Lack of potential carcinogenicity for steviol glycosides – Systematic evaluation and integration of mechanistic data into the totality of evidence

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Auteur(s): Chappell GA, Heintz MM, Borghoff SJ, Doepker CL, Wikoff DS.
Nom de la publication : Food and Chemical Toxicology 2021;150:112045. doi: 10.1016/j.fct.2021.112045
Année de publication : 2021


Steviol glycosides are present in the leaves of the Stevia rebaudiana plant, have a sweet taste, and have been used as a sweetener for centuries. To build on previous authoritative safety assessments of steviol glycosides, a systematic assessment of mechanistic data related to key characteristics of carcinogens (KCCs) was conducted. Over 900 KCC-relevant endpoints from peer-reviewed literature and high-throughput screening data (ToxCast/Tox21) were identified across individual steviol glycosides and derivatives, metabolites, and whole leaf extracts. Most data (both in vivo and in vitro, including human cells), showed inactivity. Studies were weighted according to quality and relevance. Although data were available for eight of the ten KCC, genotoxicity, oxidative stress, inflammation, and cell proliferation/cell death represent the KCCs with the most data. The data for these KCC primarily show beneficial activity (anti-inflammatory, antioxidant, and anti-proliferative). Following integration across all data, and accounting for study quality and relevance, the totality of the evidence demonstrated an overall lack of genotoxic and carcinogenic activity for steviol glycosides. This is in agreement with previous regulatory decisions, and is consistent with the lack of tumor response in two-year rodent cancer bioassays. The findings support prior conclusions that steviol glycosides are unlikely to be carcinogenic in humans.


The current systematic evaluation of all available evidence from human, animal, and mechanistic data affirms the lack of genotoxic and carcinogenic potential of steviol glycosides. The outcomes of this study are consistent with conclusions from regulatory food safety authorities worldwide supporting that steviol glycosides are safe and non-carcinogenic.

This study by Chappell et al aimed to systematically identify, evaluate and integrate all available mechanistic data related to key characteristics of carcinogens (KCC) in order to assess potential carcinogenicity of steviol glycosides using a structured, quantitative framework. A key strength of this assessment is the incorporation of mechanistic data from various sources, different study designs, and a wide array of endpoints. Over 900 KCC-relevant assay endpoints were collected from a total of 76 articles including 38 in-vitro studies, 47 animal studies, and one human exposure study, in addition to high throughput screening (HTS) assays relevant to KCCs.

The results showed that exposure to steviol glycosides is unlikely to pose a carcinogenic risk to humans, which is consistent with assessments from authoritative bodies including the Joint FAO/WHO Expert Committee on Food Additives (JECFA), the European Food Safety Authority (EFSA) and the US Food and Drug Administration (FDA).

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