
GaffneyJSetalEnvironSciTechnol21:51923(1987)
Hydroxylradicalreactionrateconstant=1.58X1011cucm/molecsecat25degC
AtkinsonRJPhysChemRefData.MonographNo1(1989)
4.3 SpectralProperties
MAXABSORPTION(GAS):178NM(LOGE=3.48)181NM(LOGE=3.60)181.5NM(LOGE=4.05)
Weast,R.C.(ed.).HandbookofChemistryandPhysics.60thed.BocaRaton,Florida:CRCPressInc.,1979.,p.C81
MAXABSORPTION(CYCLOHEXANE):290NM(LOGE=1.23)
SADTLERREFERENCENUMBER:5824(IR,PRISM)
Indexofrefraction=1.3316at20degC
2007,p.34
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IR:5645(CoblentzSocietySpectralCollection)
Lide,D.R.,G.W.A.Milne(eds.).HandbookofDataonOrganicCompounds.VolumeI.3rded.CRCPress,Inc.BocaRaton,FL.
1994.,p.V17
UV:54(OrganicElectronicSpectralData,Phillipsetal,JohnWiley&Sons,NewYork)
1994.,p.V17
NMR:6(VarianAssociatesNMRSpectraCatalogue)
1994.,p.V17
MASS:62124(NIST/EPA/MCDCMassSpectralDatabase1990Version)97(AtlasofMassSpectralData,John
WileyandSons,NY)
1994.,p.V17
RASUVNo.12511
NISTChemistryWebBook.NationalInstituteofStandardsandTechnologyStandardReferenceDatabaseNumber69March
2003Release,Availablefromthequerypageathttp://webbook.nist.gov/chemistry
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5 RelatedRecords
5.1 RelatedCompoundswithAnnotation
Download
Medications(4)
Literature(34)
DimethylSulfoxide
3DStructure(20)
Ethanol
Bioactivities(24)
Formaldehyde
Patents(325)
PolyvinylAlcohol
5.2 RelatedCompounds
SameTautomer(18)
SameConnectivity(15)
SameParent,Tautomer(246)
SameParent,Connectivity(202)
SameParent,Exact(184)
Mixtures,Components,andNeutralizedForms(1663)
SimilarCompounds(40)
SimilarConformers(462)
5.3 RelatedSubstances
All(2664)
Same(378)
Mixture(2286)
5.4 EntrezCrosslinks
PubMed(4456)
ProteinStructures(34)
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Taxonomy(8)
OMIM(9)
Gene(256)
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6 ChemicalVendors
Refine/Analyze
Vendor/Supplier
Download
PurchasableChemical
PubChemSID
AGG99107
124381093
AGH16453
126514756
49416633
126677984
99138606
241129502
99153476
241144372
00070_FLUKA
24844966
00071_FLUKA
24844967
36611_FLUKA
57649580
36611_RIEDEL
24862614
402788_SIAL
24865119
506788_SUPELCO
24873391
63990_FLUKA
24883066
PS2030_SUPELCO
24899137
W200298_ALDRICH
24900782
W200301_ALDRICH
24900783
W200328_ALDRICH
24900784
W200336_ALDRICH
24900785
W200344_ALDRICH
24900786
W200352_ALDRICH
24900787
W200360_ALDRICH
24900788
W200379_ALDRICH
24900789
W200387_ALDRICH
24900790
AC1L18NF
104294072
AC1Q2CBI
117397293
AGC84733
136383227
AGNPC0091P0
172690616
AGNPC0O8WMG
222456106
VitasMLaboratory
STL264249
152166719
AKosConsulting&Solutions
AKOS000120180
104668603
MolPort
MolPort001783184
88826168
AngeneInternational
ChemMol
SigmaAldrich
ABIChem
AngeneChemical
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RTR024198
204380833
TR024198
204939033
Mcule
MCULE6800925955
165252995
RennoTechCo.,Ltd.
RL04862
174530348
ANPharmaTech
AN23835
223680558
FT0621719
164805855
FT0621749
164805885
FT0668352
164841410
KingScientific
KSC377C9B
163806447
Chembase.cn
105715
162093851
ChemFrog
888845907
125357177
193827
85083188
193828
85083189
204617
51071761
521259
85083190
I14113209
152137299
I1457914
144104538
I146219
92252168
TCI(TokyoChemicalIndustry)
A1640
87563068
ChemExperChemicalDirectory
QMHAIX@
3135181
3B_SCI
3B40691
184608436
Ambinter
LTBB001460
118980492
Achemica
ACMC20alvc
162305666
AmadisChemical
A838317
131325508
Tractus
FinetechIndustryLimited
MPBiomedicals
ISChemicalTechnology
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7 PharmacologyandBiochemistry
7.1 Absorption,DistributionandExcretion
Penetrationofacetaldehydeintocerebrospinalfluidwasstudiedinhumanvolunteersduringcalciumcarbimide
ethanolinteraction.Resultsindicatethatacetaldehydepenetrateshumanbloodcerebrospinalfluidbarrier.
HILLBOMMEETALTOXICOLLETT9(2):1139(1981)
Intravenousinfusionof0.5to5%solutionsofacetaldehydetorabbitsresultedinrapideliminationofacetaldehyde,
atrateof710mg/min.
HepaticandbloodacetaldehydeconcentrationsduringethanoloxidationweredeterminedinC57andDBAmice.
Liveracetaldehydewasdeterminedwiththeperchloricacidthioureamethod(noartifactualacetaldehydeformation).
Levelsrangingfrom5to118nmole/gwereobserved.Atethanolconcentrationsbelow5060umole/g,liver
acetaldehydeconcentrationswerehigherinDBAcomparedwithC57mice.Apositivecorrelationwasfound
betweentheethanolandacetaldehydeconcentration,whenethanolconcentrationwasbelow25(DBA)or70
umole/g(C57).Athigherethanolconcentrationsthecorrelationstendedtobecomenegative.Hemolysiscauses
artifactualformationofacetaldehydewhenbloodacetaldehydeisdeterminedusingthioureaorsemicarbazide
methods.Themagnitudeoftheartifactuallyformedacetaldehydewasofsuchorderthatnoconclusionsregarding
theexistenceoftrueinvivobloodacetaldehydeconcentrationscouldbedrawn.
ErikssonPJetalBiochemPharmacol33(14):22136(1984)
Theeffectofethanolontissuedistributionofacetaldehydefollowingexposuretoacetaldehydewasstudiedinrats.
MaleSpragueDawleyratswereexposedto20mMacetaldehydevaporfor1hr.Theywerealsoadministered0or3
g/kgethanolintragastrically.Bloodsamplesweretakenatselectedtimesafteracetaldehydeexposurewas
discontinuedandanalyzedforacetaldehyde.Otheranimalswerekilledimmediatelyafteracetaldehydeexposureor
3hrafterethanolandtheliver,blood,kidney,spleen,heartmuscle,andskeletalweretakenforacetaldehyde
analysis.Acetaldehydedisappearedrapidlyfromthebloodwithahalflifeof3.1min.Afteracetaldehydeinhalation,
peripheralbloodhadthehighestacetaldehydecontentothertissueconcnweresimilarexceptfortheliverwhich
hadamuchloweracetaldehydecontent.Acetaldehydeconcnafterethanoladminwerehigherintheliverandblood
thaninothertissues....Bloodacetaldehydeisnottakenupbyhepatocytestoanyappreciableextentorhepatic
acetaldehydemetabolismisveryrapid....Inhalationexposureisaviablemodelforstudyingacetaldehydetoxicity.
HobaraNetalBullEnvironContamToxicol35(3):3936(1985)
CD1miceweretreatediponday10ofgestationwith4,6,or7g/kgethanol.Maternalandembryonictissueswere
analysedforethanolandacetaldehydelevels5minto24hraftertreatment....Acetaldehydewasdetectablein
maternalbloodfollowingalltreatmentsandinmaternalliverandembryosfollowingtreatmentwith7g/kgethanol.
BlakleyPM,ScottWJToxicolApplPharmacol72(2):36471(1984)
Theeffectofshorttermmaternalethanoladministrationonthedispositionofethanolintheovinematernalfetal
unitwasdetermined.Neartermpregnantewes(between125and134daysofgestationterm,147days)received1
hrivinfusionof1gofethanol/kgofmaternalbodyweightonceperdayforsixdays(N=6ewes)oranequivalent
volumeofsalineforsixdays(N=6ewes).Ontheseventhday,theethanolandsalinepretreatedanimalswere
administerd1gofethanol/kgofmaternalbodyweightonceperday.Concentrationsweredeterminedinmaternal
blood,fetalblood,andamnioticfluidsamplesobtainedatselectedtimesduringthe14hrstudy.Shortterm
maternaladministrationofoncedailymoderatedoseethanoldidnotproducemajorchangesinthedispositionof
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ethanolanditsproximatemetabolite,acetaldehyde,inthematernal,fetal,andamnioticfluidcompartmentsduring
neartermovinepregnancy.
ClarkDWetalDrugMetabDispos16(3):4648(1988)
Thedispositionkineticsofethanolandacetaldehydewereinvestigatedin10healthysubjectswhofastedovernight,
tookanoraldoseofcalciumcarbimide50mgand,2hrlater,ingested0.25g/kgethanol.Pharmacokinetic
parametersestimatedforethanolshowedstatisticallysignificant,butclinicallyunremarkable,changesfollowing
calciumcarbimideingestion.Acetaldehydedispositionwasmarkedlydifferent,withpeakbloodconcentrationsof40
242umol/lcomparedwith1.76.5umol/lafterplaceboandsignificantincreasesinapparenteliminationhalflifeand
areaundertheconcentrationtimecurve.Theinteractionofethanolandcalciumcarbimidecausedintensefacial
flushinginallsubjectstestedbeginning2030minafterdrinking.Resultsdonotsupportasignificantroleof
acetaldehydeinregulatinginvivooxidationofethanolinhumans.[JonesAWetalBrJClinPharmacol25:21321
(1988)]Fulltext:PMC1386476
...Studiesutilizingtheperfusedhumanplacentalcotyledonshowthatthehumanplacentaoxidizesethanolto
acetaldehydereleasingitintothefetalperfusate.Moreoverwhenacetaldehydeispresentinthematernalperfusate
itistransferredtothefetalsidereachingapproximately50%ofthematernallevel.
KarlPIetalScience242(4876):2735(1988)
Acetaldehydeisrapidlyabsorbedandcompletelymetabolizedinbodytissue,mostlyinmammalianlivertissue....
Lessthan5%oftheabsorbedcompoundiseliminatedastheparentinexpiredair,andnoexcretionintheurine
hasbeenfound.
Sixdogswereeachgivenasingle600mg/kgbodyweightdoseofacetaldehydebystomachtube.Intwodogs,the
maximumplasmaconcentrationwasreachedafter15minutes,whileintheothersplasmaacetaldehydewaseither
closetothelimitofdetection(2ug/ul)orwasnotdetectable.Urinaryrecoveryofacetaldehydewas<0.02%ofthe
dose.
...theresultsoftoxicitystudiesindicatethatabsorptionviathelungsandGItractdoesoccur.Thephysicaland
chemicalpropertiesofacetaldehydeindicatethatabsorptionviatheskinisalsopossible.
WHOEnvironHealthCriteria167:Acetaldehydep.48(1995)
...followingasingleintragastricadminof4500mgethanol/kgbwtomaleandfemaleWistarrats,acetaldehyde
wasdetectedinthebloodandinbraininterstitialfluidcollectedfromthecaudatenucleusandthethalamus
hypothalamusregion.Followingadminofdisulfiram...20hrpriortoexposuretoethanol,therewasa6foldincrin
theconcnofacetaldehydeinthebloodandbrain.Althoughacetaldehydewasfoundininterstitialfluid,nonewas
detectedinwholebrain....
...usedthebloodof5healthyindividuals,6alcoholicpatients,and2baboonstoshowthat,afteralcohol
consumption,mostofthebloodacetaldehydewasfoundintheredbloodcells.Invivo,theacetaldehydeconcnin
redcellswasabout10timeshigherthanthatintheplasma.Nosignificantvariationswereseenbetweenthe3
groups.
WHOEnvironHealthCriteria167:Acetaldehyep.50(1995)
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Followinginhalationbyrats,acetaldehydeisdistributedtotheblood,liver,kidney,spleen,heart,andothermuscle
tissues.Lowlevelsweredetectedinembryosaftermaternalintraperitoneal(ip)injectionofacetaldehyde(mouse)
andfollowingmaternalexposuretoethanol(mouseandrat).Potentialproductionofacetaldehydehasalsobeen
observedinratfetusesandinthehumanplacenta,invitro....Acetaldehydeistakenupbyredbloodcellsand,
followingethanolconsumptioninhumansandinbaboons,invivo,intracellularlevelscanbe10timeshigherthan
plasmalevels.
WHOEnvironmentalHealthCriteriaDocumentNo.167:Acetaldehyde(75070).Availablefrom,asofJanuary12,2009:
http://www.inchem.org/documents/ehc/ehc/ehc167.htm
...thepatternofacetaldehydeappearanceinmaternalandfetalblood/wasstudied/,maternalandfetalliverand
placentaafteroralethanoladministrationorintravenousacetaldehydeadministration(10mg/kg)topregnantWistar
rats.Thestudydemonstratedthatacetaldehydewasabletocrosstheplacentalbarrierathighconcentrations(fetal
bloodconcentrationswereonlydetectablewhenmaternalbloodconcentrationsweregreaterthan80uM).
U.S.EnvironmentalProtectionAgency'sIntegratedRiskInformationSystem(IRIS)onAcetaldehyde(75070).Availablefrom:
http://cfpub.epa.gov/ncea/iris/index.cfm?fuseaction=iris.showSubstanceListonQuerypageasofJanuary12,2009.
Retentionofacetaldehydeinhumansunder"physiologicconditions"ofbreathingrateandtidalvolumehasbeen
showntobeapproximately60%between100and200mg/cu.mforafewminutes,andretentionwasshownto
decreaseslightlyathigherconcentrations.Breathingrateandvolumeandexposureconcentrationwereshownto
influenceretention.RetentionhasnotbeendeterminedatlowerconcentrationscomparablewiththeHECestimates
derivedhere,however.Retentionofacetaldehydefromcigarettesmokewasshowntobe99%(Dalhamnetal.,
1968).Acetaldehydehasbeenshowntobeabsorbedviainhalationathighconcentrations(900010,000)for1hour.
Bindingandmetabolisminbloodandratnasalmucosahavebeendemonstrated.Ratsexposedto700ppmfor2
hoursdemonstratedonly0.7mMincirculatingblood5minutesafterexposuretermination,suggestingthatbinding
intherespiratorytractandrapidmetabolismsignificantlyreducessystemiccirculationatsteadystate.
...Acetaldehydewasaddedtotendifferenthumanplacentalhomogenatesandsubjectedtoequilibriumdialysis.
Homogenatesofplacentaeobtainedfromguineapigschronicallyexposedtoethanolthroughoutgestationwere
alsodialysedinthepresenceofacetaldehydetolookforalterationsinbindingafterchronicalcoholexposure.
Nonlinearleastsquaresregressionanalysiswasusedtocharacterizethebindingsysteminvolved....Itwasfound
thattheamountofacetaldehydeboundtohumanplacentaevariedbyasmuchas3foldamongplacentae.The
bindingprofileofacetaldehydewascharacterizedasatwositebindingsystem(Ka(1)=9.8x10+5+/0.7x10+5
L/mol,N(1)=1.1x108+/0.7x108mol/gtissueKa(2)=1.6x10+4+/0.9x10+4L/mol,N(2)=1.7x107+/0.4x
107mol/gtissue).Chronicalcoholexposurehadnoeffectonthedegreeofacetaldehydebinding....
HardMLetalPlacenta24(23)14954(2003)
Distributionofacetaldehydetobraininterstitialfluid,butnottobraincells,hasbeendemonstratedfollowing
intraperitonealinjectionofethanol
IPCSHealthandsafetyguideNo.90onAcetaldehyde(1995).Availablefrom,asofMarch9,2009:
http://www.inchem.org/documents/hsg/hsg/hsg90_e.htm
7.2 Metabolism/Metabolites
...Theeffectsofethylalcoholareindicativeofeffectsofacetaldehyde,becauseitisthemajormetaboliteofethyl
alcohol./Acetaldehydeis/...theprincipalmetabolicbuildupproductofdisulfiramtherapy.
NationalResearchCouncil.DrinkingWater&HealthVolume1.Washington,DC:NationalAcademyPress,1977.,p.687
/Intheoxidationofalcoholinliver/theprimarystepisoxidationofalcoholtoacetaldehydebyalcohol
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dehydrogenase...theacetaldehydeisconvertedtoacetylcoenzymeA,whichisthenoxidizedthroughthecitric
acidcycleorutilizedinvariousanabolicreactionsinvolvedinsynthesisofcholesterol,fattyacids&othertissue
constituents.
Gilman,A.G.,L.S.Goodman,andA.Gilman.(eds.).GoodmanandGilman'sThePharmacologicalBasisofTherapeutics.7th
ed.NewYork:MacmillanPublishingCo.,Inc.,1985.,p.379
Aculturemodelisdescribedforthestudyofacetaldehydemetabolismbyexplantedpostimplantationratand
mouseconceptuses.Theabilityof12dayratand10daymouseembryostometabolizeacetaldehydewas
demonstrated.Theeliminationrateforthe12dayratconceptususinganinitialacetaldehydeconcentrationof1
mMinthemediumwasfoundtobe1.8nmol/mgpermin.Whentheconceptuswasdividedintoembryonicand
extraembryonictissue,therateswere1.6and2.2nmol/mgpermin,respectively.Whentheacetaldehydeconcn
wasreducedto50microMtheratewas0.095nmol/mgpermin.Theresultsprovidefurtherevidencefora
functionalbarrierthatpreventsacetaldehydeentrytotheembryo.AcomparativeexperimentusingCBA/beige
mouseconceptusshowedthatacetaldehydeeliminationcharacteristicsmaybequalitativelysimilartothoseinrat
embryos,butthattheestimatedeliminationrateof0.8nmol/mgperminutewaslessthanhalfthatoftherat.Thus
themetabolicbarriermaybelessefficientinthemouse.Thismaybeimportantinviewofthegreatersensitivityof
themousetoethanolembryotoxicity.
PriscottPK,FordJRBiochemPharmacol34(4):52932(1985)
Homogenatesofrespiratoryandolfactorytissuefromtheratnasalcavitywereexaminedfortheircapacityto
catalyzetheNAD(+)dependantoxidationofformaldehyde(inthepresenceandabsenceofglutathione)andof
acetaldehyde.Bothaldehydeswereoxidizedefficientlybynasalmucosalhomogenates,andformaldehyde
dehydrogenaseandaldehydedehydrogenaseweretentativelyidentifiedinbothtissuesamples.Atleasttwo
isoenzymesofaldehydedehydrogenasedifferingeitherwithrespecttotheirapparentKmandmaxvalueswith
acetaldehydeassubstrate,werefoundinthenasalmucosa,oneofwhichmaycatalyzetheoxidationofboth
formaldehydeandacetaldehyde....Repeatedexposuresofratstoformaldehyde(15ppm,6hr/day,10days)orto
acetaldehyde(1500ppm,6hr/day,5days)didnotsubstantiallyaffectthespecificactivitiesofformaldehyde
dehydrogenaseandaldehydedehydrogenaseinnasalmucosalhomogenates.Glutathioneisacofactorfor
formaldehydedehydrogenasetheconcentrationofnonproteinsulfhydrylsinrespiratorymucosalhomogenateswas
approximately2.8umoles/gandwasnotchangedsignificantlybyrepeatedexposurestoformaldehyde(15ppm,6
hr/day,9days).Thesedataindicatethattheratnasalmucosa,whichisthemajortargetsiteforbothaldehydesin
inhalationtoxicitystudies,canmetabolizebothformaldehydeandacetaldehyde,andthatthespecificactivitiesof
formaldehydeandaldehydedehydrogenaseinhomogenatesofthenasalmucosaareessentiallyunchanged
followingrepeatedexposurestotoxicconcentrationsofeithercompound.
CasanovaSchmitzMetalBiochemPharmacol33(7):113742(1984)
Acetaldehydeisatoxicmetaboliteformedinthemammalianliverduringtheoxidationofethanol.
Concurrentadminofacetaldehyde,Lcysteine&nitritetoratsyieldednnitroso2methylthiazolidine4carboxylic
acid(cis&transisomers),>90%ofwhichwasexcretedintheurine.
Themetabolismcurvesforbothethanolandacetaldehydeafteranacuteintragastricorivadministrationtothe
mother,havebeenstudied.Metabolismofethanolfollowedaverysimilarpatterninboththepregnantandtheir
controlvirginrats,whereasthelevelsofacetaldehydederivedfromthemetabolismoftheadministeredethanol
weresignificantlyhigherinthepregnantanimals,thisfactimplyingthat,inlategestation,thereisadecreaseinthe
mother'scapacityforacetaldehydemetabolism.Atthefetalsideoftheplacenta,150minaftertheadministration,
theconcentrationofethanolwassimilartothatfoundinthemother'scirculation,thusprovingafluidtransitofthis
metabolitethroughtheplacenta.Theconcentrationofacetaldehydeinthefetuswasrelativelyhigh,afterthe
intragastricadministrationoftheethanoldose....
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EspinetC,ArgilesJMArchIntPhysiolBiochim93(5):33944(1984)
Theactivityofalcoholdehydrogenasewasdeterminedintheneartermpregnantewe.Therewaslittlealcohol
dehydrogenaseactivityinfetalliver(4.4%)andplacenta(0.2%)comparedwithmaternalliver.LowKm(uM
acetaldehyde)acetaldehydedehydrogenaseactivitywassimilarinthethreetissues.HighKm(mMacetaldehyde)
aldehydedehydrogenaseactivitywaslessinfetalliver(57%)andplacenta(16%)comparedwithmaternalliver.
Thesedataandthepharmacokineticsofethanolanditsproximatemetabolite,acetaldehyde,inthenearterm
pregnanteweindicatethatethanoleliminationfromthematernalfetalunitisregulatedprimarilybymaternal
hepaticalcoholdehydrogenasecatalyzedbiotransformationofethanol,andlowKmaldehydedehydrogenase
activityinthefetalliverandplacentaprotectsthefetusfromexposuretoethanolderivedacetaldehyde,whichis
producedprimarilyinthematernalcompartment.
ClarkeDWetalDevPharmacolTher12(1):3541(1989)
Bloodconcentrationsofethanolandacetaldehydeweredeterminedinsucklingratsafterasingleoralethanol
gavage.Afterintragastricadministrationof3g/kgbodyweightofethanol,ethanolconcentrationsweremuchhigher
insucklingratsthaninadultanimals,expeciallyat90,120,and180minafteritsadministration.Inaddition,
acetaldehydeconcentrationswereundetectableinsucklingratsasopposedtoadultrats,inwhommicromolar
concentrationsweredetected.Thus5to30dayoldratsseemtohavealimitedcapacityforinvivoethanol
metabolism.Theanalysisofhepaticalcoholdehydrogenaseactivityrevealedthatitwasverylowatbirthandit
increasedprogressivelywithtimeattainingadultlevelsafter20daysoflife.Thealcoholdehydrogenaseactivity
presentintheliverofsucklingratspresentedsimilarKmvaluesandsensitivitytopyrazoleasadultratliver.Thus,
thepatternofinvivoethanoleliminationduringthesucklingperiodisnotexplainedbyhepaticalcohol
dehydrogenaseactivity.Atbirth,hepaticaldehydedehydrogenaseactivitywaslowanditincreasedreachingadult
levelsduringthesucklingperiod.AdultlevelsforthecomponentoflowKmwereattainedearlierthanforthe
componentofhighKm.Thelowaffinityhepaticaldehydedehydrogenasecomponentinthenewbornwasdifferent
fromthatintheadultasassessedbykineticstudiesandbyitssensitivitytodisulfiram.
ZorzanoA,HerrraEAlcoholClinExpRes13(4):52732(1989)
Acetaldehyde,theprimaryhepaticoxidativemetaboliteofethanol,maycontributetofetalinjuryassociatedwith
maternalethanolingestion.Studiesutilizingtheperfusedhumanplacentalcotyledonshowthatthehumanplacenta
oxidizedethanoltoacetaldehyde,releasingitintothefetalperfusate.Moreover,whenacetaldehydeispresentin
thematernalperfusate,itistransferredtothefetalside,reachingapproximately50percentofthematernallevel.
KarlPIetalScience242(4876):2735(1988)
Theactivitiesofaldehydedehydrogenaseandalcoholdehydrogenaseweremeasuredintermplacentasof13
alcoholicwomenand16matchedcontrols.Withacetaldehyde8mmol/1assubstrate,thealdehydedehydrogenase
activitywas29.1+or12.2and34.4+or15.3u/gofwetweight(mean+orSDp>0.4)foralcoholicsand
controls,respectively.With50umolofacetaldehyde,aldehydedehydrogenaseactivitywasundetectableinboth
groups.Noalcoholdehydrogenaseactivitycouldbedetectedintheplacentas.Theweightsofplacentasand
newbornsweresignificantlylowerinthealcoholicgroup(placentas:526+or116vs653+or77g,p<0.005
newborns2,878+or417vs3,595+or346g,p<0.001.Inchronicalcoholabuse,theplacentaplaysanegligible
roleinthemetabolismofethanolandacetaldehyde.
AnderssonSetalBiolNeonate56(2):903(1989)
AldehydedehydrogenaseVAisozymesinsalivaweredetectedin96patientswithorwithoutliverdiseaseinorder
toclarifytherelationshipsofthepresenceorabsenceofaldehydedehydrogenaseVAisozymestothemetabolism
ofacetaldehydeandalcoholicliverdisease.TheincidenceofaldehydedehydrogenaseVAdeficiencywasnot
differentbetweenthepatientswithalcoholicliverdiseaseandthosewithnonalcoholicliverdisease,norbetween
thepatientswithliveranddiseaseandwithoutliverdiseaseinnorelationtoalcoholmisuse.Acetaldehyde
metabolismwasnotdifferentbetweenaldehydedehydrogenaseVAdeficientandnondeficientpatientseveninthe
aldehydedehydrogenaseIdeficientpatients.AldehydedehydrogenaseVAisozymesplayvirtuallynoroleinthe
metabolismofacetaldehydeanditsdeficiencyisnotrelatedtothedevelopmentofalcoholicliverdisease.
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TakaseSetalAlcohol24(6):54754(1989)
...Enzymecapableofconvertingethanoltoacetaldehydeiscatalase,whichbyvirtueofitsperoxidativeactivity
useshydrogenperoxidetoperformtheoxidation.However,normallythereisverylittleperoxideavailabletosupport
thereactioninhepatocytes,anditsunlikelythatcatalasecanaccountformorethan10%ofethanolmetabolism.
Thislevelcouldchangeifperoxidelevelsinhepatocyteswereelevated....Clofibrate,whichstimulatesperoxisomal
fattyacidoxidation,increasesperoxidelevelsandtherebyenchancesethanoloxidationbycatalase.
Amdur,M.O.,J.Doull,C.D.Klaasen(eds).CasarettandDoull'sToxicology.4thed.NewYork,NY:PergamonPress,1991.,p.
698
Gaschromatographicanalysisofhumanwholebloodlymphocyteculturestreatedfor10secto20minwithvinyl
acetate(5.4mM)revealedarapiddegradationofvinylacetateandformationofacetaldehyde.Duringthe20min
observationperiod,nodegradationofvinylacetateorformationofacetaldehydewereobservedincompleteculture
mediumwithoutblood,whichsuggestedthatthereactionwasenzymatic.Acetaldehydeinducedsisterchromatid
exchangesinhumanwholebloodlymphocyteculturesatconcentrations(0.1252mM)comparabletothoseusedfor
vinylacetate.Theresultsindicatethatvinylacetateinduceschromosomedamageincellculturesthroughenzyme
mediatedhydrolysistoacetaldehyde.
NorppaHetalCancerRes45(10):481621(1985)
Inhumansexposedtoacetaldehydeinairatconcentrationsupto100ppm,acetaldehydeisrapidlyabsorbedand
metabolized.AcetaldehydeisapparentlymetabolizedtoNnitroso2methylthiazolidine4carboxylicacid.This
chemicalwasdetectedintheurineofhumansubjectsduringbothoral&nasalbreathing.Afractionofthismaybe
formedasatwostepsynthesisinvivofromacetaldehydeandLcysteinetoyield2methylthiazolidine4carboxylic
acid,whichiseasilynitrosated.
Theoxidativemetabolismofacetaldehydetoacetateoccursprimarilybyaldehydedehydrogenases,widely
distributedinbodytissues.Acetateentersthepoolofintermediarymetabolism.Itisusedincellularenergy
production,eventuallyproducingcarbondioxideandwaterorthecarbonatomsareutilizedinsynthesisofcell
constituents.Afteroralorinhalationadministration,substantialfirstpassmetabolismintheliverorrespiratorytract
occurs,effectivelylimitingacetaldehydeaccesstothesystemiccirculation.
Althoughcatalaseandotheroxidasesmaycontributetometabolism..becauseofitshighaffinity,atleast90%of
acetaldehydeisoxidizedbymitochondrialALDH...reducingNAD+toNADHintheprocess.Thisstepcanbe
blockedbydisulfiram.
ALDHlocalizationintherespiratorytractofFischer344ratswasstudied....Histochemicalstudiesindicated
activityprincipallyinthenasalrespiratoryepithelium,espinthesupranuclearcytoplasmofciliatedepithelialcells.
ActivitywasalsohighintheClaracellsofthelowerbronchioles.Thetrachealepitheliapossessedonlylowlevelsof
ALDH.TheolfactoryepitheliumwasalmostdevoidofALDHactivity.
Inaninvitrostudy...studiedthemetabolismofacetaldehydeinisolateddog,rat,guineapig,andbaboonkidney
cortextubules.Acetaldehydewasfoundtobemetabolizedbythetubulesathighratesandinadosedependent
mannerinallfourspecies.Itwasnotedthat,atallacetaldehydeconcn,mostoftheacetaldehyderemovedwas
recoveredasacetateindog,guineapig,andbaboon,butnotinratkidneytubules.
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HumanliverALDHconsistsofatleast4mainisoenzymes,whicharealsopresentinmanyothertissues....
MitochondrialALDHisinactiveinatleast40%oftheOrientalpopulation.Thefrequentlyobservedintoleranceto
alcohol(the"flushing"reaction)islinkedtothisdeficiency,whichisproducedbyaninheritedpositivemutationin
thecorrespondinggene....Subjectswithphenotypicdeficiencyhavealwaysshownthepresenceofatleastone
mutantgene(heterozygousorhomozygous)....
Invitro,acetaldehyde(0.040.88g/l)wasmetabolizedathighratesandinadosedependentmannerinisolated
humankidneycortextubules....
Thefetaloxidationcapacityinliverandplacentawasshowntobelowerthanthatofthematernalliver.Athreshold
abovewhichtheremovalcapacityofacetaldehydemetabolismbythefetoplacentalunitwouldbesurpassedwas
estimatedtobe80uM(maternalbloodconcentration)inthe21daypregnantratandpossiblyloweratearly
pregnancywhenaldehydedehydrogenaseisabsentfromfetalliver.
Acetaldehyeisproducedatanintermediatelevelofsugarmetabolism,althoughnospecificdataonlevelsin
animalscouldbefoundintheliterature.
KirkOthmerEncyclopediaofChemicalTechnology.3rded.,Volumes126.NewYork,NY:JohnWileyandSons,19781984.,
p.1:97(1978)
7.3 BiologicalHalfLife
/Acetylaldehyde/hasahalflifeoflessthan15minutesinthecirculation.
7.4 MechanismofAction
...TheeffectofethanolonFanconianemia(FANC)D2mRNAlevelswasmeasuredbyquantitativerealtimePCR
usingmousebrainandhumanneuronalcells.FANCD2proteinlevelsandubiquitinationweremeasuredbyWestern
blottingandimmunocytochemistry.DNAdamageinductionbyethanol/acetaldehydewasmeasuredusingthe
CometassayandgammaH2AXimmunocytochemistry.LevelsofDNAandRNAsynthesisweremeasuredincell
strainsusing(3)Hthymidineor(3)Huridineuptake....ChronicexposuretoethanolinducedFANCD2inmouse
midbraininvivoandinthenucleusofhumanneuronalcellsinculture.However,therewasnoconcomitantincrease
intheamountofubiquitinatedFANCD2.AcetaldehydealsoinducednonubiquitinatedFANCD2protein,and...the
abilityofacetaldehydetogenerateDNAdoublestrandbreaks,lesionswhichnormallyinduceubiquitinationof
FANCD2/wasdemonstrated/.EthanolalsoinhibitedbothRNAandDNAsynthesisinproliferatingcellsconsistent
witheffectsontranscriptionandreplication....IncontrasttootherDNAdamagingagents,ethanol/acetaldehyde
generatedDNAstrandbreakswithoutinducingubiquitinationofFANCD2,despiteincreasingproteinlevelsinthe
nucleus.ThesedataareconsistentwithrecentreportsthatsuggesttheFanconianemiapathwayplaysanimportant
roleintheadultbraininresponsetoDNAdamage...
RultenSLetalAlcoholism,ClinExplRes32(7):118696(2008)
Thisstudyexaminestheeffectsoftheethanolmetabolite,acetaldehyde,ontheclinicallyrelevantdrugtransporter,
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PEPT1.Themetabolismofethanolandthefollowingacetaldehydeformationisthoughttomodulatetheuptake
capacityofPEPT1withinthegastrointestinaltractforavarietyofclinicallyimportantpeptidomimeticdrug
compounds....Glycylsarcosine([(3)H]GlySar),anonhydrolysablePEPT1specificsubstratewasused....Invitro
uptakestudieswereperformedintheCaco2andChinesehamsterovary(CHO)hPEPT1cellmodels,measuring
cellularuptakeoflabeledcompoundagainstincreasinglevelsofunlabeledcompoundinthepresenceof
acetaldehyde.Invivoabsorptionof[(3)H]GlySarwasmeasuredinmaleSpragueDawleyratsthatweretreated
withoraldoseofethanol/disulfiram(5g/kg/100mg/kg)for6days.Theseresultswerecomparedtocontrolrats
treatedwithsaline,ethanolaloneordisulfiramalone....Invitrouptakeof[(3)H]GlySarinCHOhPEPT1cells
treatedwith1mMacetaldehydewassignificantlydecreased(p<0.05)ascomparedtountreatedcontrols.The
uptakeof[(3)H]GlySarinCaco2cellmonolayerstreatedwith1mMacetaldehydewasalsosignificantlydecreased
ascomparedtotheuntreatedcontrolcells.Invivoabsorptionof[(3)H]GlySarinethanoltreatedrats,asmeasured
byAUC(012hours)weredecreasedbyapproximately50%versusthecontrolratgroup./Itwasconcluded/...that
acetaldehydesignificantlymodulatesPEPT1functionand,thereby,affectsdrugbioavailability....
FisherSJetalAlcoholism,ClinExptlRes32(1):16270(2008)
Sixtransientreceptorpotential(TRP)ionchannelsexpressedinthesensoryafferentsplayanimportantroleas
bodythermosensorsandalsoasperipheralpaindetectors....HumanandmouseTRPA1areactivatedby
acetaldehyde,anintermediatesubstanceofethanolmetabolism,intheHEK293Tcellheterologousexpression
systemandinculturedmousetrigeminalneurons.AcetaldehydefailedtoactivateothertemperaturesensitiveTRP
channelsexpressedinsensoryneurons.TRPA1antagonistscamphorandgadolinium,andageneralTRPblocker
rutheniumredinhibitedTRPA1activationbyacetaldehyde.Camphor,gadoliniumandrutheniumredalso
suppressedtheacutenociceptivebehaviorsinducedbytheintradermaladministrationofacetaldehydeintothe
mousefootpads.IntradermalcoapplicationofprostaglandinE2andacetaldehydegreatlypotentiatedthe
acetaldehydeinducednociceptiveresponses,andthiseffectwasreversedbytreatmentwiththeTRPA1antagonist
camphor.TheseresultssuggestthatacetaldehydecausesnociceptionviaTRPA1activation...
BangSetalEuJNeurosci26(9):251623(2007)
Alcoholabuseisamajorcauseofpancreatitis,aconditionthatcanmanifestasbothacutenecroinflammationand
chronicdamage(acinaratrophyandfibrosis).Itisgenerallyacceptedthatalcoholinducedpancreaticinjuryisa
consequenceofthemetabolismofalcoholbythepancreas(viatheoxidativeandnonoxidativepathways)producing
thetoxicmetabolitesacetaldehydeandfattyacidethylesters(FAEEs)respectively.Ethanoloxidationwithinthe
pancreasalsoleadstooxidantstresswithinthegland.Acetaldehyde,oxidantstressandFAEEscausenumerous
molecularchangesinpancreaticacinarcellswhichpredisposetheglandtoautodigestionandnecroinflammation.
Animportantrecentdevelopmentrelatestotheidentificationofpancreaticstellatecells(PSCs)asthekey
mediatorsofalcoholinducedpancreaticfibrosis,whenactivatedbyethanol,acetaldehydeoroxidantstress.Recent
studiesimplicatethemitogenactivatedproteinkinase(MAPK)pathway,amajorsignallingpathwayinmammalian
cells,asacriticalregulatoroftheeffectsofethanolandacetaldehydeonacinarcellsaswellasPSCs.Particularly
importantarethemodulatoryeffectsofethanolanditsmetabolitesondownstreamtranscriptionfactorsNFkappaB
andAP1(whichregulateinflammatoryresponsesviacytokineproduction)inacinarcells.InPSCs,additional
signallingmoleculesidentifiedasimportanttotheprocessofethanolandacetaldehydeinducedPSCactivation
includeproteinkinaseC(PKC),phosphatidylinositol3kinase(PI3K)andperoxisomeproliferatoractivatedreceptor
gamma(PPARgamma).Interestingly,crosstalkhasbeendemonstratedbetweenPI3KandMAPKin
acetaldehydetreatedPSCs.Theaboveadvancesintheidentificationofrelevantsignallingmoleculesmayenable
therapeutictargetingofthesepathwayssoastoprevent/reducealcoholinducedacuteaswellaschronicinjuryof
thepancreas.
ApteMetalNovartisFoundationSymposium285:20011(2007)
Accumulatingevidenceindicatesthatacetaldehyde(AcCHO)isoneofthemainmediatorsoffibrogenesisin
alcoholicliverdisease.AcCHOstimulatessynthesisoffibrillarcollagensinhepaticstellatecells,butthemolecular
eventsdirectlyinvolvedintheactivationofcollagengenesaredebatable....Peroxisomeproliferatoractivated
receptorgamma(PPARgamma)isanuclearreceptorthatisexpressedinstellatecells,anditsactivationbyspecific
ligandsinhibitscollagensynthesis.Inthisstudy,weevaluatedtheeffectsofAcCHOonPPARgamma
transcriptionalactivityanditscorrelationwiththeAcCHOinducedcollagensynthesisinhepaticstellatecells....
AcCHOtreatmentinhibitedliganddependentandindependentPPARgammatranscriptionalactivity,andthiseffect
wascorrelatedwithanincreasedphosphorylationofamitogenactivatedproteinkinasesiteatserine84ofthe
humanPPARgamma.TransfectionofthePPARgammaSer84Alamutantcompletelypreventedtheeffectof
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AcCHOonPPARgammaactivityandinparallelabrogatedtheinductionofcollagengeneexpressionbyAcCHO.
TheeffectofAcCHOonPPARgammaactivityandphosphorylationwasblockedbyextracellularsignalregulated
kinase(ERK)1/2andproteinkinaseC(PKC)deltainhibitorsaswellasbycatalase,suggestingthathydrogen
peroxideisinvolvedinthemolecularcascaderesponsibleforPPARgammaphosphorylationviaactivationofthe
PKCdelta/ERKpathway.Furthermore,inhibitionofcAblcompletelyabrogatedtheeffectofAcCHOoneither
PPARgammafunctionorcollagensynthesisinaddition,expressionofthePPARgammaSer84Alamutant
preventedtheprofibrogenicsignalsmediatedbycAblactivation./Itwasconcluded/thattheinductionofcollagen
expressionbyAcCHOinstellatecellsisdependentonPPARgammaphosphorylationinducedbyahydrogen
peroxidemediatedactivationoftheprofibrogeniccAblsignalingpathway.
Ceni,EetalGastroenterology131(4):123552(2006)
Alcoholicbeverageconsumptionisclassifiedasaknownhumancarcinogen,causallyrelatedtoanincreasedriskof
canceroftheuppergastrointestinaltract.Theformationofacetaldehydefromethanolmetabolismseemstobethe
majormechanismunderlyingthiseffect.Acetaldehydeiscarcinogenicinrodentsandcausessisterchromatid
exchangesandchromosomalaberrationsinhumancells.ThebeststudiedDNAadductfromacetaldehydeisN(2)
ethyl2'deoxyguanosine,whichisincreasedinliverDNAobtainedfromethanoltreatedrodentsandinwhiteblood
cellsobtainedfromhumanalcoholabusers.However,thecarcinogenicrelevanceofthisadductisunclearinviewof
thelackofevidencethatitismutagenicinmammaliancells.AdifferentDNAadduct,1,N(2)propano2'
deoxyguanosine(PdG),canalsobeformedfromacetaldehydeinthepresenceofhistonesandotherbasic
molecules.PdGhasbeenshowntoberesponsibleforthegenotoxicandmutageniceffectsofcrotonaldehyde.The
PdGadductcanexistineitheroftwoforms:aringclosedformoraringopenedaldehydeform.Whereasthering
closedformismutagenic,thealdehydeformcanparticipateintheformationofsecondarylesions,includingDNA
proteincrosslinksandDNAinterstrandcrosslinks.TheformationofthesetypesofcomplexsecondaryDNAlesions
resultingfromPdGmayexplainmanyoftheobservedgenotoxiceffectsofacetaldehydedescribedabove.Repairof
PdGanditsassociatedadductsiscomplex,involvingmultiplepathways.Inheritedvariationinthegenesencoding
theproteinsinvolvedintherepairofPdGanditssecondaryadductsmaycontributetosusceptibilitytoalcoholic
beveragerelatedcarcinogenesis.
BrooksPJ,TheruvathuJAAlcohol(Fayetteville,NY)35(3):187093(2005)
Alcoholicbeverageconsumptionisassociatedwithanincreasedriskofuppergastrointestinalcancer.Acetaldehyde
(AA),thefirstmetaboliteofethanol,isasuspectedhumancarcinogen,butthemolecularmechanismsunderlying
AAcarcinogenicityareunclear....Thiswork...testedthehypothesisthatpolyaminescouldfacilitatetheformation
ofmutagenicalphamethylgammahydroxy1,N2propano2'deoxyguanosine(CrPdG)adductsfrombiologically
relevantAAconcentrations....CrPdGadductscouldbeformedbyreactingdeoxyguanosinewithmuM
concentrationsofAAinthepresenceofspermidine,butnotwitheitherAAorspermidinealone.Theidentitiesof
theCrPdGadductswereconfirmedbybothliquidandgaschromatographymassspectrometry....Inthepresence
of5mMspermidine,AAconcentrationsof100uMandaboveresultedintheformationofCrPdGingenomicDNA.
TheseAAlevelsarewithintherangethatoccursinhumansalivaafteralcoholicbeverageconsumption....
Spermidine/also/directlyreactswithAAtogeneratecrotonaldehyde(CrA),mostlikelyviaanenaminealdol
condensationmechanism./Itwasproposed/thatAAderivedfromethanolmetabolismisconvertedtoCrAby
polyaminesindividingcells,formingCrPdGadducts,whichmayberesponsibleforthecarcinogenicityofalcoholic
beverageconsumption.[Theruvathu,JAetalNucleicAcidsRes33(11):351320(2005)]Fulltext:PMC1156964
...Theaimofthisstudywastodeterminewhethercentralactionsthatareoftenattributedtoethanolmayactually
bemediatedbyacetaldehyde....Theeffectsofacetaldehyde(11000uM)weretestedbytwoelectrodevoltage
clampelectrophysiologyinXenopuslaevisoocytesexpressing10differentligandgatedionchannelreceptors
[alpha1glycinealpha1beta2gamma2Sgammaaminobutyricacid(GABA)Arho1GABAc5hydroxytryptamine3A
NR1a/NR2ANMDAGluR1/GluR2AMPAGluR6/KA2kainateandalpha4beta2,alpha4beta4,andalpha2beta4
nicotinicacetylcholine]andtheGproteincoupledinwardrectifyingpotassiumchannelGIRK2....Theeffectof
acetaldehydeonthedopaminetransporter(DAT),/wasalsoevaluated/performingdopamineuptakeassaysin
oocytesexpressingDAT....Acetaldehyde(1and10uM)significantlyenhancedalpha1glycinereceptormediated
currents.Acetaldehydedidnotaffectthefunctionofanyoftheotherreceptorstestedorthepotassiumcurrents
measuredinGIRK2channels.Moreover,acetaldehydedidnotaltertheDATmediateddopamineuptake./The/
resultssuggestapotentialminorroleforacetaldehydeintheglycinereceptormediatedeffectsofethanol.
Otherwise,acetaldehydedoesnotmodulatefunctionoftheneuronalreceptorstestedinthisstudy,inGIRK
channelsorDAT,whenexpressedrecombinantlyinXenopuslaevisoocytes.
MasciaMPetalAlcoholism,ClinExptlRes25(11):157075(2001)
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Malondialdehydeandacetaldehydereacttogetherwithproteinsinasynergisticmannerandformhybridprotein
adducts,designatedasMAAadducts.MAAproteinadductsarecomposedoftwomajorproductswhosestructures
andmechanismofformationhavebeenelucidated.MAAadductformation,especiallyintheliver,hasbeen
demonstratedinvivoduringethanolconsumption.Theseproteinadductsarecapableofinducingapotentimmune
response,resultinginthegenerationofantibodiesagainstbothMAAepitopes,aswellasagainstepitopesonthe
carrierprotein.ChronicethanoladministrationtoratsresultsinsignificantcirculatingantibodytitersagainstMAA
adductedproteins,andhighantiMAAtitershavebeenassociatedwiththeseverityofliverdamageinhumanswith
alcoholicliverdisease.InvitroexposureofliverendothelialorhepaticstellatecellstoMAAadductsinducesa
proinflammatoryandprofibrogenicresponseinthesecells.Thus,duringexcessiveethanolconsumption,ethanol
oxidationandethanolinducedoxidativestressresultintheformationofacetaldehydeandmalondialdehyde,
respectively.ThesealdehydescanreacttogethersynergisticallywithproteinsandgenerateMAAadducts,whichare
veryimmunogenicandpossessproinflammatoryandprofibrogenicproperties.Byvirtueofthesepotentiallytoxic
effects,MAAadductsmayplayanimportantroleinthepathogenesisofalcoholicliverinjury.
Tuma,DJetalFreeRadBiolMed32(4):3038(2002)
Acetaldehydeformsstableandunstableadductswithproteins.Thiscanimpairproteinfunctionasevidencedby
inhibitionofenzymeactivity,impairedhistoneDNAbinding,andinhibitionofpolymerizationoftubulin...
Acetaldehydecanreactwithvariousmacromoleculesinthebody,preferentiallythosecontaininglysineresidues,
whichcanleadtomarkedalterationsinthebiologicalfunctionofthesemolecules.
IPCSHealthandsafetyguideNo.90onAcetaldehyde(1995).Availablefrom,asofMarch9,2009:
http://www.inchem.org/documents/hsg/hsg/hsg90_e.htm
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8 UseandManufacturing
8.1 MethodsofManufacturing
Theeconomicsofvariousprocessesformanufactureofacetaldehydearestronglydependentonthepriceofthe
feedstockused.Since1960,theliquidphaseoxidationofethylenehasbeentheprocessofchoice....Thereisstill
commercialproductionbythepartialoxidationofethylalcoholandhydrationofacetylene.Acetaldehydeisalso
formedasacoproductinthehightempoxidationofbutane.Arecentlydevelopedrhodiumcatalyzedprocess
producesacetaldehydefromsynthesisgasasacoproductwithethylalcoholandaceticacid.
p.V1(1991)100
...Thecatalystisanaqueoussolutionofleadchloride(PbCl2)andcopperchloride(CuCl2)....Therearetwo
variationsfortheproductionofacetaldehydebytheoxidationofethylenethetwostageprocessdevelopedby
WackerChemieandtheonestageprocessdevelopedbyFarbwerkeHoechst....
p.V1(1991)101
(1)Oxidationofethylene,(2)vaporphaseoxidationofethanol,(3)vaporphaseoxidationofpropaneandbutane,
(4)catalyticreactionofacetyleneandwater(chieflyinGermany).
(1)ethylene(Wackeroxidationprocess)(2)ethanol(catalyticdehydrogenation)(3)ethanol+oxygen(oxidation)(4)
acetylene+water(vinylation)(5)oxygenates,FischerTropsch,mixed(fractionationcoproducedwith
methanol/ethanol/isopropanol/nbutanol/isobutanol/amylalcohol,primary/acetone/methylethylketone)
Ashford,R.D.Ashford'sDictionaryofIndustrialChemicals.London,England:WavelengthPublicationsLtd.,1994.,p.10
ProducedbyoxidationofalcoholwithNa2Cr2O7andH2SO4usuallyfromacetylene,diluteH2SO4andmercuric
oxideascatalystalsobypassingalcoholvaporoveraheatedmetalliccatalyst.
O'Neil,M.J.(ed.).TheMerckIndexAnEncyclopediaofChemicals,Drugs,andBiologicals.WhitehouseStation,NJ:Merck
andCo.,Inc.,2006.,p.8
Dehydrogenationofethanol....Ethanolvaporispassedat260290degCoveracatalystconsistingofcopper
spongeorcopperactivatedwithchromiumoxideinatubularreactor.Aconversionof2550%perrunisobtained.
Bywashingwithalcoholandwater,acetaldehydeandethanolareseparatedfromtheexhaustgas,whichismainly
hydrogen.Pureacetaldehydeisobtainedbydistillationtheethanolisseparatedfromwaterandhigherboiling
productsbydistillationandflowsbacktothereactor.Thefinalacetaldehydeyieldisabout90%.Byproductsinclude
butyricacid,crotonaldehyde,andethylacetate.
Ullmann'sEncyclopediaofIndustrialChemistry.6thed.Vol1:FederalRepublicofGermany:WileyVCHVerlagGmbH&Co.
2003toPresent,p.V1136(2003)
Oxidationofethanolistheoldestandthebestlaboratorymethodforpreparingacetaldehyde.Inthecommercial
process,ethanolisoxidizedcatalyticallywithoxygen(orair)inthevaporphase.Copper,silver,andtheiroxidesor
alloysarethemostfrequentlyusedcatalysts.
Directoxidationofethylene....AnaqueoussolutionofPdCl2andCuCl2isusedascatalyst.Acetaldehyde
formationhadalreadybeenobservedinthereactionbetweenethyleneandaqueouspalladiumchloride....Inthe
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WackerHoechstprocess,metallicpalladiumisreoxidizedbyCuCl2,whichisthenregeneratedwithoxygen....Only
averysmallamountofPdCl2isrequiredfortheconversionofethylene.Thereactionofethylenewithpalladium
chlorideistheratedeterminingstep.Oneandtwostageversionsoftheprocessareonstream.Intheonestage
method,anethyleneoxygenmixturereactswiththecatalystsolution.Duringthereactionastationarystateis
establishedinwhich"reaction"(formationofacetaldehydeandreductionofCuCl2)and"oxidation"(reoxidationof
CuCl)proceedatthesamerate.Thisstationarystateisdeterminedbythedegreeofoxidationofthecatalyst....In
thetwostageprocessthereactioniscarriedoutwithethyleneandthenwithoxygenintwoseparatereactors.The
catalystsolutionisalternatelyreducedandoxidized.Atthesametimethedegreeofoxidationofthecatalyst
changesalternately.Airisusedinsteadofpureoxygenforthecatalystoxidation.
Acetaldehydeisalsoformedintheproductionofvinylacetatefromethyleneoracetylene.Itisseparatedby
distillationandisnormallyconvertedtoaceticacidforreuse.Inoneversionofthemethodstartingfromethylene,
vinylacetateandacetaldehydeareobtainedinamolarratioof1:1.Thismakestheprocessnearlyselfsufficientin
aceticacid.
8.2 Formulations/Preparations
GRADES:COMMERCIALLYAVAILAS50%AQSOLNOR99%CPINSMALLSTEELCYLINDERS.
Fenaroli'sHandbookofFlavorIngredients.Volume2.Edited,translated,andrevisedbyT.E.FuriaandN.Bellanca.2nded.
Cleveland:TheChemicalRubberCo.,1975.,p.3
AcetaldehydeisavailinUSAwithfollowingtypicalspecifications:purity,99.5%minacidity(asaceticacid),0.1%
max...tomeettherequirementsoftheFoodChemicalCodex,acetaldehydemustpassaninfraredidentification
test&meetthefollowingspecifications:purity,99.0%minacidity(asaceticacid)0.1%maxnonvolatileresidue,
0.006%max....
Grade:Technical99%
8.3 Consumption
CHEMINTFORACETICACID,61%CHEMINTFORPYRIDINE&PYRIDINEBASES,9%CHEMINTFOR
PERACETICACID,8%CHEMINTFORPENTAERYTHRITOL,7%CHEMINTFOR1,3BUTYLENEGLYCOL,
2%CHEMINTFORCHLORAL,1%OTHERUSES(INCLEXPORTS),12%(1982)
SRI
USAacetaldehydedemandin1978was1.30billionlb1979,1.35billionlb1983,1.58billionlb.
ChemMarketReporterp.9(1983)
Aceticacid,50%exports,14%miscellaneousincludinglacticacidandcrotonaldehyde,13%pyridineandpyridine
bases,8%pentaerythritol,7%peraceticacid,6%1,3butyleneglycol,2%(1986).
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CHEMICALPROFILE:Acetaldehyde,1986
AsurveyofUSAindustryontheuseoffoodadditivesreportedthat8.6thousandkgofacetaldehydewereusedin
1976asanimportantcomponentofmanyflavorsaddedtofoods,suchasmilkproducts,bakedgoods,fruitjuices,
candies,desserts&softdrinks,atusuallevels...upto0.047%(1976).
Acetaldehydeisoneofthedenaturantsapprovedforuse(atalevelof10lb/100gal(12g/l)ofalcohol)intheUSA
inspeciallydenaturedalcoholFormulaNo29.AlthoughthevolumeofthisformulausedintheUSAeachyearis
published,noinformationisavailableontheamountmadewithacetaldehyde.
Syntheticpyridinederivatives,peraceticacid,acetateestersbytheTischenkoroute,andpentaerythritolaccountfor
40%ofacetaldehydedemand.Allofthesematerialsmaybepreparedfromalternativeprocesses.
p.V1(1991)105
8.4 U.S.Production
(1969)748kilotons(1970)726kilotons(1971)680kilotons(1972)644kilotons(1973)635kilotons(1974)649
kilotons(1975)499kilotons(1976)612kilotons(1987)ca.330kilotons/Table/
p.V1(1991)105
(1985)2.86X10+12g
CHEMICALPRODUCTSSYNOPSIS:Acetaldehyde,1985
AnnualproductioncapacityasofJan.1,1994:EastmanChemicalCompany250miilionpounds,HoechstCelanese
Corp.250millionpounds,Total500millionpounds.
SRI.1994DirectoryofChemicalProducersUnitedStatesofAmerica.MenloPark,CA:SRIInternational,1994.,p.435
443000tonnes/year
AcetaldehydeislistedasaHighProductionVolume(HPV)chemical(65FR81686).ChemicalslistedasHPVwere
producedinorimportedintotheU.S.in>1millionpoundsin1990and/or1994.TheHPVlistisbasedonthe1990
InventoryUpdateRule.(IUR)(40CFRpart710subpartB51FR21438).
EPA/OfficeofPollutionPreventionandToxicsHighProductionVolume(HPV)ChallengeProgram.Availablefromthe
DatabaseQuerypageat:http://www.epa.gov/hpv/pubs/general/opptsrch.htmonAcetaldehyde(75070)asofFebruary5,2009
ProductionvolumesfornonconfidentialchemicalsreportedundertheInventoryUpdateRule.
Year
ProductionRange(pounds)
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1986
>500million1billion
1990
>500million1billion
1994
>100million500million
1998
2002
USEPANonconfidentialProductionVolumeInformationSubmittedbyCompaniesforChemicalsUnderthe19862002
InventoryUpdateRule(IUR).Acetaldehyde(75070).Availablefrom,asofJanuary29,2009:
http://www.epa.gov/oppt/iur/tools/data/2002vol.html
8.5 U.S.Imports
(1985)6.14X10+5g
BUREAUOFTHECENSUSUSIMPORTSFORCONSUMPTIONANDGENERALIMPORTS1985p.1579
8.6 U.S.Exports
(1985)5.45X10+11g
CHEMICALPRODUCTSSYNOPSIS:Acetaldehyde,1985
8.7 SamplingProcedures
EPAOSWMethod0100.SamplingforFormaldehydeandOtherCarbonylCompoundsinIndoorAir.Thismethod
providesproceduresforthesamplingofvariouscarbonylcompoundsinindoorairbyderivatizationwith2,4
dinitrophenylhydrazine(DNPH)inasilicagelcartridge.
USEPAEMMI.EPA'sEnvironmentalMonitoringMethodsIndex.Version1.1.PC#4082.Rockville,MD:Government
Institutes(1997)
8.8 AnalyticLaboratoryMethods
Acetaldehydeisdetectedinindoor&outdoorairbygaschromatography/massspectrometrywithalimitofdetection
of0.9ug/cumfor2litersamples.inindustrialemissions(air)bygaschromatographyequippedwithflame
ionizationdetector&haslimitofdetectionof1.2mg/cumfor200litersamples.
Acetaldehydeisdetectedinautomobileexhaustbyhighperformanceliquidchromatographyequippedwith
ultravioletdetection&haslimitofdetectionof18ug/cumfor20litersamplesinfluegasesfromwoodfurnaces&
stovesbygaschromatographywithflameionizationdetector(limitofdetectionisnotgiven)
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Acetaldehydeisdetectedinvolatileemissionsfromwastewaterbygaschromatographywithflameionization
detection(limitofdetectionisnotgiven)inaqueoussolutions/industrialeffluentsbygaschromatography/mass
spectrometrywithlimitofdetectionof200ug/linplants(cotton)bygaschromatography/massspectrometry(limitof
detectionisnotgiven).
Acetaldehydeisdetectedinwine&beerbyHPLC.Limitofdetectioninwineis0.01uglimitofdetectioninbeeris
notgiven.
AhighperformanceliquidchromatographicmethodforthesimultaneousdeterminationofC1toC2aldehydesand
organicacidsinaqueoussampleshasbeendeveloped.Aldehydesandorganicacidsareseparatedafter
derivatizationofthealdehydesby2,4dinitrophenylhydrazineandbygradientelutiononreversedphasematerial
(Spherisorb,RP18).MeasurementisbyUVandconductivity,respectively.Derivatizationofaldehydesstabilizes
samplesforupto5daysinthefield.Thedetectionlimitis10ug/lforacetaldehyde.
KeukenMP,SchoonebeekCAMIntJEnvironAnalChem35(4):22739(1989)
EPAMethod554.DeterminationofCarbonylCompoundsinDrinkingWaterbyDinitrophenylhydrazine
DerivatizationandHighPerformanceLiquidChromatography.Thismethodisusedforthedeterminationofselected
carbonylcompoundsinfinisheddrinkingwaterorrawsourcewater.Detectionlimit=69ug/l.
Institutes(1997)
OSWMethod8315.DeterminationofCarbonylCompoundsbyHighPerformanceLiquidChromatography(HPLC).
Thismethodisapplicabletovariousmatricesbyderivatizationwith2,4dinitrophenylhydrazine(DNPH).Detection
limit=44ug/l.
Institutes(1997)
OSWMethod8315ALLE.DeterminationofCarbonylCompoundsbyHighPerformanceLiquidChromatography
(HPLC)UsingLiquidLiquidExtraction.Thismethodisapplicabletothedeterminationoffreecarbonylcompounds
invariousmatricesbyderivatizationwith2,4dinitrophenylhydrazine(DNPH).Detectionlimit=110ug/l.
Institutes(1997)
OSWMethod8315ALSE.DeterminationofCarbonylCompoundsbyHighPerformanceLiquidChromatography
(HPLC)usingLiquidSolidExtraction.Thismethodisapplicabletothedeterminationoffreecarbonylcompoundsin
variousmatricesbyderivatizationwith2,4dinitrophenylhydrazine(DNPH).Detectionlimit=44ug/l.
Institutes(1997)
AREALMethodIP6A.DeterminationofFormaldehydeandOtherAldehydesinIndoorAirUsingaSolidAdsorbent
Cartridge.Thismethodisapplicableforthedeterminationofformaldehyde,butwithmodification,andfourteen
otheraldehydesthatcanbedetectedinindoorair.Detectionlimit=0.01ppb.
Institutes(1997)
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AREALMethodIP6B.DeterminationofFormaldehydeandOtherAldehydesinIndoorAirUsingaContinuous
ColorimetricAnalyzer.Thismethodisapplicabletothesamplingandanalysisofformaldehydeinindoorairusing
theautomatedwetchemicalcolorimetricanalyzerwithacontinuoussignaloutput.Detectionlimit=0.03ppb.
Institutes(1997)
AREALMethodIP6C.DeterminationofFormaldehydeandOtherAldehydesinIndoorAirUsingPassiveSampling
Device.Thismethodisapplicablepassivesamplingofformaldehyde(CH2O)andotheraldehydesinindoorair.
Detectionlimitunspecified.
Institutes(1997)
AREALMethodTO11.DeterminationofFormaldehydeinAmbientAirusingAdsorbentCartridgeFollowedbyHigh
PerformanceLiquidChromatography(HPLC).Thismethodisapplicablefordeterminationofformaldehydein
ambientair.Detectionlimit=0.01ppb.
Institutes(1997)
Method:EPATSC/NERL556Procedure:gaschromatographywithelectroncapturedetectorAnalyte:
acetaldehydeMatrix:finisheddrinkingwaterandrawsourcewaterDetectionLimit:0.21ug/L.
NationalEnvironmentalMethodsIndexAnalytical,TestandSamplingMethods.Availablefromhttp://www.nemi.govon
Acetaldehyde(75070)asofFebruary10,2009
Method:EPAOGWDW/TSC556.1Procedure:fastgaschromatographysystemequippedwithanelectroncapture
detectorAnalyte:acetaldehydeMatrix:finisheddrinkingwaterandrawsourcewaterDetectionLimit:0.18ug/L.
NationalEnvironmentalMethodsIndexAnalytical,TestandSamplingMethods.Availablefromhttp://www.nemi.govon
Acetaldehyde(75070)asofFebruary10,2009
Method:NIOSH2018Procedure:highperformanceliquidchromatographywithultravioletdetectionAnalyte:
acetaldehydeMatrix:airDetectionLimit:0.2ug/sample.
CDCNIOSHManualofAnalyticalMethods,4thed.Acealdehyde(75070).Availablefrom,asofFebruary11,2009:
http://www.cdc.gov/niosh/docs/2003154/
Method:NIOSH2538Procedure:gaschromatographywithflameionizationdetectorAnalyte:acetaldehyde
Matrix:airDetectionLimit:2ug/sample.
Method:NIOSH2539Procedure:gaschromatography,flameionizationdetectorandgaschromatography/mass
spectrometryAnalyte:acetaldehydeMatrix:airDetectionLimit:2ug/sample.
Method:NIOSH3507Procedure:highperformanceliquidchromatographywithultravioletdetectionAnalyte:
acetaldehydeMatrix:airDetectionLimit:0.1mg/sample.
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Method:OSHA68Procedure:gaschromatographyusinganitrogenselectivedetectorAnalyte:acetaldehyde
Matrix:airDetectionLimit:3.14ugpersample(580ppbor1050ug/cum).
U.S.DepartmentofLabor/OccupationalSafetyandHealthAdministration'sIndexofSamplingandAnalyticalMethods.
Availablefrom:http://www.osha.gov/dts/sltc/methods/toc.htmlonAcetaldehyde(75070)asofFebruary11,2009
Method:AOAC956.06Procedure:titrimetricmethodAnalyte:acetaldehydeMatrix:frozenvegetablesDetection
Limit:notprovided.
OfficialMethodsofAnalysisofAOACInternational,18thEditionOnline.Acetaldehyde(75070).Availablefrom,asof
February12,2009:http://www.aoac.org
8.9 ClinicalLaboratoryMethods
GASLIQUIDCHROMATOGRAPHICDETERMINATIONOFETHANOL&ACETALDEHYDEINBLOOD.
BRIENETALCLINCHIMACTA87(1):175(1978)
ACETALDEHYDECONCNINBLOODFROM15NORMALPTWASAPPROX60UMOL/LASDETERMINEDBY
HIGHPRESSURELIQUIDCHROMATOGRAPHY.ACETALDEHYDEWASPROBABLYBOUNDTO
NONDIALYZABLEBLOODELEMENTS.
THOMASMETALLANCET2(8245):5301(1981)
ANEWTECHNIQUEISDESCRIBEDFORMEASURINGACETALDEHYDEINTHEBREATH,BYFREEZING
OUTTHEVOLATILECOMPONENTSOFBREATHINLIQNITROGEN,THENASSAYINGTHIS
CONCENTRATEDSPECIMENBYGASCHROMATOGRAPHY.
DANNECKERJRETALANALBIOCHEM114(1):17(1981)
ACETALDEHYDEINHUMANBLOODISDETERMINEDBYGASCHROMATOGRAPHY.METHODUTILIZES
SODIUMNITRITESULFOSALICYLICACIDASANINHIBITOROFETHANOLOXIDIZINGSYSTEMSBY
MEANSOFWHICHINTERFERENCEOFETHANOLISREDUCED.
CHRISTENSENJMETALCLINCHEMACTA116(3):38995(1981)
Acetaldehydeisdetectedinbiologicalfluidsbygaschromatographyequippedwithflameionizationdetector&has
limitofdetectionof0.5to32mg/l(rangeofdetection)inmother'smilkbygaschromatography/massspectrometry
(limitofdetectionisnotgiven).
HepaticandbloodacetaldehydeconcentrationsduringethanoloxidationweredeterminedinC57andDBAmice.
Liveracetaldehydewasdeterminedwiththeperchloricacidthioureamethod(noartifactualacetaldehydeformation).
Levelsrangingfrom5to118nmole/gwereobserved.Atethanolconcentrationsbelow5060umole/g,liver
acetaldehydeconcentrationswerehigherinDBAcomparedwithC57mice.Apositivecorrelationwasfound
betweentheethanolandacetaldehydeconcentration,whenethanolconcentrationwasbelow25(DBA)or70
umole/g(C57).Athigherethanolconcentrationsthecorrelationstendedtobecomenegative.Hemolysiscauses
artifactualformationofacetaldehydewhenbloodacetaldehydeisdeterminedusingthioureaorsemicarbazide
methods.Themagnitudeoftheartifactuallyformedacetaldehydewasofsuchorderthatnoconclusionsregarding
theexistenceoftrueinvivobloodacetaldehydeconcentrationscouldbedrawn.
ErikssonPJetalBiochemPharmacol33(14):22136(1984)
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9 SafetyandHazards
9.1 HazardsIdentification
9.1.1 FireHazard
Extremelyflammable.
9.1.2 ExplosionHazard
Vapour/airmixturesareexplosive.
9.1.3 SkinHazard
Redness.Pain.
9.1.4 InhalationHazard
Cough.
9.1.5 EyeHazard
Redness.Pain.
9.1.6 IngestionHazard
Diarrhoea.Dizziness.Nausea.Vomiting.
9.1.7 FirePotential
Highlyflammableliquid.
Acetaldehydevaporleakingintoabuildingequippedonlywithflameproofelectricalequipment...ignited,possibly
oncontactwithrustedsteel,corrodedaluminumorhotsteamlines.
Mixturesof3060%ofacetaldehydevaporwithairor6080%withoxygenmayigniteonsurfacesat176&105deg
C,respectively,owingtoformation&subsequentviolentdecompofperoxyaceticacid.
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9.1.8 Skin,Eye,andRespiratoryIrritations
Corrosive.Causessevereeyeandskinburns.Serioushealthhazard.Iritatingtoskin,eyes,andrespiratorysystem.
Narcosis,nausea,andlossofconsciousnessmayresultfromexposuretohighconcentrationsofvapor.
Eyeirritationsensitivepersons:25ppm15mineyeirritation:50ppm15minirritationofrespiratorytract:134ppm
30minirritationofnoseandthroat:200ppm15min.
Verschueren,K.HandbookofEnvironmentalDataofOrganicChemicals.2nded.NewYork,NY:VanNostrandReinholdCo.,
1983.,p.141
Accordingtostudiesonhumansandanimals,acetaldehydeismildlyirritatingtotheeyesandtheupperrespiratory
tract.Inlimitedstudiesonhumanvolunteers,acetaldehydewasmildlyirritatingtotheeyesandupperrespiratory
tract.Cutaneouserythemahasalsobeenobservedinthepatchtestingofhumans.
9.2 SafetyandHazardProperties
9.2.1 LEL
4%
4%
9.2.2 UEL
60%
60% fromOSHAOccupationalChemicalDB[5]http://www.osha.gov/chemicaldata/chemResult.html?RecNo=570
9.2.3 Flammability
Lowerflammablelimit:4.0%byvolumeUpperflammablelimit:60%byvolume
ClassIAFlammableLiquid:Fl.P.below73FandBPbelow100F.
9.2.4 CriticalTemperature
Criticaltemperature:188degCcriticalpressure:63.2atm
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9.2.5 CriticalPressure
Criticaltemperature:188degCcriticalpressure:63.2atm
9.2.6 NFPAHazardClassification
Flammability:4.4=Thisdegreeincludesflammablegases,flammablecryogenicmaterials,pyrophoricliquids,and
ClassIAflammableliquids.Thepreferredmethodoffireattackistostoptheflowofmaterialortoprotect
exposureswhileallowingthefiretoburnitselfout.
Instability:2.2=Materialsthatcanundergoviolentchemicalchangesatelevatedtemperaturesandpressures.This
alsoincludesmaterialsthatmayreactviolentlywithwaterorthatmayformpotentiallyexplosivemixtureswith
water.Inadvancedormassivefiresinvolvingthesematerials,firefightingshouldbedonefromasafedistanceor
fromaprotectedlocation.
Health:2.2=Materialsthat,onintenseorcontinued(butnotchronic)exposure,couldcausetemporary
incapacitationorpossibleresidualinjury,includingthoserequiringtheuseofrespiratoryprotectiveequipmentthat
hasanindependentairsupply.Thesematerialsarehazardoustohealth,butareasmaybeenteredfreelyif
personnelareprovidedwithfullfacemaskselfcontainedbreathingapparatusthatprovidescompleteeye
protection.
FireProtectionGuidetoHazardousMaterials.13ed.Quincy,MA:NationalFireProtectionAssociation,2002.
9.2.7 NFPAFireRating
4
9.2.8 NFPAReactivityRating
2
9.2.9 NFPAHealthRating
2
9.2.10 NFPAOther
CARCINOGEN(Ca)REDUCEEXPOSURETOLOWESTFEASIBLECONCENTRATION(LOQ18ppm)
9.2.11 PhysicalDanger
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Thevapourisheavierthanairandmaytravelalongthegrounddistantignitionpossible.
9.2.12 ChemicalDanger
2000ppmNIOSHconsidersacetaldehydetobeapotentialoccupationalcarcinogen.
2005151(2005)
Contactwithairgeneratesexplosiveperoxides.Thesubstancemaypolymerizeundertheinfluenceofacidsand
alkalinehydroxidesinthepresenceoftracemetals(iron).Thisgeneratesfireandexplosionhazard.Thesubstance
isastrongreducingagent.Itreactsviolentlywithoxidants,strongacids,halogensandamines.Thisgeneratesfire
orexplosionhazard.
9.2.13 OccupationalExposureLimits
TLV:25ppm(ceilingvalue)A3(confirmedanimalcarcinogenwithunknownrelevancetohumans)(ACGIH
2003).MAK:50ppm,91mg/mCarcinogencategory:5Peaklimitationcategory:I(1)Pregnancyriskgroup:C
Germcellmutagengroup:5(DFG2007).
9.2.14 InhalationRisk
Aharmfulcontaminationoftheaircanbereachedveryquicklyonevaporationofthissubstanceat20C.
9.2.15 EffectsofShortTermExposure
Thesubstanceismildlyirritatingtotheeyes,skinandrespiratorytract.Thesubstancemaycauseeffectsonthe
centralnervoussystem.
9.2.16 EffectsofLongTermExposure
Repeatedorprolongedcontactwithskinmaycausedermatitis.Thesubstancemayhaveeffectsontherespiratory
tract.Thismayresultintissuelesions.Thissubstanceispossiblycarcinogenictohumans.
9.2.17 ExplosiveLimitsandPotential
Lower,4.1%Upper55%byvolume.
Clayton,G.D.,F.E.Clayton(eds.)Patty'sIndustrialHygieneandToxicology.Volumes2A,2B,2C,2D,2E,2F:Toxicology.4th
ed.NewYork,NY:JohnWiley&SonsInc.,19931994.,p.285
Acetaldehydeshouldnotbeallowedtoenteraconfinedspacesuchasasewer,becauseofthepossibilityofan
explosion.
Mackison,F.W.,R.S.Stricoff,andL.J.Partridge,Jr.(eds.).NIOSH/OSHAOccupationalHealthGuidelinesforChemical
Hazards.DHHS(NIOSH)PublicationNo.81123(3VOLS).Washington,DC:U.S.GovernmentPrintingOffice,Jan.1981.,p.4
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Oxidizesreadilyinairtoformunstableperoxidesthatmayexplodespontaneously.
Mayexplodewithoutwarningwhenexposedtoheat,dust,corrosives,oroxidizers.
Sittig,M.HandbookofToxicandHazardousChemicalsandCarcinogens,2002.4thed.Vol1AHNorwich,NY:Noyes
Publications,2002.,p.24
Explosivelimits,vol%inair:460 fromILOICSC[3]http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=0009
9.2.18 AcceptableDailyIntakes
TheFAO/WHOacceptabledailyintakeis0.02.5mg/kgbodyweight.Thelevelofuseasafoodadditive
(flavorings)is1300ppm.
Doull,J.,C.D.Klaassen,andM.D.Amdur(eds.).CasarettandDoull'sToxicology.2nded.NewYork:MacmillanPublishing
Co.,1980.,p.599601
9.2.19 OSHAStandards
PermissibleExposureLimit:TableZ18hrTimeWeightedAvg:200ppm(360mg/cum).
29CFR1910.1000(USDOL)U.S.NationalArchivesandRecordsAdministration'sElectronicCodeofFederalRegulations.
Availablefrom,asofJanuary26,2009:http://www.gpoaccess.gov/ecfr
Vacated1989OSHAPELTWA100ppm(180mg/cum)STEL150ppm(270mg/cum)isstillenforcedinsome
states.
NIOSH.NIOSHPocketGuidetoChemicalHazards.DHHS(NIOSH)PublicationNo.97140.Washington,D.C.U.S.
GovernmentPrintingOffice,1997.,p.359
9.2.20 NIOSHRecommendations
NIOSHconsidersacetaldehydetobeapotentialoccupationalcarcinogen.
2005151(2005)
NIOSHusuallyrecommendsthatoccupationalexposurestocarcinogensbelimitedtothelowestfeasibleconcn.
NIOSH.NIOSHPocketGuidetoChemicalHazards.DHHS(NIOSH)PublicationNo.97140.Washington,D.C.U.S.
GovernmentPrintingOffice,1997.,p.2
9.3 FirstAidMeasures
9.3.1 FirstAid
Eye:IrrigateimmediatelySkin:WaterflushpromptlyBreathing:RespiratorysupportSwallow:Medicalattention
immediately
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EYES:Firstcheckthevictimforcontactlensesandremoveifpresent.Flushvictim'seyeswithwaterornormal
salinesolutionfor20to30minuteswhilesimultaneouslycallingahospitalorpoisoncontrolcenter.Donotputany
ointments,oils,ormedicationinthevictim'seyeswithoutspecificinstructionsfromaphysician.IMMEDIATELY
transportthevictimafterflushingeyestoahospitalevenifnosymptoms(suchasrednessorirritation)develop.
SKIN:IMMEDIATELYfloodaffectedskinwithwaterwhileremovingandisolatingallcontaminatedclothing.Gently
washallaffectedskinareasthoroughlywithsoapandwater.IMMEDIATELYcallahospitalorpoisoncontrolcenter
evenifnosymptoms(suchasrednessorirritation)develop.IMMEDIATELYtransportthevictimtoahospitalfor
treatmentafterwashingtheaffectedareas.INHALATION:IMMEDIATELYleavethecontaminatedareatakedeep
breathsoffreshair.IMMEDIATELYcallaphysicianandbepreparedtotransportthevictimtoahospitalevenifno
symptoms(suchaswheezing,coughing,shortnessofbreath,orburninginthemouth,throat,orchest)develop.
Provideproperrespiratoryprotectiontorescuersenteringanunknownatmosphere.Wheneverpossible,Self
ContainedBreathingApparatus(SCBA)shouldbeusedifnotavailable,usealevelofprotectiongreaterthanor
equaltothatadvisedunderProtectiveClothing.INGESTION:DONOTINDUCEVOMITING.Volatilechemicals
haveahighriskofbeingaspiratedintothevictim'slungsduringvomitingwhichincreasesthemedicalproblems.If
thevictimisconsciousandnotconvulsing,give1or2glassesofwatertodilutethechemicalandIMMEDIATELY
callahospitalorpoisoncontrolcenter.IMMEDIATELYtransportthevictimtoahospital.Ifthevictimisconvulsing
orunconscious,donotgiveanythingbymouth,ensurethatthevictim'sairwayisopenandlaythevictimonhis/her
sidewiththeheadlowerthanthebody.DONOTINDUCEVOMITING.IMMEDIATELYtransportthevictimtoa
hospital.OTHER:Sincethischemicalisaknownorsuspectedcarcinogenyoushouldcontactaphysicianforadvice
regardingthepossiblelongtermhealtheffectsandpotentialrecommendationformedicalmonitoring.
Recommendationsfromthephysicianwilldependuponthespecificcompound,itschemical,physicalandtoxicity
properties,theexposurelevel,lengthofexposure,andtherouteofexposure.(NTP,1992)
9.3.2 FireFirstAid
Usewaterinlargeamounts,powder,alcoholresistantfoam,carbondioxide.
9.3.3 ExplosionFirstAid
Incaseoffire:keepdrums,etc.,coolbysprayingwithwater.
9.3.4 InhalationFirstAid
Freshair,rest.Referformedicalattention.
9.3.5 SkinFirstAid
Removecontaminatedclothes.Rinseandthenwashskinwithwaterandsoap.Referformedicalattention.
9.3.6 EyeFirstAid
Firstrinsewithplentyofwaterforseveralminutes(removecontactlensesifeasilypossible),thenreferformedical
attention.
9.3.7 IngestionFirstAid
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Rinsemouth.Giveoneortwoglassesofwatertodrink.Referformedicalattention.
9.4 FireFightingMeasures
Fightfirefromprotectedlocationormaximumpossibledistance.usedrychemical,"alcoholresistant"foam,or
carbondioxide.watermaybeineffective.Usewaterspraytokeepfireexposedcontainerscool.
Ifmaterialisonfireorinvolvedinafire:Donotextinguishfireunlessflowcanbestopped.Usewaterinflooding
quantitiesasfog.Solidstreamsofwatermaybeineffective.Coolallaffectedcontainerswithfloodingquantitiesof
water.Applywaterfromasfaradistanceaspossible.Use"alcohol"foam,drychemicalorcarbondioxide.
AssociationofAmericanRailroadsBureauofExplosives.EmergencyHandlingofHazardousMaterialsinSurface
Transportation.AssociationofAmericanRailroads,Pueblo,CO.2005,p.1
Evacuation:Iffirebecomesuncontrollableorcontainerisexposedtodirectflameconsiderevacuationofonehalf
(1/2)mileradius.
Inadvanced,ormassivefires,firefightingshouldbedonefromasafedistance,orfromaprotectedlocation.Use
drychemical,"alcohol"foam,orcarbondioxide.Watermaybeineffectivebutwatershouldbeusedtokeepfire
exposedcontainerscool.Ifleakorspillhasnotignited,usewaterspraytodispersevapors.Ifitisnecessarytostop
aleak,usewaterspraytoprotectmenattemptingtodoso.Waterspraymaybeusedtoflushspillsawayfrom
exposuresanddilutetononflammablemixtures.
Prager,J.C.EnvironmentalContaminantReferenceDatabookVolume1.NewYork,NY:VanNostrandReinhold,1995.,p.5
9.4.1 FireFighting
Donotextinguishfireunlessflowcanbestopped.Usewaterinfloodingquantitiesasfog.Solidstreamsofwater
maybeineffective.Coolallaffectedcontainerswithfloodingquantitiesofwater.Applywaterfromasfaradistance
aspossible.Use"alcohol"foam,drychemicalorcarbondioxide.(AAR,1999)
9.4.2 OtherFireFightingHazards
Vaporsareheavierthanairandmaytravelaconsiderabledistancetoasourceofignitionandflashback.
U.S.CoastGuard,DepartmentofTransportation.CHRISHazardousChemicalData.VolumeII.Washington,D.C.:U.S.
GovernmentPrintingOffice,19845.
9.5 AccidentalReleaseMeasures
9.5.1 SpillageDisposal
Removeallignitionsources.Evacuatedangerarea!Personalprotection:filterrespiratorfororganicgasesand
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vapoursadaptedtotheairborneconcentrationofthesubstance.DoNOTletthischemicalentertheenvironment.
Collectleakingliquidinsealablecontainers.Absorbremainingliquidinsandorinertabsorbent.Thenstoreand
disposeofaccordingtolocalregulations.DoNOTabsorbinsawdustorothercombustibleabsorbents.Remove
vapourwithfinewaterspray.
9.5.2 CleanupMethods
(1)Removeallignitionsources(2)Ventilateareatodispersegas(3)Ifingaseousform,stopflowofgas(4)Ifin
liquidform,forsmallquantitiesabsorbonpapertowels.Evaporateinsafeplace(fumehood).allowsufficienttime
forvaporstocompletelyclearhoodductwork,thenburnthepaperinalocationawayfromcombustiblematerials.
Largequantitiescanbereclaimedorcollectedandatomizedinasuitablecombustionchamber.Acetaldehyde
shouldnotbeallowedtoenteraconfinedspacesuchasasewer,becauseofpossibilityofanexplosion.Sewers
designedtoprecludetheformationofexplosiveconcentrationofacetaldehydevaporsarepermitted.
PRECAUTIONSFOR"CARCINOGENS":Ahighefficiencyparticulatearrestor(HEPA)orcharcoalfilterscanbe
usedtominimizeamtofcarcinogeninexhaustedairventilatedsafetycabinets,labhoods,gloveboxesoranimal
rooms...Filterhousingthatisdesignedsothatusedfilterscanbetransferredintoplasticbagwithout
contaminatingmaintenancestaffisavailcommercially.Filtersshouldbeplacedinplasticbagsimmediatelyafter
removal...Theplasticbagshouldbesealedimmediately...Thesealedbagshouldbelabelledproperly...Waste
liquids...shouldbeplacedorcollectedinpropercontainersfordisposal.Thelidshouldbesecured&thebottles
properlylabelled.Oncefilled,bottlesshouldbeplacedinplasticbag,sothatoutersurface...isnotcontaminated
...Theplasticbagshouldalsobesealed&labelled....Brokenglassware...shouldbedecontaminatedbysolvent
extraction,bychemicaldestruction,orinspeciallydesignedincinerators./ChemicalCarcinogens/
Montesano,R.,H.Bartsch,E.Boyland,G.DellaPorta,L.Fishbein,R.A.Griesemer,A.B.Swan,L.Tomatis,andW.Davis
(eds.).HandlingChemicalCarcinogensintheLaboratory:ProblemsofSafety.IARCScientificPublicationsNo.33.Lyon,
France:InternationalAgencyforResearchonCancer,1979.,p.15
Landspill:Digapit,pond,lagoon,holdingareatocontainliquidorsolidmaterial./SRP:Iftimepermits,pits,
ponds,lagoons,soakholes,orholdingareasshouldbesealedwithanimpermeableflexiblemembraneliner./Dike
surfaceflowusingsoil,sandbags,foamedpolyurethane,orfoamedconcrete.Absorbbulkliquidwithflyash,
cementpowder,orcommercialsorbents.Neutralizewithsodiumbisulfate(NaHSO4).
Waterspill:Addsodiumbisulfate(NaHSO4).Ifdissolved,inregionof10ppmorgreaterconcentration,apply
activatedcarbonattentimesthespilledamount.Usemechanicaldredgesorliftstoremoveimmobilizedmassesof
pollutantsandprecipitates.
Airspill:Applywatersprayormisttoknockdownvapors.
Eliminateallignitionsources.Stoporcontroltheleak,ifthiscanbedonewithoutunduerisk.Usewatersprayto
coolanddispersevapors,protectpersonnel,anddilutespillstoformnonflammablemixtures.Controlrunoffand
isolatedischargedmaterialforproperdisposal.
...Absorbliquidsinvermiculite,drysand,earth,orasimilarmaterialanddepositinsealedcontainers...
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9.5.3 DisposalMethods
[40CFR240280,300306,702799(7/1/2008)]Generatorsofwaste(equaltoorgreaterthan100kg/mo)
containingthiscontaminant,EPAhazardouswastenumberU001,mustconformwithUSEPAregulationsin
storage,transportation,treatmentanddisposalofwaste.
Generatorsofwaste(equaltoorgreaterthan100kg/mo)containingthiscontaminant,EPAhazardouswaste
numberU001,mustconformwithUSEPAregulationsinstorage,transportation,treatmentanddisposalofwaste.
40CFR240280,300306,702799(7/1/2000)
Acetaldehydeisawastechemicalstreamconstituentwhichmaybesubjectedtoultimatedisposalbycontrolled
incineration.
USEPAEngineeringHandbookforHazardousWasteIncinerationp.24(1981)EPA68033025
Agoodcandidateforliquidinjectionincinerationatatemperaturerangeof650to1,600degCandaresidence
timeof0.1to2seconds.
USEPAEngineeringHandbookforHazardousWasteIncinerationp.310(1981)EPA68033025
ThefollowingwastewatertreatmenttechnologieshavebeeninvestigatedforAcetaldehyde:BiologicalTreatment.
USEPAManagementofHazardousWasteLeachate,EPAContractNo.68032766p.E29(1982)
ThefollowingwastewatertreatmenttechnologieshavebeeninvestigatedforAcetaldehyde:Activatedcarbon.
USEPAManagementofHazardousWasteLeachate,EPAContractNo.68032766p.E128(1982)
PRECAUTIONSFOR"CARCINOGENS":Thereisnouniversalmethodofdisposalthathasbeenproved
satisfactoryforallcarcinogeniccompounds&specificmethodsofchemdestruction...publishedhavenotbeen
testedonallkindsofcarcinogencontainingwaste....Summaryofavailmethods&recommendations.../given/
mustbetreatedasguideonly./ChemicalCarcinogens/
PRECAUTIONSFOR"CARCINOGENS":Totaldestruction...byincinerationmaybeonlyfeasiblemethodfor
disposalofcontaminatedlaboratorywastefrombiologicalexpt.However,notallincineratorsaresuitable...Most
efficienttype...isprobablythegasfiredtype,inwhichafirststagecombustionwithalessthanstoichiometric
air:fuelratioisfollowedbyasecondstagewithexcessair.Some...aredesignedtoaccept...aqueous&organic
solventsolutions,otherwiseitisnecessary...toabsorbsolnontosuitablecombustiblematerial,suchassawdust.
Alternatively,chemdestructionmaybeused,espwhensmallquantities...aretobedestroyedinlaboratory.
/ChemicalCarcinogens/
PRECAUTIONSFOR"CARCINOGENS":HEPA(highefficiencyparticulatearrestor)filters...canbedisposedof
byincineration.Forspentcharcoalfilters,theadsorbedmaterialcanbestrippedoffathightemp&carcinogenic
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wastesgeneratedbythistreatmentconductedto&burnedinanincinerator....LIQUIDWASTE:...Disposal
shouldbecarriedoutbyincinerationattempthat...ensurecompletecombustion.SOLIDWASTE:Carcassesof
labanimals,cagelitter&miscsolidwastes...shouldbedisposedofbyincinerationattemphighenoughtoensure
destructionofchemcarcinogensortheirmetabolites./ChemicalCarcinogens/
PRECAUTIONSFOR"CARCINOGENS":...Smallquantitiesof...somecarcinogenscanbedestroyedusingchem
reactions...butnogeneralrulescanbegiven....Asageneraltechnique...treatmentwithsodiumdichromatein
strongsulfuricacidcanbeused.Thetimenecessaryfordestruction...isseldomknown...but12daysisgenerally
consideredsufficientwhenfreshlyprepdreagentisused....Carcinogensthatareeasilyoxidizablecanbedestroyed
withmilderoxidativeagents,suchassatsolnofpotassiumpermanganateinacetone,whichappearstobea
suitableagentfordestructionofhydrazinesorofcompoundscontainingisolatedcarboncarbondoublebonds.
Concnor50%aqueoussodiumhypochloritecanalsobeusedasanoxidizingagent./ChemicalCarcinogens/
PRECAUTIONSFOR"CARCINOGENS":Carcinogensthatarealkylating,arylatingoracylatingagentspersecan
bedestroyedbyreactionwithappropriatenucleophiles,suchaswater,hydroxylions,ammonia,thiols&thiosulfate.
Thereactivityofvariousalkylatingagentsvariesgreatly...&isalsoinfluencedbysolofagentinthereaction
medium.Tofacilitatethecompletereaction,itissuggestedthattheagentsbedissolvedinethanolorsimilar
solvents....Nomethodshouldbeapplied...untilithasbeenthoroughlytestedforitseffectiveness&safetyon
materialtobeinactivated.Forexample,incaseofdestructionofalkylatingagents,itispossibletodetectresidual
compoundsbyreactionwith4(4nitrobenzyl)pyridine./ChemicalCarcinogens/
9.5.4 OtherPreventativeMeasures
Personsnotwearingprotectiveequipmentandclothingshouldberestrictedfromareasofspillsorleaksuntil
cleanuphasbeencompleted.
Suitableprotectiveclothing,aprons,handprotection&imperviousfootprotectionshouldbeprovided.Water
showers&eyeirrigationsystemsshouldbeavailonplantarea&operatorsinformedoftheirlocation.
InternationalLabourOffice.EncyclopediaofOccupationalHealthandSafety.Vols.I&II.Geneva,Switzerland:International
LabourOffice,1983.,p.36
SRP:Thescientificliteraturefortheuseofcontactlensesinindustryisconflicting.Thebenefitordetrimental
effectsofwearingcontactlensesdependnotonlyuponthesubstance,butalsoonfactorsincludingtheformofthe
substance,characteristicsanddurationoftheexposure,theusesofothereyeprotectionequipment,andthe
hygieneofthelenses.However,theremaybeindividualsubstanceswhoseirritatingorcorrosivepropertiesaresuch
thatthewearingofcontactlenseswouldbeharmfultotheeye.Inthosespecificcases,contactlensesshouldnot
beworn.Inanyevent,theusualeyeprotectionequipmentshouldbewornevenwhencontactlensesareinplace.
PRECAUTIONSFOR"CARCINOGENS":Smoking,drinking,eating,storageoffoodoroffood&beverage
containersorutensils,&theapplicationofcosmeticsshouldbeprohibitedinanylaboratory.Allpersonnelshould
removegloves,ifworn,aftercompletionofproceduresinwhichcarcinogenshavebeenused.Theyshould...wash
...hands,preferablyusingdispensersofliqdetergent,&rinse...thoroughly.Considerationshouldbegivento
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appropriatemethodsforcleaningtheskin,dependingonnatureofthecontaminant.Nostandardprocedurecanbe
recommended,buttheuseoforganicsolventsshouldbeavoided.Safetypipettesshouldbeusedforallpipetting.
PRECAUTIONSFOR"CARCINOGENS":Inanimallaboratory,personnelshouldremovetheiroutdoorclothes&
wearprotectivesuits(preferablydisposable,onepiece&closefittingatankles&wrists),gloves,haircovering&
overshoes....clothingshouldbechangeddailybut...discardedimmediatelyifobviouscontaminationoccurs...
/also,/workersshouldshowerimmediately.Inchemicallaboratory,gloves&gownsshouldalwaysbeworn...
however,glovesshouldnotbeassumedtoprovidefullprotection.Carefullyfittedmasksorrespiratorsmaybe
necessarywhenworkingwithparticulatesorgases,&disposableplasticapronsmightprovideaddnlprotection.If
gownsareofdistinctivecolor,thisisareminderthattheyshouldnotbewornoutsideoflab./Chemical
Carcinogens/
PRECAUTIONSFOR"CARCINOGENS":...Operationsconnectedwithsynth&purification...shouldbecarried
outunderwellventilatedhood.Analyticalprocedures...shouldbecarriedoutwithcare&vaporsevolvedduring...
proceduresshouldberemoved....Expertadviceshouldbeobtainedbeforeexistingfumecupboardsareused...&
whennewfumecupboardsareinstalled.Itisdesirablethattherebemeansfordecreasingtherateofairextraction,
sothatcarcinogenicpowderscanbehandledwithout...powderbeingblownaroundthehood.Gloveboxesshould
bekeptundernegativeairpressure.Airchangesshouldbeadequate,sothatconcnofvaporsofvolatile
carcinogenswillnotoccur./ChemicalCarcinogens/
PRECAUTIONSFOR"CARCINOGENS":Verticallaminarflowbiologicalsafetycabinetsmaybeusedfor
containmentofinvitroprocedures...providedthattheexhaustairflowissufficienttoprovideaninwardairflowat
thefaceopeningofthecabinet,&contaminatedairplenumsthatareunderpositivepressureareleaktight.
Horizontallaminarflowhoodsorsafetycabinets,wherefilteredairisblownacrosstheworkingareatowardsthe
operator,shouldneverbeused...Eachcabinetorfumecupboardtobeused...shouldbetestedbeforeworkis
begun(eg,withfumebomb)&labelfixedtoit,givingdateoftest&avgairflowmeasured.Thistestshouldbe
repeatedperiodically&afteranystructuralchanges./ChemicalCarcinogens/
PRECAUTIONSFOR"CARCINOGENS":Principlesthatapplytochemorbiochemlabalsoapplyto
microbiological&cellculturelabs...Specialconsiderationshouldbegiventorouteofadmin....Safestmethodof
adminvolatilecarcinogenisbyinjectionofasoln.Adminbytopicalapplication,gavage,orintratrachealinstillation
shouldbeperformedunderhood.Ifchemwillbeexhaled,animalsshouldbekeptunderhoodduringthisperiod.
Inhalationexposurerequiresspecialequipment....unlessspecificallyrequired,routesofadminotherthaninthe
dietshouldbeused.Mixingofcarcinogenindietshouldbecarriedoutinsealedmixersunderfumehood,from
whichtheexhaustisfittedwithanefficientparticulatefilter.Techniquesforcleaningmixer&hoodshouldbe
devisedbeforeexptbegun.Whenmixingdiets,specialprotectiveclothing&,possibly,respiratorsmayberequired.
PRECAUTIONSFOR"CARCINOGENS":When...adminindietorappliedtoskin,animalsshouldbekeptin
cageswithsolidbottoms&sides&fittedwithafiltertop.Whenvolatilecarcinogensaregiven,filtertopsshouldnot
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beused.Cageswhichhavebeenusedtohouseanimalsthatreceivedcarcinogensshouldbedecontaminated.
Cagecleaningfacilitiesshouldbeinstalledinareainwhichcarcinogensarebeingused,toavoidmovingof...
contaminated/cages/.Itisdifficulttoensurethatcagesaredecontaminated,&monitoringmethodsarenecessary.
Situationsmayexistinwhichtheuseofdisposablecagesshouldberecommended,dependingontype&amtof
carcinogen&efficiencywithwhichitcanberemoved./ChemicalCarcinogens/
PRECAUTIONSFOR"CARCINOGENS":Toeliminateriskthat...contaminationinlabcouldbuildupduring
conductofexpt,periodicchecksshouldbecarriedoutonlabatmospheres,surfaces,suchaswalls,floors&
benches,&...interioroffumehoods&airducts.Aswellasregularmonitoring,checkmustbecarriedoutafter
cleaningupofspillage.Sensitivemethodsarerequiredwhentestinglabatmospheresforchemsuchas
nitrosamines.Methods...should...wherepossible,besimple&sensitive..../ChemicalCarcinogens/
PRECAUTIONSFOR"CARCINOGENS":Roomsinwhichobviouscontaminationhasoccurred,suchasspillage,
shouldbedecontaminatedbytrainedlabpersonnelengagedinexpt.Designofexptshould...avoidcontamination
ofpermanentequipment....Proceduresshouldensurethatmaintenanceworkersarenotexposed...Particularcare
shouldbetakentoavoidcontaminationofdrainsorventilationducts.Incleaninglabs,proceduresshouldbeused
whichdonotproduceaerosolsordispersalofdust,ie,wetmoporvacuumcleanerequippedwithhighefficiency
particulatefilteronexhaust,whichareavailcommercially,shouldbeused.Sweeping,brushing&useofdrydusters
ormopsshouldbeprohibited....contaminatedcleaningmaterialsshouldnotbereused...Ifgownsortowelsare
contaminated,theyshouldnotbesenttolaundry,but...decontaminatedorburnt,toavoidanyhazardtolaundry
personnel./ChemicalCarcinogens/
PRECAUTIONSFOR"CARCINOGENS":Doorsleadingintoareaswherecarcinogensareused...shouldbe
markeddistinctivelywithappropriatelabels.Access...limitedtopersonsinvolvedinexpt....Aprominently
displayednoticeshouldgivethenameoftheScientificInvestigatororotherpersonwhocanadviseinan
emergency&whocaninformothers(suchasfiremen)onthehandlingofcarcinogenicsubstances./Chemical
Carcinogens/
Evacuation:Iffirebecomesuncontrollableorcontainerisexposedtodirectflameconsiderevacuationofonehalf
mileradius.Ifmaterialleaking(notonfire)considerevacuationfromdownwindareabasedonamountofmaterial
spilled,locationandweatherconditions.
Respiratorsmaybeusedwhenengineeringandworkpracticecontrolsarenottechnicallyfeasible,whensuch
controlsareintheprocessofbeinginstalled,orwhentheyfailandneedtobesupplemented.
Clothingwetwithliquidacetaldehydeshouldbeplacedinclosedcontainersforstorageuntilitcanbediscardedor
untilprovisionismadefortheremovalofacetaldehydefromtheclothing.Iftheclothingistobelaunderedor
otherwisecleanedtoremovetheacetaldehyde,thepersonperformingtheoperationshouldbeinformedof
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acetaldehyde'shazardousproperties.Anyclothingwhichbecomeswetwithliquidacetaldehydeshouldberemoved
immediatelyandnotrewornuntiltheacetaldehydeisremovedfromtheclothing.
SRP:Contaminatedprotectiveclothingshouldbesegregatedinsuchamannersothatthereisnodirectpersonal
contactbypersonnelwhohandle,dispose,orcleantheclothing.Qualityassurancetoascertainthecompletenessof
thecleaningproceduresshouldbeimplementedbeforethedecontaminatedprotectiveclothingisreturnedforreuse
bytheworkers.Contaminatedclothingshouldnotbetakenhomeatendofshift,butshouldremainatemployee's
placeofworkforcleaning.
Wherethereisanypossibilitythatemployee'seyesmaybeexposedtoliquidacetaldehydeaneyewashfacility
shouldbeprovidedwithintheimmediateworkareaforemergencyuse.
Skinthatbecomeswetwithliquidacetaldehydeshouldbepromptlywashedorshoweredtoremoveany
acetaldehyde.
Inadditiontorespiratorselection,acompleterespiratoryprotectionprogramshouldbeinstitutedwhichincludes
regulartraining,maintenance,inspection,cleaning,andevaluation.
Personnelprotection:Avoidbreathingvapors.Keepupwind....Avoidbodilycontactwiththematerial....Donot
handlebrokenpackagesunlesswearingappropriatepersonalprotectiveequipment.Washawayanymaterialwhich
mayhavecontactedthebodywithcopiousamountsofwaterorsoapandwater.
Ifmaterialisnotonfireorinvolvedinafire:Keepsparks,flames,andothersourcesofignitionaway.Keep
materialoutofwatersourcesandsewers.Builddikestocontainflowasnecessary.Attempttostopleakifwithout
unduepersonnelhazard.Usewaterspraytodispersevaporsanddilutestandingpoolsofliquid.
Theworkershouldimmediatelywashtheskinwhenitbecomescontaminated.
2005151(2005)
Workclothingthatbecomeswetshouldbeimmediatelyremovedduetoitsflammabilityhazard(i.e.,forliquidswith
aflashpoint<100degF)..
2005151(2005)
SRP:Contaminatedprotectiveclothingshouldbesegregatedinsuchamannersothatthereisnodirectpersonal
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contactbypersonnelwhohandle,dispose,orcleantheclothing.Qualityassurancetoascertainthecompletenessof
thecleaningproceduresshouldbeimplementedbeforethedecontaminatedprotectiveclothingisreturnedforreuse
bytheworkers.Contaminatedclothingshouldnotbetakenhomeatendofshift,butshouldremainatemployee's
placeofworkforcleaning.
SRP:Wastewaterfromcontaminantsuppression,cleaningofprotectiveclothing/equipment,orcontaminatedsites
shouldbecontainedandevaluatedforsubjectchemicalordecompositionproductconcentrations.Concentrations
shallbelowerthanapplicableenvironmentaldischargeordisposalcriteria.Alternatively,pretreatmentand/or
dischargetoaPOTWisacceptableonlyafterreviewbythegoverningauthority.Dueconsiderationshallbegivento
remediationworkerexposure(inhalation,dermalandingestion)aswellasfateduringtreatment,transferand
disposal.Ifitisnotpracticabletomanagethechemicalinthisfashion,itmustmeetHazardousMaterialCriteriafor
disposal.
9.6 HandlingandStorage
9.6.1 NonfireSpillResponse
Keepsparks,flames,andothersourcesofignitionaway.Keepmaterialoutofwatersourcesandsewers.Build
dikestocontainflowasnecessary.Attempttostopleakifwithoutunduepersonnelhazard.Usewatersprayto
dispersevaporsanddilutestandingpoolsofliquid.Applywatersprayormisttoknockdownvapors.Landspill:Dig
apit,pond,lagoon,holdingareatocontainliquidorsolidmaterial.Dikesurfaceflowusingsoil,sandbags,foamed
polyurethane,orfoamedconcrete.Absorbbulkliquidwithflyash,cementpowder,orcommercialsorbents.
Neutralizewithsodiumbisulfate(NaHSO4).Waterspill:Addsodiumbisulfate(NaHSO4).Ifdissolved,inregionof
10ppmorgreaterconcentration,applyactivatedcarbonattentimesthespilledamount.Usemechanicaldredges
orliftstoremoveimmobilizedmassesofpollutantsandprecipitates.(AAR,1999)
9.6.2 SafetyStorage
Fireproof.Separatedfromincompatiblematerials.SeeChemicalDangers.Cooled.Keepinthedark.Storeonlyif
stabilized.
9.6.3 StorageConditions
Storeinacool,dry,wellventilatedlocation.Insidestorageshouldbeinastandardliquidsstoragewarehouse,
room,orcabinet.Separatefromoxidizingmaterialandotherreactivehazards.Storebulkquantitiesindetached
tanksprovidedwithrefrigerationandinertgascover.
Itisrecommendedthatsteelstoragetanksofsuitablestdbeused...Storagevesselsshouldbefittedwithtemp
gauges&automaticwatersprays....Alltanks&equipmentmustbeearthed.Transferofmaterialbypipelinemust
bebypressureofnitrogen....Drumscontainingacetaldehydeshouldneverbestoredindirectsunlightorother
warmareas.
InternationalLabourOffice.EncyclopediaofOccupationalHealthandSafety.Vols.I&II.Geneva,Switzerland:International
LabourOffice,1983.,p.36
PRECAUTIONSFOR"CARCINOGENS":Storagesiteshouldbeascloseaspracticaltolabinwhichcarcinogens
aretobeused,sothatonlysmallquantitiesrequiredfor...exptneedtobecarried.Carcinogensshouldbekeptin
onlyonesectionofcupboard,anexplosionproofrefrigeratororfreezer(dependingonchemicophysicalproperties
...)thatbearsappropriatelabel.Aninventory...shouldbekept,showingquantityofcarcinogen&dateitwas
acquired...Facilitiesfordispensing...shouldbecontiguoustostoragearea./ChemicalCarcinogens/
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Intransportingorstoringacetaldehyde,precautionmustbetakentopreventleaks&toensuresafeconditions,
becausethisaldehydeboilsatroomtemp.
Sullivan,J.B.Jr.,G.R.Krieger(eds.).HazardousMaterialsToxicologyClinicalPrinciplesofEnvironmentalHealth.Baltimore,
MD:WilliamsandWilkins,1992.,p.981
...Metalcontainersinvolvingthetransferofacetaldehydeshouldbegroundedandbonded.Drumsmustbe
equippedwithselfclosing,pressurevacuumbungs,andflamearresters.Useonlynonsparkingtoolsand
equipment,especiallywhenopeningandclosingcontainers.
9.7 ExposureControlandPersonalProtection
9.7.1 REL
Ca
CARCINOGEN(Ca)REDUCEEXPOSURETOLOWESTFEASIBLECONCENTRATION(LOQ18ppm)
9.7.2 PEL
TWA200ppm(360mg/m3)
9.7.3 PELTWA
200ppm
360mg/m3
9.7.4 IDLH
Ca[2000ppm]
2000ppm
9.7.5 Conversion
1ppm=1.80mg/m3
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9.7.6 ThresholdLimitValues
Ceilinglimit:25ppm
AmericanConferenceofGovernmentalIndustrialHygienistsTLVsandBEIs.ThresholdLimitValuesforChemicalSubstances
andPhysicalAgentsandBiologicalExposureIndices.Cincinnati,OH,2008,p.10
A3Confirmedanimalcarcinogenwithunknownrelevancetohumans.
andPhysicalAgentsandBiologicalExposureIndices.Cincinnati,OH,2008,p.10
9.7.7 OtherOccupationalPermissibleLevels
GUIDELINE:AustraliaTWA180mg/cum,100ppm(1978)FinlandTWA90mg/cum,50ppm,&STEL135
mg/cum,75ppm(1981)FederalRepublicofGermanyTWA90mg/cum,50ppm(1984)ItalyTWA100mg/cu
m,55ppm(1978)NetherlandsTWA180mg/cum,100ppm(1978)RomaniaTWA100mg/cum,200mg/cum
(maxium)(1975)SwedenTWA45mg/cum,25ppm,&STEL90mg/cum,50ppm(1981).
REGULATION:BelgumTWA180mg/cum,100ppm(1978)CzechoslovakiaTWA200mg/cum,400mg/cum
(ceiling/10min)(1976)GermanDemocraticRepublicTWA100mg/cum,100mg/cum(maximum/30min)(1977)
PolandCeiling100mg/cum(1976)SwitzerlandTWA180mg/cum,100ppm(1978)USSR5mg/cum
(Maximum)(1977)Yugoslavia360mg/cum,200ppm(Ceiling)(1971).
EmergencyResponsePlanningGuidelines(ERPG):ERPG(1)10ppm(nomorethanmild,transienteffects)forup
to1hrexposureERPG(2)200ppm(withoutserious,adverseeffects)forupto1hrexposureERPG(3)1000ppm
(notlifethreatening)upto1hrexposure.
AmericanInduustrialHygieneAssociation.AIHAEmergencyResponsePlanningGuidelines(ERPG)&Workplace
EnvironmentalExposureLevels(WEEL).Fairfax,VA.2008,p.24
9.7.8 PersonalProtection
Skin:PreventskincontactEyes:PreventeyecontactWashskin:WhencontaminatedRemove:Whenwet
(flammable)Change:NorecommendationProvide:Eyewash,Quickdrench
9.7.9 RespiratorRecommendations
NIOSHAtconcentrationsabovetheNIOSHREL,orwherethereisnoREL,atanydetectableconcentration:(APF
=10,000)Anyselfcontainedbreathingapparatusthathasafullfacepieceandisoperatedinapressuredemandor
otherpositivepressuremode(APF=10,000)Anysuppliedairrespiratorthathasafullfacepieceandisoperatedin
apressuredemandorotherpositivepressuremodeincombinationwithanauxiliaryselfcontainedpositivepressure
breathingapparatusEscape:(APF=50)Anyairpurifying,fullfacepiecerespirator(gasmask)withachinstyle,
frontorbackmountedorganicvaporcanisterAnyappropriateescapetype,selfcontainedbreathingapparatus
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9.7.10 FirePrevention
NOopenflames,NOsparksandNOsmoking.NOcontactwithhotsurfaces.
9.7.11 ExplosionPrevention
Closedsystem,ventilation,explosionproofelectricalequipmentandlighting.DoNOTusecompressedairforfilling,
discharging,orhandling.Usenonsparkinghandtools.
9.7.12 ExposurePrevention
AVOIDALLCONTACT!
9.7.13 InhalationPrevention
Useventilation.Uselocalexhaustorbreathingprotection.
9.7.14 SkinPrevention
Protectivegloves.
9.7.15 EyePrevention
Wearsafetygogglesoreyeprotectionincombinationwithbreathingprotection.
9.7.16 IngestionPrevention
Donoteat,drink,orsmokeduringwork.
9.7.17 ProtectiveEquipmentandClothing
Protectiveclothingshouldbefreelyavailableandoperatorsinstructedinitsuse.Chemicaleyeandfaceprotection
ofanapproveddesignshouldbemandatoryinplantarea,and,formaintenancework,plasticfaceshieldsshould
alsobeworn
Employeesshouldbeprovidedwithandrequiredtousesplashproofsafetygoggleswherethereisanypossibilityof
thiscompoundcomingincontactwiththeeyes.
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PRECAUTIONSFOR"CARCINOGENS":...Dispensersofliqdetergent/shouldbeavailable./...Safetypipettes
shouldbeusedforallpipetting....Inanimallaboratory,personnelshould...wearprotectivesuits(preferably
disposable,onepiece&closefittingatankles&wrists),gloves,haircovering&overshoes....Inchemical
laboratory,gloves&gownsshouldalwaysbeworn...however,glovesshouldnotbeassumedtoprovidefull
protection.Carefullyfittedmasksorrespiratorsmaybenecessarywhenworkingwithparticulatesorgases,&
disposableplasticapronsmightprovideaddnlprotection....Gowns.../shouldbe/ofdistinctivecolor,thisisa
reminderthattheyarenottobewornoutsidethelaboratory./ChemicalCarcinogens/
Employeesshouldbeprovidedwithandrequiredtouseimperviousclothing,gloves,faceshields(eightinch
minimum),andotherappropriateprotectiveclothingnecessarytopreventrepeatedorprolongedskincontactwith
liquidacetaldehyde.
Wearappropriatepersonalprotectiveclothingtopreventskincontact.
2005151(2005)
Wearappropriateeyeprotectiontopreventeyecontact.
2005151(2005)
Eyewashfountainsshouldbeprovidedinareaswherethereisanypossibilitythatworkerscouldbeexposedtothe
substancethisisirrespectiveoftherecommendationinvolvingthewearingofeyeprotection.
2005151(2005)
Facilitiesforquicklydrenchingthebodyshouldbeprovidedwithintheimmediateworkareaforemergencyuse
wherethereisapossibilityofexposure.[Note:Itisintendedthatthesefacilitiesprovideasufficientquantityorflow
ofwatertoquicklyremovethesubstancefromanybodyareaslikelytobeexposed.Theactualdeterminationof
whatconstitutesanadequatequickdrenchfacilitydependsonthespecificcircumstances.Incertaininstances,a
delugeshowershouldbereadilyavailable,whereasinothers,theavailabilityofwaterfromasinkorhosecouldbe
consideredadequate.]
2005151(2005)
RespiratorRecommendations:AtconcentrationsabovetheNIOSHREL,orwherethereisnoREL,atany
detectableconcentration:
Assigned
Protection
Factor(APF)
RespiratorRecommendation
APF=10,000
Anyselfcontainedbreathingapparatusthathasafullfacepieceandisoperatedinapressure
demandorotherpositivepressuremode.
Anysuppliedairrespiratorthathasafullfacepieceandisoperatedinapressuredemandor
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APF=10,000
otherpositivepressuremodeincombinationwithanauxiliaryselfcontainedpositivepressure
breathingapparatus.
2005151(2005)
RespiratorRecommendations:Escapeconditions:
Assigned
Protection
Factor(APF)
RespiratorRecommendation
APF=50
Anyairpurifying,fullfacepiecerespirator(gasmask)withachinstyle,frontorbackmounted
organicvaporcanister/Anyappropriateescapetype,selfcontainedbreathingapparatus
2005151(2005)
9.8 StabilityandReactivity
9.8.1 ReactivitiesandIncompatibilities
Reactswithoxidizingmaterials,halogens,amines,strongalkalies,andacids.
Oxygenationofacetaldehydeinpresenceofcobaltacetateat20degCcausedprecipitationof1hydroxyethyl
peroxyacetate(acetaldheydehemiperacetate),whichexplodedviolentlyonstirring.Ozoneoruvlightalsocatalyzes
theautoxidation.
Strongoxidizers,acids,bases,alcohols,ammonia&amines,phenols,ketones,HCN,H2S[Note:Prolonged
contactwithairmaycauseformationofperoxidesthatmayexplodeandburstcontainerseasilyundergoes
polymerization].
2005151(2005)
Interaction/ofhydrogenperoxidewithacetaldehydeordesiccants/givestheextremelyexplosivepoly(ethylidene)
peroxide,alsoformedonwarmingperoxidizeddiethylether.
Directcombination/ofdinitrogenpentaoxide&acetaldehyde/toproduceethylidenedinitrateat196degCis
violentlyexplosive,butuneventfulwhentheacetaldehydeisdilutedwithnitrogen.
Someoftheproductsofinteractionofacetaldehyde&mercury(II)salts(chlorateorperchlorate)arehighlyexplosive
&extremelyshocksensitive.
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Adrumcontaminatedwithaceticacidwasfilledwithacetaldehyde.Theensuingexothermicpolymerizationreaction
causedamilderuptionlastingseveralhours.
Oxygenleakedintoafreespaceinanacetaldehydestoragetanknormallypurgedwithnitrogen.Accelerating
exothermicoxidationledtodetonation.
Maydissolverubber.
Strongoxidizers,acids,bases,alcohols,ammonia&amines,phenols,ketones,HCN,H2S[Note:Prolongedcontact
withairmaycauseformationofperoxidesthatmayexplodeandburstcontainerseasilyundergoespolymerization.]
AIRANDWATERREACTIONS:Itformsexplosivemixturewithairabove100C(3060%ofthevaporinair)owing
toformationofperoxyaceticacid[White,A.G.etal.,J.Soc.Chem.Ind.,1950,69,p.206).CHEMICAL
PROFILE:Incontactwithstrongacids,basesortracesofmetalsitwillundergoaviolent,exothermiccondensation
reaction.Itcanreactvigorouslywithoxidizingreagents.Itcanreactviolentlywithacidanhydrides,alcohols,
ketones,phenols,ammonia,hydrogencyanide,hydrogensulfide,halogens,phosphorus,isocyanates,andaliphatic
amines.Reactionswithcobaltchloride,mercury(II)chlorateorperchlorateformsensitive,explosiveproducts[Sax,
9thed.,1996,p.5].Anxygenationreactionofacetaldehydeinthepresenceofcobaltacetateat20Cexploded
violentlyonstirringduetoperoxyacetateformation[PhillipsB.etal.,J.Am.Chem.Soc.,1957,79,p.5982].
(REACTIVITY,1999)
9.9 TransportInformation
9.9.1 DOTEmergencyGuidelines
/GUIDE129:FLAMMABLELIQUIDS(Polar/WaterMiscible/Noxious)/FireorExplosion:HIGHLYFLAMMABLE:
Willbeeasilyignitedbyheat,sparksorflames.Vaporsmayformexplosivemixtureswithair.Vaporsmaytravelto
sourceofignitionandflashback.Mostvaporsareheavierthanair.Theywillspreadalonggroundandcollectinlow
orconfinedareas(sewers,basements,tanks).Vaporexplosionhazardindoors,outdoorsorinsewers.Those
substancesdesignatedwitha(P)maypolymerizeexplosivelywhenheatedorinvolvedinafire.Runofftosewer
maycreatefireorexplosionhazard.Containersmayexplodewhenheated.Manyliquidsarelighterthanwater.
U.S.DepartmentofTransportation.2012EmergencyResponseGuidebook.Washington,D.C.2012
/GUIDE129:FLAMMABLELIQUIDS(Polar/WaterMiscible/Noxious)/Health:Maycausetoxiceffectsifinhaledor
absorbedthroughskin.Inhalationorcontactwithmaterialmayirritateorburnskinandeyes.Firewillproduce
irritating,corrosiveand/ortoxicgases.Vaporsmaycausedizzinessorsuffocation.Runofffromfirecontrolor
dilutionwatermaycausepollution.
/GUIDE129:FLAMMABLELIQUIDS(Polar/WaterMiscible/Noxious)/PublicSafety:CALLEmergencyResponse
TelephoneNumberonShippingPaperfirst.IfShippingPapernotavailableornoanswer,refertoappropriate
telephonenumberlistedontheinsidebackcover.Asanimmediateprecautionarymeasure,isolatespillorleakarea
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foratleast50meters(150feet)inalldirections.Keepunauthorizedpersonnelaway.Stayupwind.Keepoutoflow
areas.Ventilateclosedspacesbeforeentering.
/GUIDE129:FLAMMABLELIQUIDS(Polar/WaterMiscible/Noxious)/ProtectiveClothing:Wearpositivepressure
selfcontainedbreathingapparatus(SCBA).Structuralfirefighters'protectiveclothingwillonlyprovidelimited
protection.
/GUIDE129:FLAMMABLELIQUIDS(Polar/WaterMiscible/Noxious)/Evacuation:LargeSpill:Considerinitial
downwindevacuationforatleast300meters(1000feet).Fire:Iftank,railcarortanktruckisinvolvedinafire,
ISOLATEfor800meters(1/2mile)inalldirectionsalso,considerinitialevacuationfor800meters(1/2mile)inall
directions.
/GUIDE129:FLAMMABLELIQUIDS(Polar/WaterMiscible/Noxious)/Fire:CAUTION:Alltheseproductshavea
verylowflashpoint:Useofwaterspraywhenfightingfiremaybeinefficient.SmallFire:Drychemical,CO2,water
sprayoralcoholresistantfoam.Donotusedrychemicalextinguisherstocontrolfiresinvolvingnitromethaneor
nitroethane.LargeFire:Waterspray,fogoralcoholresistantfoam.Donotusestraightstreams.Movecontainers
fromfireareaifyoucandoitwithoutrisk.FireinvolvingTanksorCar/TrailerLoads:Fightfirefrommaximum
distanceoruseunmannedhoseholdersormonitornozzles.Coolcontainerswithfloodingquantitiesofwateruntil
wellafterfireisout.Withdrawimmediatelyincaseofrisingsoundfromventingsafetydevicesordiscolorationof
tank.ALWAYSstayawayfromtanksengulfedinfire.Formassivefire,useunmannedhoseholdersormonitor
nozzlesifthisisimpossible,withdrawfromareaandletfireburn.
/GUIDE129:FLAMMABLELIQUIDS(Polar/WaterMiscible/Noxious)/SpillorLeak:ELIMINATEallignition
sources(nosmoking,flares,sparksorflamesinimmediatearea).Allequipmentusedwhenhandlingtheproduct
mustbegrounded.Donottouchorwalkthroughspilledmaterial.Stopleakifyoucandoitwithoutrisk.Prevent
entryintowaterways,sewers,basementsorconfinedareas.Avaporsuppressingfoammaybeusedtoreduce
vapors.Absorborcoverwithdryearth,sandorothernoncombustiblematerialandtransfertocontainers.Useclean
nonsparkingtoolstocollectabsorbedmaterial.LargeSpill:Dikefaraheadofliquidspillforlaterdisposal.Water
spraymayreducevaporbutmaynotpreventignitioninclosedspaces.
/GUIDE129:FLAMMABLELIQUIDS(Polar/WaterMiscible/Noxious)/FirstAid:Movevictimtofreshair.Call911
oremergencymedicalservice.Giveartificialrespirationifvictimisnotbreathing.Administeroxygenifbreathingis
difficult.Removeandisolatecontaminatedclothingandshoes.Incaseofcontactwithsubstance,immediatelyflush
skinoreyeswithrunningwaterforatleast20minutes.Washskinwithsoapandwater.Incaseofburns,
immediatelycoolaffectedskinforaslongaspossiblewithcoldwater.Donotremoveclothingifadheringtoskin.
Keepvictimwarmandquiet.Effectsofexposure(inhalation,ingestionorskincontact)tosubstancemaybe
delayed.Ensurethatmedicalpersonnelareawareofthematerial(s)involvedandtakeprecautionstoprotect
themselves.
9.9.2 ShipmentMethodsandRegulations
Nopersonmay/transport,/offeroracceptahazardousmaterialfortransportationincommerceunlessthatperson
isregisteredinconformance...andthehazardousmaterialisproperlyclassed,described,packaged,marked,
labeled,andinconditionforshipmentasrequiredorauthorizedby.../thehazardousmaterialsregulations(49CFR
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171177)./
49CFR171.2U.S.NationalArchivesandRecordsAdministration'sElectronicCodeofFederalRegulations.Availablefrom,
asofFebruary15,2006:http://www.gpoaccess.gov/ecfr/
TheInternationalAirTransportAssociation(IATA)DangerousGoodsRegulationsarepublishedbytheIATA
DangerousGoodsBoardpursuanttoIATAResolutions618and619andconstituteamanualofindustrycarrier
regulationstobefollowedbyallIATAMemberairlineswhentransportinghazardousmaterials.
InternationalAirTransportAssociation.DangerousGoodsRegulations.47thEdition.Montreal,QuebecCanada.2006.,p.131
TheInternationalMaritimeDangerousGoodsCodelaysdownbasicprinciplesfortransportinghazardouschemicals.
Detailedrecommendationsforindividualsubstancesandanumberofrecommendationsforgoodpracticeare
includedintheclassesdealingwithsuchsubstances.Ageneralindexoftechnicalnameshasalsobeencompiled.
Thisindexshouldalwaysbeconsultedwhenattemptingtolocatetheappropriateprocedurestobeusedwhen
shippinganysubstanceorarticle.
InternationalMaritimeOrganization.InternationalMaritimeDangerousGoodsCode.London,UK.2004.,p.45
9.9.3 DOTIDandGuide
1089129
9.9.4 PackagingandLabelling
Unbreakablepackaging.Putbreakablepackagingintoclosedunbreakablecontainer.
9.9.5 ECClassification
Symbol:F+,XnR:1236/3740S:(2)163336/37
9.9.6 UNClassification
UNHazardClass:3UNPackGroup:I
9.9.7 EmergencyResponse
TransportEmergencyCard:TEC(R)30S1089.NFPACode:H2F4R2.
9.10 RegulatoryInformation
9.10.1 DOTEmergencyResponseGuide
129FLAMMABLELIQUIDS(Polar/WaterMiscible/Noxious)
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POTENTIALHAZARDS
FIREOREXPLOSION
*HIGHLYFLAMMABLE:Willbeeasilyignitedbyheat,sparksorflames.*Vaporsmayformexplosivemixtures
withair.*Vaporsmaytraveltosourceofignitionandflashback.*Mostvaporsareheavierthanair.Theywill
spreadalonggroundandcollectinloworconfinedareas(sewers,basements,tanks).*Vaporexplosionhazard
indoors,outdoorsorinsewers.*Thosesubstancesdesignatedwitha"P"maypolymerizeexplosivelywhenheated
orinvolvedinafire.*Runofftosewermaycreatefireorexplosionhazard.*Containersmayexplodewhenheated.
*Manyliquidsarelighterthanwater.
HEALTH
*Maycausetoxiceffectsifinhaledorabsorbedthroughskin.*Inhalationorcontactwithmaterialmayirritateor
burnskinandeyes.*Firewillproduceirritating,corrosiveand/ortoxicgases.*Vaporsmaycausedizzinessor
suffocation.*Runofffromfirecontrolordilutionwatermaycausepollution.
PUBLICSAFETY
*CALLEmergencyResponseTelephoneNumberonShippingPaperfirst.IfShippingPapernotavailableorno
answer,refertoappropriatetelephonenumberlistedontheinsidebackcover.*Asanimmediateprecautionary
measure,isolatespillorleakareaforatleast50meters(150feet)inalldirections.*Keepunauthorizedpersonnel
away.*Stayupwind.*Keepoutoflowareas.*Ventilateclosedspacesbeforeentering.
PROTECTIVECLOTHING
*Wearpositivepressureselfcontainedbreathingapparatus(SCBA).*Structuralfirefighters'protectiveclothingwill
onlyprovidelimitedprotection.
EVACUATION
LargeSpill
*Considerinitialdownwindevacuationforatleast300meters(1000feet).
Fire
*Iftank,railcarortanktruckisinvolvedinafire,ISOLATEfor800meters(1/2mile)inalldirectionsalso,
considerinitialevacuationfor800meters(1/2mile)inalldirections.
EMERGENCYRESPONSE
FIRE
CAUTION:Alltheseproductshaveaverylowflashpoint:Useofwaterspraywhenfightingfiremaybeinefficient.
SmallFire
*Drychemical,CO2,watersprayoralcoholresistantfoam.*Donotusedrychemicalextinguisherstocontrolfires
involvingnitromethaneornitroethane.
LargeFire
*Waterspray,fogoralcoholresistantfoam.*Donotusestraightstreams.*Movecontainersfromfireareaifyou
candoitwithoutrisk.
FireinvolvingTanksorCar/TrailerLoads
*Fightfirefrommaximumdistanceoruseunmannedhoseholdersormonitornozzles.*Coolcontainerswith
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floodingquantitiesofwateruntilwellafterfireisout.*Withdrawimmediatelyincaseofrisingsoundfromventing
safetydevicesordiscolorationoftank.*ALWAYSstayawayfromtanksengulfedinfire.*Formassivefire,use
unmannedhoseholdersormonitornozzlesifthisisimpossible,withdrawfromareaandletfireburn.
SPILLORLEAK
*ELIMINATEallignitionsources(nosmoking,flares,sparksorflamesinimmediatearea).*Allequipmentused
whenhandlingtheproductmustbegrounded.*Donottouchorwalkthroughspilledmaterial.*Stopleakifyoucan
doitwithoutrisk.*Prevententryintowaterways,sewers,basementsorconfinedareas.*Avaporsuppressingfoam
maybeusedtoreducevapors.*Absorborcoverwithdryearth,sandorothernoncombustiblematerialand
transfertocontainers.*Usecleannonsparkingtoolstocollectabsorbedmaterial.
LargeSpill
*Dikefaraheadofliquidspillforlaterdisposal.*Waterspraymayreducevaporbutmaynotpreventignitionin
closedspaces.
FIRSTAID
*Movevictimtofreshair.*Call911oremergencymedicalservice.*Giveartificialrespirationifvictimisnot
breathing.*Administeroxygenifbreathingisdifficult.*Removeandisolatecontaminatedclothingandshoes.*In
caseofcontactwithsubstance,immediatelyflushskinoreyeswithrunningwaterforatleast20minutes.*Wash
skinwithsoapandwater.*Incaseofburns,immediatelycoolaffectedskinforaslongaspossiblewithcoldwater.
Donotremoveclothingifadheringtoskin.*Keepvictimwarmandquiet.*Effectsofexposure(inhalation,
ingestionorskincontact)tosubstancemaybedelayed.*Ensurethatmedicalpersonnelareawareofthe
material(s)involvedandtakeprecautionstoprotectthemselves.
9.10.2 CleanWaterActRequirements
Acetaldehydeisdesignatedasahazardoussubstanceundersection311(b)(2)(A)oftheFederalWaterPollution
ControlActandfurtherregulatedbytheCleanWaterActAmendmentsof1977and1978.Theseregulationsapply
todischargesofthissubstance.Thisdesignationincludesanyisomersandhydrates,aswellasanysolutionsand
mixturescontainingthissubstance.
40CFR116.4(USEPA)U.S.NationalArchivesandRecordsAdministration'sElectronicCodeofFederalRegulations.
9.10.3 CERCLAReportableQuantities
PersonsinchargeofvesselsorfacilitiesarerequiredtonotifytheNationalResponseCenter(NRC)immediately,
whenthereisareleaseofthisdesignatedhazardoussubstance,inanamountequaltoorgreaterthanits
reportablequantityof1000lbor454kg.ThetollfreenumberoftheNRCis(800)4248802.Therulefor
determiningwhennotificationisrequiredisstatedin40CFR302.4(sectionIV.D.3.b).
9.10.4 TSCARequirements
Section8(a)ofTSCArequiresmanufacturersofthischemicalsubstancetoreportpreliminaryassessment
informationconcernedwithproduction,exposure,andusetoEPAascitedinthepreamblein51FR41329.
Effectivedate9/30/91Reportingdate:11/27/91.
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Pursuanttosection8(d)ofTSCA,EPApromulgatedamodelHealthandSafetyDataReportingRule.Thesection
8(d)modelrulerequiresmanufacturers,importers,andprocessorsoflistedchemicalsubstancesandmixturesto
submittoEPAcopiesandlistsofunpublishedhealthandsafetystudies.Acetaldehydeisincludedonthislist.
Effectivedate9/30/91Sunsetdate:6/30/98.
9.10.5 RCRARequirements
U001Asstipulatedin40CFR261.33,whenacetaldehyde,asacommercialchemicalproductormanufacturing
chemicalintermediateoranoffspecificationcommercialchemicalproductoramanufacturingchemical
intermediate,becomesawaste,itmustbemanagedaccordingtoFederaland/orStatehazardouswaste
regulations.Alsodefinedasahazardouswasteisanyresidue,contaminatedsoil,water,orotherdebrisresulting
fromthecleanupofaspill,intowaterorondryland,ofthiswaste.Generatorsofsmallquantitiesofthiswastemay
qualifyforpartialexclusionfromhazardouswasteregulations(40CFR261.5).
9.10.6 FDARequirements
Syntheticflavoringsubstancesandadjuvants/forhumanconsumption/thataregenerallyrecognizedassafefor
theirintendeduse,withnthemeaningofsection409oftheAct.Acetaldehydeisincludedonthislist.
21CFR182.60(USFDA)U.S.NationalArchivesandRecordsAdministration'sElectronicCodeofFederalRegulations.
Syntheticflavoringsubstancesandadjuvants/foranimaldrugs,feeds,andrelatedproducts/thataregenerally
recognizedassafefortheirintendeduse,withinthemeaningofsection409oftheAct.Acetaldehydeisincludedon
thislist.
21CFR582.60(USFDA)U.S.NationalArchivesandRecordsAdministration'sElectronicCodeofFederalRegulations.
9.11 OtherSafetyInformation
9.11.1 ToxicCombustionProducts
Toxicgasesandvapors(suchascarbonmonoxide)maybereleasedinafireinvolvingacetaldehyde.
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10 Toxicity
10.1 ToxicologicalInformation
10.1.1 Carcinogen
Evaluation:Thereisinadequateevidenceinhumansforthecarcinogenicityofacetaldehyde.Thereissufficient
evidenceinexperimentalanimalsforthecarcinogenicityofacetaldehyde.Overallevaluation:Acetaldehydeis
possiblycarcinogenictohumans(Group2B).
A3Confirmedanimalcarcinogenwithunknownrelevancetohumans.
andPhysicalAgentsandBiologicalExposureIndices.Cincinnati,OH2010,p.10
Acetaldehyde:reasonablyanticipatedtobeahumancarcinogen.
DHHS/NationalToxicologyProgramEleventhReportonCarcinogens:Acetaldehyde(75070)(January2005).Availablefrom,
asofJuly31,2009:http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s001acet.pdf
CLASSIFICATION:B2probablehumancarcinogen.BASISFORCLASSIFICATION:Basedonincreased
incidenceofnasaltumorsinmaleandfemaleratsandlaryngealtumorsinmaleandfemalehamstersafter
inhalationexposure.HUMANCARCINOGENICITYDATA:Inadequate.ANIMALCARCINOGENICITYDATA:
Sufficient./basedonformerclassificationsystem/
U.S.EnvironmentalProtectionAgency'sIntegratedRiskInformationSystem(IRIS).SummaryonAcetaldehyde(75070).
Availablefrom,asofMarch15,2000:http://www.epa.gov/iris/
CancerClassification:GroupB2ProbableHumanCarcinogen
USEPAOfficeofPesticidePrograms,HealthEffectsDivision,ScienceInformationManagementBranch:"Chemicals
EvaluatedforCarcinogenicPotential"(April26,2006)
TLVA3,IARC2B,NIOSHCa,NTPR,EPAB2
10.1.2 ExposureRoutes
Thesubstancecanbeabsorbedintothebodybyinhalationandbyingestion.
inhalation,ingestion,skinand/oreyecontact
10.1.3 Symptoms
irritationeyes,nose,throateye,skinburnsdermatitisconjunctivitiscoughcentralnervoussystemdepression
delayedpulmonaryedemainanimals:kidney,reproductive,teratogeniceffects[potentialoccupationalcarcinogen]
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10.1.4 TargetOrgans
Eyes,skin,respiratorysystem,kidneys,centralnervoussystem,reproductivesystem
10.1.5 CancerSites
[inanimals:nasalcancer]
10.1.6 Interactions
Llv.52hasbeenshowntobringoutafastereliminationofacetaldehydefromthebodyandthuspreventalcoholic
liverdamage.OthertoxiceffectsofalcoholmayalsobeduetoacetaldehydeandmaybepreventedbyLiv.52.In
thisstudy,ratsweregiven20(v/v)ethanolindrinkingwater,duringthegestationperiod,andtheeffectonmaternal
bodyweightandfetaloutcomewasnoted.TheprotectiveeffectofLiv.52administrationduringthegestationperiod
wasstudied.Theresultsshowthatethanolingestioncausedadecreaseingestationalweightgain,totalfetal
weight,andnumberoflavefetuses.Therewereincreasesinresorptions.Liv.52administrationreducedthe
deleteriouseffectsofethanol.Theconcentrationofacetaldehydeintheamnioticfluidofethanolconsuming
animalswas0.727ug/ml.Liv.52administrationlowereditto0.244ug/ml.TheprotectiveeffectofLiv.52couldbe
duetotherapideliminationofacetaldehyde.
GopumadhavanSetalAlcoholClinExpRes17(5):108992(1993)
Thepossibilitythatacetaldehydeaccumulationpotentiatestheacutetoxicityofethanolwasstudiedbypretreating
ratswithcyanamide,analdehydedehydrogenaseinhibitor.Atdeath,theconcnofacetaldehydeinheart,blood,and
cerebrospinalfluidwas7to9timeshigherthaninratsgivenethanolonly.
HillbomMEetalToxicolApplPharmacol70(1):1339(1983)
Calciumpantothenate,calcium4'phosphopantothenate...pantethine...substantiallydecreasedthetoxicityofip
administeredacetaldehydeinmice.Thepantothenateswereadministered2030minutespriorto...acetaldehyde
/administration/.
MoiseenokAGKhimfarmZh17(11):12936(1983)
...Combinationsofacetaldehydeplusnicotine,acetaldehydepluscaffeine,andacetaldehydeplusdopamine...
exhibitedlethalsynergy/inrats/.Protectionagainstthelethalsynergyofthesecombinationscouldbedemonstrated
byoralpretreatmentwithlascorbicacid,lcysteine,orphenoxybenzamine(alphaadrenergicblocker),butnot
propranolol(betaadrenergicblocker).
SprinceHetalNutrRepInt23(1):4354(1981)
Administrationofacetaldehydebyinhalationorip(inrepeateddoses)/torats/provokes...micronecrosisinthe
myocardium.Administrationofacetaldehyde...potentiatesthecardionecroticactionofadrenalin.Pretreatment
withLDOPApotentiateswhilethatofLalphamethylDOPAoralphamethyltyrosineavertsthenecroticactionof
acetaldehyde.
ZabirovaIGetalBillEkspBiolMed94(12):6567(1982)
Chinesehamsterovarycellsexposedtoultravioletlight,methylmethanesulfonate,mitomycinCorbleomycinand
thenposttreatedwithacetaldehyde(0.01or0.02%)containedmorechromosomalaberrationsthancellsexposedto
themutagenicagentsalone.Chromatidexchangeswerepredominantlyincreasedinculturestreatedfirstwiththe
ultravioletlight,methylmethanesulfonate,ormitomycinCandthenwithacetaldehyde,whereaschromosome
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breaksandchromatidexchangewerethemajortypesofaberrationsincreasedintheculturestreatedwith
bleomycinandacetaldehyde.
LinYCetalMutatRes216(2):939(1989)
Disulfiraminhibitsenzymaticoxidationofacetaldehydetoacetatewhichoccursintheliverduringnormalalcohol
catabolism.Disulfiramcompeteswithnicotinamideadeninedinucleotideforaldehydedehydrogenase.Whensmall
amountsofalcoholareingestedafterdisulfiramadministration,theacetaldehydeconcentrationinbloodmay
increaseto5to10timestheconcentrationobservedafterthemetabolismofthesameamountofalcoholused
alone.Highbloodconcentrationsofacetaldehydemayproducetheunpleasantsymptomsofthedisulfiramalcohol
reaction(theacetaldehydesyndrome).Othersfeelthatthecarbondisulfidemetaboliteofdisulfiramproducesmany
ofthedisagreeblesymptoms.
Ellenhorn,M.J.andD.G.Barceloux.MedicalToxicologyDiagnosisandTreatmentofHumanPoisoning.NewYork,NY:
ElsevierSciencePublishingCo.,Inc.1988.,p.425
Theeffectsofethanolandacetaldehydeontheclastogenicityofultravioletlight(UV),methylmethanesulfonate,
mitomycinC,andbleomycinwereinvestigatedinChinesehamsterovarycells.Bothethanolandacetaldehyde
synergisticallypotentiatedtheclastogenicityofthetestedclastogens.Whileethanolitselfdidnotinduceapparent
chromosomeaberrationsinducedbythevariousclastogens.Chromatidexchangeswerepredominantlyincreasedin
culturestreatedwithUV,methylmethanesulfonate,ormitomycinCfollowedbyethanol,whereaschromosome
breaksandchromatidexchangeswerethemajortypesofaberrationspotentiatedinculturestreatedwithbleomycin
andethanol.PosttreatmentwithacetaldehydealsopotentiatedthechromosomeaberrationsinducedbyUV,
methylmetehanesulfonate,mitomycinC,andbleomycinthemaintypesofaberrationswhichwereincreasedwere
similartothoseincreasedbyposttreatmentwithethanol.
LinYCetalMutatRes216(2):939(1989)
Ethanol,invivo,inhibitsthemetabolismofethylcarbamateinmice.Tocharacterizetheenzymesystem
responsible,themetabolicproductsofethanolmetabolismwerestudiedtodeterminewhetherethanolorits
metabolitesisinhibitory.Acetaldehyde(400mg/kg)isapotentinhibitorofethylcarbamatemetabolismforabout2
hrinvitro,butsodiumacetateisnot.Disulfiram(200mg/kg)hasaprolongedinhibitoryeffectthiseffectis
enhancedandextendedwhenthedisulfiramiscombinedwithacetaldehyde(400mg/kg).Acetaldehydeisan
inhibitorofthemetabolismofethylcarbamate.
KurataNetalDrugMetabDispos18(4):5047(1990)
Inpreliminarystudieswithmice,bloodwasobtainedfromthetailsofmice(C57B1/6)whichhadbeengiven
ethanol,4.8g/kg,90minearlier.Acetaldehydelevelsinbloodremainedrelativelyconstantovera6hrperiodafter
ethanoladmin,whilebloodethanollevelsdeclinedbetweenthe90minand480minassaytimes.Pretreatmentof
micewithmethionineorfructose(350mg/kg)hadlittleeffectontheconcnofethanolfoundinbloodofC57BL/6or
DBA/2miceat90,180,360,or480minafterethanol.Methioninesignificantlyreducedcirculatingacetaldehyde
levelswithoutalteringcirculatinglevelsofethanol.Hepaticlevelsofacetaldehydewerealsoloweredbymethionine.
GroupsofDBA/2mice(n=6)weregiven4.8g/kgethanolbymouth,alongwithoneofthefollowingtreatments:1)
0.9%salinebymouth0.15ml/10gbodywt,1hrbeforereceivingethanol2)970mg/kgmethionine,bymouth,1hr
beforeethanol3)970mg/kgmethionineip,1hrbeforeethanolor4)970mg/kgmethionineip,1hrafterethanol.
At90minafterethanoladmin,bloodacetaldehydelevelsofgroups2and3differedsignificantlyfromtheother2
groups(p<0.05)andat210mingroup4wassignificantlydifferentfromgroup1(p<0.05).
TabakoffBetalAlcoholClinExpRes13(2):16471(1989)
MaleAAandANAratswereadminsolutionscontainingD,Lmethionine(900mg/kg,peros),potassiumcitrate(250
mg/kg)andpyridoxalphosphate(2mg/kg).Themethioninesolnorvehiclewasadmin1hrbeforetheratsreceived
ethanol(1.5g/kip),andtailblood(0.2mL)wasobtainedat60,120,and180minafterethanoladmin.Methionine
significantlyreducedcirculatingacetaldehydelevelswithoutalteringcirculatinglevelsofethanol.ANAratsexhibited
highercirculatinglevelsofacetaldehydecomparedtoAArats.Incertainrats,liveracetaldehydelevelswere
determined,195minafterreceivingethanol.Hepaticlevelsofacetaldehydewerealsoloweredbymethionine.
AcetaldehydelevelsinliverofAAratswereloweredfrom6uMto1uM,andforANAratsfrom19uMto8uM.
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EthanolandacetaldehydepotentiateMPTPtoxicityinmice,selectivelyenhancingdopaminedepletioninthe
striatumandmarkedlyincreasinglossofDAneuronsinthesubstantianigra.Severalmonthsafterthesecombined
treatmentsthereisnoevidenceofanyrecovery.Invivoexperimentsindicatedthatrelativelylowdosesofethanolor
acetaldehydepotentiatedirectlyMPP+toxicity,apparentlywithoutinterferingwithitspharmacokinetics.However
whenhigherdosesofthesedrugswereadministered,theyalsodecreasedMPP+clearancefromthestriatum.
AcetaldehydealsoincreasedinitialMPTPaccumulationinthewholebrainbutfailedtoenhanceMPP+levels,thus
indicatingtheacetaldehydeeffectisnotrelatedtoMPTPmetabolism.Invitrostudiesconfirmedthatacetaldehyde
doesnotmodifyMPTPmetabolisminstriatalormesencephalicastrocytesinculture.Inmesencephalicneuronal
culturesacetaldehydedoesnotchangethelevelsofMPP+uptake(MPP+isaccumulatedinputativedopamine
neuronsinvitrowithamechanismsimilartothatofthedopaminehighaffinityuptake)noritsspontaneousrelease.
TheslowerMPP+clearancefromthestratumafteracetaldehydeisnotrelatedtoadirecteffectofacetaldehydeon
dopamineneuronsorastrocytes.
ZuddasAetalBrainRes501(1):1122(1989)
Inaseriesofstudiesonlysinedependentenzymes,wereabletodemonstratethatincubationofpurifiedenzymes
withacetaldehydefor1hrat37degCledtoinhibitionoftheircatalyticactivity.Lysinenondependentenzymes
werenotaffectedbythistreatment.AsimilarstudyinvolvingtheincubationofratliverhistoneH1withphysiological
concentrationsofacetaldehydeshowedthatspontaneouslystableadductswereformedonlysineresiduesatthe
carboxyterminus,asitecrucialforitsfunctionasaeukaryoticrepressor.ThisacetaldehydemodifiedhistoneH1
showedimpairedDNAbindingactivity.
AcetaldehydereactswithnucleosidesanddeoxynucleosidesatpH6.5and37degCinvitrotoformunstable
adductsbybindingtotheexocyclicaminogroupsofadenine,cytosine,andguanine.Additionofareducingagent
(sodiumborohydride)leadstotheformationofstableadducts,ofwhichthemainonewasidentifiedasN8
ethylguanosineusingmassspectrometryandNMR.Similardatafortheformationofunstableadductsformedby
reactingacetaldehydewithribonucleosidesanddeoxyribonucleosides.Whenethanolwaspresentinthereaction
mixture,adifferenttypeofadductwasformed,whichwasidentifiedbyfastatombombardmentandprotonNMRto
beamixedacetal.Theseadductswerefoundtohavehalflivesvaryingfrom2.5to24hratpH7.5and37degC,
dependingonthebaseinvolved.
Acetaldehydecanreactwithnucleophilicgroups,suchasamino,hydroxyl,andsulfydrylgroups,throughnucleophilic
attackonthecarbonylcarbonatomofacetaldehydetogivebothstableandunstableadducts.Severaladduct
structures,formedwhenacetaldehydereactswithproteinsinvitro,havebeenidentified,buthavenotyetbeen
describedfully.
...Oraltreatmentwithdisulfiram16hrpriortotreatmentwithethanol(n=19)causedsignificantincreases(p<0.05)
inthelevelofGOTandserumtriglycerideswithin48hr,andaslightfattydegenerationoftheliverwasobserved.
Aftercombinedtreatment,theserumacetaldehydeconcentration(n=3)was9.4mg/Lat30minand8.7mg/Lat
180min.Ipinjectionofethanol(4g/kg)aftertreatmentwithdisulfiramproducedanincreaseinglutamicoxaloacetic
transaminase(p<0.05)butnotserumtriglycerideswithin48hr.Fattydegenerationandhepaticnecrosiswere
observedin2of6animals.
StrubeltOetalToxicolLett39(1):7784(1987)
Althoughapoorsubstrateforoxidation,crotonaldehydeisaneffectiveinhibitoroftheoxidationofacetaldehydeby
mitochondrialaldehydedehydrogenase,byintactmitochondria,andbyisolatedhepatocytes.Inhibitionby
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crotonaldehydewascompetitivewithrespecttoacetaldehyde,andtheKiforcrotonaldehydewasapprox520uM.
...Crotonaldehydeincreasedtheaccumulationofacetaldehyde>10fold,indicatingthatcrotonaldehyde,besides
inhibitingtheoxidationofaddedacetaldehyde,alsoinhibitedtheoxidationofacetaldehydegeneratedbythe
metabolismofethanol....Crotonaldehydewasapotentinhibitorofmitochondrialoxidationofformaldehyde,but
hadnoeffectontheactivityofformaldehydedehydrogenase.Inhepatocytes,crotonaldehydeproducedapprox30
40%inhibitionofformaldehydeoxidation,whichwassimilartotheinhibitionproducedbycyanamide....
DickerE,CederbaumAIArchBiochemBiophys234(1):18796(1984)
Tostudythetoxicinteractionbetweenacetaldehydeandcrotonaldehyde,theacutetoxicitytestswithmice
intubatedorally,themutagenicitytestswithSalmonellatyphimuriumLT2hisstrainsand,theDNAsynthesis
inhibitiontestswithHelacellswerecarriedout.Thecombinedacutetoxiceffectsofthetwoaldehydesareadditive.
AcetaldehydeisnotmutagenicinAmestest,butslightlyinhibitscellDNAsynthesisatconcentration400ug/ml,
whilecrotonaldehydeshowsthemutageniceffectonthestrainTA100withoutS9andinhibitsDNAsynthesis
significantly.BoththemutagenicactivityandinhibitioneffectonDNAsynthesisofcrotonaldehydeshowedno
changeinthepresenceofacetaldehyde.
ZengXChinJPrevMed19(5):27880(1986)
10.1.7 ToxicitySummary
IDENTIFICATION:Acetaldehydeisacolorlessvolatileliquidwithapungentsuffocatingodor.Acetaldehydeisa
highlyflammableandreactivechemicalthatismiscibleinwaterandmostcommonsolvents.HUMANEXPOSURE:
Acetaldehydeisametabolicintermediateinhumans.Ithasbeenidentifiedinfood,beveragesandcigarettesmoke.
Byfar,themainsourceofexposuretoacetaldehydeinthegeneralpopulationisthroughmetabolismofethanol
alcohol.Inregardstoothermedia,thegeneralpopulationisexposedtoacetaldehydefromfoodproductsand
beveragesandtoalesserextentfromair.Thecontributionfromdrinkingwaterisnegligible.Itisalsopresentin
vehicleexhaustandinwastesfromvariousindustries.Degradationofhydrocarbons,sewageandsolidbiological
wastesproducesacetaldehyde,aswellastheopenburningandincinerationofgas,fueloilandcoal.Workersmay
beexposedinsomemanufacturingindustriesandduringalcoholfermentation,wheretheprincipalrouteof
exposureismostlikelyinhalationwithpossibledermalcontact.Severalisoenzymicformsofacetaldehyde
dehydrogenase(ALDH),havebeenidentifiedinthehumanliverandothertissues.Thereispolymorphismfor
mitochondrialALDH.SubjectsthatarehomozygousorheterozygousforapointmutationinthemitochondrialADLH
correspondinggenehavelowactivityofthisenzyme,metabolizeacetaldehydeslowlyandareintolerantofethanol
alcohol.Thereissomemetabolismofacetaldehydeinhumanrenaltubules,theliveristhemostimportant
metabolicsite.Limitedstudiesinvolvinghumanvolunteershaveshownthatacetaldehydewasmildlyirritatingtothe
eyesandupperrespiratorytractfollowingshorttermexposures.Acetaldehydehasbeenimplicatedastheputatively
toxicmetaboliteintheinductionofethanolalcoholassociatedliverdamage,facialflushinganddevelopmental
effects.ANIMALSTUDIES:Inrepeateddosestudies,boththeoralandinhalationroutes,toxiceffectsatrelatively
lowconcentrationswerelimitedtothesitesofinitialcontact.Inastudywhereratswereadministeredacetaldehyde
intheirdrinkingwatereffectswerelimitedtoslightfocalhyperkeratosisoftheforestomach.Respiratoryeffectswere
notedinhamstersexposedtoacetaldehydebyinhalation,degenerativechangeswereobservedinthetrachea.
Degenerativechangesinrespiratoryepitheliumandlarynxwerenotedathigherconcentrations.Followinginhalation
byrats,acetaldehydeisdistributedtotheblood,liver,kidney,spleen,heartandothertissues.Lowlevelswere
detectedinembryosaftermaternalipinjectionofacetaldehyde(mouse)andfollowingmaternalexposuretoethanol
(mouseandrat).Parenteralexposureofpregnantratsandmicetoacetaldehydeinducedfetalmalformations.
Acetaldehydeisgenotoxicinvitro,inducinggenemutations,clastogeniceffectsandsisterchromatidexchanges
(SCEs)inmammaliancellsintheabsenceofexogenousmetabolicactivation.Negativeresultswerenotedwith
Salmonella.Followingipinjection,acetaldehydeinducedSCEsinthebonemarrowofChinesehamstersandmice.
Thischemicaladministeredipdidnotincreasethefrequencyofmicronucleiinearlymousespermatids.Increased
incidencesoftumorshavebeennotedininhalationstudiesonratsandhamstersexposedtoacetaldehyde.Inrats,
thereweredoserelatedincreasesinnasaladenocarcinomasandsquamouscellcarcinomas....Inhamsters,
increasesinnasalandlaryngealcarcinomaswerenonsignificant.Distributionofacetaldehydetobraininterstitial
fluid,butnottobraincellshasbeendemonstratedfollowingipinjectionofethanol.Acetaldehydeistakenupbyred
bloodcellsfollowingconsumptioninbaboons.Followingoraladministration,virtuallynounchangedacetaldehydeis
excretedintheurine.Themajorpathwayforthemetabolismofacetaldehydeisbyoxidationtoacetateunderthe
influenceofnicotinamideadeninedinucleotide(NAD(b)dependentADLH.Acetateentersthecitricacidcycleas
acetylCoA.ThereareseveraldifferentisoenzymesofADLHwithdifferentkineticandbindingparametersthat
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influenceacetaldehydeoxidationrates.ALDHactivityhasbeenlocalizedintherespiratorytractepithelium
(excludingolfactoryepithelium)inrats,intherenalcortexandtubulesinthedog,rat,guineapigandbaboonandin
thetestesinthemouse.Thischemicalismetabolizedbymouseandratembryonictissueinvitro.Acetaldehyde
crossestheratplacenta,inspiteofplacentalmetabolism.Metabolismofacetaldehydecanbeinhibitedby
crotonaldehyde,dimethylmaleate,phorone,disulfiramandcalciumcarbamide.
WorldHealthOrganizationEnvironmentalHealthCriteria167:Acetaldehyde.pp.1926(1995)
10.1.8 AntidoteandEmergencyTreatment
Immediatefirstaid:Ensurethatadequatedecontaminationhasbeencarriedout.Ifpatientisnotbreathing,start
artificialrespiration,preferablywithademandvalveresuscitator,bagvalvemaskdevice,orpocketmask,as
trained.PerformCPRasnecessary.Immediatelyflushcontaminatedeyeswithgentlyflowingwater.Donotinduce
vomiting.Ifvomitingoccurs,leanpatientforwardorplaceonleftside(headdownposition,ifpossible)tomaintain
anopenairwayandpreventaspiration.Keeppatientquietandmaintainnormalbodytemperature.Obtainmedical
attention./AldehydesandRelatedCompounds/
Currance,P.L.Clements,B.,Bronstein,A.C.(Eds).EmergencyCareForHazardousMaterialsExposure.3Rdedition,
ElsevierMosby,St.Louis,MO2005,p.266
Basictreatment:Establishapatentairway(oropharyngealornasopharyngealairway,ifneeded).Suctionif
necessary.Watchforsignsofrespiratoryinsufficiencyandassistventilationsifnecessary.Aggressiveairway
managementmaybenecessary.Administeroxygenbynonrebreathermaskat10to15L/min.Anticipateseizures
andtreatifnecessary....Monitorforshockandtreatifnecessary....Monitorforpulmonaryedemaandtreatif
necessary....Foreyecontamination,flusheyesimmediatelywithwater.Irrigateeacheyecontinuouslywith0.9%
saline(NS)duringtransport....Donotuseemetics.Foringestion,rinsemouthandadminister5ml/kgupto200
mlofwaterfordilutionifthepatientcanswallow,hasastronggagreflex,anddoesnotdrool.Administeractivated
charcoal..../AldehydesandRelatedCompounds/
Advancedtreatment:ConsiderConsiderorotrachealornasotrachealintubationforairwaycontrolinthepatientwho
isunconscious,hasseverepulmonaryedema,orisinsevererespiratorydistress.Intubationshouldbeconsideredat
thefirstsignofupperairwayobstructioncausedbyedema.Positivepressureventilationtechniqueswithabag
valvemaskdevicemaybebeneficial.Considerdrugtherapyforpulmonaryedema....Consideradministeringa
betaagonistsuchasalbuterolforseverebronchospasm....StartIVadministrationofD5W/SRP:"Tokeepopen",
minimalflowrate/.Use0.9%saline(NS)orlactatedRinger's(LR)ifsignsofhypovolemiaarepresent.For
hypotensionwithsignsofhypovolemia,administerfluidcautiously.Considervasopressorsifpatientishypotensive
withanormalfluidvolume.Watchforsignsoffluidoverload....Treatseizureswithdiazepamorlorazepam....
Useproparacainehydrochloridetoassisteyeirrigation..../AldehydesandRelatedCompounds/
10.1.9 MedicalSurveillance
Newemployeeswhomaybeexposedtoacetaldehydeshouldbeexaminedpriortoandperiodicallyafterbeginning
workwithcarefulattentiontotheeyes,skin,andrespiratorysystem....Chestradiographsandscreeningpulmonary
functionstudiescanprovideusefulbaselineinformation.
Sullivan,J.B.Jr.,G.R.Krieger(eds.).HazardousMaterialsToxicologyClinicalPrinciplesofEnvironmentalHealth.Baltimore,
MD:WilliamsandWilkins,1992.,p.981
Thefollowingmedicalproceduresshouldbemadeavailabletoeachemployeewhoisexposedtoacetaldehydeat
potentiallyhazardouslevels:initialmedicalscreeningforhistoryofcertainmedicalconditions,ie,chronic
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respiratory,liver,kidney,orskindiseaseswhichmightplacetheemployeeatincreasedriskfromacetaldehyde
exposure.Periodicmedicalexamination:anyemployeedevelopingtheabovelistedconditionsshouldbereferred
forfurthermedicalexaminations.
PRECAUTIONSFOR"CARCINOGENS":Whenevermedicalsurveillanceisindicated,inparticularwhenexposure
toacarcinogenhasoccurred,adhocdecisionsshouldbetakenconcerning.../cytogeneticand/orother/teststhat
mightbecomeusefulormandatory./ChemicalCarcinogens/
10.1.10 HumanToxicityExcerpts
/HUMANEXPOSURESTUDIES/Healthyvolunteers(3malesand3females)weregiven150mLoftomatojuice,
containing0or100mg/kgLmethionineintheevening,andat8:00amthenextdaythesubjectsreceivedL
methionine(0or100kg)intomatojuicecontainingfructose(350mg/kg).Onehrafterthemorningdoseof
methionineorplacebo,thesubjectsweregiven0.5gofethanol/kgbodywt.Breathsampleswerecollectedat20,
30,45,60,75,90,120,150,and180minaftertheendofethanolingestion.Humansingestingmethionine
exhibitedontheavga22%declineinbreathacetaldehydelevelsoverthetimeofmeasurements.Differencesin
acetaldehydeconcentrationsofplaceboandmethioninetreatedsubjectswerestatisticallysignificant(p<0.03)
Differencesinbreathethanolconcnwerealsostatisticallysignificant(p<0.05).Peakcalculatedbloodethanolfor
thoseconcntreatedwithplacebowas14.8+or3.3mMandconcnformethioninetreatedsubjectswas13.3+or
2.6mM.Peakcalculatedbloodacetaldehydeconcnwere20.1+or6.4uM(placebo)and14.3+or7.9uM
(methionine).
/HUMANEXPOSURESTUDIES/Astrongandhighlysignificantcorrelationwasobservedbetweenserum
aspartatetransaminaseactivityandanindexofthecytotoxicactivityassociatedwithserumproteinsmodifiedby
acetaldehydeinagroupof24heavydrinkers.Aweakerbutsignificantcorrelation(R=0.564,p=0.008)wasfound
betweentotalserumcreatinekinaseactivityandthisindexofserumcytotoxicity.Asitislikelythattheconcentration
ofcirculatingmodifiedproteinwaslargelydeterminedbythequantityoffreeacetaldehydegeneratedintheliver
andthattheaspartatetransaminaseactivitywasmainlyderivedfromdamagedhepatocytes,thedataindicatea
correlationbetweenhepaticacetaldehydegenerationandhepatocytedamage.Onlythecreatinekinaseisoenzyme
presentinskeletalmuscle(CKMM)wasdemonstrableintheseruminallbutoneofthepatients.[Wickramasinghe
SNetalJClinPathol42(3):2959(1989)]Fulltext:PMC1141872
/HUMANEXPOSURESTUDIES/Amajorityof...unacclimatedsubjects...experiencedeyeirritationat50ppm
after15minuteshowever,eyeirritationinsensitivepersonsoccurredafterexposureatconcentationsaslowa25
ppmfor15minutes.Thisstudyalsoreportedthatat200ppmallsubjectshadredeyesandtransientconjunctivitis,
andamajorityofthesubjectssufferedfromnoseandthroatirritation.
/HUMANEXPOSURESTUDIES/Allofthe14humansexposedincontrolledstudiestoacetaldehydevaporat135
ppm(240mg/cum)for30minutesreportedmildirritationtotheupperrespiratorytract.
/HUMANEXPOSURESTUDIES/Humansubjectsweregivenintravenousinfusionstoraisebloodlevelto0.2to
0.7mg%(about10timesnormal).Attheselevelsanincreaseinheartrateandrespiratoryventilationoccurs,and
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asensationisnoted.
Patty,F.(ed.).IndustrialHygieneandToxicology:VolumeII:Toxicology.2nded.NewYork:IntersciencePublishers,1963.,p.
1973
/HUMANEXPOSURESTUDIES/Acetaldehydeabsorbedorgeneratedsystemicallyhasnotbeenknowntobe
toxictotheeye,butexperimentalobservationsonhuman...reportedfromCzechoslovakiaindicatethatat
concentrationof0.012mg/cumofair,"changesinlightsensitivityoftheeye"werefound,andchangesinauditory
sensitivitywerefoundat0.050mg/cum.
Grant,W.M.ToxicologyoftheEye.2nded.Springfield,Illinois:CharlesC.Thomas,1974.,p.76
/HUMANEXPOSURESTUDIES/Agroupof14healthymalevolunteers,aged1845years,wereexposedina100
cumchambertoameasuredconcentrationofacetaldehydevapourof240mg/cum(134ppm)for30min.This
concentrationwassaidtobemildlyirritatingtotheupperrespiratorytract.Nootherclinicalsignswerereported.
/HUMANEXPOSURESTUDIES/...Theaimofthisstudywastodeterminetheconcentrationofethanol(ETOH)
andacetaldehyde(ACTDH),atoxicmetaboliteofETOH,inthealveolarair(AA)ofsubjectsexposedtolowETOH
vaporconcentrationsbyinhalation.Fivehealthyadults(2women,3men),nonsmoking,2555yrofage,were
exposedfor6consecutivehoursto25,100,or1000ppmETOHandwereaskedtoprovideAAsamplesatvarious
intervalsduringandaftereachexposuresession,forETOHandACTDHmeasurements.Resultsshowedthatthe
concentrationsofACTDHandETOHinAAmeasuredafter2hrofexposureat25ppmwere0.06ppmand7.5
ppm,respectively.Overall,therewasasignificantcorrelationbetweenETOHexposureandETOH(R(2)=0.92,p
<.001)andACTDH(R(2)=0.99,p<.001)inAA.TheratiosbetweenACTDHandETOHinAAafter4hrof
exposureto25.9ppm,101.7ppm,and990.8ppmETOHwere0.005,0.008,and0.006,respectively.
TardifRetalInhalToxicol16(4):2037(2004)
/HUMANEXPOSURESTUDIES/...Theeffectofinhaledacetaldehydeonairwaytoneincomparisonwitheither
methacholineorAMP/wasinvestigated/in16asthmatics.Furthermore,therepeatabilityoftheacetaldehyde
challengewasassessedin14subjectswithmildasthma.Theresponsetoeachbronchoconstrictoragentwas
measuredbythePC20(provocativeconcentrationrequiredtoproducea20%fallinFEV1).Thegeometricmean
(range)PC20valueswere3.1mmol/L(0.546.0mmol/L)formethacholine,883.1mmol/L(190.71816.1mmol/L)
foracetaldehyde,and50.1mmol/L(3.21152.1mmol/L)forAMP.Thus,acetaldehydewas18foldlesspotentthan
AMPincausingbronchoconstriction.AsimilarcorrelationwasobservedbetweenPC20acetaldehydeandeither
PC20AMP(r=0.58,p=0.02)orPC20methacholine(r=0.56,p=0.02).Thechallengeprocedurewith
acetaldehydewasmoderatelyrepeatable(coefficientofrepeatability=+/1.4doublingconcentrations,intraclass
correlationcoefficient=0.64)...
PrietoLetalJInvestAllergologyClinImmunol12(2):918(2002)
/HUMANEXPOSURESTUDIES/Atotalof78adults(43subjectswithallergicrhinitis,16asthmaticsand19
healthysubjects)werechallengedwithincreasedconcentrationsofacetaldehydeandmethacholine.Theresponse
toeachbronchoconstrictoragentwasmeasuredbytheprovocativeconcentrationrequiredtoproducea20%fallin
FEV(1)(PC(20)).RESULTS:ThegeometricmeanPC(20)acetaldehydevalueforasthmaticswas35.5mg/ml
comparedwith67.6mg/mLinsubjectswithallergicrhinitisandwith80.0mg/mLinhealthysubjects(p<0.001).
ThePC(20)acetaldehydevaluesintheallergicrhinitisgroupwerealsosignificantlylowerthaninthehealthycontrol
group(p=0.04).Allofthesubjectswithallergicrhinitisandincreasedresponsivenesstoacetaldehydeshowed
airwayhyperresponsivenesstomethacholine,but9patientswithhyperresponsivenesstomethacholinefailedto
respondtoacetaldehyde....
PrietoLetalRespiration69(2):12935(2002)
/HUMANEXPOSURESTUDIES/Intravenousinfusionof5%acetaldehyde[purityunspecified]atarateof20.6
82.4mg/minforupto36minintonormalhumansubjectscausedanincreaseinheartrate,ventilationanddead
space,andadecreaseinalveolarcarbondioxidelevels.Thesesymptomsarequalitativelyandquantitativelysimilar
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tothoseseenafterethanolintakeinsubjectspreviouslytreatedwithdisulfiram(Antabuse),aknowninhibitorof
ALDH.
/HUMANEXPOSURESTUDIES/ThreeAsiansubjectswhoreportedexperiencingseverefacialflushingin
responsetoethanolingestionweresubjectsofpatchtestingtoaliphaticalcoholsandaldehydes.Anaqueous
suspensionof75%(v/v)ofeachalcoholandaldehydewaspreparedand25uLwasusedtosaturateashlessgrade
filterpapersquareswhichwerethenplacedontheforearmofeachsubject.PatcheswerecoveredwithParafilm
andleftinplacefor5minuteswhenthepatcheswereremovedandtheareagentlyblotted.Sitesshowing
erythemaduringthenext60minuteswereconsideredpositive.Allthreesubjectsdisplayedpositiveresponsesto
ethyl,propyl,butyl,andpentylalcohols.Intensepositivereactions,withvariableamountsofedema,wereobserved
forallthealdehydestested(valeraldehydeaswellasacetaldehyde,propionaldehyde,andbutyraldehyde).
UnitedNationsEnvironmentProgramme:ScreeningInformationDataSheetsonnValeraldehyde(110623)(October2005)
Availablefrom,asofJanuary15,2009:http://www.chem.unep.ch/irptc/sids/OECDSIDS/sidspub.html
/SIGNSANDSYMPTOMS/Acetaldehydevaporirritationofthehumaneyeisdetectableat50ppminairand
becomesexcessiveforchronicindustrialexposureabove200ppm.Higherconcnandextendedexposuremayinjure
thecornealepithelium,causingpersistentlacrimation,photophobiaandforeignbodysensation.Asplashofliquid
acetaldehydecanbeexpectedtocausepainfulbutsuperficialinjuryofthecornea,withrapidhealingtheliquid
evaporatessorapidlyatbodytemperaturethatcontactisbriefandselflimited.
Grant,W.M.ToxicologyoftheEye.3rded.Springfield,IL:CharlesC.ThomasPublisher,1986.,p.32
/SIGNSANDSYMPTOMS/Clinicaleffectsofexposuretoacetaldehydevaporsincludeconcentrationdependent
erythema,coughing,pulmonaryedema,andnarcosis.Athighconcentrations,paralysisleadingtodeathcanoccur.
/SIGNSANDSYMPTOMS/Largedosesmaycausedeathbyrespiratoryparalysis.Symptomsofchronic
intoxicationresemblethoseofchronicalcoholism.
Budavari,S.(ed.).TheMerckIndexEncyclopediaofChemicals,DrugsandBiologicals.Rahway,NJ:MerckandCo.,Inc.,
1989.,p.7
/SIGNSANDSYMPTOMS/Wheninfusedintravenously(andperhapswheningested),acetaldehydeis
sympathomimetic,asevidencedbytachycardiaandhypertension.Thisreactionisduetonorepinephrinerelease
fromadrenergicnerveendings.
Gosselin,R.E.,R.P.Smith,H.C.Hodge.ClinicalToxicologyofCommercialProducts.5thed.Baltimore:WilliamsandWilkins,
1984.,p.II186
/SIGNSANDSYMPTOMS/Repeatedexposuretovaporscausesdermatitisandconjunctivitis.
Dreisbach,R.H.HandbookofPoisoning.12thed.Norwalk,CT:AppletonandLange,1987.,p.186
/SIGNSANDSYMPTOMS/Asplashofliquidacetaldehydewasreportedtocauseaburningsensation,
lachrymationandblurredvision.Prolongedperiodsofcontactwiththeskinresultinerythemaandburnsrepeated
contactmayresultindermatitis,dueeithertoprimaryirritationortosensitization.
/SIGNSANDSYMPTOMS/Analysisoftheoxidativemodificationofplasmaanderythrocyteghostproteinsof
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chronicalcoholicsubjectsandhealthynonalcoholicshasbeenperformed.Itwasfoundthatincreasedlevelsof
proteincarbonylsinbothplasmaanderythrocyteghostsfromalcoholicsubjectsoccurredincomparisontothelevels
foundinpreparationsfromnonalcoholics.Plasmaproteinsfromalcoholicsubjectsdidnotshowevidenceofcross
linking,althoughplasmaproteinconcentrationandcompositionwerechanged.Inalcoholicsubjectswhodisplayed
noevidenceofabnormalerythrocytemorphologynocrosslinkingoferythrocyteghostproteinswasdetectable,
whereastheghostsobtainedfromalcoholicsubjectswhodisplayedmorphologicallyabnormalerythrocytes
containedcrosslinkedproteins.Theinvitrotreatmentwithacetaldehydeoferythrocytesfromnonalcoholicscaused
increasedlevelsofproteincarbonylsandcrosslinkingproductsinerythrocyteghostpreparationswhichweresimilar
tothosefoundinseverealcoholics.
TyulinaOVetalBIochimicaetBiophysicaActa1762(5):55863(2006)
/SIGNSANDSYMPTOMS/Acetaldehydeisthefirstactivebreakdownproduct(ie,metabolite)generatedduring
alcoholmetabolism.Ithastoxicpropertiesbutalsoexertsotheractionsonthebody(ie,haspharmacological
properties).Recentstudieshaveshownthatthedirectadministrationofacetaldehyde,especiallyintothebrain,
inducesseveraleffectsthatmimicthoseofalcohol.Highdosesofacetaldehydeinducesedativeaswellas
movementandmemoryimpairingeffects,whereaslowerdosesproducebehavioraleffects(eg,stimulationand
reinforcement)thatarecharacteristicofaddictivedrugs.Whenacetaldehydeaccumulatesoutsidethebrain(ie,in
theperiphery),adverseeffectspredominateandpreventfurtheralcoholdrinking.Toinvestigatetheroleof
acetaldehydeinmediatingalcohol'seffects,investigatorshavepharmacologicallymanipulatedalcoholmetabolism
andtheproductionofacetaldehydewithinthebody(ie,endogenousacetaldehydeproduction).Studies
manipulatingtheactivityoftheenzymecatalase,whichpromotesacetaldehydeproductioninthebrain,suggest
thatacetaldehydecontributestomanybehavioraleffectsofalcohol,especiallyitsstimulantproperties.However,it
remainscontroversialwhetheracetaldehydeconcentrationsobtainedundernormalphysiologicalconditionsare
sufficienttoinducesignificantpharmacologicaleffects.Currentevidencesuggeststhatthecontributionof
acetaldehydetoalcohol'seffectsisbestexplainedbyaprocessinwhichacetaldehydemodulates,ratherthan
mediates,someofalcohol'seffects.
QuertemontE,DidoneVAlcoholResHlth29(4):25865(2006)
/SIGNSANDSYMPTOMS/Acomplexclinicalandlaboratoryexaminationof169patientswithreactiveformof
alcoholwithdrawalsyndrome/wasconducted/.Progressivetoxemiawithacetaldehyde(keypathogeneticstage)and
volemicchangeswerefollowedbyhomeostasisdisordersandgradualdecompensationofthenaturaldetoxification
system.Thepatientswiththisformofalcoholwithdrawalsyndromedidnotexhibitphysicalandpsychicdependence
onalcohol....
Remennik,AGetalBullExptlBiolMed139(6):7324(2005)
/EPIDEMIOLOGYSTUDIES/Averylimitedinvestigationwasperformedonanunspecifiednumberofpeople,
selectedfrom150workerswhohadbeenemployedfor20yearsormoreinachemicalfactory....Inpartsofthe
factory,therewasexposuretoavarietyofchemicals.Inonearea,17mgacetaldehyde/cumhadbeenmeasured,
togetherwith570mgbutyraldehyde/cum,17mgcrotonaldehyde/cum,26mgnbutanol/cum,andabout15mg
ethylhexanol/cum.Otherareasofthefactorywereknowntohavehigherconcentrationsofvapoursofaldehydes
andaldol,whichcausedirritationoftheeyesandupperrespiratorytract.
/EPIDEMIOLOGYSTUDIES/...MEDLINEwassearchedfrom1980to2000usingthekeywordsacetaldehyde,
pharmacokinetics,andalcoholismforcontrolledtrialsreportingbloodorbreathacetaldehydelevelsinalcoholicsand
nonalcoholics.Separately,usingthekeywordsfetalalcoholsyndrome,epidemiology,prevalence,incidence,and
frequency,articleswereidentifiedreportingalcoholrelatedbirthdefects(ARBD)incidencesamongtheoffspringof
heavydrinkers.Of23articlesreportingacetaldehydelevelsinalcoholics,fourmettheinclusioncriteria.Fortythree
studiesreportedontherateofARBDinheavydrinkers,and14wereaccepted.Thirtyfourpercentofheavydrinkers
hadachildwithARBD,and43%ofchronicalcoholicshadhighacetaldehydelevels.Thesimilarfrequenciesofhigh
acetaldehydelevelsamongalcoholicsandtheratesofARBDamongalcoholicwomenprovideepidemiologic
supporttothehypothesisthatacetaldehydemayplayamajorroleinthecauseofARBD.
HardMLetalTherapDrugMonit23(4):42734(2001)
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/EPIDEMIOLOGYSTUDIES//ALDH2(normalorwildtype,withoutasuperscript)ispolymorphicitsmutantallele,
ALDH2(withsuperscript2),whichleadstoenzymeinactivity,isprevalentinAsianpopulations./AJapanesecase
controlstudyofALDH2relatedriskforesophagealsquamouscellcarcinomainalcoholics(40casesand55
controls)andnonalcoholicdrinkers(29casesand28controls)during199195showedahigherriskforesophageal
cancerinthosewithoneALDH2(withsuperscript2)alleleinbothalcoholics(crudeoddsratio,7.695%confidence
interval(CI),2.820.7)andnonalcoholicdrinkers(oddsratio,12.195%CI,3.442.8).MantelHaenszeladjustment
forageanddailyalcoholconsumptionhadvirtuallynoinfluenceontheriskestimates[adjustedoddsratiosnot
given].AspersonswhohavethemutantALDH2(withsuperscript2)allelehaveahighconcentrationofblood
acetaldehydeafterdrinkingalcohol,theresultsofthisstudywereinterpretedasstronglysuggestingacarcinogenic
roleofacetaldehydeinhumans.
/EPIDEMIOLOGYSTUDIES/Inasurveyofchemicalplants(withoutpriorhypothesis)intheGermanDemocratic
Republic,ninecancercaseswerefoundinafactorywherethemainprocesswasdimerizationofacetaldehydeand
wherethemainexposuresweretoacetaldol(3hydroxybutanal),acetaldehyde,butyraldehyde,crotonaldehydeand
otherhigher,condensedaldehydes,aswellastotracesofacrolein.Ofthecancercases,fivewerebronchialtumors
andtwowerecarcinomasoftheoralcavity.Allninepatientsweresmokers.Therelativefrequenciesofthese
tumorswerereportedtobehigherthanthoseexpectedintheGermanDemocraticRepublic.
/GENOTOXICITY/Humanlymphocytes(fromknownalcoholics)wereexposedtoacetaldehydeconcnof0.02
mg/mLand0.04mg/mL.Resultsindicatethatchromosomalaberrationsoccurredatbothconcentrations.
BadrFM,HussainFGenetics86:S23(1977)ascitedinUSEPAChemicalHazardInformationProfile:Acetaldehyde(Draft)
p.29(1983)
/GENOTOXICITY/...Acetaldehydeinducedsisterchromatidexchangesinhumanwholebloodlymphocytecultures
atconcentrations(0.1252mM)...
NorppaHetalCancerRes45(10):481621(1985)
/GENOTOXICITY/Humanleukocyteswereincubatedinthepresenceofvinylacetateoracetaldehyde(1020mM)
for4hrat37degCinvitro.DNAdamagewasanalysedbyalkalineelution.Noneofthecompoundsinduceda
detectableincreaseinthefrequencyofDNAstrandbreaks.Cellsexposedto5GyofXrayimmediatelyafter
treatmentandbeforealkalineelutionshowedaclear,dosedependentretardationoftheelutionrateincomparison
withXirradiatedcontrolcells.TheseresultsdemonstratethatbothvinylacetateandacetaldehydeinduceDNA
crosslinksinhumancells.
LambertBOetalMutatRes146:3013(1985)
/GENOTOXICITY/Acetaldehydeinduceschromosomalaberrationandsisterchromatidexchangeinavarietyof
testsystems.Themutageniceffectofacetaldehydewasstudiedatthehypoxanthineguaninephosphoribosyl
transferaselocusinhumanlympocytesinvitrobyselectionofmutantcellclonesinmediumcontainingthioguanine.
Cellstreatedwith1.22.4mMacetaldehydefor24hror0.20.6mMacetaldehydefor48hrshowedadose
dependentdecreaseofcellsurvivalanda3to16foldincreaseofthemutantfrequency.Theinverserelationship
betweencellsurvivalandmutantfrequencywaslineardowntoarelativesurvivalof15%.FortyonemutantTcell
clonesderivedfromculturestreatedwith1.2or2.4mMacetaldehydeand15fromuntreatedcontrolswerestudied
fordeletionmutation.Intheculturewitha16foldincreaseofmutantfrequency,4of10independentmutants
(40%)showedpartialdeletionsextendingbeyondthe3'codingsequencesofthehypoxanthineguanine
phosphoribosyltransferasegene.Acetaldehydeiscapableofinducinggenemutationatthehypoxanthineguanine
phosphoribosyltransferaselocusinhumancells,anddeletionmutationaffectingthe3'endofthegenemaybea
majortypeofacetaldehydeinducedmutationofthislocus.
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HeSM,LambertBEnvironMolMutagen16(2):5763(1990)
/GENOTOXICITY/TheconditionsunderwhichacetaldehydeinducessisterchromatidexchangeandDNAdamage
inhumanlymphocytesinvitrowereinvestigated.Lymphocyteswerecollectedfromthebloodofhealthydonors,and
cultured.AcetaldehydeexposuregaverisetoDNAcrosslinks,whichwerelikelyreponsibleforatleastpartofits
sisterchromatidexchangeinducingeffecttheinductionofsisterchromatidexchangebyacetaldehydewaslargely
dependentonthecontinuouspresenceofacetaldehydeintheculturemediumcellsweremoresensitivetothe
sisterchromatidexchangeinducingeffectofacetaldehydeinlateG1thaninearlyG1andthesisterchromatid
exchangeinducingactivityofacetaldehydeincellsinculturemediumremainedalmostconstantforabout96hours,
suggestingthatthecapacityofhumanlymphocytestometabolizeacetaldehydewasverylowifpresentatall.The
apparentinabilityofhumanlymphocytestodetoxifyacetaldehydeanditspotentsisterchromatidexchangeinducing
effectwhencontinuouslypresentintheculturemediumsuggeststhatrepeatedorcontinuousexposureresultingin
concentrationsof10to100uM/literofacetaldehydeinthebloodwillhaveasmallbutdetectablesisterchromatid
exchangeinducingeffect.
LambertB,HeSMAnnalsoftheNewYorkAcademyofSciences534:36976(1988)
/GENOTOXICITY/AcetaldehydeDNAadductshavebeenobservedingranulocytesandlymphocytesofhuman
alcoholabusers.
/GENOTOXICITY/Chronicalcoholconsumptionisamajorriskfactorforupperaerodigestivetractcancers,
includingcanceroftheesophagus.Whereasalcoholassuchisnotthoughttobedirectlycarcinogenic,
acetaldehyde,itsfirstmetabolite,hasbeenprovengenotoxicandmutagenicintheHPRTgene.Asmutationsin
thetumorsuppressorgeneTP53arethemostcommongeneticalterationsinvolvedinhumancancers,especially
esophagealtumours,theaimofthisworkwastoestablishthemutationalpatterninducedbyacetaldehydeinvitro
ontheTP53gene,andtocomparethispatternwiththatfoundinhumanalcoholrelatedtumors.Forthispurpose,
....afunctionalassayinyeast,theFASAY(functionalanalysisofseparatedallelesinyeast)/wasused/afterin
vitroexposureofhumannormalfibroblastsAG1521toacetaldehyde....35mutations/werenoted/,ofwhich32
weresinglenucleotidesubstitutionsincluding2nonsenseand30missensemutations.Thepatternshowedthatthe
mainmutationswereG>Atransitions(n=23,ofwhich14inCpGsites),followedbyG>Ttransversions(n=4),A>G
transitions(n=2)andA>Ttransversions(n=2).Othermutationswereonebaseinsertionandtwodeletions,leading
toframeshifts.Elevenmutations(31%)werelocatedinTP53hotspotsincodons245,248,249and273.Finally,
wecomparedthispatternwiththatfoundforesophagealcancersinhumans.Theseresultssupportthenotionthat
acetaldehydeplaysaroleinTP53mutationsinesophagealcancers...
PagetVetalMutatRes652(1):129(2008)
/GENOTOXICITY/...BecauseDNAadductsareimportantincarcinogenesis,wehaveusedliquidchromatography
electrosprayionizationtandemmassspectrometry(LCESIMS/MS)toexplorethepresenceinhumanliverDNAof
themajoracetaldehydeDNAadduct,N2ethylidenedeoxyguanosine,1.DNAwasisolatedandenzymatically
hydrolyzedinthepresenceofNaBH3CN,whichquantitativelyconvertsadduct1toN2ethyldeoxyguanosine(N2
ethyldGuo,2).[15N5]N2EthyldGuowassynthesizedandusedasaninternalstandard.Adduct2wasenriched
fromthehydrolysatebysolidphaseextractionandanalyzedbyLCESIMS/MS.Clearpeakswereobservedfor
adduct2inanalysesofhumanliverDNA,calfthymusDNA,andratliverDNA.Thesepeakswerenotobserved,or
weremuchsmaller,whentheNaBH3CNstepwasomitted.WhentheDNAwassubjectedtoneutralthermal
hydrolysispriortoNaBH3CNtreatment,adduct2wasnotobserved.Controlexperimentsusing[13C2]acetaldehyde
demonstratedthatadducts1and2werenotformedasartifactsduringDNAisolationandanalysis.Theseresults
stronglyindicatethatadduct1ispresentinhumanliverDNAanddemonstratethatitcanbequantifiedasadduct2.
Levelsofadduct2measuredin12humanliversampleswere534+/245fmol/micromoldGuo(mean+/SD).The
resultsofthisstudyestablishthepresenceofanacetaldehydeadductinhumanliverDNAandsuggestthatitisa
commonlyoccurringendogenousDNAadduct.[Wang,MetalChemResToxicol19(2):31924(2006)]Fulltext:
PMC3199962
/GENOTOXICITY/TheeffectsofDNAdamageinducedbythetypicalenvironmentalpollutantacetaldehydewere
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studiedwithsinglecellgelelectrophoresis(SCGE)andhighperformanceliquidchromatographywith
electrochemicaldetection(HPLCEC).TheresultsshowedthatacetaldehydenotonlycouldcauseDNAstrand
breakagebutalsoDNADNA,DNAproteincrosslinksoflymphocytesofhumanperipheralblood.Thereactionof
acetaldehydewithDNAinvitrowasweak,buttheoxidativeabilitywasenhancedandthereactioncouldproducea
numberof8OHdGadductsmediatedbytheFe2+...
Xi,ZGetalBianJi,ZhongguoKeXueYuanHuanJingKeXueWeiYuanHui25(3):1025(2004)
/GENOTOXICITY/TheinfluenceofethanolandacetaldehydeonDNAinhumanlymphocytes,gastricmucosa
(GM)andcolonicmucosa(CM)wasinvestigatedbyusingthecometassay.Allkindsofcellswereexposedto
ethanolandacetaldehydeintworegimens:thecellswereincubatedwitheitherchemicalandanalysedortheywere
exposedfirsttoethanol,washedandthenexposedtoacetaldehydeandanalysed.Lymphocyteswereexposedto
ethanolatfinalconcentrationsof30mMandacetaldehydeat3mM.GMcellswereincubatedwithethanolat1M
andacetaldehydeat100mM.CMcellswereexposedtoethanolat10mMandacetaldehydeat100mM.In
combinedexposure,thecellsweresubsequentlyexposedtoethanolandacetaldehydeatallcombinationofthe
concentrationsoftheagents.EthanolcausedDNAstrandbreaks,whichwererepairedduring4hr,exceptwhenthis
agentwasappliedinGMcellsataconcentrationof1M.Adosedependentdecreaseinthetailmomentofall
typesofacetaldehydetreatedcellswasobserved.SimilarresultswereobtainedwhenarecognizedDNA
crosslinkingagent,formaldehyde,wasused.Theseresultssuggestthatacetaldehydemayformcrosslinkswith
DNA.Thesecrosslinkswerepoorlyrepaired.CMcellsshowedthehighestsensitivityofallcelltypestoethanolthan
lymphocytesandGMcells.Therewerenodifferencesinthesensitivitytoacetaldehydeofallthecelltypes./The
authorsstatedthatthe/resultsclearlyindicatethatethanolandacetaldehydecancontributetocancersofthe
digestivetract.
BlasiakJetalToxicolInVitro14(4):28795(2000)
/GENOTOXICITY/Freshlyisolatedhumanlymphocytesfromtwohealthydonorswereincubatedwith0,1.56,6.25,
25,and100mMof...acetaldehydeincompletemediumfor1hr....Acetaldehydeinducedbothsinglestrand(even
atthelowestconcentrationof1.56mM)anddoublestrandbreaks(onlyatthehighestconcentrationof100mM).
Followingexposuretoacetaldehyde,cellswereincubatedincompletemediumfor30,60,and120min.Duringthis
incubationperiod,mostcellswereunabletorepairDNAsingleanddoublestrandbreakscausedbyacetaldehyde.
...Asignificantcellloss/wasalsoobserved/afterexposuretoacetaldehyde...
SinghNPetalMutatRes337(1):917(1995)
/GENOTOXICITY/...PreexistinginvivoHPRTmutantswereremovedfromPHA/phytohemagglutinin/stimulated
Tlymphocytesbeforeinvitrotreatmentwith2.4mMacetaldehydefor24hr.Followingcellgrowthtoallowmutation
expression,independent6thioguanineresistantmutantswereselectedfromlargenumbersofsubculturesshowing
a3foldinductionofmutantfrequencyonaverage.Atotalof73inducedand36spontaneousmutantswerefound
tocarryamissense,nonsense,frameshiftorsplicemutation.Basesubstitutionswereidentifiedinthecodingor
splicingsequencesof55inducedand26controlmutants.TheinducedbasechangesweremainlyG>Atransition
(40%,Gonnontranscribedstrand)followedbyA>Ttransversions(14.5%,Aonnontranscribedstrand).The
controlmutantshadsignificantly(P=0.04)lessG>Atransition(15.4%)andcompletelylackedA>T
transversions....5'AGG3'or5'AAG3'/werealsoidentified/aspotentialtargetsequencesforacetaldehyde
inducedG>Atransitions.ThisspecificmutationalspectruminducedbyAAisconsistentwiththeknownformation
andpersistencyofN(2)ethyl2'guanosineadductandwiththepredominanceofG>Atransitionsandmutationsat
A:Tbasepairsinthep53geneofesophagealtumors.
NooriP,HouSMCarcinogenesis22(11):182530(2001)
/GENOTOXICITY/Inhumanlymphocytes/acetaldehyde/inducedgenemutationsandsisterchromatidexchanges
and,inaddition,chromosomalaberrationsandbothpositiveandnegativecentromerestainingmicronuclei.Itdid
notcausemorphologicaltransformationinculturedmammaliancellswhentestedalone,butpositiveresultswere
obtainedwhenitwasusedincombinationwiththetumorpromoter12Otetradecanoylphorbol13acetate....
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/GENOTOXICITY/AcetaldehydecausedDNAstrandbreaksandcrosslinksinhumanlymphocytesinvitrowithout
metabolicactivation,butnotinhumanbronchialepithelialcellsandinhumanleukocytes....
/GENOTOXICITY/SCEwasinducedbyacetaldehyde(1.3106ug/mL)intheabsenceofexogenousmetabolic
activationin...humanlymphocytecultures....AdditionofNAD+andALDHtohumanlymphocyteculturesexposed
toacetaldehydedecreasedSCEinduction.Additionof1aminocyclopropanol,aninhibitorofALDH,tohuman
lymphocytesenhancedSCEinductionbyacetaldehyde.
/ALTERNATIVEandINVITROTESTS/Hepatocytesfromliversofhumanswithalcoholichepatitisweremore
susceptibletocytotoxicityofacetaldehydethanhepatocytesfromnormalliverofhumansthatwerenon
symptomaticorwithviralhepatitis,alcoholicfattyliver,orstablealcoholiccirrhosis.
KakumaSetalProcSocExpBiolMed168(3):3259(1981)
/ALTERNATIVEandINVITROTESTS/Theeffectsofseveralaldehydesandperoxidesongrowthand
differentiationofnormalhumanbronchialepithelialcellswerestudied.Cellswereexposedtoformaldehydeand
acetaldehyde.Theeffectofeachagentonthefollowingparameterswasmeasured:(a)clonalgrowthrate(b)
squamousdifferentiation(c)DNAdamage(d)ornithinedecarboxylaseactivity(e)nucleicacidsynthesis(f)aryl
hydrocarbonhydroxylaseactivityand(g)arachidonicacidandcholinerelease.Noneoftheagentsweremitogenic,
andtheireffectswereassessedatconcentrationswhichreducedgrowthrate(populationdoublingsperday)to50%
ofcontrol.The50%ofcontrolconcentrationsforthe6hrexposurewerefoundtobe0.21mMformaldehydeand30
mMacetaldehyde.Cellsincontrols(mediancellplanararea,1150sqmu),acetaldehydeexposedcellswerelarger
thancontrols(mediancellsplanararea,3200sqmu).Allagentsincreasedtheformationofcrosslinkedenvelopes
anddepressedRNAsynthesismorethanDNAsynthesis.Formaldehydecauseddetectableamountsofbothsingle
strandbreaksandDNAproteincrosslinks.
SankaranHetalBiochemPharmacol34(16):285963(1985)
/ALTERNATIVEandINVITROTESTS/Acetaldehyde(220mM)significantlyinhibiteduptakeofalpha
aminoisobutyricacidinhumanplacentalvillustissueinvitro.Inhibitionby10mMwaspartiallyreversible.Thus,
humanplacentaisresistanttoacuteethanolassociatedeffectsuponaminoacidtransportinvitro.
FisherSEetalLifeSci29(12):12838(1981)
/ALTERNATIVEandINVITROTESTS/...Humantissuesampleswerepreparedfromthelungsresectedfrom
patientswithlungcancer.Theeffectofacetaldehydeonairwaymuscletoneandtheconcentrationofchemical
mediatorsreleasedintheorganbathweremeasuredbeforeandafteracetaldehydestimulation.Mastcellswere
preparedfromlungparenchymabytheimmunomagneticmethodandthenstimulatedwithacetaldehydeto
determinethechemicalmediatorsreleased....Acetaldehyde(>3x104M)increasedairwaymuscletone,which
wasassociatedwithasignificantincreaseinthereleaseofhistamine,butnotthromboxaneB2orcysteinyl
leukotrienes.Ahistamine(H1receptor)antagonistcompletelyinhibitedacetaldehydeinducedbronchialsmooth
musclecontraction.Acetaldehydealsoinducedasignificanthistaminereleasefromhumanlungmastcellsand
degranulationofmastcells.
KawanoTetalInternatArchAllergyImmunol134(3):2339(2004)
/ALTERNATIVEandINVITROTESTS/...Thepurposeofthisstudywastodeterminetheeffectofacetaldehyde
oncytokineproductionandnuclearfactorkappaB(NFkappaB)activationinhumanbronchialtissues.Human
bronchiwerepreparedfromnormalpartsoflungtissuesresectedforlungcancer(n=11).Thebronchiwere
culturedinthepresenceof5x104Mofacetaldehydefor24hoursandtheconcentrationsofeotaxin,granulocyte
macrophagecolonystimulatingfactor(GMCSF),interleukin5,interleukin8,andregulatedonactivation,normalT
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cellsexpressedandsecretedinculturedsupernatantsweredeterminedbyenzymelinkedimmunosorbentassay.
TissuesalsowereimmunohistochemicallystainedforNFkappaBp65.AcetaldehydesignificantlyincreasedGM
CSFproductionfromhumanbronchiandnucleartranslocationofNFkappaBp65inairwayepitheliumbuthadno
effectsonothercytokines.
MachidaIetalAllergyAsthmaProc24(5):36771(2003)
/ALTERNATIVEandINVITROTESTS/...HPVimmortalized,nontumorigenichumanoralkeratinocytes/were
treated/withacetaldehydeatvariousconcentrationsandforvarioustimesand...severalparametersofJun/AP1
expressionandfunction/weremeasured/....cJunmRNAandproteinlevelsincreasedintheacetaldehydetreated
cellscomparedtountreatedcontrolcells.Moreover,Jun/AP1DNAbindingactivitywasrapidlyactivatedby
acetaldehydeinadosedependentfashion.TheincreasesinJunproteinandAP1DNAbindingactivitywere
accompaniedbyincreasedtransactivationofanAP1responsivereporterconstructaswellasincreasedtranscript
levelsofacandidateAP1responsivegene,stromelysin3.Thelevelsofacetaldehydeemployedwereminimally
toxictothecellsasdeterminedbyMTTassays.Thus,acetaldehydewasfoundtoactivatetheexpressionand
activityofanoncogenictranscriptionfactorinHPVinitiatedcells.
Timmons,SRetalOralOncology38(3):28190(2002)
/OTHERTOXICITYINFORMATION/Hepatocytesfromliversofhumanswithalcoholichepatitisweremore
susceptibletocytotoxicityofacetaldehydethanhepatocytesfromnormalliverofhumansthatwerenon
symptomaticorwithviralhepatitis,alcoholicfattyliver,orstablealcoholiccirrhosis.
KakumaSetalProcSocExpBiolMed168(3):3259(1981)
/OTHERTOXICITYINFORMATION/Inhalationathigherconcentrations(greaterthan100200ppm)cancause
irritationtothemucousmembranesandciliastaticeffectsontheupperrespiratorytract.Acetaldehydemayfacilitate
theuptakeinthehumanbodyofotheratmosphericcontaminantsbythebronchialepitheliumbecauseofits
ciliotoxicandmucuscoagulatingeffect.
AmericanConferenceofGovernmentalIndustrialHygienists,Inc.DocumentationoftheThresholdLimitValuesandBiological
ExposureIndices.6thed.VolumesI,II,III.Cincinnati,OH:ACGIH,1991.
/OTHERTOXICITYINFORMATION/Thesaturatedaldehydesbyinhalationshowdecreasingtoxicitywith
increasingchainlengthintheorderacetaldehyde,propionaldehyde,isobutyraldehyde,nbutyraldehyde,n
valeraldehydeandisovaleraldehye.
Gosselin,R.E.,R.P.Smith,H.C.Hodge.ClinicalToxicologyofCommercialProducts.5thed.Baltimore:WilliamsandWilkins,
1984.,p.II186
/OTHERTOXICITYINFORMATION/...Thedetectionofacetaldehydeadductsinthebrainregionofahuman
alcoholics/wasperformed/.Brainsamplescollectedfromanalcoholicautopsiedcasewereused.Determinationof
acetaldehydeadductswasperformedusingafluorescenceimmmunohistochemicalstainingmethodwithantibodies
againstacetaldehydeadducts....Acetaldehydeadducts/werefound/inthefrontalcortexandthemidbrainofan
alcoholics....
NakamuraKetalArchToxicol77(10):5913(2003)
/OTHERTOXICITYINFORMATION/Approximately3.6%ofcancersworldwidederivefromchronicalcohol
drinking,includingthoseoftheupperaerodigestivetract,theliver,thecolorectumandthebreast.Althoughthe
mechanismsforalcoholassociatedcarcinogenesisarenotcompletelyunderstood,mostrecentresearchhas
focusedonacetaldehyde,thefirstandmosttoxicethanolmetabolite,asacancercausingagent.Ethanolmayalso
stimulatecarcinogenesisbyinhibitingDNAmethylationandbyinteractingwithretinoidmetabolism.Alcoholrelated
carcinogenesismayinteractwithotherfactorssuchassmoking,dietandcomorbidities,anddependsongenetic
susceptibility.
SeitzHK,StickelFNatRevisCancer7(8):599612(2007)
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/OTHERTOXICITYINFORMATION/...138consecutiveadultpatientsundergoingbonemarrowaspirationdueto
macrocytosis(MCVvaluesabove99fL)/werestudied/.Assessmentincludedcompletebloodcounts,morphologic
review,assessmentofalcoholconsumption,andbiochemicalandimmunocytochemicalassaysforacetaldehyde
adducts....Therewere68patients(49%)withahistoryofexcessivealcoholconsumption,28(20%)ofwhomwere
patientswithseveredependence.Thebloodsmearspreparedfromthealcoholicpatientswithmacrocytosisalso
containedstomatocytesandknizocytes.Bonemarrowaspiratesfrom12alcoholicpatientsshowedvacuolizationof
pronormoblastsandthepresenceofringsideroblastswasnotedin8cases.Inimmunocytochemicalanalysesofthe
peripheralblooderythrocytes,acetaldehydederivedepitopeswerefoundtooccurbothonthecellmembraneand
insidetheerythrocytes.Bonemarrowaspiratesalsoshowedpositivestainingforacetaldehydeadductsinthe
erythropoieticcellsin8of11(73%)consecutivealcoholicpatients.Separationoftheerythrocyteproteinsfromthe
samplesofalcoholicsonHPLCchromatographyrevealedtheformationoffastelutinghemoglobinfractions,which
alsoreactedwithantibodiesagainstacetaldehydeadducts.[LatvalaJetalMolMed7(6):4015(2001)]Fulltext:
PMC1950047
10.1.11 NonHumanToxicityExcerpts
/LABORATORYANIMALS:AcuteExposure/...Catsinhaling380ppmshownonoticeableeffect,evenafterseven
hrifdoseisincreasedfourfold,temporaryirritationofairpassagesisobserved.
AmericanConferenceofGovernmentalIndustrialHygienists.DocumentationoftheThresholdLimitValuesandBiological
ExposureIndices.5thed.Cincinnati,OH:AmericanConferenceofGovernmentalIndustrialHygienists,1986.,p.3
/LABORATORYANIMALS:AcuteExposure/Irritationofrabbitskinwasmildfollowingtopicalapplicationof500
mgandthetreatedarealeftopentotheatmosphererabbiteyeirritationwasreportedasseverefollowing
instillationof40mgacetaldehyde.
/LABORATORYANIMALS:AcuteExposure//Acetaldehydeinhalationindogs/showedthatexposureat134ppm
for30minresultedinmildupperrespiratorytractirritation.Higherconcentrationsdecreased/the/respiratoryrateby
inhibitionofCNS.Exposureat50ppmproducedeyeirritation200ppm.../caused/conjunctivitis....
/LABORATORYANIMALS:AcuteExposure/Ivadministrationofacetaldehydeinguineapigsproducedan
immediateandsignificantincreaseinmeanarterialpressurefollowedbyitsprogressivedecreaseresultingin
hypotension.Heartrateincreasedsignificantly.
MOHANMETALINDIANJPHYSIOLPHARMACOL25(3):24652(1981)
/LABORATORYANIMALS:AcuteExposure/Toxicityofacetaldehydetocerebralcortexofratswastestedby
superfusionofintactdurafor1hr.Tissueconcentrationof30mMcausedaxonalandterminaldegeneration,
whereas11mMwasnottoxic.Intermsoftissueconcentration,itwas27timesmoretoxicthanethanol.
PHILLIPSSCNEUROPATHOLAPPLNEUROBIOL7(3):20516(1981)
/LABORATORYANIMALS:AcuteExposure/MaleWistarratswereusedtostudythecapabilityofacetaldehyde
(suppliedexogenouslyormetabolicallyfromethanol)toinitiateliverdamageasindicatedbyenzymeleakage,
hepaticfataccumulation,andhistologicchanges.Measurementofglutamicoxaloacetictransaminase,glutamic
pyruvictransaminase,andsorbitoldehydrogenaseinserumwasusedtoassesshepatotoxicity.Acetaldehydegiven
orally(17.9or35.8mmol/kg)orip(4.5or9.0mmol/kg)didnotaffectglutamicoxaloacetictransaminase,glutamic
pyruvictransaminase,sorbitoldehydrogenase,enzymeactivities,triglyceridelevelsorcausehistologicchanges
whencomparedtocontrols.Pretreatmentwithdisulfiramintylosesuspension(1g/kgorally,16hrpriorto
acetaldehyde)causednoeffectsdifferentfromcontrolswhenacetaldehydewasexogenouslyadministered.
Treatmentofratswithethanol(6g/kgorallyasa40%solution,n=6)orwithdisulfiram(1g/kgorallyin20ml/kg
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tylose,n=6)aloneinducednomeasurablehepatotoxicresponse.Oraltreatmentwithdisulfiram16hrpriorto
treatmentwithethanol(n=19)causedsignificantincreases(p<0.05)inthelevelofGOTandserumtriglycerides
within48hr,andaslightfattydegenerationoftheliverwasobserved.Aftercombinedtreatment,theserum
acetaldehydeconcentration(n=3)was9.4mg/Lat30minand8.7mg/Lat180min.Ipinjectionofethanol(4g/kg)
aftertreatmentwithdisulfiramproducedanincreaseinglutamicoxaloacetictransaminase(p<0.05)butnotserum
triglycerideswithin48hr.Fattydegenerationandhepaticnecrosiswereobservedin2of6animals.
StrubeltOetalToxicolLett39(1):7784(1987)
/LABORATORYANIMALS:AcuteExposure/Ratsweregivenasingledoseofacetaldehyde(0.5mg/kg)ip.The
animalswerekilled0.5,1,2,4,6,9,12,and24hraftertreatmentfordeterminationoflipidperoxidelevelsinliver
homogenateanditssubcellularfractions.Malondialdehydelevelsinliverhomogenatewerehighest(630+or60
pmol/mg)ahalfhouraftertheacutedoseanddeclinedtocontrollevelsofabout500pmol/mgby6hr.
Mitochondrialmalondialdehydelevelswereelevatedat2and4hoursaftertreatment(maximum837+or110
pmol/mg)beingsimilartothecontrol(682+or77pmol/mg)beforeandafterthisperiod.
UysalMetalJApplToxicol9(3):1558(1989)
/LABORATORYANIMALS:SubchronicorPrechronicExposure/...Ina4weekstudy,groupsof10maleand10
femaleratswereexposedto0,400,1000,2200,or5000ppmacetaldehydefor6hr/day,5days/wk.Treatment
relatedchangesobservedatthe5000ppmlevelincludeddyspneaandexcitationduringthefirst30minofeach
exposure,yellowbrownfur,severegrowthretardation,increasednumbersofneutrophilsintheblood,reduced
productionofurinewhichresultedinahighurinespecificgravity,increasedlungweight,andseveredegenerative
hyperplasticandmetaplasticchangesofthenasal,laryngeal,andtrachealepithelium.
AppelmanLMetalToxicol23(4):293308(1982)
/LABORATORYANIMALS:SubchronicorPrechronicExposure/Twogroupsof12maleWistarratsreceivedeither
243ppmofacetaldehydeor5.7ppmofformaldehydefor8hraday,5daysaweekduring5weeks.Theselevels
representthreetimesthethresholdlimitvaluesforthesesubstancesinBrazilianlegislation.Theanimalswere
evaluatedbypulmonaryfunctiontestsbeforeandafterexposuretothepollutants.Thedataobtainedfromthese
ratswerecomparedwiththoseof12controls,housedinidenticalconditionsforthesamelengthoftimebut
breathingnormalair.Theresultsshowedanincreaseofthefunctionalresidualcapacity,residualvolume,totallung
capacityandrespiratoryfrequencyintheratsexposedtoacetaldehydeatmosphere.Theanimalsexposedto
formaldehydedidnotpresentpulmonaryfunctionalterationswhencomparedwiththecontrols.Damagewascaused
byacetaldehydetotheperipheralregionsofthelungparenchyma,affectingsmallairwaysoralteringpulmonary
elasticproperties.
SaldivaPNHetalJApplToxicol5(5):28892(1985)
/LABORATORYANIMALS:SubchronicorPrechronicExposure/Ipinjectionofmalealbinoratswith200mg
acetaldehyde/kgbw,daily,for10days,withadditionalpyrazoletreatmenttoinhibittheconversionofacetaldehyde
toethanol,causedfattyaccumulationintheliver,asindicatedbyaccumulationoftotallipids,triacylglycerols,and
totalcholesterol,incrglycogenolysis,andashiftinmetabolismfromthecitricacidcycletowardsthepentose
phosphatepathwayintheliver.Serumtriacylglycerol,totalcholesterol,andfreefattyacidlevelswerealsoincr.
Changesweresimilarinratsnotreceivingpyrazolepretreatment....Thesametreatmentalteredthyroidfunction,
asindicatedbylowerserumT4anddecriodineuptakeinmalealbinorats,thoughtheseeffectsmayhavebeen
secondarytotheobservedhepaticchanges...andhistopathologicalchangesofthepancreas,withresulting
changesintrypsinogenlevelsandamylasesecretionandactivityinfemaleSpragueDawleyrats....
/LABORATORYANIMALS:SubchronicorPrechronicExposure/Groupsof20Syrianhamsterswereexposedto
acetaldehydevaporat0,700,2400,or8200mg/cum(0,390,1340,or4560ppm)for6hr/day,5days/wk,for13
wk.Increasedrelativelungandheartweightsaswellasgrowthretardationwerereportedafterexposureto8200
mg/cum,thoughtherewerenoincreasesinmortalityinanyoftheexposedgroups....Atthehighest
concentration,therewereseveredegenerative,hyperplastic,andmetaplasticchangesintheepitheliumaswellas
subepithelialglandsandturbinatebones.Rhinitiswasobserved,withabundantnasaldischargeandsalivation.The
epitheliumofthelarynx,trachea,andlungswasdamaged,withsomefocalhyperplasiaandmetaplasia,
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accompaniedbytracheitisandfocalbronchopneumonia.Changesinthetrachealepitheliumwerealsoobservedat
2400mg/cum....(NOEL:700mg/cumLOEL:2400mg/cum).
/LABORATORYANIMALS:SubchronicorPrechronicExposure/Asubacuteoraltoxicitystudyofacetaldehydeand
formaldehydewascarriedoutinrats.Maleandfemale5wkoldratsreceivedoneofthealdehydesinthedrinking
waterforaperiodof4wk,acetaldehydebeinggivenatdoselevelsof25,125and675mg/kgbodyweight/dayand
formaldehydeatdoselevelsof5,25,and125mg/kgbodyweight/day.Hyperkeratosisoftheforestomach,observed
onlyinthetopdoserats,wastheonlyadverseeffectofacetaldehydedetected.Effectsofformaldehyde,also
observedonlyinthetopdosegroup,wereyellowdiscolorationofthefur,decreasedproteinandalbuminlevelsin
thebloodplasma,thickeningofthelimitingridgeandhyperkeratosisintheforestomach,andfocalgastritisinthe
glandularstomach.Inthisstudythenoobservedadverseeffectlevelsofacetaldehydeandformaldehydewere125
and25mg/kgbodyweight/day,respectively.
TilHPetalFoodChemToxicol26(5):44752(1988)
/LABORATORYANIMALS:SubchronicorPrechronicExposure/MaleWistarratsexposedto243ppm[437mg/cu
m]acetaldehydeatmospheresfor8hrperdayonfivedaysperweekforfiveweeksshowedincreasesinfunctional
residualcapacity,residualvolume,totallungcapacityandrespiratoryfrequency.Thesechangeswereinterpretedas
beingcausedbydamagetotheperipheralregionsofthelungparenchyma.
/LABORATORYANIMALS:SubchronicorPrechronicExposure/GroupsofweanlingmaleandfemaleWistarrats
weregivenacetaldehydeinthedrinkingwatertoprovidedosesof0,25,125and675mg/kgbwperdayforfour
weeks.Foodandwaterconsumptionwasreducedandslighttomoderatehyperkeratosisoftheforestomachwas
observedinbothsexesatthehighestdoselevel.
/LABORATORYANIMALS:SubchronicorPrechronicExposure/Groupsof10maleand10femaleWistarratswere
exposedtoacetaldehydeat0,720,1800,3950,or9000mg/cum(0,400,1000,2200,or5000ppm)for6hr/day,5
days/week,for4weeks.Mortalitywasslightlyincreasedat3950and9000mg/cum,whereasgrowthwasretarded
at1800mg/cumandaboveinmales,andat9000mg/cuminfemales.At9000mg/cum,relativeliverweight
decreased,andrelativelungweightinmalesincreased.Notreatmentrelatedhistopathologicalchangeswere
observedintheliver.Degenerativechangesofthenosewereobservedafterexposuretoallconcentrations(720
mg/cumto9000mg/cum),withhyperplasiaandmetaplasiaoccurringatconcentrationsof3950mg/cumormore.
ANOELwasnotidentified(LOEL:720mg/cum).
/LABORATORYANIMALS:SubchronicorPrechronicExposure/...A90dayinhalationstudyinhamsters
(10/sex/concentration)/wasconducted/.Thehamsterswereexposedtoacetaldehydevaporatconcentrationsof0,
390,1340,or4560ppm(0,127,435.5or1482mg/cum,adjustedforduration,respectively),for6hours/day,5
days/weekfor90days.Histopathologicalchangesattributabletoexposurewereobservedonlyintherespiratory
tract.At4560ppm,bodyweightsweresignificantlyreducedandtherelativeweightsofheart,kidney,brain,testicle,
andlungweresignificantlyincreased.Histopathologicalchangesofthenasalcavity,larynx,trachea,andbronchi
includednecrosis,inflammatorychanges,andhyperplasiaandmetaplasiaoftheepithelium.Mildeffectsobserved
at1340ppmconsistedofstatisticallysignificantincreasedkidneyweightinmales,andsmallareasofstratified
epitheliuminthetracheainbothsexes(30%oftheanimals).At390ppm,withtheexceptionofatinyfocusof
metaplasticepitheliuminthetracheaof1outofthe20animalsexamined,noadverseeffectswereobserved.The
390ppmconcentrationwasidentifiedbytheauthorsasaNOAEL.Thestudy...identifiedasimilarlevel(400ppm)
asaLOAEL[LOAEL(HEC)=16.9mg/cum]forWistarrats,butsurfaceareavaluesinhamstersarenotavailable
sothatacomparisononHECvaluescouldnotbemadetodeterminetherelativesensitivitiesofthespeciesto
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acetaldehyde.TheLOAELfortheextrarespiratoryeffects(effectonkidneyweight)is1340ppmandtheNOAEL
alsoat390ppm.TheNOAEL(HEC)forextrarespiratoryeffectsis127mg/cum.
/LABORATORYANIMALS:SubchronicorPrechronicExposure/...MaleWistarrats(12/group)/wereexposed/to0
or243ppm(442mg/cum)ofacetaldehyde8hours/day,5days/weekfor5weeks.Durationadjustedvaluesare0
and105mg/cum,respectively.Theanimalswereevaluatedforpulmonarymechanicsbeforeandafterthe
exposureperiod,andgrossandparaffinembeddedsampleobservationsweremadeafterexposure,especiallyof
therespiratorysystem.IncreasesinRF(respiratoryfailure),FRC(functionalresidualcapacity),RV(residual
volume),andTLC(totallungcapacity)weresignificantlydifferentfromcontrolvalues.Damagetodistalairwayswas
suggestedsincefunctionaltestsfordamagetoelasticityorforsevereobstructionwerenotdemonstrated.
Histopathologicalinvestigationshowedanintenseinflammatoryreactionwitholfactoryepitheliumhyperplasiaand
polymorphonuclearandmononuclearinfiltrationofthesubmucosa.Cannulationprecludedevaluationoftracheal
effectsandnodifferencesbetweenthecontrolandexposedanimalswereobservedforthelowerrespiratorytract.
Althoughthisstudypresentsthepathologydatainonlyadescriptivefashion,itidentifiesaLOAELfornasaleffects
of105mg/cum(HEC=13.7mg/cum)thatisconsistentwiththeprincipalstudies.TheLOAEL(HEC)forthoracic
effectsonpulmonaryfunctionis220.5mg/cum.
/LABORATORYANIMALS:SubchronicorPrechronicExposure/Wistarrats(10/sex/group)/wereexposed/for6
hours/day,5days/weekfor4weeksto0,400,1000,2200,or5000ppmacetaldehyde(0,728,1820,4004and
9100mg/cum,respectively).Durationadjustedconcentrationsare0,130,325,715and1625mg/cum,
respectively.Thegeneralconditionandbehavioroftheratswerecheckeddaily.Bloodpicture(Hb,Hct,RBC,total
anddifferentialWBC,andplasmaprotein)andchemistrywereexaminedattheendofthetreatmentperiod.
Activitiesofplasmaglutamicoxalacetictransaminase,glutamicpyruvictransaminase,andalkalinephosphatase
werealsodetermined.Urinewasanalyzedfordensity,volume,pH,protein,glucose,occultblood,ketones,and
appearance.Thekidneys,lungs,liver,andspleenwereweighed.Microscopicexaminationwasperformedonthe
lungs,trachea,larynx,andnasalcavity(3transversesections)ofallanimalsandonthekidneys,liver,andspleenof
allcontrolandhighconcentrationgroups.Duringthefirst30minutesofeachexposureatthe5000ppmlevel,rats
exhibitedseveredyspneathatgraduallybecamelesssevereduringthesubsequentexposureperiod.Twoanimals
diedatthislevel(1female,1male)andonemalediedatthe2200ppmlevel,butthecauseofdeathcouldnotbe
determinedduetoautolysisorcannibalism.Growthwasretardedinmalesatthethreehighestexposure
concentrationsandinfemalesatthe5000ppmlevel.Thepercentageoflymphocytesinthebloodwaslowerand
thepercentageofneutrophilicleukocyteshigherinmalesandfemalesofthe5000ppmgroupthanincontrols.
Therewereafewstatisticallysignificantdifferencesinseveralbloodchemistryparametersbetweentheexposure
groupsandthecontrolgroupbutnoneofthemwereconcentrationrelated.Statisticallysignificantchangesinorgan
tobodyweightratiosincludeddecreasedliverweightsinbothsexesandincreasedlungweightsinmalesatthe
5000ppmlevel.Malesinthe5000ppmlevelproducedlessurine,butitwasofhigherdensity.Compoundrelated
histopathologicalchangeswereobservedonlyintherespiratorysystem.Thenasalcavitywasmostseverely
affectedandexhibitedaconcentrationresponserelationship.Atthe400ppmlevel,compoundrelatedchanges
included:slighttoseveredegenerationofthenasalolfactoryepithelium,withouthyperandmetaplasia,and
disarrangementofepithelialcells.Atthe1000and2200ppmlevels,moreseveredegenerativechangesoccurred,
withhyperplasticandmetaplasticchangesintheolfactoryandrespiratoryepitheliumofthenasalcavity.
Degenerationwithhyperplasia/metaplasiaalsooccurredinthelaryngealandtrachealepitheliumattheselevels.At
5000ppmchangesincludedseveredegenerativehyperplasticandmetaplasticchangesofthenasal,laryngeal,and
trachealepithelium.Basedonthedegenerativechangesobservedintheolfactoryepithelium,the400ppmlevelis
designatedasaLOAEL.TheLOAEL(HEC),basedontheventilationratesforfemalerats,is16.9mg/cu.m.No
NOAELwasidentified.
/LABORATORYANIMALS:ChronicExposureorCarcinogenicity/Groupsof35maleSyriangoldenhamsterswere
exposedto0or1500ppm(2700mg/cum)acetaldehydevaporfor7hr/dayon5days/weekfor52wk,&toweekly
intratrachealinstillationsof0,0.0625,0.125,0.25,0.5or1.0mgbenzo(a)pyrenesuspendedinsalineforsametime
period.Groupsof5animalswerekilledat52wk&remainderallowedtosurviveuntreatedforanadditional26wk.
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Therewasnosignificantdifferenceinmortalitybetweenanimalsexposedtoacetaldehyde&thoseexposedtoair,
exceptforthesubgrouptreatedwiththehighestdoseofbenzo(a)pyreneforwhichthemortalityintheacetaldehyde
exposedanimalswasincrmorerapidlythanthemortalityinthecorrespondingbenzo(a)pyrenegroupexposedtoair
(p<0.001inbothgroups).Notumorwasfoundinhamstersexposedtoacetaldehydeonlybut3/30,4/30,9/30,
25/39&26/28hamstersexposedtobenzo(a)pyrenealonedevelopedresptracttumors&1/28,5/29,8/29,16/29&
29/30hamstersexposedtobenzo(a)pyrene&acetaldehydevapordevelopedthesametypeoftumor.
/LABORATORYANIMALS:ChronicExposureorCarcinogenicity/Groupsof36male&36femaleSyriangolden
hamsters,6wkofage,wereexposedfor7hr/dayfor5days/wktoroomair(chambercontrols)ortodecrconcnof
acetaldehyde(distilled&analyzedbygaschromatography)(initialconcn,2500ppm(4500mg/cum)finalconcn,
1650ppm(2970mg/cum))for52wk.Sixanimalskilled&examfromeachgrouphadnotumor.Theremaining
animalswereobserveduntil81wk&killed.Theincidencesofrespiratorytracttumorswere0/30,8/29,0/28&5/29
incontrolmales,exposedmales,controlfemales&exposedfemales,respectively(p<0.05).Theacetaldehyde
inducedtumorswerepredominantlylaryngealcarcinomaswithafewlaryngealpolyps,&nasalpolyps&carcinomas.
/LABORATORYANIMALS:ChronicExposureorCarcinogenicity/Sevengroupsof35maleand35femaleSyrian
goldenhamsters,11wkold,weregiventhefollowingtreatmentsweeklyorbiweeklyfor52wk:intratracheal
instillationsofsaline(0.2mlweeklyvehiclecontrols)acetaldehydealone(twogroups:onereceiving0.2mL2%
acetaldehydeweekly,&onereceiving0.2mL4%acetaldehydeweekly)acetaldehydeplusbenzo(a)pyreneorN
nitrosodiethylamineorbenzo(a)pyreneorNnitrosodiethylamine(positivecontrols).After13,26&52weeks,three
animals/sex&pergroupwerekilled&autopsied.Exptwasterminatedatwk104,whensurvivorswerekilled.At
thattime,overallmortalitywas83%inmales&97%infemales.Intratrachealinstillationsofacetaldehydealone
producedextensive"peribronchiolaradenomatoidlesions"inthelung,butnotumor....Benzo(a)pyrene&N
nitrosodiethylamineinducedavarietyoftumorsinseveralsegmentsoftheresptract.Thistumorresponsewasnot
influencedbysimultaneoustreatmentwithacetaldehyde.
/LABORATORYANIMALS:ChronicExposureorCarcinogenicity/Progressionand/orregressionofnasalmucosal
damagewasstudiedinfourgroupsof30maleand30femaleSPFbredWistarratsexposedto0,750,1500,or
3000/1500ppmofacetaldehydefor6hr/day,5days/wk,for52weekswitharecoveryperiodof26or52weeks.
Acetaldehydeconcentrationforthehighexposuregroupwasgraduallydecreasedfrom3000ppm(day0141)to
1500ppm(day313onwards)duetogrowthretardationandearlymortality.Fromeachexposuregroup,10male
and10femaleratswereexaminedfollowinga26wkrecoveryperiod,and20maleand20femaleratswere
examinedfollowinga52wkrecoveryperiod.Attheendof52wkexposuretothehighestacetaldehyde
concentration,mostanimalsexhibitedlaboredrespirationandmouthbreathing.Adosedependentincreasein
frequencyofadenocarcinomas,nasaltumors,andsquamouscellcarcinomaswasnotedformaleandfemalerats
following52wkacetaldehydeexposure,andduringa26wkpostexposurerecoveryperiod.Varyingdegreesof
pathologicalalterationsincludingdegenerationofolfactoryepithelium,hyperandmetaplasticchangesinrespiratory
epithelium,andrhinitiswereobservedforanimalsfollowingacetaldehydeexposureatallconcentrations.
Restorativeactivityofolfactoryepitheliumwasobservedforratsduringthe26and52wkrecoveryperiodsfollowing
exposuretolowandmidacetaldehydelevels,butnotforthegroupexposedto3000/1500ppm.
WoutersenRA,FeronVJToxicology47(3):295305(1987)
/LABORATORYANIMALS:ChronicExposureorCarcinogenicity/Wistarrats(55/sexperdose)wereexposedfor
life(6hr/day,5days/wk,for28mo)toacetaldehydeconcnof1350,2700,or18005400mg/cum(thelast
concentrationwasgradualyreducedfrom5400mg/cuminwk20to1800mg/cuminwk52).Satellitegroupsof5
10additionalratsofeachsexwerekilledat13,26,and52wk.Growthretardationoccurredthroughoutthestudyat
alldoselevels.Mortalitywasgreaterthanincontrolsinalldosegroupsandalloftheanimalsinthehighdose
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grouphaddiedbywk102.Atwk52,thereweregenerativechangesintheolfactorynasalepitheliumatalldose
levelsinclslighttoseverehyperplasiaandkeratinizedstratifiedmetaplasiaofthelarynx(highdoseonly)and
generativechangesoftheupperrespiratoryepithelium(inclpapillomatoushyperplasiaatthetopdoseonly).Inthe
trachea,therewasfocalflatteningandirregulararrangementoftheepitheliumin3/10topdosemalesat52wk.In
satellitegroupsof30ratspersex,forwhichtherewasa26wkrecoveryperiodafter52wkofexposure,therewas
evidenceofpartialregenerationoftheolfactoryepitheliuminthelowandmiddosegroupstherewasalso
progressionfromhyperplasiaandmetaplasiatoneoplasiainsomeanimals.At28mo,carcinomasofthenose
developedinallexposedgroups....Althoughtumorincidencewasdoserelated,thelatencyperiodappearedtobe
independentofconcn.Firsttumorsinallgroupsappearedduringthe12thmoofexposure.Theincidenceoftumors
wasnotincinthelungs,larynx,andtrachea.
/LABORATORYANIMALS:ChronicExposureorCarcinogenicity/Prospectiveepidemiologicstudieshavereported
anincreasedriskofrectalcancerfollowingchronicethanolingestion.Theeffectofchronicethanoladministrationon
acetoxymethylmethylnitrosamineinducedrectalcancerandthepossibleroleofacetaldehydeinthisprocesswere
investigated.Chronicethanoladministrationresultedinanearlieroccurrenceofrectaltumorsinthisanimalmodel.
Becausetheconcomitantadministrationofcyanamide,apotentacetaldehydedehydrogenaseinhibitor,showeda
positivetrendtowardincreasedincidencesoftumors,acetaldehydecouldbeinvolvedintheethanolassociated
carcinogenesis.Tomeasurecolonicacetaldehyde,12chronicallyethanolfedandcontrolratsreceivedanacute
doseofethanol(2.5g/kgbodywt).Themucosalconcentrationofacetaldehydewassignificantlyhigherinthe
rectumcomparedwiththececum(198vs,120nmoles/gcolon),butwasnotaffectedbychronicethanolfeeding.
Furthermore,germfreeratshadsignificantlyloweracetaldehydeconcentrationsintherectumandinthececum
comparedwithconventionalanimals,andthiswasparalleledbythenumberoffecalbacteriainthe2intestinal
segments.Inaddition,todeterminetheeffectofchronicethanolfeedingoncolorectalcellturnover,30animals
werepairfedliquiddiets.Bythemetaphasearresttechnique,alcoholfeedinginducedrectal,butnotcecal
hyperregeneration.Thiswasaccompaniedbyanincreaseinthecryptproliferativecompartmentandincreased
mucosalornithinedecarboxylaseactivity.Chronicethanolingestionaccelerateschemicallyinducedrectal
carcinogenesisandacetaldehydeprobablygeneratedthroughbacterialethanoloxidationmaybeinvolvedinthis
process.
SeitzHKetalGastroenterology98(2):40613(1990)
/LABORATORYANIMALS:ChronicExposureorCarcinogenicity/...fourgroupsof105maleand105female
Cpb:WUalbinoWistarrats,sixweeksofage,wereexposedbywholebodyinhalationtoconcentrationsof0,750,
1500or3000(reducedprogressivelyoveraperiodof11monthsto1000ppmduetotoxicity)ppm[0,1350,2700or
54001800mg/cum]acetaldehydevapour[purityunspecified]for6hrperdayonfivedaysperweekforamaximum
of27months.Eachgroupcomprisedfivesubgroups,threeofwhichwereusedforinterimkillsatweeks13,26and
52,respectively.Oftheanimalskilledattheseintervals,onlyonehadatumouroftherespiratorytract:afemalein
thehighdosegroupkilledinweek53,bearinganasalsquamouscellcarcinoma.Atday468,themortalityratein
thehighdosegroupwas50%(28/55)formalesand42%(23/55)forfemales.Byday715,allhighdoseratshad
diedand,atterminationofthestudyatday844,onlyafewanimalswerestillaliveinthemiddosegroup.Atthe
endofthestudy,theincidencesofnasalcarcinomas(carcinomasinsitu,squamouscellcarcinomasand
adenocarcinomas)wereinmales:1/49,17/52,41/53and37/49inthecontrol,low,midandhighdosegroups,
respectivelyandinfemales:0/50,6/48,34/53and43/53inthecontrol,low,midandhighdosegroups,
respectively.Onecarcinomainsituofthelarynxwasfoundinafemaleofthemiddosegroupandonefemaleof
thelowdosegroupdevelopedapoorlydifferentiatedadenocarcinomainthelung.
/LABORATORYANIMALS:ChronicExposureorCarcinogenicity/Theprogressionandregressionofnasallesions
werestudiedingroupsof30maleand30femaleWistarratsexposedtoacetaldehydebyinhalationfor6hrperday
onfivedaysperweekatconcentrationsof0,750,1500and3000ppm[0,1350,2700and5400mg/cum](thelast
dosewasgraduallyreducedto1500ppmfromweek20toweek44)for52weeks.Theanimalswerekilledafter
recoveryperiodsof26or52weeks.Themaintreatmentrelatedeffectsincluded(1)focalbasalcellhyperplasiaof
theolfactoryepitheliumin750and1500ppmgrouprats,(2)hyperplasiaandmetaplasiaoftherespiratory
epithelium,oftenaccompaniedbykeratinizationandsometimesbyproliferationofatypicalbasalcells,in3000
/1500ppmgroupratsand(3)rhinitisinsomeof3000/1500ppmgrouprats.Therewasnorestorationofthe
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respiratoryepitheliumamong3000/1500ppmgrouprats,evenafterarecoveryperiodof52weeks.Progressionof
thehyperplasiaandmetaplasiaintherespiratoryepitheliumtosquamouscellcarcinomasoccurredduringthefirst
26weeksin11malesandfourfemales,butdegenerationoftheepitheliumwaslesspronouncedinthesucceeding
26weeks.Regenerationoftheolfactoryepitheliumoccurredinthe750and1500ppmgroups,butnotinthe3000
/1500ppmgroup.
/LABORATORYANIMALS:ChronicExposureorCarcinogenicity/...Whetherinhalingpeakconcentrationsof
aldehydesseveraltimesdailyismoredamagingthansemicontinuouslyinhalinglowdosealdehydes/was
investigatedbyexposing/...Xpa/p53+/knockoutmiceeitherintermittentlyorsemicontinuouslytomixed
acetaldehyde,formaldehyde,andacrolein.Theintermittentregimenentailedexposuretothealdehydes7minevery
45min,12times/day,5days/week,correspondingtoconcentrationsinhaledbysmokers.Semicontinuously
exposedanimalsreceivedhalfthedoseofaldehydesin8h/day,5days/week.Somemiceineachgroupwere
sacrificedafter13weeksofexposuretherestbreathedcleanairuntiltheendof1year.Miceinjected
intratracheallywithbenzo[a]pyreneformedapositivecontrolgroup.Thenasalcavity,lungs,andany
macroscopicallyabnormalorgansofallmicewereanalysedhistopathologically.After13weeksofexposure,the
subacute,overall,histopathologicalchangesinducedbytheinhalationdifferednoticeablybetweentheintermittently
andsemicontinuouslytreatedXpa/p53+/knockoutmice.After13weeksofmixedaldehydeexposure,atrophyof
theolfactoryepitheliumgenerallyappeared,butdisappearedafter1year(adaptationand/orrecovery).Respiratory
epithelialmetaplasiaoftheolfactoryepitheliumoccurredatahigherincidenceat1year.Exceptforasignificantly
greaternumberoftumorsobservedinknockoutmicecomparedtowildmice(semicontinuousaldehydeexposure
andcontrols),nodifferencesbetweenthesemicontinuousandintermittentexposuregroupswereobserved.
CasseeFRetalFdChemToxicol46(2):52736(2008)
/LABORATORYANIMALS:ChronicExposureorCarcinogenicity/Formaldehydewasadministeredfor104weeksin
drinkingwatersuppliedadlibitumatconcentrationsof1500,1000,500,100,50,10,or0mg/Ltogroupsof50
maleand50femaleSpragueDawleyratsbeginningatsevenweeksofage.Controlanimals(100malesand100
females)receivedtapwateronly.Acetaldehydewasadministeredto50maleand50femaleSpragueDawleyrats
beginningatsixweeksofageatconcentrationsof2,500,1,500,500,250,50,or0mg/L.Animalswerekeptunder
observationuntilspontaneousdeath.Formaldehydeandacetaldehydewerefoundtoproduceanincreaseintotal
malignanttumorsinthetreatedgroupsandshowedspecificcarcinogeniceffectsonvariousorgansandtissues.
SoffrittiMetalAnnNYAcadSci982:87105(2002)
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Femalemicewereinjectedivwith
acetaldehydeonsingleormultipledays,&examinedon10or12thdayofgestation.Multipledayexposures
resultedinhighincidenceofembryonicresorptionshowever,neuraltubedefectswereencounteredinsurviving
embryosfromsingledayinjections.[O'SHEAKS,KAUFMANMHJANAT132(1):10718(1981)]Fulltext:
PMC1233399
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Ina...studywithpregnantrats,damswere
givenintraperitonealinjectionsof50to100mg/kgacetaldehydeongestationaldays8to15.Adosedependent
increaseinresorptionsandfetaldeathanddoseresponsetrendsintheotherindicatorsofintrauterinegrowth
retardationwereobserved.Malformationsintheface,forelimbs,andhindlimbs,aswellasretardedskeletal
ossification(ontheorderof1to2days)wereseen.
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Inratsreceivingintraamnioticinjectionsof
0.02mLofa1%or10%solutionofacetaldehydeonday13ofgestation,thefetalmortalitywaselevatedinthe
concurrentvehiclecontrolgroupsascomparedwithuntreatedcontrolshowever,fetalmortalitywaselevated
substantiallyintheacetaldehydetreatedgroups.Thesurvivinglowdoseembryoshadanincreasedincidenceof
malformations(80%comparedto14%inthecontrols).
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/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Acetaldehyde,themetaboliteofethanol,was
administeredtopregnantCFratsip(50mg/kg)fromday8through15ofgestationandfetusesfromdifferent
motherswerecollectedfromday16through21ofgestation.Fetuseswereprocessedforalizarinskeletalstaining.
Therewassignificantdelayinossificationbesidescertainskeletalmalformationssuchaswavyribs.Thedelayin
ossificationmaybeoneofthereasonsforreducedbirthweightandincreasedpostnatalmortalityandgrowth.
SreenathanRNetalDrugAlcoholDepend14(2):16574(1984)
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity//Inrats/acetaldehydecouldmediatea
numberofthetoxiceffectsofalcoholbothin.../femalerats/andtheiroffspring.Thus,/anassessmentof/the
bloodacetaldehyderesponsetoethanol(3g/kg)atvariousstagesofthefemalereproductivecycle/was
accomplished/.Bloodlevelswerelowthroughoutthevariousphasesoftheestrouscycleandduringmostof
pregnancy.Bycontrast,a4foldriseinmaternalbloodacetaldehydeoccurredattheendofpregnancy(day20),
continuedtoincreaseduringlactation(17foldatday14)andreturnedtononpregnantvaluesafterweaningorafter
pupremovalatbirth.BothenhancedrateofethanoloxidationanddecreasedactivityofthelowKmaldehyde
dehydrogenaseinlivermitochondriacontributedtotheincreasedacetaldehydelevels.Acetaldehydewasdetectable
infetalblood,butonlyasmallfractionofthehighmaternalvaluesinpregnancyreachedthefetusthroughthe
umbilicalvein.Chronicalcoholadministrationresultedindecreasedfetalsizeandstrikingenlargementofthe
placentawithpossibleimplicationofabnormalfetaldevelopment.
GordonBHetalAlcohol2(2):2715(1985)
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Theobjectivesofthisstudyweretoelucidate
theontogenyoftheactivityofalcoholdehydrogenase,lowKmaldehydedehydrogenase,andhighKmaldehyde
dehydrogenaseintheliverandplacentaoftheguineapig.Therewaslowalcoholdehydrogenaseactivityinfetal
liverandplacentathroughoutgestationandinneonatalliver.ThefetalliverlowKmaldehydedehydrogenase
activityincreasedprogressivelyand,at60daysofgestation,wassimilartoadultliveractivity,aswasalsothecase
forneonatalliverenzymeactivity.PlacentallowKmaldehydedehydrogenaseactivitywaslessthanadultliver
activitythroughoutgestation.FetalhepatichighKmaldehydedehydrogenaseactivityincreasedduringgestation,
butwaslessthanadultliveractivity,aswasalsothecaseforneonatalliverenzymeactivity.PlacentalhighKm
aldehydedehydrogenaseactivitywaslowthroughoutgestation.Fororaladministrationof0.5gethanol/kgmaternal
bodyweighttopregnantguineapigsatmidgestation(34days),thematernalbloodandfetalbodyethanol
concentrationtimecurvesweresimilar.Acetaldehydewasmeasureableinmaternalbloodandfetalbodyatsimilar
concentrations,whichwere100to1000foldlessthantherespectiveethanolconcentrations.Themajordifferences
inthedipositionofethanolandacetaldehydeatneartermpregnancy,comparedwithmidgestation,wasthelackof
measurableacetaldehydeinfetalblood.Theguineapigfetusthroughoutgestationhasvirtuallynocapacityto
oxidizeethanol,anditsdurationofexposuretoethanolisregulatedbymaternalhepaticalcoholdehydrogenase
catalyzedbiotransformationofethanol.Thefetus,however,appearstohaveincreasinglowKmaldehyde
dehydrogenasedependentcapacitytooxidizeethanolderivedacetaldehydeduringdevelopment,andwouldappear
tobeincreasinglyprotectedfromexposuretoacetaldehydeasgestationprogresses.
CardSEetalBiochemPharmacol38(15):253541(1989)
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Theinfluenceofethanolandacetaldehydeon
skeletogenesiswasinvestigatedinSpragueDawleyrats.Pregnantanimalsweredividedintothreegroupsas
follows:I,Controls(distilledwater,intragastricallyandip),II.Ethanol(0.015mL/gbodyweight,25%v/v,
intragastrically,III.Acetaldehyde(200mg/kgbodyweight,3%solution,ip).Theanimalsweretreatedfrom
gestationalday6through18,andonday20,externalanomalieswerenotdetectedinanyofthefetuses.Fetal
weightwassignificantlyreducedinfetusesexposedtoethanolandacetaldehydeandintheethanoltreatedgroup
CR/crownrump/lengthwasalsosignificantlylessthanthecontrolvalue.Bothaxialandappendicularskeletal
boneswereaffectedintheirdevelopmentfollowinginuteroexposuretoethanolandacetaldehyde,withahigher
frequencyofdefectsinfetusesexposedtoethanol.Anomaliesoftheribsandvertebraewerecommonlyseenin
bothtreatmentgroups.Thecranialbones,sternum,hyoidbone,andthemetacarpalandmetatarsalboneswere
retardedintheirdevelopmentwithsignsofdelayedossificationandhypoplasia.
FadelRA,PersaudTVNTeratol41(5):553(1990)
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/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Pregnantratsweretreatedfromday9
through12ofgestationwith12.5%ethanol,25%ethanol,1%acetaldehyde,cyanamide(aninhibitoroftheenzyme
aldehydedehydrogenase),oracombinationofcyanamideandethanol.Embryoswererecoveredongestationalday
12andwerequantitativelyassessedonthebasisof16recognizabledevelopmentalendpoints(morphological
scores).Theheadandthecrownrumplengthsoftheembryoswerealsomeasured.Totalresorptionoccurredintwo
animalstreatedwithcyanamideandtwotreatedwithcyanamideandethanol.Acetaldehydeandethanol(atboth
concentrations)werefoundtoreducetheheadlengthoftheembryosbuthadnosignificanteffectson
morphologicalscoresandcrownrumplength.Thecombinationofethanolwithcyanamidecausedagreater
reductioninheadlengthandalsosignificantlyreducedcrownrumplength,aswellasthemorphologicalscores.
AliF,PersaudTVExpPathol33(1):1721(1988)
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Ratembryoswereexplantedondays9.5or
10ofgestationandculturedfor48to30hr,respectively,Inratserumcontaining0,3,6,9mg/mLofethanol0,
10,20ug/mLofacetaldehyde3mg/mLethanol+10ug/mLacetaldehyde.Attheendofthecultureperiodthe
embryoswereevaluatedforvitality,andscored.Someofthemwerealsoexaminedhistologically.Embryos
exposedtoethanolfromday9.5showedadoserelatedgrowthretardationassociatedwithahighfrequencyof
malformations(openneuraltube,heartdefects,branchialarchhypoplasia).Theexposureof9.5dayembryosto20
ug/mLacetaldehyderesultedin100%embryolethalitywhereas10ug/mlinducedgrowthretardationandteratogenic
effects.When10dayembryoswereexposedto3mg/mLethanolor10ug/mLacetaldehydenoeffectswere
observed,butthehighestlevelsofethanolproducedamoderategrowthretardationandmorphologicdefects.
Exposureto20ug/mLacetaldehydeinducedhypoplasiaofthefirstarch,butdidnotalterthescorevalue.The
histologicexaminationoftheseembryosrevealedseverelesionsattheleveloftheneuroepitheliumandofthe
branchialmesenchyma.Similareffectswereobservedinembryosexposedsimultaneouslyto3mg/mLethanoland
10ug/mLacetaldehyde.
GiaviniEetalInVitroCellDevBiol28A(3Pt1):20510(1992)
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Theeffectsofintakeofacetaldehyde,the
proximalmetaboliteofethanol,werestudiedintwogroupsofFischerstrainrats.Virginratswerematedat3
monthsofageorat8monthsofage.Theacetaldehydeintakegroupwasgivena2%aqueoussolutionof
acetaldehydeforthefirsttimeonthefirstdayofpregnancy.Thesolutionwasthengivenonceaday,oralnet
acetaldehyde240mg/kgbwthroughgestation,laborandlactation.Thecontrolgroupwasnotexposedto
acetaldehyde.Comparativeobservationsweremadeonbothmaternalratsandtheiroffspring1)Maternalbody
weightgainbetweenthefirstand20thdayofpregnancywassignificantlylowintheacetaldehydegroupcompared
withthecontrolgroup(3montholdplessthan0.05.Asforplacentalweight,3montholdacetaldehydemothers
showednosignificantdifferencesfromthecontrols,whereas8montholdacetaldehydemothersweighed
significantlylessthanthoseinthecontrolgroup(plessthan0.01.Histological/examination/disclosedthatthe
brain,liver,andkidneyhadslightchangesinallacetaldehydemothers,whereasthecontrolgroupshowedalmost
nochanges.2)Theaveragenumberoffetusesatthe20thdayofgestation,neonatesperlitter,didnotsignificantly
differamongthegroups.3)Asforthebodyweightoftheoffspringof3montholdmothers,theacetaldehyde
neonatesand10dayoldoffspringweighedsignificantlylessthanthoseinthecontrolgroup(plessthan0.01,pless
than0.01).Inthecaseof8montholdmothers,theacetaldehydefetusesatthe20thdayofgestationandneonates
weighedsignificantlylessthancontrols(plessthan0.01,plessthan0.01).4)Histological/examination/ofthe
brain,lung,liver,kidney,andthymusinoffspringrevealedremarkablevisceralimmaturityandhemorrhageinthe
acetaldehydegroup,ascomparedtocontrols.
ImalT,OmotoMArukoruKenkyutoYakubutsuIson27(3):33454(1992)
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Day10ratembryosgrowninpresenceof
acetaldehydeinvitro/exhibited/significantretardationingrowthanddevelopment.Aconcentrationresponserange
foracetaldehydeinducedembryotoxicitywasdefined,fromnoeffectat5mMtolethalityofallembryosat100mM
....Directembryotoxicityeffectsofacetaldehyde,theprimarymetaboliteofethanol,/occurred/atconcentrationsas
lowas25mM.
CampbellMAetalLifeSci32(23):26417(1983)
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/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/...Theaimofthepresentstudywasto
investigatethepossiblemechanismsunderlyingethanolinducedfetalalcoholsyndrome(FAS)inthedeveloping
embryo.First,ethanolinduceddevelopmentalabnormalitieswereinvestigatedinvitro.Postimplantationembryosat
gestationday(GD)9.5wereculturedfor48hrandobservedformorphologicalchanges.Ethanolmediatedchanges
inproteinsregulatedapoptosis(p53andbcl2),antioxidant(vitaminEandcatalase)activities,generationof
reactiveoxygenspecies(ROS),andoxidativeDNAdamageshownas8hydroxy2'deoxyguanosine(8OHdG)were
measuredinembryonicmidbraincells.Alcoholoracetaldehydesignificantlyinducedcytotoxicityinculturedrat
embryonicmidbraincells.Thelevelsofp53,bcl2,and8OHdGwereconcomitantlychangedbyalcoholand
acetaldehydetreatmentinmidbraincells.InjuredcellsinducedbyROSwereincreasedbyalcoholoracetaldehyde
treatmentinmidbraincells.Cotreatmentwithalcoholoracetaldehydeandcatalasedecreasedcytotoxicityin
midbraincells.Inpostimplantationembryoculture,alcoholoracetaldehydetreatedembryosshowedretardationof
embryonicgrowthanddevelopmentinaconcentrationdependentmanner.Theseresultsindicatethatalcoholand
itsmetaboliteacetaldehydeinducefetaldevelopmentalabnormalitiesbydisruptingcellulardifferentiationand
growth...
LeeRDetalJToxicolEnvHlthPtA68(234):214762(2005)
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Alcoholabusebypregnantwomencanresult
infetalalcoholeffects(FAE)andfetalalcoholsyndrome(FAS).Bothethanolitselfanditsmainmetabolite,
acetaldehyde(Ach),areabletoproducespecificFASrelatedmalformations....Previousinvitrostudies...
documentedthat10dayoldratembryosexposedtoAchshowacharacteristicembryonicAchsyndrome,
histologicallycharacterizedbymarkedcellulardeath.Asbothnecrosisandpathologicalapoptosisareteratological
mechanisms,theaimofthisworkwastoevaluateifcellulardeath,observedinAchexposedembryos,canbe
relatedtonecroticorapoptoticevents.TendayoldratembryoswereculturedinthepresenceofAch3060ug/mL
andstainedwiththevitaldyeacridineorangetovisualizeapoptoticareas.Afterfixation,theTUNEL[3'terminal
deoxynucleotidetransferase(TdT)mediateddUTPbiotinnickendlabeling]methodwasusedtohistologically
identifyapoptosis.BothacridineorangeandTUNELstainingshowedsignsofphysiologicalapoptosisincontrols
andabnormalapoptoticregionsinAchexposedembryos./The/resultsshowaclearcorrelationbetweenmalformed
organsandapoptoticembryonicdistricts.
MenegolaEetalAlcohol(Fayetteville,NY)23(1):350(2001)
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/Theembryotoxicityoftwoethanol
metabolites,acetaldehydeand2,3butanediol,havebeenexaminedincultured10dayalbinoWistarratembryos
overa2dayperiod.Atacetaldehydeconcentrationsof100and260uM,nosignificanteffectswereobservedon
embryonicprotein,DNA,somitedevelopment,grossmorphology,orviability.800uMwas...toxiccausingrapid
deathandnecrosis.2,3Butanediolataculturemediumconcentrationof25mMhadnoeffectonanyoftheabove
parameters....
Priscott,PKBiochemPharmacol34(4):52932(1985)
/LABORATORYANIMALS:DevelopmentalorReproductiveToxicity/HumanandratO6methylguaninetransferase
areinhibitedinvitrobyethanolatconcentrationsof10to50mMandbyacetaldehyde,thefirstmetaboliteof
ethanol,atconcentrationsaslowas0.01uM.Severalotherenzymes,includingglyceraldehyde3phosphate
dehydrogenaseandyeastalcoholdehydrogenase,whichlikeO6methylguaninetransferasehavecysteinesintheir
activesites,werenotinhibitedbyacetaldehydeatthelevelsthatinhibitedO6methylguaninetransferase.
Disulfiram,anacetaldehydedehydrogenaseinhibitor,enhancedtheinhibitoryeffectofethanolinvivo.The
inhibitoryeffectofethanolonO6methylguaninetransferaseactivityismediatedprimarilyviaitsmetabolite,
acetaldehyde.
EspinaNetalCarcinogenesis9(5):7616(1988)
/LABORATORYANIMALS:Neurotoxicity/Ratswhichreceivedacetaldehydebyipinjectiononasingleoccasion
sustainedneuraldegenerationinthecerebralcortexdetectablewithbothlightandelectronmicroscopy.The
degenerationwasmoreintenseandincludedthehippocampuswhenacetaldehydeexposurewasgivenon5
consecutivedaysintheformofethanolvaporinhalationanddisulfiraminjections.Pretreatmentofanimalswitha
combination2.5glysine/kgplus50mgpyridoxylphosphate/kgdidnotalterthedegreeofdegenerationresponseto
eitherasingleinjectionofacetaldehydeor5daysacetaldehydetreatment.Penicillamineinjections(1.2g/kg)did
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offersome(butnotcomplete)cytoprotectivevalueagainsttheneurotoxicityofacetaldehyde.Thiscytoprotective
actionwaseffectiveatconcentrationsofacetaldehydewhicharenotdistantfromclinicallyobservedconcentrations.
PhillipsSCToxicolApplPharmacol98(3):55360(1989)
/LABORATORYANIMALS:Neurotoxicity/Primaryculturesofadultmousesensoryneuronsmaintainedfor8days
invitro,inboththepresenceofnonneuronalcelloutgrowthandinnonneuronalcellreducedcultures,were
exposedtoethanol,acetaldehyde.LD50'sof600uMacroleinand100mMpropanolwereobtainedafter2hr
exposuresandafter48hrwith1mMacetaldehydeand500mMethanol.Morphologicaleffectswereevidentby
scanningelectronmicroscopywithsubacutedosesforeachagent,usingbothlowerconcentrationsandshorter
exposures.Membranepittingoftheperikaryonandareductionintheproportionofneuronsbearingneuriteswere
commonsignsoftoxicinsult.Theneuritesoftreatedcellswerethickerandmoreirregularthanthoseofuntreated
cellsthisprovedagoodindicatorofspecificneurotoxicityratherthanmerelyacytotoxicresponse.
SmithRAetalVirchowsArch(B)58(5):32350(1990)
/LABORATORYANIMALS:Neurotoxicity/Neurologicaleffectsfollowingexposurebyroutesmostrelevantto
environmentalandoccupationalexposure(ie,inhalationandingestion)werelimitedtobiochemicalchangesinthe
braininshorttermstudiesonratsandmiceexposedtorelativelyhighconcentrationsofacetaldehyde(75013230
mg/cum).Reportedeffectsincludedchangesinthephospholipidfractionsandincreasesintheconcentrationsof
monoaminesandNa+/K+ATPase.Manifestationsofneurotoxicitywerenotexaminedinanyofthesestudies.
/GENOTOXICITY/MethylationofDNAatthe5'positionofcytosine(5MeC)isassociatedwithcontrolofgene
expression.TheeffectofdietaryethanolandtheethanolmetaboliteacetaldehydeonDNAmethylationwas
investigatedasapotentialcontributingfactortotheteratologyseeninthefetalalcoholsyndrome.Nineday
pregnantmiceweregivenethanol(3g/kg)orallytwiceadayfor3days.FetalnucleiandDNAwereisolated5hours
afterthelastethanoltreatment.Nuclearmethylaseactivity,assayedbytheincorporationof3HCH3donatedbyS
adenosylmethionine,wassignificantlydepressedinthealcoholfedanimals.TheDNAofthesefetusesalsowas
showntobehypomethylatedrelatedtocontrolsbyitsabilitytoserveasaCH3acceptorusingHPaIImethylase,
whichproduces5MeCinthesequenceGGCC.
GarroAetalFASEBJ4(3):A364(1990)
/GENOTOXICITY/Acuteethanoladministration(3g/kgtwiceaday)topregnantmice,fromthe9ththroughthe
11thdayofgestation,resultedinhypomethylationoffetaldeoxyribonucleicacid(DNA).Nucleiisolatedfromthe
fetusesoftheethanoltreatedmicehadlowerlevelsofmethylaseactivityrelativetocontrolseveninthepresence
ofexcessSadenosylmethionine,whichservesasthemethyldonorfortheenzymeDNAmethyltransferase.
Acetaldehyde,atconcentrationsaslowas3to10uM,inhibitedDNAmethyltransferaseactivityinvitro.SinceDNA
methylationisthoughttoplayanimportantroleintheregulationofgeneexpressionduringembryogenesis,ethanol
associatedalterationsinfetalDNAmethylationmaycontributetothedevelopmentalabnormalitiesseeninthefetal
alcoholsyndrome.
GarroAJetalAlcoholClinExpRes15(3):3958(1991)
/GENOTOXICITY/SeveralaldehydesandperoxidesweretestedformutagenicityusingSalmonellatyphimurium
testerstrainsTA97a,TA100,TA102andTA104,inthepresenceandabsenceofAroclorinducedliverS9mixfrom
F344ratsandB6C3F1mice,ineitherpreincubationorvaporphaseprotocols.Somechemicalsweretestedin
additionalSalmonellastrains.Benzaldehyde,butyraldehyde,benzoylperoxide,4chlorobenzaldehyde,
isobutyraldehyde,propionaldehydeandveratraldehydewerenonmutagenic.Acetaldehydeanddicumylperoxide
gaveinconsistentresultsandfurfuralgaveequivocalresponsesinTA100andTA104.Cumenehydroperoxide,
formaldehydeandglutaraldehydeweremutagenicinTA100,TA102andTA104.transCinnamaldehydeexhibiteda
weakmutagenicresponseinTA100withmouseliverS9only.2,4,5Trimethoxybenzaldehydewasmutageniconlyin
strainTA1538withratliverS9.Withtheexceptionofbutanoneperoxide,whichwasmutageniconlyinTA104,all
chemicalsmutagenicinstrainsTA102and/orTA104werealsomutagenicinTA100.Thedatadonot,therefore,
supportthepreferentialuseofstrainsTA102andTA104forscreeningaldehydesandperoxidesformutagenicity.
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ForanumberofthesechemicalstheadvantagesofusingTA102orTA104wasintheincreasedresponses
comparedwiththoseobtainedwithTA100.Twoofthefourperoxidesweremutagenicandoneofthesewas
mutageniconlywithTA104.
DillonDetalMutagenesis13(1):19(1998)
/GENOTOXICITY/Chinesehamstersreceivedacetaldehydeat0.01,0.1and0.5mg/kgbyipinjection,&bone
marrowmetaphaseswereanalyzedwithrespecttosisterchromatidexchanges.Thesisterchromatidexchange
frequencieswereelevatedbyacetaldehydeat0.5mg/kg,butnotbythelowerdoses.
KORTEA,OBEGMUTATRES88:38995(1981)
/GENOTOXICITY/AlkalineelutionwasemployedtostudyDNAdamageinChinesehamsterovaryKlcellstreated
withaseriesofbioticandxenobioticaldehydes.DNAcrosslinkingwasmeasuredintermsofthereductioninthe
effectofmethylmethanesulphonateonthekineticsofDNAelutionandwasobservedincellstreatedwith
formaldehyde,acetaldehyde,methylglyoxalandmalonaldehyde.Propionaldehyde,valeraldehyde,hexanal,and4
hydroxynonenalproducedDNAsinglestrandbreaks,orlesionswhichwereconvertedtobreaksinalkali.Bothtypes
ofDNAdamageoccurredincellsexposedtomalonaldehyde.Thesefindingssupportthehypothesisofa
carcinogeniceffectofthealdehydicproducts(malonaldehyde,methylglyoxal,propionaldehyde,hexanal,4
hydroxynonenal)releasedinbiomembranesduringlipidperoxidation.AcetaldehydedidnotcauseDNAbreaks.
MarinariUMetalCellBiochemFunct2(4):2438(1984)
/GENOTOXICITY/Acetaldehydewas...testedformutagenicityusingtheSalmonella/microsomepreincubation
assayusingthestandardprotocolapprovedbytheNationalToxicologyProgram(NTP).Acetaldehydewastestedat
dosesof0.033,0.10,0.33,1.0,3.3,and10mg/plateinasmanyas5Salmonellatyphimuriumstrains(TA1535,
TA1537,TA97,TA98,andTA100)inthepresenceandabsenceofratorhamsterliverS9./Acetaldehydewas
negativeinthesetestsand/thehighestineffectivedosetestedinanySalmonellatyphimuriumstrainwas10
mg/plate.TotalclearingofthebackgroundbacteriallawnwasexhibitedinsomeculturesusingstrainsTA100,
TA1535,andTA1537atthehighdosewithoutactivation.
MortelmansKetalEnvironMutagen8:1119(1986)
/GENOTOXICITY/Acetaldehydewas.../tested/fortheinductionofsexlinkedrecessivelethalmutationsin
DrosophilamelanogasterusingastandardprotocolapprovedbytheNationalToxicologyProgram....CantonS
wildtypemalesweretreatedwithconcentrationsofthetestchemicalthatresultinapproximately30%mortality....
Followingtreatment,maleswerematedindividuallyto3haremsofBascvirginfemalestoproduce3broods.
Acetaldehydeatadoseof22,500ppm,whenadministeredtomalesbyinjection,waspositiveinthisassay.
WoodruffRCetalEnvironMutagen7:677702(1985)
/GENOTOXICITY/TheDrosophilawingsomaticmutationandrecombinationtestwasappliedtoaseriesof
chemicalstodetermineitssuitabilityingenotoxicityscreening.Chronicfeedingofacetaldehydefor48hrata
concentrationof0.18mMgaveweakbutreproducibleeffectsforallthreecategoriesofspots:smallsingle,large
single,andtwin.
GrafUetalMutatRes222(4):35973(1989)
/GENOTOXICITY/Thetesticulargenotoxiceffectsofvinylacetateanditshydrolysisproduct,acetaldehyde,were
studiedinmicebyanalyzingtheinductionofmorphologicallyabnormalspermandmeioticmicronuclei.Vinyl
acetatesignificantlyincreasedthefrequencyofspermabnormalitiesat500mg/kg/daywhilelowerdoseswere
ineffective.Acetaldehydedidnotinduceabnormalsperm.Neitherofthecompoundsinfluencedthefrequencyof
meioticmicronuclei.Vinylacetate,butnotacetaldehyde,causedadosedependentdecreaseinspermproduction
andareductionoftesticularweightat500and125mg/kg/day.
LahdetieJMutatRes202(1):1718(1988)
/GENOTOXICITY/...InculturedChinesehamstercells,acetaldehydeinducedanincreaseofaneuploidyand
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chromosomebreaksandexchanges.Ethanolonlyinducedanincreaseofachromaticlesions(gaps).However,
followingtreatmentwithacetaldehyde,themostnotableeffectwasanincreaseofhypodiploidcellsandaparallel
increaseofmultinucleatedinterphasecells,thefrequencyofhyperdiploidcellsbeingconsiderablylower.Astrong
correlationhasbeenfoundoncomparingthefrequencyofhypodiploidcellstothefrequencyofhyperdiploidplus
multinucleatedinterphasecells.Thereexistsahigherchanceofhypodiploidcellsreachingthesecondmitosisafter
treatmentandthemaineffectofacetaldehydeistheinductionofhypodiploidyratherthanhyperdiploidyand
chromosomeaberrations.
DuloutFN,FurnusCCMutagenesis3(3):20711(1988)
/GENOTOXICITY/Acetaldehydehasbeenshowntoinducemutagenicandcytogenicchangesinmanymutagenic
assays.Usinginvitromammalianassays,additionofacetaldehydehasproducedsisterchromatidexchangesin
humanlymphocytesandinculturedChinesehamsterovarycellsinadoserelatedmannerchromosomalbreaks
andaberrationswerealsoinducedinadoserelatedmanner.AcetaldehydecausedmutationsinEscherichiacoli
systemsandDrosophilamelanogaster.
/GENOTOXICITY/AcetaldehydecausedadosedependentinductionofchromosomalaberrationsinViciafaba
roottipmeristems.
/GENOTOXICITY/Acetaldehydeinducedchromosomemalsegregationandmitoticcrossover(yA2marker)in
AspergillusnidulansdiploidstrainP1duringearlyconidialgermination....
/GENOTOXICITY/Invitroandwithoutexogenousmetabolicactivation,acetaldehydeinducedgenemutationsin
mouselymphomaL5178Tcells,sisterchromatidexchangesinChinesehamsterovarycellsandaneuploidyin
embryonicChinesehamsterdiploidfibroblasts....Itdidnotinducemicronucleiinearlyspermatidsofmice.
/GENOTOXICITY/AcetaldehydecausedDNAstrandbreaksandcrosslinksinhumanlymphocytesinvitrowithout
metabolicactivation,butnotinhumanbronchialepithelialcellsandinhumanleukocytes....
/GENOTOXICITY/Acetaldehydeisgenotoxicinvitro,inducinggenemutations,clastogeniceffects,andsister
chromatidexchanges(SCEs)inmammaliancellsintheabsenceofexogenousmetabolicactivation.However,
negativeresultswerereportedin...testsonSalmonella.Followingintraperitonealinjection,acetaldehydeinduced
SCEsinthebonemarrowofChinesehamstersandmice.However,acetaldehydeadministeredintraperitoneallydid
notincreasethefrequencyofmicronucleiinearlymousespermatids.Thereisindirectevidencefrominvitroandin
vivostudiestosuggestthatacetaldehydecaninduceproteinDNAandDNADNAcrosslinks.
/GENOTOXICITY/SCEwasinducedbyacetaldehyde(1.3106ug/mL)intheabsenceofexogenousmetabolic
activationinChinesehamsterovarycells....TheincreaseinSCEsinChinesehamsterovarycellswasless
pronouncedafteradditionofanexogenousmetabolicactivatingsystem....
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/GENOTOXICITY/Therepairofacetaldehyde/crotonaldehydeinducedguanine(N2)guanine(N2)interstrandcross
links(ICLs),3(2deoxyribos1yl)5,6,7,8(N2deoxyguanosyl)6(RorS)methylpyrimido[1,2alpha]purine10(3H)one,
wasstudiedusingashuttleplasmidbearingasitespecificICL.SincetheauthenticICLscanrevertto
monoadducts,achemicallystablemodelICL,1,3bis(2'deoxyguanosN2yl)butanederivative,wasalsoemployedto
probetheICLrepairmechanism.SincetheremovalofICLdependsonthenucleotideexcisionrepair(NER)
mechanisminEscherichiacoli,theplasmidbearingthemodelICLfailedtoyieldtransformantsinNERdeficient
hostcells,provingthestabilityofthisICLincells.TheauthenticICLsyieldedtransformantsintheNERdeficient
hoststherefore,thesetransformantsareproducedbyplasmidbearingspontaneouslyrevertedmonoadducts.In
contrast,inNERdeficienthumancells,themodelICLwasremovedbyanNERindependentrepairpathway,which
isuniquetohighereukaryotes.Thisrepairdidnotassociatewithatranscriptionalevent,butwithreplication.The
analysisofrepairedmoleculesrevealedthattheauthenticandmodelICLswererepairedmostly(>94%)inanerror
freemannerinbothhosts.ThemajormutationsthatwereobservedwereG>Ttransversionstargetingthecross
linkeddGlocatedinthelaggingstrandtemplate.Theseresultssupportoneofthecurrentmodelsforthe
mammalianNERindependentICLrepairmechanism,inwhichaDNAendonuclease(s)unhooksanICLfromthe
leadingstrandtemplateatastalledreplicationforksitebyincisingonbothsidesoftheICLandthentranslesion
synthesisisconductedacrossthe"halfexcised"ICLattachedtothelaggingstrandtemplatetorestoreDNA
synthesis.[LiuXetalBiochemistry45(42):12898905(2006)]Fulltext:PMC2518849
/ALTERNATIVEandINVITROTESTS/Inaninvitrostudy,asuppressiveeffectonrattesticularsteroidogenesis
wasreportedatconcnaslowas50uM(2.2ug/mL)acetaldehyde.
/ALTERNATIVEandINVITROTESTS/Preimplantationtwocellstagemouseembryos,obtainedfrom
superovulatedCF1mice,wereexposedtoacetaldehydethroughtheculturemediumfor60minfollowedbya105
hrincubationperiod.Scoringwasbasedonasystemwhichrecognizedeightdifferentstagesofdevelopment,zero
fordeadcellsofthetwoandfourcellstageto7forhatchingblastocyst.Embryostreatedwith5and10mg
acetaldehydeper100mlwerenotdifferentfromcontrols.Treatmentsof50mgacetaldehyde/100mLmediumand
higherwerecompletelylethal.
KalmusGW,BuckenmaierCCExperientia45(5):4847(1989)
/ALTERNATIVEandINVITROTESTS/Acetaldehyde...hadnoeffecton/fetalmouse/thymocytesubpopulation
ratiosorcellnumbersataphysiologicconcn(50uM)/inorganculture/.
BrayLAetalCellImmunol151(1):1223(1993)
/ALTERNATIVEandINVITROTESTS/Theeffectoftreatmentofratswithacetaldehydeonthesubcellular
nicotinamideadeninedinucleotide(+)aldehydedehydrogenaseactivitiesandacetaldehydeoxidationbyisolated
intactmitochondriaoftheliverandthebrainwasstudied.Inhalationofacetaldehydecausedasignificantdecrease
inthelivermitochondriallowKmaldehydedehydrogenaseactivity,whilebrainmitochondrialaldehyde
dehydrogenaseactivityremainedunchanged.Acetaldehydeoxidationbyisolatedintactlivermitochrondria
decreasedsignificantlybutthatbybrainmitochrondriaremainedunchangedafteracetaldehydeinhalation.
ShioharaEetalToxicol30(1):2530(1984)
/ALTERNATIVEandINVITROTESTS/Incubationofacetaldehyde(100mg%)withisolatedhepatocytesfor60
minsignificantlyincreasedlipidperoxideformation,whichwasinhibitedbyprioradditionofantioxidantssuchas
vitaminEorglutathione.
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/ALTERNATIVEandINVITROTESTS//Acetaldehyde/hasbeenshowntointerferewithmitochondrialoxygen
consumptioninratliverand...energyproduction.
/ALTERNATIVEandINVITROTESTS/Incorporationof(3H)thymidineintoDNAwassignificantlydiminishedby
treatmentwithethanolandacetaldehydeinregeneratingratliver,ratcellsinculture,andratfetaltissues.
DreostietalAlcoholism(NY)5(3):35762(1981)
/ALTERNATIVEandINVITROTESTS/Inexperimentsconductedundernearphysiologicalconditionsof
temperatures,pH,andionicstrength,acetaldehydeatconcentrationssimilartothosefoundinliverafterhighdoses
ofethanolactedasareversibleinhibitorofthenicotinamideadeninedinucleotidedependentethanoloxidation.
DawsonAGBiochemPharmacol30(16):234952(1981)
/ALTERNATIVEandINVITROTESTS/Theciliotoxicityofformaldehyde,acrolein,acetaldehyde,crotonaldehyde,
andmethacroleinontrachealmucosawasinvestigated.Tracheaswereexposedinvitrotofivedifferent
concentrationsofeachsubstance.Ciliaryactivityafterexposurewascomparedtothatmeasuredbeforeexposure.
Aerosolsofthetestsubstances,designedtosimulatecigarettesmoke,werepassedovertrachealtissueinan
observationchamber....Theconcentrationoftheirritantwastheprimaryfactoraffectingitseffect....Amarked
increaseinformaldehydetoxicitywasachievedwithonlyaslightincreaseinconcentration,whiletoxicityof
acetaldehydeandacroleinincreasedmoreslowlywithincreasingconcentration.Crotonaldehydeandmethacrolein
toxicityincreasedleastwithincreasingconcentration....
DalhamnT,RosengrenAArchOtolarygol93(5):496500(1971)
/IMMUNOTOXICITY/InastudyonCD1miceexposedto324mg/cum,3hr/dayfor5days,thebacteriocidal
activityofalveolarmacrophageswasreducedby15%.However,acetaldehydedidnotaffectmortalityfollowing
streptococcalinfection.
/IMMUNOTOXICITY/Ininvitrostudies,0.01%acetaldehydecausedasignificantinhibitionofhumangranulocyte
chemotaxis.At0.03%,acetaldehydeinhibitedthereleaseoflysozymefrommonocytes,butgranulocyteswere
unaffected.Thegenerationofoxygenradicalsbyzymosanparticlestimulatedmonocytesandgranulocyteswas
inhibitedbyacetaldehydeinadosedependentmanner.Inasimilarstudyinwhichperipheralmononuclearcells
wereincubatedwithacetaldehyde,decreasedlyticactivityagainstK562cellswasobservedatconcentrationshigher
than12umolperliter.Inanotherstudy,acetaldehydedecreased3Hthymidineincorporationinto
phytohaemagglutininorConcanavalinAstimulatedhumanlymphocytes.
/OTHERTOXICITYINFORMATION/Noextravasationofsodiumfluoresceinfromcapillariesofthecerebralcortex
&retinacouldbedemonstratedinratsduringseverenonlethalethanol&/oracetaldehydepoisoning.Theresultsdo
notexcludethepossibilitythatrepeatedintoxicationsmaygraduallyopenthebloodbrain&bloodretinalbarriers,
butdoindicatetheabsenceofaneffectduringacuteintoxication.
HILLBOMME,TERVOTMEXPERIENTIA37(9):9368(1981)
/OTHERTOXICITYINFORMATION/Acetaldehyde,thehepaticmetaboliteproductofethanoloxidation,has
negativeinotropiceffectsatbloodconcentrationsthatoccurafteramoderateethanolintake.Athigher
concentrations,acetaldehydereleasescatecholamineshenceitproducessympathomimeticeffects.Suchaneffect
graduallydecreaseswithaldehydesofincreasingchainlength.
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Amdur,M.O.,J.Doull,C.D.Klaasen(eds).CasarettandDoull'sToxicology.4thed.NewYork,NY:PergamonPress,1991.,p.
442
/OTHERTOXICITYINFORMATION/Theethanolandacetaldehydeuptakebythelactatingratmammaryglandas
wellastheireffectsonthisglandattheultrastructurallevelwerestudied.Theextractionofacetaldehydewas
greaterthanthatofethanolbothafterchronicandacuteethanoltreatment.Chronicethanoladministrationresulted
inalossofthemammarycellpolarization,inareductionoftheGolgidictyosomalelementsandinseveral
abnormalitiesatthelevelofcaseinmaturationandsecretion,whereaslipidsynthesisandsecretiondidnotseemto
beaffected.Normalsphericalcaseinmicellestookonafilamentlikestructureandcaseinvesiclesappearedfused
togetherformingmacrovesicles.Allthesealterationswerespecificofethanoland/oracetaldehydeactionandwere
notduetotheassociatedmalnutrition,asdeducedfromthelackofeffectsinthenutritionalcontrolgroup.
Vilar'oSetalAlcoholClinExpRes13(1):12836(1989)
/OTHERTOXICITYINFORMATION/Inrats,ethanolintakeaslowas4g/kg/dayinducedmitochondrialalterations,
detectedbyadecreaseinmitochondrialO2uptakesupportedbysubstratesenteringatthethreesitesofcoupled
phosphorylation.Sinceacetaldehydeoxidationoccursmainlyinsidethemitochondria,linkedtotherespiration
chain,theeffectofdailypreviousadministrationoflowdosesofethanolontheacetaldehydeoxidationrateby
intactratlivermitochondriawasstudied.DeterminationofacetaldehydeoxidationrateandO2uptake
accompanyingacetaldehyderemovalbylivermitochondriaindicatesthatthemeanvalueoftheseparameters
studiedinratsconsuminglowamountofethanol(0.53.0g/kg/day)wassignificantlyhigherthanthatofcontrols
drinkingonlywater(instate3,andinstate4).Thisenhancingeffectofethanolcannotbeascribedtoanuncoupling
ofoxidativephosphorylationandalsonottoachangeinaldehydedehydrogenaseactivitywhichwasmeasuredin
disruptedmitochondria.Ontheotherhand,highethanolconsumption(47g/kg/day),whichaltersmitochondrial
function,didnotdecreasemitochondrialacetaldehydeoxidation,ascomparedtoratsdrinkingwateronly.This
resultdiffersfromthedecreaseinducedbyhigherlevelsofpreviousethanolintake(1214g/kg/day).
QuintanillaME,TampierLToxicol63(1):11321(1990)
10.1.12 NonHumanToxicityValues
LD50Ratoral1930mg/kg
ITII.ToxicandHazardousIndustrialChemicalsSafetyManual.Tokyo,Japan:TheInternationalTechnicalInformationInstitute,
1988.,p.1
LD50Ratsc640mg/kg
LD50Mousesc560mg/kg
LD50Ratoral661mg/kg
LC50Ratinhalation37g/cum/30min
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LC50Mouseinhalation1500ppm/4hr
LD50Mouseiv212mg/kg
LD50Rabbitskin3540mg/kg
LC50Hamsterinhalation17,000ppm/4hr
LD50Hamsterintratracheal96mg/kg
LD50Mouseoral1230mg/kg
LD50Dogoral>600mg/kg
LC50Ratinhalation24g/m3/4hr
LC50Syrianhamsterinhalation31g/m3/4hr
LD50Mouseip500mg/kg
LD50Pregnantmouseiv165mg/kg
10.1.13 EcotoxicityValues
LC50Anasplatyrhynchos(Mallardduck)diet>5000ppmfor8days
USEPA,OfficeofPesticideProgramsPesticideEcotoxicityDatabase(2000)onAcetaldehyde(75070).Availablefrom,as
ofDecember22,2008:http://cfpub.epa.gov/ecotox/quick_query.htm
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LC50Colinusvirginianus(Northernbobwhite)diet808(495.641091)ppmfor8days
LC100Aphid0.25%acetaldehydefor2hr(fumigationflask)
AharoniYetalJEconEntomol72:4935(1979)ascitedinUSEPAChemicalHazardInformationProfile:Acetaldehydep.40
(1983)
LC100Aphid1.52.0%acetaldehydefor23hr(inairtightjars)
StewartJKetalHortSci15(2):1489(1982)ascitedinUSEPAChemicalHazardInformationProfile:Acetaldehydep.40
(1983)
EC50Species:Pimephalespromelas(Fatheadminnow)Conditions:flowthroughbioassasywithmeasured
concentrations,23.9degC,dissolvedoxygen7.2mg/L,hardness53.0mg/Lcalciumcarbonate,alkalinity43.2
mg/Lcalciumcarbonate,andpH7.63Concentration:30.8mg/Lfor96hr(confidencelimit28.034.0mg/L)Effect:
lossofequilibrium
Brooke,L.T.,D.J.Call,D.T.GeigerandC.E.Northcott(eds.).AcuteToxicitiesofOrganicChemicalstoFatheadMinnows
(PimephalesPromelas).Superior,WI:CenterforLakeSuperiorEnvironmentalStudiesUniv.ofWisconsinSuperior,1984.,p.
29
LC50Species:Pimephalespromelas(Fatheadminnow)Conditions:flowthroughbioassaywithmeasured
concentrations,21.6degC,dissolvedoxygen7.5mg/L,hardness46.6mg/Lcalciumcarbonate,alkalinity40.5
mg/Lcalciumcarbonate,andpH7.1Concentration:37.2mg/Lfor96hr(confidencelimit31.144.4mg/L)
GeigerD.L.,D.J.Call,L.T.Brooke.(eds.).AcuteToxicitiesofOrganicChemicalstoFatheadMinnows(Pimephales
Promelas).Vol.V.SuperiorWI:UniversityofWisconsinSuperior,1990.,p.33
LC50Species:Pimephalespromelas(Fatheadminnow,age30days,0.076gwetweight)Conditions:freshwater,
static,21.4degC,pH6.97,hardness48.0mg/LCaCO3,alkalinity40.5mg/LCaCO3,dissolvedoxgyen76.4%
Concentration:43100ug/Lfor96hr(95%confidencelimit:3980046800ug/L)/99%purity/
BrookeLCenterforLakeSuperiorEnvironStud,UnivofWisconsinSuperior:24(1987)Availablefrom,asofDecember22,
2008:http://cfpub.epa.gov/ecotox/quick_query.htm
LC50Species:Poeciliareticulata(Guppy,10laboratoryrearedandacclimatedfish,23monthsold)Conditions:
semistaticConcentration:35mg/L
WHOEnvironHealthCriteria167:Acetaldehyep.57(1995)
LC50Species:Lepomismacrochirus(Bluegill)Conditions:staticConcentration:53mg/Lfor96hr
LC50Species:Lepomismacrochirus(Bluegill)Conditions:freshwater,staticConcentration:2100ug/Lfor96hr
(95%confidencelimit:18002400ug/L)/94.9%purity/
LC50Species:Oncorhynchusmykiss(Rainbowtrout)Conditions:freshwater,staticConcentration:2200ug/Lfor
96hr(95%confidencelimit:18002400ug/L)/94.9%purity/
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EC50Species:Daphniamagna(Waterflea)Conditions:staticConcentration:42mg/Lfor48hrEffect:
immobilization
EC50Species:Chlorococcales(Greenalgaeorder)Conditions:freshwater,staticConcentration:270000ug/Lfor
24hrEffect:physiology,assimilationefficiency
KrebsFDeutscheGewasserkundlicheMitteilungen35(5/6):161170(1991)Availablefrom,asofDecember22,2008:
http://cfpub.epa.gov/ecotox/quick_query.htm
EC50Species:Pseudokirchneriellasubcapitata(Greenalgae,exponentialgrowthphase,15000cells/mL,UTEX
1648)Conditions:static,24degC,dissolvedoxygen12mg/LConcentration:3359ug/Lfor48hrEffect:
physiology,decreasedphotosynthesis
ChenCYetalEnvironToxicolChem24(5):106773(2005)Availablefrom,asofDecember22,2008:
EC50Species:Pseudokirchneriellasubcapitata(Greenalgae,exponentialgrowthphase,15000cells/mL,UTEX
1648)Conditions:static,24degC,dissolvedoxygen12mg/LConcentration:4439ug/Lfor48hrEffect:
decreasedpopulationgrowthrate
LC50Species:Gammaruspseudolimnaeus(Scud,adult,0.034gwetweight)Conditions:freshwater,flow
through,21.6degC,pH7.05,hardness46.6mg/LCaCO3,alkalinity58.0mg/LCaCO3,dissolvedoxygen86%
Concentration:19300ug/Lfor96hr(95%confidencelimit:1500024900ug/L)/99%purity/
10.1.14 TSCATestSubmissions
ChronictoxicityandoncogenicityofacetaldehydewereevaluatedingroupsofmaleandfemaleWistarrats
(105/sex/group)exposedviainhalationfor6hrs/day,5days/weekforamaximumof27monthsto0,750,1500
ppmacetaldehydeorinitiallyto3000ppmwhichwasgraduallydecreasedtoafinalconcentrationof1000ppmin
week52andbeyond.Asignificantdifferencebetweentreatedanimalsandcontrolswasobservedinthefollowing:
mortality(doserelatedincreaseinalltreatedgroups),bodyweights(doserelateddecreaseinallmalegroupsand
femalesofthemidandhighdosegroups),alkalinephosphataseactivityinthebloodplasma(increasedinallhigh
doseanimals),noselesions(doserelatedincreaseinnumberandseverityatalldoselevels),squamousmetaplasia
accompaniedbyslighttoseverehyperkeratosisoftherespiratoryepithelium(foundinmostofthemidandhigh
dosegroups,noneofthelowdosegroupsorcontrols),squamouscellcarcinomas(doserelatedincrease,found
mainlyinmidandhighdosegroups),adenocarcinomas(increasedinalltreatedgroups),andlarynxhyperplasia
andkeratinizedsquamousmetaplasiaoftheepitheliuminthevocalcordregion(foundinmostanimalsinthemid
andhighdosegroups).
CIVOInstituteTNOLifeSpan(27Month)InhalationCarcinogenicityStudyofAcetaldehydeinRats(FinalReport)withCover
LetterDated071285.(1985),EPADocumentNo.888600015,FicheNo.OTS05036961
SubchronicinhalationtoxicitywasevaluatedwithmalealbinoSPFWistarrats(10/group)exposedtoacetaldehyde
(AA)for6hrs/day,5days/weekfor4weeksusingdifferentexposureprofiles.Animalswereexposedtonominal
concentrationsof0,150or500ppmeithercontinuouslyfor6hrsorintwo3hrperiodswithaninterruptionof1.5
hrs.Also,animalswereexposedto500ppmcontinuouslyfor6hrs/daywith34superimposed5minutepeak
exposures/periodof25003500ppmorexposedto110ppmfortwo3hrperiodswith4superimposed5minute
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peakexposures/periodof660ppm.Comparedtocontrols,animalsexposedtoAAexhibitedstatisticallysignificantly
decreaseinthenumber,viabilityandphagocytosingcapacityofmacrophagesinlunglavagesfromthehighdose
groups(noadditionaleffectsduetointerruptionorpeakexposures).Therewerenosignificantdifferencesbetween
animalsexposedornotexposedtoAAinbodyweight,lungweightsandbiochemicalparametersdeterminedin
lunglavages,orgrossexaminationatautopsy.Histopathologicalchangeswereobservedinthenoseofanimals
exposedto500ppmAAcharacterizedbylossofmicrovilliaccompaniedbythinninganddisarrangementofthelayer
ofolfactoryepithelium(noadditionaleffectsduetointerruptionorpeakexposures).Nocompoundrelatedeffectson
thepulmonarymacrophagesorhistopathologywerenotedinthegroupsexposedtoatleast150ppmwithor
withoutpeakexposures.
CivoInstituteTNOFixedVersusVariableLevelsofExposureinInhalationToxicityTestingwithReferencetotheWorkplace:
StudieswithAcetaldehydeandCarbonTetrachloride,FinalReport.(1985),EPADocumentNo.FYIAX06850413,FicheNo.
OTS00004130
10.1.15 PopulationsatSpecialRisk
Anincrsensitivitytoethanolwithrespecttofacialflushingwasobservedincertainhumanpopulations(espof
Orientalorigin),whichwasascribedtogeneticdifferencesinacetaldehydeelimination,duetoaldehyde
dehydrogenasepolymorphism....
10.2 EcologicalInformation
10.2.1 ICSCEnvironmentalData
Thesubstanceisharmfultoaquaticorganisms.
10.2.2 EnvironmentalFate/ExposureSummary
Acetaldehyde'sproductionanduseinthemanufactureofaceticacidandaceticanhydride,nbutanol,2
ethylhexanol,peraceticacid,aldol,pentaaerythritol,pyridines,chloral,1,3butyleneglycol,andtrimethylolpropane,
andsyntheticflavorsmayresultinitsreleasetotheenvironmentthroughvariouswastestreams.Acetaldehydeis
alsopresentineffluentfrompulpmills,autoexhaust,tobaccosmoke,andfrompowerplantsusingfossilfuels,
woodortrash.Acetaldehydeisfoundinplantssinceitisanintermediateproductofrespirationinhigherplants.
Acetaldehydeisanaturalproductofcombustionandphotooxidationofhydrocarbonscommonlyfoundinthe
atmosphereitalsoisanintermediateproductinthemetabolismofethanolandsugars.Ifreleasedtoair,avapor
pressureof902mmHgat25degCindicatesacetaldehydewillexistsolelyasagasintheatmosphere.Gasphase
acetaldehydewillbedegradedintheatmospherebyreactionwithphotochemicallyproducedhydroxylradicalsthe
halflifeforthisreactioninairisestimatedtobe24hours.Thehalflifeforthereactionofacetaldehydewithnitrate
radicalshasbeencalculatedinseparatestudiesas72hrand13days.Acetaldehydeisbothproducedand
consumedunderphotochemicalsmogconditionsandthehalflifewillbeamaximumofafewhours.Acetaldehyde
absorbssolarradiation(>290nm)anddissociatestoformfreeradicalsthephotolysishalflivesrangefrom8.4to
16hrs.Ifreleasedtosoil,acetaldehydeisexpectedtohaveveryhighmobilitybaseduponanestimatedKocof16.
VolatilizationfrommoistsoilsurfacesisexpectedtobeanimportantfateprocessbaseduponaHenry'sLaw
constantof6.67X105atmcum/mole.Acetaldehydemayvolatilizefromdrysoilsurfacesbaseduponitsvapor
pressure.Acetaldehydereached80%ofitstheoreticalBODusingactivatedsewageintheJapaneseMITItest,
suggestingthatbiodegradationmaybeanimportantenvironmentalfateprocess.Ifreleasedintowater,
acetaldehydeisnotexpectedtoadsorbtosuspendedsolidsandsedimentbasedupontheestimatedKoc.
Volatilizationfromwatersurfacesisexpectedtobeanimportantfateprocessbaseduponthiscompound'sHenry's
Lawconstant.Estimatedvolatilizationhalflivesforamodelriverandmodellakeare11hoursand5.3days,
respectively.AnestimatedBCFof3suggeststhepotentialforbioconcentrationinaquaticorganismsislow.
Hydrolysisisnotexpectedtobeanimportantenvironmentalfateprocesssincethiscompoundlacksfunctional
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groupsthathydrolyzeunderenvironmentalconditions.Occupationalexposuretoacetaldehydemayoccurthrough
inhalationofthiscompoundatworkplaceswhereacetaldehydeisproducedorused.Monitoringdataindicatethat
thegeneralpopulationmaybeexposedtoacetaldehydeviainhalationofambientair,ingestionoffoodand
beverages,anddermalcontactwithproductscontainingacetaldehyde.(SRC)
10.2.3 NaturalOccurringSources
Acetaldehydeisanaturalproductofcombustionandphotooxidationofhydrocarbonscommonlyfoundinthe
atmosphere(1).Acetaldehydeisanintermediateproductinthemetabolismofethanolandsugars(1)therefore
occursintracequantitiesinhumanblood(1).Itispresentinsmallamountsinallalcoholicbeverages,e.g.,beer,
wine,andspiritsandinplantjuicesandessentialoils,roastedcoffeeandtobaccosmoke(1).Acetaldehydeisfound
inplantssinceitisanintermediateproductofrespirationinhigherplants(2).Acetaldehydeisfoundinallripefruits
thathavetarttastesbeforeripening(2).Forestfires,volcanos,animalwastes,andinsectsaresourcesof
acetaldehyde(3).Acetaldehydeisemittedfrombloomingrape(4).Acetaldehydewasdetectedintheemissionsof
quakingaspen,cottonwood,Gambeloak,Douglasfir,Engelmannspruce,RockyMountainJuniper,Pinyonpine,
andponderosapinetreesfromCibolaNationalforestinSocorro,NM(5).
(1)IARCMonographsontheEvaluationoftheCarcinogenicRiskofChemicalstoMan.Geneva,Switzerland:WHO,71:320
(1999)(2)HagemeyerHJKirkOthmerEncyclChemTechnol4thed.NY,NY:JohnWileyandSons1:94109(1991)(3)
GraedelTEChemicalCompoundsintheAtmosphere.NY,NY:AcademicPress,p.7190,158169(1978)(4)MullerKetal
Chemosphere49:124756(2002)(5)MartinRSetalEnvironSciTechnol33:218692(1999)
10.2.4 ArtificialSources
Acetaldehyde'sproductionanduseinthemanufactureofaceticacidandaceticanhydride,nbutanol,2
ethylhexanol,peraceticacid,aldol,pentaaerythritol,pyridines,chloral,1,3butyleneglycol,andtrimethylolpropane,
andsyntheticflavors(1)mayresultinitsreleasetotheenvironmentthroughvariouswastestreams(SRC).
Acetaldehydeisfoundinpulpmilleffluent(2),autoexhaust,andtobaccosmoke(35).Emissionsofacetaldehyde
occursfrompowerplantsusingfossilfuels,woodortrash(4,6).
(1)LewisRJSr,edHawley'sCondensedChemDict.15thed.NY,NY:JohnWileyandSonsInc,p.5(2007)(2)SunitoLRet
alChemosphere17:124990(1988)(3)GraedelTEChemicalCompoundsintheAtmosphereAcademicPressNewYorkpp.
15869(1978)(4)NationalResearchCouncilFormaldehydeandotherAldehydesp.352USEPA600/682002(1978)(5)
ZweidingerRBetalEnvironSciTechnol22:95662(1988)(6)LipariFetalEnvironSciTechnol18:32630(1984)
10.2.5 EnvironmentalFate
TERRESTRIALFATE:Basedonaclassificationscheme(1),anestimatedKocvalueof16(SRC),determinedfrom
alogKowof0.34(2)andaregressionderivedequation(3),indicatesthatacetaldehydeisexpectedtohavevery
highmobilityinsoil(SRC).Volatilizationofacetaldehydefrommoistsoilsurfacesisexpectedtobeanimportant
fateprocess(SRC)givenaHenry'sLawconstantof6.67X105atmcum/mole(4).Acetaldehydeisexpectedto
volatilizefromdrysoilsurfaces(SRC)baseduponavaporpressureof902mmHg(5).Acetaldehydereached80%of
itstheoreticalBODusingactivatedsewageintheJapaneseMITItest(6),suggestingthatbiodegradationmaybean
importantenvironmentalfateprocessinsoil(SRC).Acetaldhydewasoxidizedinasiltyclayloambutnorateswere
given(7).
(1)SwannRLetalResRev85:1728(1983)(2)BioByteClogPforWindowsProgram.BioByteCorp.,Claremont,CA(1995)
(3)LymanWJetalHandbookofChemicalPropertyEstimationMethods.Washington,DC:AmerChemSocpp.49(1990)(4)
GaffneyJSetalEnvironSciTechnol21:51923(1987)(5)BoublikTetalThevaporpressuresofpuresubstances.Vol.17.
Amsterdam,Netherlands:ElsevierSci.Publp.125(1984)(6)NITEChemicalRiskInformationPlatform(CHRIP).
BiodegradationandBioconcentration.Tokyo,Japan:NatlInstTechEval.Availableathttp://www.safe.nite.go.jp/english/db.html
asofJan2009.(7)GriebelGE,OwensLDSoilBiolBiochem4:18(1972)
AQUATICFATE:Basedonaclassificationscheme(1),anestimatedKocvalueof16(SRC),determinedfromalog
Kowof0.34(2)andaregressionderivedequation(3),indicatesthatacetaldehydeisnotexpectedtoadsorbto
suspendedsolidsandsediment(SRC).Volatilizationfromwatersurfacesisexpected(3)baseduponaHenry'sLaw
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constantof6.67X105atmcum/mole(4).UsingthisHenry'sLawconstantandanestimationmethod(3),
volatilizationhalflivesforamodelriverandmodellakeare11hoursand5.3daysrespectively(SRC).Accordingto
aclassificationscheme(5),anestimatedBCFof3(SRC),fromitslogKow(2)andaregressionderivedequation(6),
suggeststhepotentialforbioconcentrationinaquaticorganismsislow(SRC).Acetaldehydereached80%ofits
theoreticalBODusingactivatedsewageintheJapaneseMITItest(7),suggestingthatbiodegradationmaybean
importantenvironmentalfateprocessinwater(SRC).Inadieawaytestinseawater,acetaldehydeconcnsdeclined
toapproximately25%ofinitialvaluesin1hr,whereasnodeclineinconcnwasobservedinsterilecontrols(8).
Acetaldehydeisnotexpectedtoundergohydrolysisintheenvironmentduetothelackoffunctionalgroupsthat
hydrolyzeunderenvironmentalconditions(9).
(1)SwannRLetalResRev85:1728(1983)(2)BioByteClogPforWindowsProgram.BioByteCorp.,Claremont,CA(1995)
(3)LymanWJetalHandbookofChemicalPropertyEstimationMethods.Washington,DC:AmerChemSocpp.49,151to
1529(1990)(4)GaffneyJSetalEnvironSciTechnol21:51923(1987)(5)FrankeCetalChemosphere29:150114(1994)
(6)MeylanWMetalEnvironToxicolChem18:66472(1999)(7)NITEChemicalRiskInformationPlatform(CHRIP).
BiodegradationandBioconcentration.Tokyo,Japan:NatlInstTechEval.Availableathttp://www.safe.nite.go.jp/english/db.html
asofJan2009.(8)MopperK,StahovecWLMarChem19:30512(1986)(9)LymanWJetalHandbookofChemicalProperty
EstimationMethodsWashington,DC:AmerChemSocp.74(1990)
ATMOSPHERICFATE:Accordingtoamodelofgas/particlepartitioningofsemivolatileorganiccompoundsinthe
atmosphere(1),acetaldehyde,whichhasavaporpressureof902mmHgat25degC(2),isexpectedtoexistsolely
asagasintheambientatmosphere.Gasphaseacetaldehydeisdegradedintheatmospherebyreactionwith
photochemicallyproducedhydroxylradicals(SRC)thehalflifeforthisreactioninairisestimatedtobe24
hours(SRC),calculatedfromitsrateconstantof1.58X1011cucm/moleculesecat25degC(3).Acetaldehyde
absorbssolarradiation(>290nm)(4)anddissociatestoformfreeradicals(5).Thehalflifeintheatmosphere
resultingfromphotolysisisreportedas8.4hr(5)and16hr(6).Acetaldehydealsoreactswithseveralatmospheric
species,suchasnitrogendioxideandthenitrateradical(5,710).Thehalflifeforthereactionofacetaldehydewith
nitrateradicalshasbeencalculatedinseparatestudiesas72hr(9)and13days(10).Acetaldehydeisbothproduced
andconsumedunderphotochemicalsmogconditionsandthehalflifewillbeamaximumofafewhours(11,12).
(1)BidlemanTFEnvironSciTechnol22:361367(1988)(2)BoublikTetalThevaporpressuresofpuresubstances.Vol.17.
Amsterdam,Netherlands:ElsevierSciPublp.125(1984)(3)AtkinsonRJPhysChemRefData.Monograph1(1989)(4)
GrasselliJGAtlasofSpectralDataandPhysicalConstantsforOrganicCompounds.ChemicalRubberCo(1973)(5)Graedel
TEChemicalCompoundsintheAtmosphere.NY,NY:AcademicPress,pp.15869(1978)(6)WeaverJDissAbstrIntB
197737:3427(1976)(7)AtkinsonR,PittsJNJrJChemPhys68:35814(1978)(8)DavisAM,CorcoranWHIndEngChem
Fundam11:4319(1972)(9)AtkinsonRetalJPhysChem88:12105(1984)(10)AndresenOetalinProceedingsfromthe
EuroTrac2Symposium,MidgleyPMetal.eds.,SpringerVerlag,Berlin5pp(2001)(11)AltshullerAP,BufaliniJJEnviron
SciTechnol5:3964(1971)(12)LeoneJA,SeinfeldJHEnvironSciTechnol18:2807(1984)
10.2.6 Biodegredation
AEROBIC:Acetaldehyde,presentat100mg/L,reached80%ofitstheoreticalBODin2weeksusinganactivated
sludgeinoculumat30mg/LandtheJapaneseMITItest(1).Acetaldehydewasalsoeasilybiodegradedbybiological
sewagetreatment(2).Laboratorytestsconfirmthedegradabilityofacetaldehydebyacclimatedsludgeand
sewage(37)withtheoreticalBODsof28%in24hr(3),100%in5hr(4),40.5%in5days(8),and70%in5days(5).
Unlessspecialcarewastaken,someofthelossesreportedcouldbeduetovolatilization(SRC).Acetaldehydewas
oxidizedinasiltyclayloambutnoratesweregiven(9).Inadieawaytestinseawater,acetaldehydeconcns
declinedtoapproximately25%ofinitialvaluesin1hr,whereasnodeclineinconcnwasobservedinsterile
controls(10).
(1)NITEChemicalRiskInformationPlatform(CHRIP).BiodegradationandBioconcentration.Tokyo,Japan:NatlInstTech
Eval.Availableathttp://www.safe.nite.go.jp/english/db.htmlasofJan2009.(2)ThomNS,AggARProcRoySocLondB189:
34757(1957)(3)GerholdRM,MalaneyGWJWaterPollutControlFed38:56279(1957)(4)HatfieldRIndEngChem49:
1926(1957)(5)HeukelekianH,RandMCJWaterPollutControlAssoc29:104053(1955)(6)RogovskayaTetalInst
VodosnakzhKanalizGidrotekhnSooruzheniiIInzhGidrogeol1962pp.178213(1963)(7)LudzackJR,EttingerMBJWater
PollutControlAssoc32:11732000(1960)(8)TakemotoSetalSuishitsuOdakuKenkyu4:8090(1981)(9)GriebelGE,
OwensLDSoilBiolBiochem4:18(1972)(10)MopperK,StahovecWLMarChem19:30512(1986)
ANAEROBIC:Acetaldehdyedegradesbyanaerobicbiologicaltreatment(14)with97%utilizationbeingreportedin
asystemwitha20dayhydraulicretentiontime(2)and67%beingremovedinananaerobiclagoon(4).
(1)SpeeceREEnvironSciTechnol17:416A27A(1983)(2)ChouWLetalBiotechBioengSymp8:391414(1979)(3)
HoviousJCetalAnaerobicTreatmentofSyntheticOrganicWastes.USEPA.WaterPollutControlResearchSeries12020
DIS01/72(1972)(4)SCSEngineersSelectedBiodegradationTechniquesforTreatmentand/orUltimateDisposalofOrganic
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Materials.USEPA600/279006(1979)
10.2.7 AbioticDegredation
Therateconstantforthevaporphasereactionofacetaldehydewithphotochemicallyproducedhydroxylradicalsis
1.58X1011cucm/moleculesecat25degC(1).Thiscorrespondstoanatmospherichalflifeofabout24hoursat
anatmosphericconcnof5X10+5hydroxylradicalspercucm(SRC).Acetaldehydeabsorbssolarradiation(>290
nm)(2)anddissociatestoformfreeradicals(3).Thehalflifeintheatmosphereresultingfromthisphotolysisis
reportedas8.4hr(3)and16hr(4).Anotherinvestigatorcalculatesaphotolysishalflifeat55degNlatitudeas34hr
insummerand296hrinwinter(5).Oneofthemainproductsofthephotooxidationofacetaldehydeinpollutedairis
peroxyacetylnitrate(6).Acetaldehydealsoreactswithseveralatmosphericspecies,suchasnitrogendioxideandthe
nitrateradical(3,710).Thehalflifeforthereactionofacetaldehydewithnitrateradicalshasbeencalculatedas72
hr(9)and13days(10).Acetaldehydeisbothproducedandconsumedunderphotochemicalsmogconditionsandthe
halflifewillbeamaximumofafewhours(11,12).Acetaldehydeisphotochemicallyproducedinunsterilizedand
sterilizedseawater,presumablyfromnaturaldissolvedorganicmatter,uponirradiationwithmiddaysunlightfor48
hr(13).Acetaldehydeconcnsinseawaterplacedoutsideshowedcleardiurnalvariationsconcnsreacheda
maximumduringthelateafternoonandquicklydecreasedtopredawnlevelsaftersunset(13).Acetaldehydeisnot
expectedtoundergohydrolysisintheenvironmentduetothelackoffunctionalgroupsthathydrolyzeunder
environmentalconditions(14).
(1)AtkinsonRJPhysChemRefData.Monograph1(1989)(2)GrasselliJGAtlasofSpectralDataandPhysicalConstants
forOrganicCompounds.ChemicalRubberCo(1973)(3)GraedelTEChemicalCompoundsintheAtmosphere.NY,
NY:AcademicPress,pp.15869(1978)(4)WeaverJDissAbstrIntB197737:3427(1976)(5)BottenheimJW,StrauszOPJ
Photochem9:1213(1978)(6)GrosjeanDEnvironSciTechnol16:25462(1982)(7)AtkinsonR,PittsJNJrJChemPhys
68:35814(1978)(8)DavisAM,CorcoranWHIndEngChemFundam11:4319(1972)(9)AtkinsonRetalJPhysChem88:
12105(1984)(10)AndresenOetalinProceedingsfromtheEuroTrac2Symposium,MidgleyPMetal,eds.,Springer
Verlag,Berlin5pp(2001)(11)AltshullerAP,BufaliniJJEnvironSciTechnol5:3964(1971)(12)LeoneJA,SeinfeldJH
EnvironSciTechnol18:2807(1984)(13)MopperK,StahovecWLMarChem19:30521(1986)(14)LymanWJetal
HandbookofChemicalPropertyEstimationMethodsWashington,DC:AmerChemSocp.74(1990)
10.2.8 Bioconcentration
AnestimatedBCFof3wascalculatedinfishforacetaldehyde(SRC),usingalogKowof0.34(1)andaregression
derivedequation(2).Accordingtoaclassificationscheme(3),thisBCFsuggeststhepotentialforbioconcentrationin
aquaticorganismsislow(SRC).
(1)BioByteClogPforWindowsProgram.BioByteCorp.,Claremont,CA(1995)(2)MeylanWMetalEnvironToxicolChem
18:66472(1999)(3)FrankeCetalChemosphere29:150114(1994)
10.2.9 SoilAdsorption/Mobility
TheKocofacetaldehydeisestimatedas16(SRC),usingalogKowof0.34(1)andaregressionderived
equation(2).Accordingtoaclassificationscheme(3),thisestimatedKocvaluesuggeststhatacetaldehydeis
expectedtohaveveryhighmobilityinsoil.
(1)BioByteClogPforWindowsProgram.BioByteCorp.,Claremont,CA(1995)(2)LymanWJetalHandbookofChemical
PropertyEstimationMethods.Washington,DC:AmerChemSocpp.49(1990)(3)SwannRLetalResRev85:1728(1983)
10.2.10 VolatilizationfromWater/Soil
TheHenry'sLawconstantforacetaldehydeis6.67X105atmcum/mole(1).ThisHenry'sLawconstantindicates
thatacetaldehydeisexpectedtovolatilizefromwatersurfaces(2).BasedonthisHenry'sLawconstant,the
volatilizationhalflifefromamodelriver(1mdeep,flowing1m/sec,windvelocityof3m/sec)(2)isestimatedas11
hours(SRC).Thevolatilizationhalflifefromamodellake(1mdeep,flowing0.05m/sec,windvelocityof0.5
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m/sec)(2)isestimatedas5.3days(SRC).Acetaldehyde'sHenry'sLawconstantindicatesthatvolatilizationfrom
moistsoilsurfacesmayoccur(SRC).Acetaldehydeisexpectedtovolatilizefromdrysoilsurfaces(SRC)basedupon
avaporpressureof902mmHg(3).
(1)GaffneyJSetalEnvironSciTechnol21:51923(1987)(2)LymanWJetalHandbookofChemicalPropertyEstimation
Methods.Washington,DC:AmerChemSocpp.151to1529(1990)(3)BoublikTetalThevaporpressuresofpure
substances.Vol.17.Amsterdam,Netherlands:ElsevierSci.Publp.125(1984)
10.2.11 WaterConcentrations
DRINKINGWATER:Ina10citysurveyrepresentingdifferentsourcesandtypesofcontaminationofrawwater
supply,acetaldehydewasdetectedin5(Miami,FL,Seattle,WA,Ottuma,IA,Philadelphia,PA,Cincinnati,OH)of
10supplies(12)theconcnofacetaldehydeinthewatersuppliesofPhiladelphiaandSeattlewere0.1ppb(12).
AcetaldehydewasdetectedbutnotquantifiedinthedrinkingwaterofNewOrleans,LA(3),Cincinnati,OH,Miami,
FL,Ottuma,IA(4),andDurham,NC(2).Medianconcnsofacetaldehydeindrinkingwaterfrom35UStreatment
plantswere2.7,2.6,and1.8ppbinSummer1988,Fall1988,andWinter1989,respectively(5).Acetaldehydewas
detectedindrinkingwatersamplesfromtheSeaofGalilee,IsraelwatertreatmentplantsinJulyof2000andnot
detectedDec1998,May,SeptemberandNovof1999(6).
(1)USEPAPreliminaryAssessmentofSuspectedCarcinogensinDrinkingWater.InterimReporttoCongress(1975)(2)
NationalResearchCouncilFormaldehydeandOtherAldehydespp.352USEPA600/682002(1978)(3)KeithLHetalpp.
32973inIdentificationandAnalysisofOrganicPollutantsinWater.AnnArbor,MI:AnnArborPress(1976)(4)USEPANew
Orleansareawatersupply.DraftanalyticalreportbythelowerMississippiRiverFacility,SlidellLA(1974)(5)KrasnerSWet
alJAmerWaterWorksAssoc81:4153(1989)(6)RichardsonSDetalEnvironSciTechnol37:378293(2003)
SURFACEWATER:AcetaldehydewasdetectedbutnotquantifiedintheMississippiRiveratNewOrleans,LA(1).
TheconcentrationofacetaldehydeinsurfaceseawateroffthesouthwestcoastofFloridawas19nMatmid
afternoon(maxconcentration)and2nMat6AM(2).
(1)DowtyetalEnvironSciTechnol9:7625(1975)(2)MopperK,StahovecWLMarChem19:30521(1986)
RAIN/FOG/SNOW:Analysisofrain,mistanddewsamples,collectedinPetten,TheNetherlandsduring1987and
1988,showedacetaldehydelevelsof5to185ug/Lforrain(N=8),15and200ug/Lfordewand30ug/Lformist(1).
Therangeofconcnsofacetaldehydeinicefog(Fairbanks,AK),rain(5sitesCalifornia),clouds(California),mist(2
sitesCalifornia),andfog(4sitesCalifornia)were0.0070.13ppm,00.11ppm(2of6sitespositive),00.59ppm,
0.100.11ppm,and00.17ppm,respectively(2).CloudandrainwatersampleswerecollectedintheSpringof1991
intheVosgesmountains,Franceandanalyzedforacetaldehydethemeanconcnofacetaldehydewas17ug/L
(range,notdetected(detectionlimitunspecified)to58ug/L)and12ug/L(range,8to17ug/L)forcloudandrain
watersamples,respectively(3).ThemeanandrangeofconcnsofacetaldehydeinprecipitationoverHanover,
Germanywere12.0and1.520.5ppb,respectively(4).Acetaldehydewasdetectedininterstitialairofsnowatthe
arcticatmosphereboundary,insamplestakenFeb16andApril22,2000at<50and100300parts/trillion,
respectively(5).
(1)KeukenMP,SchoonebeekCAMIntJEnvironAnalChem35:22739(1989)(2)GrosjeanD,WrightBAtmosEnviron17:
20936(1983)(3)LevsenKetalInternJEnvironAnalChem52:8797(1993)(4)LevsenKetalChemosphere21:103761
(1990)(5)GuimbaudCetalAtmosEnviron36:274352(2002)
10.2.12 EffluentsConcentrations
Theconcnofacetaldehyefromgasolineengineexhaustwas0.84.9ppm(1)theconcnindieselexhaustwas3.2
ppm(1).Acetaldehydewasidentified,notquantified,inrushhourtrafficairsamplestakenattheOaklandSan
FranciscoBayBridgetollplaza4/23/2001,57pm,4/24/2001,610am,and37pm(2).Acetaldehydeemissions
fromatwostroke,9.9horsepower,Evinrudeenginewere0.030.14g/kWhour,andfromafourstroke,9.9horse
power,Hondaenginewere0.0040.01g/kWhour(3).AcetaldehydewasfoundinhighwaytunnelsinTuscaroralight
dutytrucksemitted0.643mg/kmtraveledor9.488mg/Lfuelused,heavydutytrucksemitted3.951mg/kmtraveled
or12.445mg/Lfuelused(4).Acetaldehydeconcnsfromautomobileexhaustwere781240ppbvinmodelsfrom
1971,1975,1977and1982(5).Acetaldehydeemissionsfromatwostrokeengine(chainsaw)usingaliphatic
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gasoline,regulargasoline,andethanolwere0.220.41,0.200.31,and7.512g/kWh,respectively(6).Usingthe
sametwostrokeengine,emissionsofacetaldehydefromaliphaticgasolinemixedwithethanolat15,50,and85%
were1.22.0,3.75.9,and6.710g/kWh,respectively,andregulargasolinemixedwithethanolat15,50,and85%
were1.21.8,3.76.4,and6.210g/kWh,respectively(6).Acetaldehydewasmeasuredintheemissionsofgasoline
poweredmotorvehiclesatarateof3940ug/kmand301,000ug/kmforcatalystequippedenginesandnoncatalyst
equippedengines(7).AcetaldehydeemissionsfromanautomobilerunningonSwedishenvironmentalclassified
dieselfuelwere19.1mg/kmandthesameautomobilerunningonEuropeanprogramemissionsfuelwerealso15.5
mg/km(8).
(1)VerschuerenKHandbookofEnvironmentalDataonOrganicChemicals.4thedNY,NY:JohnWileyandSonsInc,pp.957
(2001)(2)DestaillatsHetalEnvironSciTechnol36:222735(2002)(3)GabelePA,PyleSMEnvironSciTechnol34:368
72(2000)(4)GrosjeanDetalEnvironSciTechnol35:4553(2001)(5)KawamuraKetalAtmosEnviron34:417591(2000)
(6)MagnussonRetalEnvironSciTechnol36:165664(2002)(7)SchauerJJetalEnvironSciTechnol36:116980(2002)
(8)WesterholmRetalEnvironSciTechnol35:174854(2001)
AcetaldhydewasdetectedintheeffluentfromchemicalplantsintoMobileRiver(Alabama)andPacoletand
EnoreeRiver(SouthCarolina)(1).Effluentfromsewagetreatmentplantscontainedacetaldehye(1),althoughithas
notbeendeterminedwhethertheacetaldehydewasintheinfluentorformedasaproductofmicrobial
degradation(2).
(1)ShackelfordWM,KeithLHFrequencyofOrganicCompoundsIdentifiedinWater.USEPA600/476062(1976)(2)National
ResearchCouncilFormaldehydeandOtherAldehydespp.352USEPA600/682002(1982)
Acetaldehydewasemittedfromsixnewvehicleinteriorsatanaverageof44ug/hourinnewvehicles,30ug/hrin20
dayoldvehiclesand29ug/hourin40dayoldvehicles(1).Acetaldehydewasmeasuredinthegasesofmedium
class1998modelautomobilefirewithaconcnof0.53g/kgwithatotalconcnof63g(2).Acetaldehydewas
releasedasfireplaceemissionsat301and450mg/kgoffuelburntforsoftandhardwood,respectively(3).
Acetaldehydewasfoundinemissionsfromawoodstoveusinghardwoodat360mg/kgandusingsyntheticfuelat
45mg/kg(3).Acetaldehydewasdetectedincoffeeroastingoperations(range,1422mg/cum),fromalithographic
platecoater(range,0.54.1mg/cum),fromanautomobilespraybooth(range,2.53.4mg/cum),fromplants
manufacturingacrylicacid(concnsunspecified),andfromafatrenderingplant(range,3.46.8mg/cum)(4).The
emissionofacetaldehydefromanewcarpetwasmeasuredinalargescaleenvironmentalchamberthespecific
massemissionofacetaldehydefromatexturedloop,100%nylon6,solutiondyedcarpetovera168hourperiod
was2.52mg/sqm(5).Theemissionrateofacetaldehydeduringtheoperationofdryprocessphotocopiersranged
frombelowthedetectionlimitto1,600ug/hrpercopier(6).Acetaldehydemayreach2040%ofvolatilesgivenoffof
waterbasedadhesivesfortextilewallcoveringsandinfloorcleaningproducts(7).Acetaldehydeisemittedfrom
PVCcoatedcorktile(8).Acetaldehydewasmeasuredintheemissionsofburntwoodat1704,823,and1021mg/kg
ofpine,oak,andeucalyptus,respectively(9).
(1)BauhofH,WnsingMinOrganicIndoorAirPollutants.Occurrence,Measurement,Evaluation,SalthammerT,ed.,Wiley
VCH:NY,NYpp10515(1999)(2)LonnermarkA,BlomqvistPChemosphere62:104356(2005)(3)McDonaldJDetal
EnvironSciTechnol34:208091(2000)(4)IARCMonographsontheEvaluationoftheCarcinogenicRiskofChemicalsto
Man.Geneva,Switzerland:WHO36:107(1985)(5)HodgsonATetalJAirWasteManageAssoc43:31624(1993)(6)
LeovicKetalJAirWasteManageAssoc48:91523(1998)(7)PersonAetalinIndoorAir'90:Proc5thIntConfIndoorAir
QualClimate:Toronto,29July3August1990pp.60510(1990)(8)SaarelaKinOrganicIndoorAirPollutants,Occurrence,
Measurement,Evaluation.SalthammerT,ed.,WileyVCH:NY,NYpp185202(1999)(9)SchauerJJetalEnvironSci
Technol35:171628(2001)
10.2.13 AtmosphericConcentrations
RURAL/REMOTE:Theavgconcnofacetaldehydeovera24hrperiodatPtBarrows,Alaskawas0.24ppb,witha
rangeof00.3ppbin7of25samplespositivesamples(1).AttworuralsitesnearTuscon,AZ18sampleshada
meanconcnof6.9ppbforacetaldehyde(2).Acetaldehyde,analyzedoutsideofAthens,Greece,JunetoDecember
2000,wasdetectedatLikovrisiatconcnsof2.721.3ug/cum(3).Acetaldehydewasdetectedinthearctic
atmosphereboundary,insamplestakenFeb16andApril22,2000atapproximately100and50parts/trillion,
respectively(4).Acetaldehyde,testedMarchandApril1998inBalbina,Amazonia,wasmeasuredat<1ppb(5).
Acetaldehydewasdetectedat0.076.8ug/cuminFortMorris,GAinsamplestakenDec1995toNov1996(6).In
studiesacrossNorthAmerica,acetaldehydewasdetectedat0.110.22ug/cum(Alert,NorthwestTerritories,
Canada,Barrow,AK,NiwotRidge,CO,KumukahandMaunaLoa,HI)(7).Acetaldehydewasdetectedinall2479
samplesinurban/suburbanandrural/remotelocationsthroughoutMNatconcnsof1.148.76ug/cum(8).
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(1)CavanaghLetalEnvironSciTechnol3:2517(1969)(2)SniderJR,DawsonGAJGeophysRes90:3797805(1985)(3)
BakeasEBetalChemosphere52:80513(2003)(4)GuimbaudCetalAtmosEnviron36:274352(2002)(5)KesselmeierJ
etalAtmosEnviron34:406372(2000)(6)MacintoshDLetalEnvironMonitAssess63:40929(2000)(7)McCarthyMCet
alJAirWasteManageAssoc56:311(2005)(8)PrattGCetalEnvironHealthPerspect108:81525(2000)
URBAN/SUBURBAN:TheannualavgconcnofacetaldehydebetweenJuly1982May1983atBrookhavenNational
Laboratory,Upton,NYwas2.9ppbv(1)seasonalmeanlevelsofacetaldehydeare1,8.4,3.5,and3.2ppbin
Winter,Spring,Summer,andFall,respectively(1).AttheUniversityofSouthernCalifornia,LosAngeles,CA,the
concnofacetaldehydewas239ppbv(2).AttheUCLAcampus,LosAngeles,CAduringlighttomoderatesmog,
theconcnofacetaldehydewas032ppb(3).AtClaremont,CAduringseveresmog,theconcnofacetaldehyde(day
ornighttime)was335ppbtheconcninairparticulatematterwas2406ng/cum(3).Ina1985studyin
Claremont,CAforoverfivedaysinSept,acetaldehydeconcnswere1.09.0ppbwithamedianconcnof4.0
ppb(4)highestvalueswereobservedintheafternoons(4).AoneyearstudyatsixlocationsinsouthernCalifornia
found24hrambientlevelsreaching13ppbandlocationavgvaluesof2.94.8ppb(5).AtTuscon,AZ,themean
concnofacetaldehydewas23ppb(6).ThemeanconcnofacetaldehydeatfiveUScitieswere:Pittsburgh,1.4ppb
Chicago,2.1ppbDowney,CA,8.5ppbHouston,2.2ppbDenver,1.0ppb(7).Ambientlevelsofacetaldehyde
from24sampleswerecollectedeverydayat6SouthernCalifornialocationsbetweenSept2,1988andSept25,
1989avgconcnsinAnaheim,Azusa,Burbank,Hawthorne,Upland,andW.LosAngeleswere3.5ppb(max,7.8
ppb),3.1ppb(max,7.7ppb),4.8ppb(max,10.0ppb),2.9ppb(max,9.4ppb),3.9ppb(max,13.2ppb),and3.8
ppb(max,9.3ppb),respectively(8).ThemeanconcnofacetaldehydeinoutdoorsuburbanairfromcentralNJinJun
21toAug5,1992was2.64ppbwitharangeof0.99to12.66ppb(9).AcetaldehydewasdetectedinLasAngeles
(UCLAcampus,MontereyPark,NewberryPark,LaHabra)at0.231.58ppbvinsamplestakenOct1984(10).
Acetaldehydewasdetectedin36winterand36summer,1999,NewYorkCitysamplesat2.78and4.15ug/cum,
respectively(11).Acetaldehydewasdetectedat0.086.70,0.087.60,0.086.90,and0.087.40ug/cumatafire
station,LathropAve,PresidentSt.,andthewaterworksinSavannah,GAinsamplestakenDec1995toNov
1996(12).Acetaldehydewasdetectedin13of13samplestakenacrosstheUS(3inLA,4inTX,5inVT,1inNJ)
fromSept1996toAug1997at1>10ppb(13).Acetaldehydewasdetectedinall2479samplesinurban/suburban
andrural/remotelocationsthroughoutMNatconcnsof1.148.76ug/cum(14).In584samplesfrom21sitesacross
CA,taken1989to1990,acetaldehydewasfoundatconcnsof0.1113ppb(15).
(1)TannerRL,MengZEnvironSciTechnol18:7236(1984)(2)GrosjeanD,FungKJAirPollutControlAssoc34:53743
(1984)(3)GrosjeanDEnvironSciTechnol16:25462(1978)(4)GrosjeanDAtmosEnviron22:163748(1988)(5)Grosjean
DEnvironSciTechnol25:7105(1991)(6)SniderJR,DawsonGAJGeophysRes90:3797805(1985)(7)SalasLJ,Singh
HBAtmosEnviron20:13014(1986)(8)GrosjeanDEnvironSciTechnol25:71015(1991)(9)ZhangJetalEnvironSci
Technol28:14652(1994)(10)KawamuraKetalAtmosEnviron34:417591(2000)(11)KinneyPLetalEnvironHealth
Perspect110:53946(2002)(12)MacintoshDLetalEnvironMonitAssess63:40929(2000)(13)MohamedMFetal
Chemosphere47:86382(2002)(14)PrattGCetalEnvironHealthPerspect108:81525(2000)(15)LoscutoffWV,Poore
MWAmbientAirToxicsDataFromCalifornia'sToxicAirContaminantMonitoringProgram.ManagingHazardousAir
PollutantsStateoftheArt:191203(1993)
URBAN/SUBURBAN:Acetaldehyde,analyzedinAthens,Greece,JunetoDecember2000,wasdetectedat
PatissionStreetatconcnsof4.349ug/cum(1).AcetaldehydewasdetectedinairfromSanPaulo,Brazilat2.37
ppbinsamplestakenJuly1988(2)andGrenoble,Franceat110ppbinsamplestakenMay1995(3).Theconcnof
acetaldehydeinairfromRome,Italyrangedfrom3.117.4ppbbetweenJunJul1994andfrom2.96.6ppb
betweenJanMar1995(4).TheconcnofacetaldehydeattheUnivofMexicocampusbetweenMarMay1993was
2.066.7ppb(5).AcetaldehydewasdetectedinLilleValby,Denmarkatconcnsof0.23.6ppbvinsamplestaken
MaytoJuly1995(6).Acetaldehydewasdetectedataverageconcnsof3.42620.627ug/cuminRiodeJaneiro,
BrazilOct1999toNov2000(7).Acetaldehydewasdetectedatanavgconcnof9ug/cumin5%ofsamplestaken
inPingTungandat7ug/cumin3%ofsamplestakeninChaoChou,Taiwan(8).Acetaldehydewasdetectedat1.5
ppbin13of13HelsinkisamplestestedMaytoSep1997(9).RoadsidesamplestakennearHongKongPolytechnic
Universityhadconcnsofacetaldehydeof0.166.75ug/cuminsamplestakenApril1999toApril2000(10).
Acetaldehydewasdetectedat0.622.0ppbvinsamplestakenatthetopofan11storybuildingonthecampusof
HongKongUniversityScienceandTechnology(11).Acetaldehydewasdetectedinsamplestakenin1999,inSao
PauloCity,BrazilatAquaFundaandCidadeUniversityat1.450.9and1.256.6ppbv,respectively(12).
AcetaldehydewasdetectedinSantiago,Chileatmosphericsamplesat0.723.2ppbvinNov2003(13).
Acetaldehydewasdetectedat1.37,2.65,and2.71ug/cuminFrohnau,Nansenstrasze,andFrankfurterAllea,
respectively,inBerlin,GermanyfromsamplestakenJunAug1996(14).
(1)BakeasEBetalChemosphere52:80513(2003)(2)GrosjeanDetalAtmosEnviron24B:1016(1990)(3)FerrariCPet
alChemosphere37:15871601(1998)(4)PossanziniMetalAtmosEnviron30:375764(1996)(5)BaezAPetalEnviron
Pollut89:1637(1995)(6)ChristensenCSetalAtmosEnviron34:28796(2000)(7)GrosjeanDetalEnvironSciTechnol
36:138995(2002)(8)HsiehCC,TsaiJHChemosphere50:54556(2003)(9)JurvelinJAetalJAirWasteManageAssoc
53:56073(2003)(10)HoKF,LeeSCSciTotalEnviron289:14558(2002)(11)HoSSH,YuJZEnvironSciTechnol38:862
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70(2004)(12)MonteroLetalEnvironSciTechnol35:307181(2001)(13)RubioMAetalChemosphere62:101120(2005)
(14)ThijsseTRetalJAirWasteManageAssoc49:1394404(1999)
SOURCEDOMINATED:IntheUS,therangeandmedianconcnsofacetaldehydeatsourcedominatedlocations
were2.0to69ppb,and7.8ppb(36samples),respectively(1).Acetaldehyde,emittedfromautomobiles,was
detectedinattachedgaragesof16housesovertwowintersatconcnsof0.3662.6ng/L(2).Acetaldehydewas
detectedinkitchenexhaustatconcnsof24.756.9ppbv(3).
(1)BodzinskyRSinghHBVolatileOrganicChemicalsintheAtmosphere:AnAssessmentofAvailableData.MiloPark,CA:
SRIIntp.19868023452(1982)(2)GrahamLAetalJAirWasteManageAssoc54:56384(2004)(3)HoSSH,YuJZ
EnvironSciTechnol38:86270(2004)
RURAL/REMOTE:Theavgconcnofacetaldehydeovera24hrperiodatPtBarrows,Alaskawas0.24ppb,witha
rangeof00.3ppbin7of25samplespositivesamples(1).AttworuralsitesnearTuscon,AZ18sampleshada
meanconcnof6.9ppbforacetaldehyde(2).Acetaldehyde,analyzedoutsideofAthens,Greece,JunetoDecember
2000,wasdetectedatLikovrisiatconcnsof2.721.3ug/cum(3).Acetaldehydewasdetectedinthearctic
atmosphereboundary,insamplestakenFeb16andApril22,2000atapproximately100and50parts/trillion,
respectively(4).Acetaldehyde,testedMarchandApril1998inBalbina,Amazonia,wasmeasuredat<1ppb(5).
Acetaldehydewasdetectedat0.076.8ug/cuminFortMorris,GAinsamplestakenDec1995toNov1996(6).In
studiesacrossNorthAmerica,acetaldehydewasdetectedat0.110.22ug/cum(Alert,NorthwestTerritories,
Canada,Barrow,AK,NiwotRidge,CO,KumukahandMaunaLoa,HI)(7).Acetaldehydewasdetectedinall2479
samplesinurban/suburbanandrural/remotelocationsthroughoutMNatconcnsof1.148.76ug/cum(8).
(1)CavanaghLetalEnvironSciTechnol3:2517(1969)(2)SniderJR,DawsonGAJGeophysRes90:3797805(1985)(3)
BakeasEBetalChemosphere52:80513(2003)(4)GuimbaudCetalAtmosEnviron36:274352(2002)(5)KesselmeierJ
etalAtmosEnviron34:406372(2000)(6)MacintoshDLetalEnvironMonitAssess63:40929(2000)(7)McCarthyMCet
alJAirWasteManageAssoc56:311(2005)(8)PrattGCetalEnvironHealthPerspect108:81525(2000)
INDOORAIR:Theconcnofacetaldehydein14homesandasmallofficebuildinginnorthernItalywas148ug/cu
mwithameanconcnof17ug/cum(1).Theratiooftheminimum,maximum,mean,andmedianconcninindoor
versusoutdoorairwas0.5,24,6.0,and3.6,respectively(1).TheconcnofacetaldehydemeasuredinEPA
headquartersbuildinginWashington,DCwas3.811.1ug/cumwithamedianvalueof5.2ug/cum(2).
Acetaldehydewasdetectedatameanconcnof2.42ug/cumin345samplestakenat15UStruckingterminals
sampled2004to2006(3).Acetaldehydewasfoundatconcnsof319ppbinnewmanufacturedandat1257ppbin
sitebuilthouses(4).Acetaldehydewasfoundin15of15indoorresidencesatavgconcnof10.1ppband9of9
workplacesatavgconcnof2.6ppbinHelsinkisamplestestedMaytoSep1997(5).Acetaldehydewasdetectedin
agreenhouseontheUCLAcampus,LosAngeles,CAat0.240.36ppbv(6).Acetaldehydewasdetectedin36
winterand41summerindoor,NewYorkCitysamples(WestCentralHarlemHighSchool)at15.6and14.98ug/cu
m(7).Acetaldehydewasreportedatlevelsof17mg/cumintheworkroomairofanaldehydefactoryinGermany
afterequipmentleakages(8).
(1)DeBortoilMetalEnvironInternat12:34350(1986)(2)USEPAIndoorAirQualityandWorkEnvironmentStudy.EPA
HeadquartersBuildingsVol.2:ResultsofIndoorAirEnvironmentalMonitoringStudy.ResearchTrianglePark,NC:AtmosRes
ExposAssesLab(1990)(3)DavisMEetalEnvironSciTechnol41:71528(2007)(4)HodgsonATetalIndoorAir10:17892
(2000)(5)JurvelinJAetalJAirWasteManageAssoc53:56073(2003)(6)KawamuraKetalAtmosEnviron34:417591
(2000)(7)KinneyPLetalEnvironHealthPerspect110:53946(2002)(8)IARCMonographsontheEvaluationofthe
CarcinogenicRiskofChemicalstoMan.Geneva,Switzerland:WHO36:106(1985)
10.2.14 FoodSurveyValues
Theacetaldehydeconcnin18Europeanbeerswasreportedtorangefrom2.613.5mg/L..../Itwasdetected/in
commercialwinesamplesinJapanatlevelsof0.21.2mg/L.IthasalsobeenidentifiedinCubaintheaqueous
condensateobtainedfromtheconcentrationofsweetorangejuice.Acetaldehydehasbeendetectedincheese,
heatedskimmilk,cookedbeef,cookedchicken,andrum.Tracequantities...arepresentinaflavoringusedto
impartabutterlikeflavortoprocessedfoods,especiallymargarine.
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Acetaldehydewasdetectedbutnotquantifiedinpineapples,apples,grapefruit,bananas,peaches,pears,
blackcurrants,strawberries,oranges,grapesandraspberries(1).Acetaldehydewasdetectedincoffee(2),kiwi
fruit(3),chickenbreast(4),androastedfilberts(5).Theacetaldehydeconcnin18Europeanbeerswasreportedto
rangefrom2.613.5mg/L(6).AcetaldehydewasdetectedincommercialwinesamplesinJapanatlevelsof0.21.2
mg/L(6).AcetaldehydehasalsobeenidentifiedinCubaintheaqueouscondensateobtainedfromtheconcnof
sweetorangejuice(6).Acetaldehydehasbeendetectedincheese,heatedskimmilk,cookedbeef,cookedchicken,
andrum(6).Tracequantitiesofacetaldehydearepresentinaflavoringusedtoimpartabutterlikeflavorto
processedfoods,especiallymargarine(6).Theconcnsofacetaldehydeincookedsweetcornproducts,suchas
cannedcream,cannedkernel,frozenkernel,andfreshkernel,were1.4,1.0,1.2,and1.7ppm,respectively(7).The
concnofacetaldehydeinpopcornwas4.6mg/kg(8).InJapan,acetaldehydewasdetectedinsakeat14.860.2
ppm,wineat32.865.9ppm,beerat5.2311.7ppm,whiskeyat25.0102.0ppm,applejuiceat11.8ppm,nonfat
milkat0.82ppm,wholemilkat1.65ppm,colaat0.461ppm,rootbeerat0.579ppm,orangejuiceat9.82ppm,
nonfatyogurtat5.28ppm,soysauceat4.33ppm,instantcoffeeat1.09ppm,roastedcoffeebeansat1.08ppm,
instantteaat0.585ppm,cocoaat0.616ppm,andgreenteaat0.472ppm(9).Acetaldehydewasgivenoffof
soybeanoil,peanutoil,andlardatratesof0.031.55,0.031.36,and0.041.04ppm/mgminwhenheatedto150
400degC(10).
(1)NationalResearchCouncilFormaldehydeandOtherAldehydespp.352USEPA600/682002(1982)(2)AeschbacherHU
etalFoodChemToxicol27:22732(1989)(3)BartleyJP,SchwedeAMJAgricFoodChem37:10235(1989)(4)GreyTC,
SchrimptonDHBritPoultrySci8:233(1967)(5)KinlinTEetalJAgricFoodChem20:1021(1972)(6)IARCMonographs
ontheEvaluationoftheCarcinogenicRiskofChemicalstoMan.Geneva,Switzerland:WHO36:108(1985)(7)ButteryRGet
alJAgricFoodChem42:7915(1994)(8)ButteryRGetalJAgricFoodChem45:83742(1997)(9)MiyakeT,ShibamotoT
JAgricFoodChem41:196870(1993)(10)LinJM,LiouSJBullEnvironContamToxicol64:81724(2000)
10.2.15 PlantConcentrations
Acetaldehydeisfoundinplantssinceitisanintermediateproductofrespirationinhigherplants(1).Acetaldehydeis
foundinallripefruitsthathavetarttastesbeforeripening(1).Acetaldehydewasdetectedintheemissionsof
quakingaspen,cottonwood,Gambeloak,Douglasfir,Engelmannspruce,RockyMountainJuniper,Pinyonpine,
andponderosapineatratesof1122,5464,49,588,111,106,49,and286494ng/ghourintreesfromCibola
NationalForestinSocorro,NMtestedthesummerof1996(2).Acetaldehydewasemittedfromrapeduringthe
bloomingperiodatarateof1.19and1.81ppbvduringMay8and9,1998(3).
(1)HagemeyerHJKirkOthmerEncyclChemTechnol4thed.NY,NY:JohnWileyandSons1:94109(1991)(2)MartinRSet
alEnvironSciTechnol33:218692(1999)(3)MullerKetalChemosphere49:124756(2002)
10.2.16 AnimalConcentrations
Acetaldehyeisproducedatanintermediatelevelofsugarmetabolism,althoughnospecificdataonlevelsin
animalscouldbefoundintheliterature.
KirkOthmerEncyclopediaofChemicalTechnology.3rded.,Volumes126.NewYork,NY:JohnWileyandSons,19781984.,
p.V1:97(1978)
10.2.17 MilkConcentrations
ENVIRONMENTAL:Fourofeightsamplesofmother'smilkwerepositiveforacetaldehyde(1).Acetaldehydehas
beendetectedinheatedskimmilk(2).InJapan,acetaldehydewasdetectedinnonfatmilkat0.82ppmandwhole
milkat1.65ppm(3).
(1)PellizzariEDetalBullEnvironContamToxicol28:3228(1982)(2)IARCMonographsontheEvaluationofthe
CarcinogenicRiskofChemicalstoMan.Geneva,Switzerland:WHO36:108(1985)(3)MiyakeT,ShibamotoTJAgricFood
Chem41:196870(1993)
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10.2.18 OtherEnvironmentalConcentrations
Acetaldehydeisdetectedincigarettesmokeatconcnsof0.181.44mg/cigarette(1).Environmentaltobaccosmoke
wasanalyzedaftersmokingofresearchcigarettesbyamachineinanexperimentalchamber13.6cumin
volume(2).Acetaldehydeconcns(ug/cum)were16and12withnosmoking,87and94withonecigaretteevery30
min,and205and233withonecigaretteevery15min(2).Concnsofacetaldehydeusingcommercialbrandsof
cigarettesinthechamberandinatavernsettingweresimilartothoseproducedbytheresearchcigarettes(2).
Acetaldehydehasbeendetectedinmarijuanacigarettesataconcnof1,200ug/cigarette(3).Acetaldehydewas
detectedintobaccosmokeatconcnsof600700ug/cum(4).
(1)NationalResearchCouncilFormaldehydeandotherAldehydepp.352USEPA600/682002(1982)(2)LofrothGetal
EnvironSciTechnol23:6104(1989)(3)IARCMonographsontheEvaluationoftheCarcinogenicRiskofChemicalstoMan.
Geneva,Switzerland:WHO36:108(1985)(4)ShaughnessyRJetalEnvironSciTechnol35:275864(2001)
10.2.19 ProbableRoutesofHumanExposure
NIOSH(NOESSurvey19811983)hasstatisticallyestimatedthat216,533workers(97,770ofthesewerefemale)
werepotentiallyexposedtoacetaldehydeintheUS(1).Occupationalexposuretoacetaldehydemayoccurthrough
inhalationanddermalcontactwiththiscompoundatworkplaceswhereacetaldehydeisproducedorused.
Monitoringdataindicatethatthegeneralpopulationmaybeexposedtoacetaldehydeviainhalationofambientair,
ingestionoffoodandbeverages,anddermalcontactwithproductscontainingacetaldehyde(SRC).
(1)NIOSHNOES.NationalOccupationalExposureSurveyconductedfrom19811983.Estimatednumbersofemployees
potentiallyexposedtospecificagentsby2digitstandardindustrialclassification(SIC).Availableathttp://www.cdc.gov/noes/
asofJan2009.
Personalairsamplestakenfrom15UStruckingterminalsfoundacetaldehydemeanconcnsof5.63,8.78,6.27,
and45.00ug/cumin234nonsmokingdrivers,62smokingdrivers,65loadingdockworkers,and17mechanicshop
workers,respectively(1).Acetaldehydewasfoundin15of15personalairsamplesatameanconcnof7.9ppbfrom
samplestakeninHelsinki,testedMaytoSep1997(2).Acetaldehydewasdetectedin36winterand42summer
personalairsamplesfromWestCentralHarlemHighSchoolstudentsat13.0and20.2ug/cumin1999(3).
(1)DavisMEetalEnvrionSciTechnol41:17528(2007)(2)JurvelinJAetalJAirWasteManageAssoc53:56073(2003)
(3)KinneyPLetalEnvironHealthPerspect110:53946(2002)
10.2.20 AverageDailyIntake
InSwedenbetweenDec1986toAug1987,themeanyearlyexposuretoacetaldehydefromairpollutionwas1.0
ug/cum(1).
(1)BostromCEetalEnvironHealthPerspect102:3947(1994)
10.2.21 BodyBurdens
FourofeightsamplesofMother'smilkwerepositiveforacetaldehyde(1).Theconcnofacetaldehydeinexhaled
humanbreathrangedfrom3to7ppbfor3subjectsbreathingmedicalair5minpriortomeasurement(2)theconcn
ofacetaldehydeinexhaledhumanbreathrangedfromnotdetectedto89.5ppbfor8subjectsbreathingpurified
air(2).Inanotherstudy,theconcnofacetaldehydeinexpiredairfromhumansubjectsrangedfrom8.5to79.0
ug/hr(3).Acetaldehyeisproducedatanintermediatelevelofsugarmetabolisminthebodyandthereforeoccursin
tracequantitiesinblood(4).Acetaldehydeistheprimaryhepaticoxidativemetaboliteofethanol(5).
(1)PellizzariEDetalBullEnvironContamToxicol28:3228(1982)(2)FenskeJD,PaulsonSEJAirWasteManageAssoc
49:5948(1999)(3)ConkleJPetalArchEnvironHealth30:2905(1975)(4)HagemeyerHJKirkOthmerEncyclChem
Technol.4thed.NY,NY:Wiley1:94109(1991)(5)KarlPIetalScience242(4876):2735(1988)
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11 Literature
11.1 DepositorProvidedPubMedCitations
DepositorProvidedPubMedCitationCount(4456)
11.2 NLMCuratedPubMedCitations
AllNLMCuratedPubMedCitations
ReferencesbyMeSHSubheading
administrationanddosage
chemistry
physiology
adverseeffects
classification
poisoning
agonists
deficiency
radiationeffects
analogsandderivatives
diagnosticuse
secretion
analysis
economics
standards
antagonistsandinhibitors
immunology
therapeuticuse
biosynthesis
isolationandpurification
toxicity
blood
metabolism
urine
cerebrospinalfluid
pharmacokinetics
chemicalsynthesis
pharmacology
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12 Patents
12.1 DepositorSuppliedPatentIdentifiers
Refine/Analyze
1to10of111,837
3 ... 11,184
Download
Relevance
Patent
Submitted
Substitutednorbornaneperfumecompositions[US4123393]
19781031
Tricyclo{85.2.1.0{hu2,6{b{9decanemethyloloritsloweralkyloralkenylesterorether
derivativesinperfumecompositions[US4123394]
19781031
Compositionscontainingnonionicsurfactantandsulfonatedaromaticcompatibilizing
agent[US4123395]
19781031
HeatstabilizedPVCcompositions[US4123400]
19781031
Stabilizersystemforstabilizingstyrenepolymers[US4123418]
19781031
Metallizedpolyazodyesderivedfromacouplingcomponentobtainedbyacidic
condensationofformaldehydewithatleastonephenoliccompound[US4123428]
19781031
2Methyl5fluoroindanol3aceticacid[US4123457]
19781031
Preparationofcisandtransaconiticacidsandtheirsalts[US4123458]
19781031
Processforthepreparationofaldehydes[US4123464]
19781031
Antibacterialoralcomposition[US4123512]
19781031
Granted
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13 BiomolecularInteractionsandPathways
13.1 ProteinBound3DStructures
Refine/Analyze
MMDBID:116463
MMDBID:116462
MMDBID:115958
Download
MMDBID:114790
13.2 BiosystemsandPathways
Download
1to10of35,043
3 ... 3,505
BioSystem
superpathwayofthreoninemetabolism[22]
ethanoldegradationI[136]
threoninedegradationIV[169]
3phenylpropionateand3(3hydroxyphenyl)propionatedegradation[174]
2oxopentenoatedegradation[178]
superpathwayofpurinedeoxyribonucleosidesdegradation[215]
superpathwayofpyrimidinedeoxyribonucleosidesdegradation[216]
mixedacidfermentation[236]
Glycolysis/Gluconeogenesis[287]
Phenylalaninemetabolism[327]
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14 BiologicalTestResults
14.1 BioAssayResults
Refine/Analyze
1to10of259
Activity
Substance
3 ... 26
Download
Relevance
BioAssay
inactive
17390069
Potency
qHTSAssayforIdentifyingtheCellMembranePermeableIMPaseInhibitors:
PotentiationwithLithium[AID:1457]
inactive
17390069
Potency
qHTSAssayforInhibitorsofTyrosylDNAPhosphodiesterase(TDP1)[AID:485290]
inactive
17390069
Potency
qHTSAssayforInhibitorsof12hLO(12humanlipoxygenase)[AID:1452]
inactive
17390069
Potency
qHTSAssayforEnhancersofSMN2SpliceVariantExpression[AID:1458]
active
48413129
DSSTox(CPDBAS)CarcinogenicPotencyDatabaseSummaryMultiCellCallResults
[AID:1205]
active
48413129
DSSTox(CPDBAS)CarcinogenicPotencyDatabaseSummarySingleCellCallResults
[AID:1189]
active
48413129
DSSTox(CPDBAS)CarcinogenicPotencyDatabaseSummaryHamsterBioassay
Results[AID:1191]
inactive
48413129
DSSTox(CPDBAS)CarcinogenicPotencyDatabaseSalmonellaMutagenicity[AID:
1194]
active
48413129
DSSTox(CPDBAS)CarcinogenicPotencyDatabaseSummaryRatBioassayResults
[AID:1208]
active
48414938
DSSTox(EPAFHM)EPAFatheadMinnowAcuteToxicity[AID:1188]
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15 Classification
15.1 Ontologies
15.1.1 MeSHTree
Refine/Analyze
ListView
1to1of1
Download
TreeView
Acetaldehyde
fromMeSH[11]http://www.nlm.nih.gov/mesh/meshhome.html
15.1.2 ChEBIOntology
Refine/Analyze
ListView
1to2of2
Download
TreeView
acetaldehyde
alkanal
fromChEBI[12]http://www.ebi.ac.uk/chebi/userManualForward.do#ChEBI%20Ontology
15.1.3 GeneOntology:BiologicalProcess
Refine/Analyze
ListView
1to4of4
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TreeView
thyroidhormonereceptorbetaisoform2[Rattusnorvegicus]
estrogennuclearreceptoralpha[Homosapiens]
ARprotein[Homosapiens]
cytochromeP450,family19,subfamilyA,polypeptide1,isoformCRA_a[Homosapiens]
fromGeneOntology[14]http://amigo.geneontology.org/amigo/term/GO:0008150
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15.1.4 GeneOntology:CellularComponent
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15.1.5 GeneOntology:MolecularFunction
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ListView
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ARprotein[Homosapiens]
cytochromeP450,family19,subfamilyA,polypeptide1,isoformCRA_a[Homosapiens]
15.1.6 KEGG:Carcinogen
Refine/Analyze
ListView
1to1of1
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TreeView
Acetaldehyde
fromKEGG[13]http://www.genome.jp/dbgetbin/www_bget?brite:br08008
15.1.7 WIPOIPC
Refine/Analyze
Download
111/114
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1to10of18,999
ListView
3 ... 1,900
TreeView
A61P11/04forthroatdisorders
A61P11/06Antiasthmatics
A61P11/08Bronchodilators
A61P11/10Expectorants
A61P11/12Mucolytics
A61P11/14Antitussiveagents
A61P11/16Centralrespiratoryanaleptics
A61P13/00Drugsfordisordersoftheurinarysystem
A61P13/02ofurineoroftheurinarytract,e.g.urineacidifiers
A61P13/04forurolithiasis
fromWIPO[17]http://www.wipo.int/classifications/ipc/
15.2 SubstanceCategorizationClassification
Download
BioassayScreeningResults(2)
BiologicalProperties(12)
ChemicalReactions(3)
DatabaseVendor(2)
JournalPublishers(3)
MetabolicPathways(4)
NIHMolecularLibraries(2)
Patents(247)
PhysicalProperties(14)
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Protein3DStructures(34)
SubstanceVendors(54)
TheoreticalProperties(4)
Toxicology(8)
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16 InformationSources
1. ACETALDEHYDEfromHSDB230http://toxnet.nlm.nih.gov/cgibin/sis/search/r?
dbs+hsdb:@term+@rn+@rel+75070
2. AcetaldehydefromEPAChemicalDataReport75070http://www.epa.gov/cdr/
3. ACETALDEHYDEfromILOICSC0009http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=0009
PeerReviewStatus:27.11.2003Validated
4. AcetaldehydefromNIOSHPocketGuidenpgd0001http://www.cdc.gov/niosh/npg/npgd0001.html
5. ACETALDEHYDEfromOSHAOccupationalChemicalDB570
http://www.osha.gov/chemicaldata/chemResult.html?RecNo=570
6. ECHA2008368http://echa.europa.eu/
7. Wiki313http://en.wikipedia.org/wiki/Acetaldehyde
8. FDA/SPLIndexingdataGO1N1ZPR3B
http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm377913.htm
9. PubChemhttp://pubchem.ncbi.nlm.nih.gov
DatadepositedinorcomputedbyPubChem
10. AcetaldehydefromMeSH68000079http://www.ncbi.nlm.nih.gov/mesh/68000079
11. MeSHTreefromMeSHDescTreehttp://www.nlm.nih.gov/mesh/meshhome.html
MeSH(MedicalSubjectHeadings)istheNLMcontrolledvocabularythesaurususedforindexingarticlesforPubMed.
12. ChEBIOntologyfromChEBIOBOhttp://www.ebi.ac.uk/chebi/userManualForward.do#ChEBI%20Ontology
TheChEBIOntologyisastructuredclassificationoftheentitiescontainedwithinChEBI.
13. CarcinogenfromKEGGbr08008http://www.genome.jp/dbgetbin/www_bget?brite:br08008
Carcinogens
14. biologicalprocessfromGeneOntologyGO_ROOT_486550
http://amigo.geneontology.org/amigo/term/GO:0008150
TheGeneOntology(GO)http://www.geneontology.org/projectprovidesacontrolledvocabularyoftermsfordescribingthe
functionsofgeneproducts,andisdividedintothreedomains.Eachterminthebiologicalprocessesdomain,shownhere,
representsrecognizedseriesofevents,oracollectionofmoleculareventswithadefinedbeginningandend.Mutant
phenotypesoftenreflectdisruptionsinbiologicalprocesses.Thetermsbelowapplytothegene/proteintarget(s)testedby
theBioAssay.
15. cellularcomponentfromGeneOntologyGO_ROOT_486551
functionsofgeneproducts,andisdividedintothreedomains.Thecellularcomponentsdomain,shownhere,describes
locations,atthelevelsofsubcellularstructuresandmacromolecularcomplexes.Anexampleofacellularcomponentisthe
nuclearinnermembrane,withthesynonyminnerenvelope.Generally,ageneproductislocatedinorisasubcomponentofa
particularcellularcomponent.Thetermsbelowapplytothegene/proteintarget(s)testedbytheBioAssay.
16. molecularfunctionfromGeneOntologyGO_ROOT_486552
functionsofgeneproducts,andisdividedintothreedomains.Eachterminthemolecularfunctionsdomain,shownhere,
representaprotein'sjobsorabilities.Thesemayincludetransportingthingsaround,bindingtothings,holdingthingstogether
andchangingonethingintoanother.Thisisdifferentfromthebiologicalprocessesthegeneproductisinvolvedin,which
involvemorethanoneactivity.Thetermsbelowapplytothegene/proteintarget(s)testedbytheBioAssay.
17. InternationalPatentClassification2015fromWIPOIPChttp://www.wipo.int/classifications/ipc/
TheWorldIntellectualPropertyOrganization(WIPO)InternationalPatentClassification(IPC)providesforahierarchical
systemoflanguageindependentsymbolsfortheclassificationofpatentsandutilitymodelsaccordingtothedifferentareasof
technologytowhichtheypertain.
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