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A two-year dietary carcinogenicity study of (2R,4R)-monatin salt in mice
Witty A Brathwaite1, Christine M Crincoli2, Alex K Eapen2
1Cargill Limited, 300-240 Graham Avenue Winnipeg, MB, R3C 4C5, Canada.
Abstract:
Groups of Crl:CD-1 (ICR) mice (60/group/sex) were fed 0 (2 control groups), 5000, 20,000, or 40,000 ppm of enzymatically sourced (2R,4R)-monatin salt ("R,R-monatin") in the diet for up to two years. There were no adverse effects on survival, incidence of palpable masses and tumors, feed consumption, hematology or serum chemistry parameters, organ weights, or ophthalmic, macroscopic, and microscopic examinations. The only notable effect was statistically significantly lower mean body weights and body weight gains in all treated groups, which generally occurred throughout the study and were most likely a result of caloric dilution of the test diets and not considered adverse. There were no test article-related changes in the incidence or occurrence of neoplastic diseases in mice on this study. The no-observed-effect-level (NOEL) for carcinogenicity of R,R-monatin fed to mice for 24 months was 40,000 ppm, the highest dietary concentration tested, which was equivalent to approximately 6502 and 7996 mg/kg bw/day in males and females, respectively.
Insights
Enzymatically sourced (2R,4R)-monatin salt (R,R-monatin) showed no adverse effects in a two-year mouse study. The highest dose tested did not increase tumors, establishing a high no-observed-effect-level (NOEL) for carcinogenicity.
Area of Science:
- Toxicology
- Carcinogenicity Studies
- Dietary Administration
Background:
- Monatin is a non-caloric sweetener with potential applications.
- Assessing the long-term safety of novel food ingredients is crucial.
Purpose of the Study:
- To evaluate the carcinogenic potential of enzymatically sourced (2R,4R)-monatin salt (R,R-monatin) in mice.
- To determine the no-observed-effect-level (NOEL) for carcinogenicity.
Main Methods:
- Groups of Crl:CD-1 (ICR) mice (60/group/sex) were fed diets containing 0, 5000, 20,000, or 40,000 ppm R,R-monatin for up to two years.
- Comprehensive toxicological assessments including survival, tumor incidence, hematology, serum chemistry, organ weights, and histopathology were performed.
Main Results:
- No adverse effects were observed on survival, tumor incidence, hematology, serum chemistry, organ weights, or gross/microscopic pathology.
- The only observed effect was reduced body weight and weight gain, attributed to caloric dilution and deemed non-adverse.
- No test article-related changes in neoplastic disease incidence were found.
Conclusions:
- The no-observed-effect-level (NOEL) for carcinogenicity of R,R-monatin in mice was 40,000 ppm (highest dose tested).
- R,R-monatin demonstrated a lack of carcinogenic potential in this long-term rodent study.
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