Evaluation of the safety and potential genotoxicity of a high-purity mogroside ingredient containing siamenoside I produced from a modified strain of <i>Yarrowia lipolytica</i>.
The high-purity mogroside ingredient appears safe in rats, with no genotoxic effects observed at high doses. Human studies are needed for confirmation.
Where it sits
this study against the rest of the nad+ (nicotinamide adenine dinucleotide) corpusSummary and findings
A high-purity mogroside ingredient containing siamenoside I was evaluated for safety and genotoxicity using in vitro assays and animal studies. No biologically-relevant mutagenic or genotoxic effects were observed at concentrations up to 5000 µg/mL. The NOAEL was determined to be 50,000 ppm in both 28-day and 90-day studies in rats.
Abstract
A fermentation process-derived mogroside mixture (≥91.9% total mogrosides) containing high levels of siamenoside I (≥73%) was assessed in a bacterial reverse mutation assay, <i>in vitro</i> micronucleus assay, 28-day repeat-dose dose range-finding study, and 90-day repeat-dose oral toxicity study. Mogrosides, including siamenoside I, are cucurbitane glycoside derivatives of monk fruit (<i>Siraitia grosvenorii</i>) recognized as natural sweeteners. While monk fruit extracts containing concentrated levels of mogrosides (primarily mogroside V) have been marketed in the United States and evaluated by the European Food Safety Authority (EFSA), a safety assessment of fermentation process-derived mogrosides has not been previously conducted. No biologically-relevant mutagenic or genotoxic effects were reported in a bacterial reverse mutation or <i>in vitro</i> micronucleus assay conducted per Good Laboratory Practices (GLP) and relevant OECD test guidelines (OECD TG 471; OECD TG 487) at concentrations up to 5000 µg/mL in each study. A no-observed-adverse-effect-level (NOAEL) of 50,000 ppm (calculated time-weighted average [TWA] equivalent to 4410 mg/kg-bw/day in males and 4112 mg/kg-bw/day in females) was reported in a non-GLP-compliant 28-day dose-range finding study. Similarly, in the 90-day study conducted per GLP in accordance with OECD TG 408 at concentrations of 0, 12,500, 25,000, or 50,000 ppm in the diet, the NOAEL was 50,000 ppm in male (calculated TWA equivalent to 3309 mg/kg-bw/day) and female rats (calculated TWA 3362 mg/kg-bw/day). In the context of low anticipated consumer exposure in adults and children, these results support the safety of this mogroside mixture in foods.
Background
This study addresses the safety and potential genotoxicity of a high-purity mogroside ingredient containing siamenoside I, derived from a fermentation process. Mogrosides are natural sweeteners found in monk fruit, with prior evaluations mainly focused on mogroside V. The study is significant as it evaluates fermentation-derived mogrosides, which have not been previously assessed for safety.
Methods
The study utilized a bacterial reverse mutation assay and an in vitro micronucleus assay, alongside a 28-day dose-range finding study and a 90-day oral toxicity study in rats. The mogroside mixture was tested at concentrations up to 5000 µg/mL in vitro and dietary concentrations of 0, 12,500, 25,000, or 50,000 ppm in the animal studies. The primary outcome was the determination of the NOAEL.
Results
No biologically-relevant mutagenic or genotoxic effects were observed in the in vitro assays at concentrations up to 5000 µg/mL. In the 28-day study, a NOAEL of 50,000 ppm was reported, equivalent to 4410 mg/kg-bw/day in males and 4112 mg/kg-bw/day in females. The 90-day study confirmed a NOAEL of 50,000 ppm, with equivalent doses of 3309 mg/kg-bw/day in males and 3362 mg/kg-bw/day in females.
Interpretation
The findings suggest that the high-purity mogroside ingredient is not mutagenic or genotoxic at tested concentrations. The NOAEL values indicate a high safety margin, although the clinical relevance is limited due to the animal model. The non-GLP compliance of the 28-day study is a notable limitation, and further human studies are needed to confirm safety in humans.
Key findings
- ≥91.9% total mogrosides in mixture.
- ≥73% siamenoside I in mixture.
- No mutagenic effects at 5000 µg/mL in vitro.
- NOAEL of 50,000 ppm in 28-day study.
- NOAEL of 50,000 ppm in 90-day study.
Limitations
- 28-day study non-GLP-compliant
- Conducted in rats, not humans
- No human data available
- Potential differences in human metabolism