Re‐evaluation of neotame (E 961) as food additive

The present opinion deals with the re-evaluation of neotame (E 961) as a food additive. Neotame is the chemically manufactured compound N-[N-(3,3-dimethylbutyl)-l-α-aspartyl]-l-phenylalanine 1-methyl ester. The main impurity of neotame (E 961) is also a degradation product (de-esterified form), N-[N-(3,3-dimethylbutyl)-l-α-aspartyl]-l-phenylalanine (NC-00751) and the primary metabolite. No new data were received following the call for biological and toxicological data. A summary of the toxicological studies available in the EFSA opinion of 2007 is presented and studies gathered from the literature are summarised. Neotame is rapidly absorbed and pre-systemically metabolised, systemic intact neotame is likely to be excreted in the urine with its metabolites. The potential aneugenic effects at the site of contact are not expected to occur; overall, there is no concern for genotoxicity of neotame (E 961) at the maximum permitted levels or reported use levels. A review of the other endpoints from the already available toxicological database did not indicate an adverse effect for neotame at the highest doses tested. The Panel established an acceptable daily intake (ADI) of 10 mg/kg bw per day for neotame based on the no observed adverse effect level (NOAEL) of 1000 mg/kg bw per day from a 52-week chronic and 104-week carcinogenicity studies in rats. This ADI replaces the ADI of 2 mg/kg bw per day established by EFSA in 2007. The resulting exposure to methanol and its metabolite formaldehyde from the use of neotame at the ADI of 10 mg/kg bw per day does not raise a concern. The dietary exposure estimates of neotame (E 961) for the different population groups of all exposure scenarios did not exceed the ADI. The Panel concluded that there is no safety concern for neotame (E 961) at the currently permitted and reported uses and use levels. The Panel recommended the European Commission to consider revising the EU specifications of neotame (E 961).

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Publication Details

Journal
EFSA Journal
Published
2025-07-01
DOI
https://doi.org/10.2903/j.efsa.2025.9480
Primary Topic
Carcinogens and Genotoxicity Assessment
Type
article
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article

Re‐evaluation of neotame (E 961) as food additive

Þórhallur I. Halldórsson, Josef Daniel Rasinger, Camilla Smeraldi, Oliver Lindtner et al.
EFSA Journal
Carcinogens and Genotoxicity Assessment
article

Re‐evaluation of neotame (E 961) as food additive

Þórhallur I. Halldórsson, Josef Daniel Rasinger, Camilla Smeraldi, Oliver Lindtner, Biagio Fallico, Consuelo Civitella, Maria de Lourdes Bastos, Gabriele Aquilina, Bettina Grasl‐Kraupp, Monika Batke, Rainer Gürtler, Ellen Bruzell, Cristina Fortes, José Cortiñas Abrahantes, Alexandra Tard, Éric Gaffet, Ursula Gundert‐Remy, Francesca Riolo, Riccardo Crebelli, Stefania Barmaz, Federica Lodi, Patrik Le Gall, Henriqueta Louro, Anna K. Undas, Matthew Wright, Panagiota Zakidou, Peter T. Furst, Jan Mast, Patrícia Morales, Sabina Passamonti, Rex FitzGerald, Agnieszka Mech, Manuela Mirat, Monica Andreassen, Alicja Mortensen, Polly Boon, Ana Maria Rincon, Maria José Frutos Fernandez, Eric Houdeau, Marcin Kurek, Elena Mazzoli, Jean‐Charles Leblanc, Katrin Loeschner, Laurence Castle, James Kevin Chipman, Cheyns Karlien
article en

Abstract

The present opinion deals with the re-evaluation of neotame (E 961) as a food additive. Neotame is the chemically manufactured compound N-[N-(3,3-dimethylbutyl)-l-α-aspartyl]-l-phenylalanine 1-methyl ester. The main impurity of neotame (E 961) is also a degradation product (de-esterified form), N-[N-(3,3-dimethylbutyl)-l-α-aspartyl]-l-phenylalanine (NC-00751) and the primary metabolite. No new data were received following the call for biological and toxicological data. A summary of the toxicological studies available in the EFSA opinion of 2007 is presented and studies gathered from the literature are summarised. Neotame is rapidly absorbed and pre-systemically metabolised, systemic intact neotame is likely to be excreted in the urine with its metabolites. The potential aneugenic effects at the site of contact are not expected to occur; overall, there is no concern for genotoxicity of neotame (E 961) at the maximum permitted levels or reported use levels. A review of the other endpoints from the already available toxicological database did not indicate an adverse effect for neotame at the highest doses tested. The Panel established an acceptable daily intake (ADI) of 10 mg/kg bw per day for neotame based on the no observed adverse effect level (NOAEL) of 1000 mg/kg bw per day from a 52-week chronic and 104-week carcinogenicity studies in rats. This ADI replaces the ADI of 2 mg/kg bw per day established by EFSA in 2007. The resulting exposure to methanol and its metabolite formaldehyde from the use of neotame at the ADI of 10 mg/kg bw per day does not raise a concern. The dietary exposure estimates of neotame (E 961) for the different population groups of all exposure scenarios did not exceed the ADI. The Panel concluded that there is no safety concern for neotame (E 961) at the currently permitted and reported uses and use levels. The Panel recommended the European Commission to consider revising the EU specifications of neotame (E 961).

EFSA JournalVol. 23(7)
Openalex Percentile: Top 78%
Carcinogens and Genotoxicity Assessment
DOIOpen Access PDFOpenAlex
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