BackgroundPaper BP-395E

LAUNDRY DETERGENT: THE TOXICOLOGYAND CARCINOGENICITY OF NTA

William MurrayScienceandTechnologyDivision

January1995

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~LAUNDRY DETERGENT: THE TOXICOLOGYAND CARCINOGENICITY OF NTA

iNTRODUCTION *

American oncology studies during the mid-1970sindicateda link betweena

commoncomponentoflaundrydetergent,nitrilotriaceticacid(NTA), andanincreasedincidence

of urinarytracttumoursin testmiceandrats.~This finding raisedconcernwith respectto human

exposureto NTA, which haswidespreaddomesticandindustrialuse,andpromptedextensive

investigationson the effectsOf NTA on mammalianandenvironmentalsystems. This paper

briefly describesthe chemicalpropertiesof NTA, its role asa detergentcomponent,and the

environmentalandtoxicologicalassessmentsconductedso far.

CHEMISTRY

NTA, first synthesizedin 1862, is an aminotricarboxylicacidthatcan sequester

*~*~ metalionsaswatersolublecomplexes.It isarelativelylargemoleculewith a molecularweight

of 191. 14 g. Its chemicalformulais N(CH2COOH)3. Physically,thecentralnitrogenatomhas

a moleculeof aceticacid attachedat eachof its threebondingsites. Chemicalmanufacturers

synthesizeNTA in its sodiumsalt form, in which thehydrogenatomof theaceticacidcarboxyl

group (COOll) is replacedby sodium(COONa) ~TheNTA sodiumsalt hasbindingproperties

which make it useful in detergentsasa watersoftener When NTA is dissolvedin water the

sodiummoiety easily dissociatesaway from theNTA giving free Na~~ions.~This leavesa

negativelychargedbonding site at the endof eachcarboxylgroup (COO) which attractsand

tightly bonds calcium (Ca~)andmagnesium(Mg~)ions More simply put, sodiumions

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detachfrom the NTA moleculeand are replacedby the causativeagentsof “hard” water

(calciumandmagnesiumions), thereby“softening” thewater.

DETERGENTS

~ A detergentis any materialthat increasest1~c~aning~effect of wateron soiled

objects. Laundry detergentsareroutinelycomposedof 15-25% surfactants,30-40% builders,

5 % anti-corrosionsilicates, and 1% auxiliary agents (optical brighteners,foam stabilizers,

enzymesandantiredepositioncompounds),with the balanceconsistingof inert inorganicsalts

to give the driedproductgoodphysicalandmechanicalproperties.

Surfactants,alsocalledsurfaceactiveagents,greatlylowerthesurfacetensionof

water. Many substancesthat can adhereto a fabric exhibit hydrophobicity; thatis, they repel

water. Reducingsurfacetensionreduceshydrophobicityandallowswaterto comeinto contact

with thesoiledspot. Many surfaceactiveagentsdo not workwell in eitherhardwateror water

with a low pH value.

Builders, compoundsthat act as water softenersand deflocculants,contribute

greatly to the overall detergenteffect. Only threebuildersareusedextensivelyin detergents:

NTA, condensedphosphates(sodiumtripolyphosphate,STP), andzeolites. NTA softensthe

wash water, making the surfactantmoreactive, and it alsoactsasa deflocculant. Its strong

ability to bond with calciumallows it to excisecalcium from soil clumps,breakingthecalcium

* bridgesthatbind soil to itself and to fabrics.

STP used to be the builder compoundof choice in detergentformulations.

However,the STP releasedin laundrywastewaterswas found to degradeto phosphate(P04),

an essentialplant nutrientusuallypresentin naturalwatersat concentrationslow enoughto limit

vegetativegrowth. The increaseddischargeof phosphateinto streamsandlakesreversedthis

naturalgrowth limitatio~nd~stimtdatedalgae~growth;thus~severely~upsettingthe ecological

balancein water bodies. Canadianregulationsthat limited the maximum concentrationof

elementalphosphorousin laundrydetergentsto 2.2% (ona weightbasis)appearedin theCanada

Gazette,Part 11, on 8 November1989

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Such stringentregulationsto limit the concentrationof phosphorousin laundry

detergentshaveforced detergentmanufacturersworld-wide to useeither NTA or zeolitesas

buildersin their products. Naturalzeoliteis hydratedalkali-aluminumsilicate;*i~hasa porous

structureandiscapableofexchangingalkali ionsfor calciumandmagnesiumbutit is nothighly

valuedasabuilding agent Variousformsof syntheticallyproducedzeolitedo exhibit excellent

deflocculantandwater-softeningproperties Syntheticzeolitemanufactureis apatentedprocess

controlledby onechemicalcompany,however;asaresult,manydetergentmanufacturersprefer

to useNTA astheir builderagent.

TOXICOLOGY AND ENVIRONMENT STUDIES

A. Toxicity and Teratology

The minimum lethal oral doseof NTA sodiumsalt for ratsis 4 g per kg body

weight.°~Assumingthat thetoxicity of NTA is constantfor all mammals,it would requirethe

ingestionof 227g (halfa pound)of NTA to kill a 57 kg (125 lb.) humanbeing. Thus, NTA

is not a very toxic substance.

Chronicdosingof rats andmice with NTA was found to causedose-dependent

healthproblemsandbirth defects. This is not unexpected;regularlargedosesofNTA would

continuallyextractcalcium andmagnesium,andotherpositively chargedionsfrom bodycells

anddisrupttheir function. ~In regardto birth defects,inducedcalciumdeficiencyin a pregnant

mammalwould arrestnormal foetal bonedevelopment. Becausea high doseis requiredto

induce such effects in animals, NTA is poorly absorbedby humans,and there is a low

environmentalconcentrationof NTA, the InternationalJointCommission,in its reportto The

Great Lakes ResearchAdvisory Board (1972), concludedthat NTA representsa low health

hazardto humans.

(1) M. Windholz, Ct a!. editors, TheMerck Index,An Encyclopediaof ChemicalsandDrugs, 9th edition,Merck & Co., Inc., Rahway, N.J., 1976,p. 854.

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B. Carcinogenicity

ThepotentialofNTA to causecancerin miceandratswasexaminedby a number

of American laboratoriesduring themid-197Os.~In its assessmentof the carcinogenicityof

NTA, baseduponexperimentsconductedat two differentlaboratories,theUnitedStatesNational

CancerInstitutereportedthatdaily ingestionofdietscontainingNTA ataconcentrationof0.258

g/kg body weight,for periodsofup to 24 months,i~sultedin urinarytract tumours~inmiceand

rats. Thesestudiescannotbe regardedas having definitively establishedNTA as a human

carcinogen,however,asthetestingproceduresdid not simulatereal-lifeconditions.

Assuming that humanshavethe samecancerresponseto NTA asdo rats and

mice, daily NTA consumptionof 0.258 g/kg body weightperday (14.7 gperday for a 57 kg

adult) shouldinduceurinarytract tumours. In Canada,the only non-deliberatesourceof NTA

is drinking water, which, accordingto the CanadianWaterQuality Guidelines,hasan average

concentrationof NTA of 2.8 microgramsper litre. Therefore,a 57 kg adult would haveto

drink 5,252,937litres of Canadiantapwaterdaily to receivea doseof NTA equivalentto the

onethat causedcancersin ratsandmice.

Suchcancerdataservelittle real-worldpurposeandraisethequestionofwhy they

were generated.The internationalstandardsfor cancerresearchandcarcinogenclassification

havebeenestablishedby the InternationalAgency for Research(IARC). Canceroccurrences

can bevery rareanddifficult to correlatewith a particularsubstancein normalenvironmental

or occupationalconcenfratióñ~In testing,theentireprocedurecan Usuallybe speededup by

subjectinganimals “to a maximumtolerateddoseof a substanceover their lifetimes.“(3) In

cancerstudies, such “heroic dosing” can saveboth time and money; however, it can also

producedataof questionableutility when, asin the caseof NTA, massivedosesof a mildly

toxic sUbstanceareadministered.

(2) R.L. Anderson, eta!. , “A Reviewof theEnvironmental and Mammalian ToxicologyofNitrilotriaceticAcid, “ CRC Critical Reviewsin Toxicology, Vol. 15, p. 1-101, 1985.

(3) R.J. Moolenaar, “Overhauling Carcinogen Classification,” Issuesin Scienceand Technology,Vol. 8,1992,p. 70-75.

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Thisaberrationin theTARC cancer-testingmethodologyisa recognizedproblem

and efforts~are being made to change either the methodologyOr the IARC carcinogen

classificationsystem.~4~Reformis hamperedbecausethe world needsa standardizedcancer-

testingregimeandthepresentsystemhasbeenin placefor sometime. Theoretically,theIARC

~systemshouldnotcauseproblems,for non-real-worlddataareusuallyignoredby knowledgable

professionals The United StatesEnvironmentalProtectionAgency (EPA), however, stnctly

adheresto the IARC classificationsystem.~5~Once the EPA lists a chemicalas a possible

carcinogen,environmentalgroupsand the mediaareat liberty to describethat chemicalas

cancer-causingor aslinked to cancer.

On a positivenote, the EPA recentlyannouncedthat it hasbegunto revise its

guidelines for carcinogenicrisk assessmentwith plans to take into consideration“realistic

exposurescenariosand mechanisms[of action] when calculating a chemicals’shazard to

humans.,~(6)

Following the AmericanNTA carcinogenicityinvestigation,a large numberof

independentstudieswereinitiated. All thesestudiesindicatedthatNTA posesno humanhealth

risk at the concentrationsto which humansarenormally exposed. According to Dr. Robert

Squire,Professor,JohnsHopkinsUniversity and former AssociateChief of Pathologyat the

NationalCancerInstitute,“At thelevelsthat I understandNTA humanexposurewill occuras

a result of detergentuse, it [NTA] is completely safein all respects. In fact the risk of

* * carcinogeniceffectat humanexposurelevels mustbeconsideredasvirtually zerobasedon the

scientificevidenceavailable.“~

(4) Ibid.

(5) Ibid.

(6) D.J. Hanson,“EPA to ReviseCancerGuidelinesto IncorporateMoreThanTumours,”Chemicaland

EngineeringNews, 26 September1994,p. 21-22.(7) MonsantoCanadaInc., “NTA PreparednessStatementsRe: CanadianPressStory - March 15/93,”

MonsantoNews Release,p. 6, March1993.

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C. EnvironmentalConsiderations

The environmentaleffectsof NTA havealsobeenwell investigated. Although

NTA is alargemolecule,it isnotacomplexsubstance.Its molecularstructure,anitrogenatom

andthreemoleculesof aceticacid(vinegar),is easilybiodegraded.

A Germanresearchscientist,Dr H Bernhardt,publisheda study in 1984which

showedthat theNTA concentrationin wastewaterwasreducedby over 95% afterthewater’s

normal passagethrougha sewagetreatmentplant. Lower levels of NTA destructionwere

observedin sewagetreatmentplantsonly (i) at temperaturesbelow 5-7°C,(ii) in instancesof

high sewagetreatmentplant loadings (wheredilution or sewagewashoutresultedfrom heavy

storm runoff), or (iii) where bacterial acclimation to NTA had not been established.~

Bacterialpopulationsacclimatedto NTA degradationhavebeenisolatedin thevicinity ofsewage

plantoutfalls, in groundwater,lakesandrivers. Accordingly,nearlyall oftheNTA thatpasses

througha sewagetreatmentplantcan be expectedto be degradedin thenaturalenvironment.

DISCUSSION

The toxicology, carcinogenicityandenvironmentalfate of NTA havereceived

extensiveinvestigation. This chemicaldegradesrapidly in theenvironmentand is found asa

contaminantof drinking wateronly at very low concentrations.Humanexposureto NTA is so

limited as to poseno identifiable healthrisk. Indeed,~NTA is so safeandenvironmentally

benign that EnvironmentCanadahas awardeda numberof detergentscontainingNTA its

environmentalchoice “Eco-logo” label.

(8) H. Bernhardt,et a!., Studie uber die aquatischeUmweltvertraglichkeitvon Nitrilotriacetate (NTA),VerglaghansRicharz,SanktAugustan,1984