A 90-day oral (dietary) toxicity study of the 2R,4R-isomer of monatin salt in Sprague-Dawley rats.

Abstract

The root bark of Sclerochitin ilicifolius contains an intensely sweet substance analytically identified as isomers of 2-hydroxy-2-(indol-3-ylmethyl)-4-aminoglutaric acid and generically coined "monatin." Groups of male and female Crl:CD(SD) rats were fed 0 (control), 5000, 10,000, 20,000 or 35,000 ppm R,R-monatin salt in the diet for 90 days. There were no toxicologically relevant clinical or histopathological findings in any of the test article-treated groups. Significantly lower cumulative body weight gains were noted in the 35,000 ppm group. Mean body weights in the 35,000 ppm group males and females were 7% and 12% lower, respectively, than the control group at study week 13. In the absence of other observations associated with systemic toxicity and lower food consumption, the magnitude of the body weight difference in the 35,000 ppm group females relative to the control group exceeded 10%, which indicated attainment of a maximum tolerated dose (MTD) level. Based on the results of this study, and conservatively assuming the body weight observations at the MTD to be indicative of an adverse effect, the dietary no-observed-adverse-effect level (NOAEL) of R,R-monatin salt for 90 days was 20,000 ppm in female rats (approximately 1544 mg/kg bw/day) and 35,000 ppm in male rats (approximately 2368 mg/kg bw/day).

• Authors: J Hlywka, W A Brathwaite, M O Rihner, A I Nikiforov, A K Eapen
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 49 Issue 12 Pg. 3249-57 (Dec 2011) ISSN: 1873-6351 [Electronic] England
• PMID: 21925562 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• 4-hydroxy-4-(indol-3-ylmethyl)glutamic acid
• Indoles
• Glutamic Acid

Topics

• Administration, Oral
• Animals
• Body Weight (drug effects)
• Diet
• Dose-Response Relationship, Drug
• Female
• Glutamic Acid (administration & dosage, analogs & derivatives, toxicity)
• Indoles (administration & dosage, toxicity)
• Male
• No-Observed-Adverse-Effect Level
• Organ Size (drug effects)
• Rats
• Rats, Sprague-Dawley
• Sex Factors
• Toxicity Tests, Subchronic (methods)