EU, U.S., and Third World Country Regulations and Japanese Legislation - Sweeteners: Nutritional Aspects, Applications, and Production Technology - page 311

thattheresultsoftheirstudynotonlyconirmbutalsoreinforcetheirirstexperimentaldemonstra-
tion(publishedin2005and2006)ofASP'smultipotentialcarcinogenicityatadoselevelcloseto
thehumanADI.Basedontheresultsofthisstudy,theauthorsfurtherpostulatedthat,whenlife-
spanexposuretoASPbeginsduringfetallife,itscarcinogeniceffectsareincreased.
Thepanelconcludedasfollows(EFSA2009a):

• Theevaluationofaggregatedmalignanttumorincidencesasevidenceofthecarcinogenicpotential

ofthetestcompoundcanonlybeperformedbasedonathoroughconsiderationofalltumordata,
includingonset,anddataonnonneoplastic,hyperplastic,andpreneoplasticlesions,butthesedata
werenotprovidedbytheauthors.

• InaccordancewiththepreviousviewoftheAFC,thelymphomasandleukemiasmighthavedevel-

opedinapopulationofratssufferingfromchronicrespiratorydisease.

• The increase in incidence of mammary carcinoma is not considered indicative of a carcinogenic

potentialofASP,becausetheincidenceofmammarytumorsinfemaleratsisratherhighandvar-
iesconsiderablybetweencarcinogenicitystudies.Thepanelalsonotedthatanincreasedincidence
ofmammarycarcinomaswasnotreportedinthepreviousERFstudywithASP,whichusedmuch
higherdosesofthecompound.

• Overall,onthebasisofalltheevidencecurrentlyavailablefromthisERFstudyandpreviousevalu-

ations, there is no indication of any genotoxic or carcinogenic potential of ASP, and there is no
reasontorevisethepreviouslyestablishedADIforASPof40mg/kgbw.

Thesugarequivalentinmilligramsis8000,takingintoaccountthattherelativesweetnessis
200.Theterm“sugarequivalent”referstotheamountofsugarthatwouldbeneededtoachievethe
samesweetnesseffectastheindicatedamountofsweetener.Tocalculateit,weneedtoknowthe
relativesweetnessoflow-caloriesweeteners.
ASPisstableatroomtemperature.Themajordegradationproductathighertemperaturesisdik-
etopiperazine.Thesetwocompoundshavebeensatisfactorilyassessedinalargenumberofstudies
inhumans,andanADIhasbeenestablishedforeachofthem:40mg/kgbwforASPand7.5mg/
kgbwfordiketopiperazine.
ThemetabolitesofASPinhumansarecompoundsthatarefoundinnormalfoodsandarealso
produced by endogenous cellular metabolism. ASP is a minor source of phenylalanine, aspartic
acid,andmethanolcomparedwiththestandarddietaryintakeofthesesubstances.Theycannot,
therefore,bethesourceofthetoxicneurologicaleffectsattributedtoASP(AFSSA2002).
Genetic toxicity assays have demonstrated that ASP and diketopiperazine are not genotoxic
(AFSSA2002).
Noneofthecarcinogenicityteststhathavebeenconductedonrodentsindicatedarelationship
betweentreatmentwithASPandtheappearanceofbraintumors.
TheepidemiologicalstudyofOlneyetal.(1996)suggestedthatalinkbetweentheplacingonthe
marketofASPandapossibleincreaseinthefrequencyofbraincancersinhumansdidnotprovideany
scientiicevidencetojustifyordemonstrateabasisforthissuggestion;todate,ithasnotbeenconirmed.
Analysisofthescientiicliteraturehasdemonstrated alackofevidencebasedonthecurrent
stateofknowledge,whichwouldenableacausallinktobeestablishedbetweentheconsumptionof
ASPandtheoccurrenceofepilepticseizuresoranomaliesonanelectroencephalogram.
IthasbeenveriiedinFrancethatnoanticonvulsivemedicationcontainshighquantitiesofASP.
TheconsumptionofASPinhumans,eveninparticularlyexposedpopulationssuchasdiabeticchil-
dren,doesnotexceedtheADI,notablyinFrance.
In conclusion, the French Food Safety Agency ( Agence Francaise de Securite Sanitaire des
Aliments ;AFSSA)considersthatthecurrentstateofscientiicknowledgedoesnotenablearelation-
shiptobeestablishedbetweentheexpositiontotheASPandbraintumorsinhumansoranimals.
Diabetic children are considered an at-risk group for the consumption of sweeteners, irst,
because the diabetic diet partially excludes simple carbohydrates and, second, because of their