title: A dietary embryo/fetal developmental toxicity study of arruva, an R,R-monatin salt isomer, in Crl:CD(SD) rats.
abstract: 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 35,000 ppm arruva in the diet for 90 days. 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 50,000 ppm 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 50,000 ppm. A developmental effect, in the form of lower mean fetal body weight, was noted in the 50,000 ppm 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 30,000 ppm (equivalent to 2564 mg/kg bw/day) based on reductions in maternal and fetal body weights.
authors: Cargill Limited, Winnipeg, MB, Canada. Electronic address: witty_brathwaite@cargill.com.
authors: W A
authors: WA
authors: Brathwaite
authors: P L
authors: PL
authors: Casterton
authors: A I
authors: AI
authors: Nikiforov
authors: M O
authors: MO
authors: Rihner
authors: E D
authors: ED
authors: Sloter
authors: J J
authors: JJ
authors: Hlywka
mesh_terms: D000015:Abnormalities, Multiple / Q000139:chemically induced; D000821:Animal Feed; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D007211:Indoles / Q000633:toxicity*; D008297:Male; D018811:Maternal Exposure; D008813:Mice, Inbred ICR; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D013549:Sweetening Agents / Q000633:toxicity; D018675:Toxicity Tests / Q000379:methods*; D014599:Uterus / Q000187:drug effects
chemical_list: C414924:4-hydroxy-4-(indol-3-ylmethyl)glutamic acid; D007211:Indoles; D013549:Sweetening Agents; D018698:Glutamic Acid
keywords: Arruva; Embryotoxicity; Fetal development; Oral; R,R-monatin; Sweetener