In vitro and in vivo assessment of the mutagenic activity of N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-l-phenylalanine 1-methyl ester, monohydrate (advantame)

Advantame (N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-l-phenylalanine 1-methyl ester, monohydrate), an N-substituted analogue of aspartame, has been developed as a high-intensity sweetener. It is approximately 100 and 20,000 times sweeter than aspartame and sucrose, respectively. In this study the safety of advantame has been evaluated using a series of in vitro and in vivo genotoxicity assays including, bacterial mutation, mammalian cell mutation, and mouse micronucleus tests. Advantame did not induce reverse mutations in Salmonella typhimurium and Escherichia coli at concentrations of up to 5000 μg/plate. In the mammalian cell mutation assay, advantame did not induce mutation at the Hprt locus of L5178Y mouse lymphoma cells in two independent experiments, either in the absence or presence of S9. In vivo, there was no effect on the incidence of micronucleated immature or mature erythrocytes in bone marrow after oral administration of the test substance at any dose level (up to 2000 mg/kg body weight) or sampling time (24 and 48 h). The results of these studies demonstrate that advantame is without genotoxic potential.

► Advantame has been developed as a high intensity sweetener.
► Advantame was tested in an Ames, L5178Y mouse lymphoma, and an in vivo mouse micronucleus assay.
► Advantame was not genotoxic in any of the test systems.