A dietary embryo/fetal developmental toxicity study of arruva, an R,R-monatin salt isomer, in Crl:CD(SD) rats

• Published in: Food and chemical toxicology 2013-12, Vol.62, p.68-75
• Main Authors: Brathwaite, W.A., Casterton, P.L., Nikiforov, A.I., Rihner, M.O., Sloter, E.D., Hlywka, J.J.
• Format: Article
• Language: English
• Subjects: abnormal development; Abnormalities, Multiple - chemically induced; Animal Feed; Animals; Arruva; bark; Biological and medical sciences; Body Weight - drug effects; congenital abnormalities; Diet; Embryology: invertebrates and vertebrates. Teratology; Embryotoxicity; feed conversion; Female; females; Fetal development; Fetal Weight - drug effects; Fundamental and applied biological sciences. Psychology; Glutamic Acid - analogs & derivatives; Glutamic Acid - toxicity; Indoles - toxicity; ingredients; isomers; Male; Maternal Exposure; Medical sciences; mice; Mice, Inbred ICR; No-Observed-Adverse-Effect Level; Oral; Pregnancy; R,R-monatin; rats; Rats, Sprague-Dawley; roots; Sweetener; sweeteners; Sweetening Agents - toxicity; Teratology. Teratogens; Toxicity Tests - methods; Toxicology; Uterus - drug effects; weight gain
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.08.027

•No toxicologically relevant effects in pregnant rats fed arruva from gestation days 6–21.•Arruva does not induce fetal malformations, variations, or intrauterine survival effects.•Lower mean fetal body weights in the 50,000ppm group occurred with maternal toxicity.•Arruva’s body weight effects were similar to results seen in 90-day rodent studies. R,R-Monatin is an intensely sweet substance originally identified in the root bark of Sclerochiton ilicifolius. R,R-Monatin salt, commonly known as “arruva”, has potential for use as a high-potency sweetener food ingredient. Previously, arruva was concluded to present no toxicologically relevant effects to Crl:CD(SD) rats and Crl:CD-1(ICR) mice fed up to 35,000ppm arruva in the diet for 90days. In the present study, groups of mated Sprague–Dawley rats (25 Crl:CD(SD) females/group) were exposed continuously to 0 (control), 15,000, 30,000, or 50,000ppm arruva in the diet during gestation days 6–21. There were no fetal malformations or developmental variations that were attributable to arruva at any exposure level, nor were there any test article-related effects on intrauterine survival. Maternal toxicity, evidenced by lower mean body weights, body weight gains and feed efficiency, was observed at 50,000ppm. A developmental effect, in the form of lower mean fetal body weight, was noted in the 50,000ppm group in the presence of maternal toxicity. Therefore, the dietary no-observed-adverse-effect level (NOAEL) for maternal and embryo/fetal developmental toxicity of arruva in pregnant rats during gestation days 6–21 was 30,000ppm (equivalent to 2564mg/kgbw/day) based on reductions in maternal and fetal body weights.