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CHA,and,inally,afactorof5.5toadjustforthefactthatonly18%oftheingestedcyclamicacid
wouldbeconvertedtoCHAbythegutmicrolorainhumans.Followingareviewofnewdatain
1980,theJECFAmaintainedthetemporaryADIof0-4mg/kgbw/day(JECFA1980a).Finally,in
1982,anADIof0-11mg/kgbw/dayexpressedascyclamicacid,forcyclamicacid,anditscalcium
andsodiumsaltswereallocatedbasedonthenewdata(JECFA1982a,b).ThisADIwasbasedon
theNOAELof100mg/kgbw/dayforCHAandadjustedforthepercentageofabsorptionofcycla-
matebyhumansandthehumanconversionrateofcyclamatetoCHA.
14.7.1.4 Neohesperidin Dihydrochalcone (E959)
The SCF expressed its opinion on neohesperidin dihydrochalcone (DC) for the irst time in
1984.Thecommitteeconcludedthatthecompoundwasnottoxicologicallyacceptableduetothe
lackofdata(SCF1985).However,in1988,theSCFestablishedanADIforneohesperidinDCof
0-5mg/kgbw/day(SCF1989).
ThesweetenerhasnotbeenevaluatedbytheJECFA.
14.7.1.5 Neotame (E961)
AsafetyevaluationofneotamewasperformedbytheEFSAin2007.TheAFCPanelofEFSA
establishedanADIforneotameof0-2mg/kgbw/daybasedontheapplicationofasafetyfactor(at
presentreferredbytheEFSAasanuncertaintyfactor)toaNOAELof200mg/kgbw/dayfroma
52-weekdogstudyforanincreaseinserumalkalinephosphatase,whichwasconsideredthecritical
endpointbytheAFCPanel(EFSA2007).
NeotamewasevaluatedbytheJECFAonits61stmeetinginJune2003.TheJECFAestablished
anADIof0-2mg/kgbw/dayforneotameonthebasisofaNOELof200mg/kgbw/dayina1-year
study in dogs and a 100-fold safety factor (JECFA 2003a,b). According to the JECFA, the only
consistenttreatment-relatedeffectobservedwasanincreaseinserumalkalinephosphataseactivity
inthe13-weekand1-yearstudiesindogsfedneotameinthediet.Whiletheincreaseinalkaline
phosphatase was moderate, reversible, and not accompanied by other evidence of liver toxicity,
theobservedchangewasreproducible,ofhighstatisticalsigniicance,andtreatmentrelated.The
JECFAagreedthatthedatawereinsuficienttodiscountthiseffectand,therefore,acceptedthedog
asthemostsensitivespecieswithaNOELforneotameof200mg/kgbw/dayonthebasisofthe
1-yearstudyindogs.
14.7.1.6 Saccharin (E954)
Therehasbeencontroversyoverthesafetyofsaccharininthepast.Ratfeedingstudiesindi-
catedthatsaccharinathighdosesproducedtumorsinthebladderofmalerats(SCF1977).Since
then,severalanimalstudieshaveprovidedinformationonthemechanismsbehindthiscarcinogenic
response in the male rat and demonstrated no carcinogenic effect of saccharin in other animal
species.Furthermore,extensiveresearchonthehumanpopulationhasestablishednoassociation
betweensaccharinandcancer.
Saccharinanditssodium,potassium,andcalciumsaltswereirstevaluatedbytheSCFin1977
whenatemporaryADIof0-2.5mg/kgbw/daywasallocated(SCF1977).TheSCFagainreviewed
saccharinin1984anddecidedtomaintainthetemporaryADIsetin1977untilthequestionscon-
cerningthemechanismandrelevanceofthemaleratbladdertumorswouldbeclariiedbynewdata
(SCF1985).Followingthesubmissionofnewdataandarequestfromtheindustryforareevalua-
tionofthetemporaryADI,theSCFconsideredsaccharinin1988(SCF1989).ThetemporaryADI
wasnotchanged.First,in1995,theSCFremovedthetemporarystatusandestablishedanADIfor
sodiumsaccharinof0-5mg/kgbw/day(whichis0-3.8mg/kgbw/daywhentheADIisexpressed
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