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R,R-莫那甜盐异构体阿鲁瓦在Crl:CD(SD)大鼠中的膳食胚胎/胎儿发育毒性研究。

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

作者信息

Brathwaite W A, Casterton P L, Nikiforov A I, Rihner M O, Sloter E D, Hlywka J J

机构信息

Cargill Limited, Winnipeg, MB, Canada.

出版信息

Food Chem Toxicol. 2013 Dec;62:68-75. doi: 10.1016/j.fct.2013.08.027. Epub 2013 Aug 23.

DOI:10.1016/j.fct.2013.08.027
PMID:23973404
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.

摘要

R,R-莫那甜是一种甜度极高的物质,最初是在硬叶柯的根皮中发现的。R,R-莫那甜盐,通常称为“阿鲁瓦”,有潜力用作高效甜味剂食品成分。此前,已得出结论,对于在饮食中摄入高达35,000 ppm阿鲁瓦达90天的Crl:CD(SD)大鼠和Crl:CD-1(ICR)小鼠,阿鲁瓦未呈现出毒理学相关影响。在本研究中,将交配后的斯普拉格-道利大鼠分组(每组25只Crl:CD(SD)雌性大鼠),在妊娠第6至21天期间,使其持续摄入饮食中含0(对照)、15,000、30,000或50,000 ppm阿鲁瓦的饲料。在任何暴露水平下,均未发现因阿鲁瓦导致的胎儿畸形或发育变异,也未发现与受试物相关的对子宫内存活的影响。在50,000 ppm时观察到母体毒性,表现为平均体重、体重增加和饲料效率降低。在存在母体毒性的情况下,50,000 ppm组出现了以平均胎儿体重降低形式的发育影响。因此,基于母体和胎儿体重的降低,在妊娠第6至21天的怀孕大鼠中,阿鲁瓦对母体和胚胎/胎儿发育毒性的饮食无观察到有害作用水平(NOAEL)为30,000 ppm(相当于2564 mg/kg bw/天)。

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