Crincoli Christine M, Brathwaite Witty A, Casterton Phillip L, Rihner Marisa O, Nikiforov Andrey I, Sloter Eddie D, Harris Stephen B
Cargill, Incorporated, 15407 McGinty Rd West, Wayzata, MN 55391, USA.
Cargill Limited, 300-240 Graham Avenue Winnipeg, MB R3C 4C5, Canada.
Food Chem Toxicol. 2016 May;91:167-80. doi: 10.1016/j.fct.2015.10.015. Epub 2015 Oct 26.
(2R,4R)-Monatin salt [sodium/potassium 2R,4R-2-amino-4-carboxy-4-hydroxy-5-(3-indolyl) pentanoate] was fed at 5000, 15,000, or 35,000 ppm to Crl:CD(SD) rats over two generations. Reduced body weights were observed at all dose levels. Sustained effect on body weight gain at 35,000 ppm in the F0 and F1 parental animals was associated with lower feed efficiency, soft stool, and slightly lower numbers of implantation sites. Lower numbers of pups born and live litter size at 35,000 ppm were considered secondary to slightly lower numbers of former implantation sites in the dams. Spermatogenic endpoints, estrous cyclicity, reproductive performance, mean gestation length, and parturition were unaffected in the F0 and F1 generations. There were no effects on F1 and F2 generation postnatal survival. Reduced pre-weaning pup body weights at 35,000 ppm resulted in lower F1 and F2 body weights at study termination. Slight delays in pubertal landmarks in the F1 offspring were considered secondary to the reduced pup body weights. The no-observed-adverse-effect level (NOAEL) was 15,000 ppm for systemic, reproductive, and neonatal effects based on test article-related effects on body weight and food efficiency, slight decrease in maternal implantation sites and corresponding reduction in live litter size, and reductions in pre-weaning pup body weights at 35,000 ppm.
将(2R,4R)-莫那甜盐[2R,4R-2-氨基-4-羧基-4-羟基-5-(3-吲哚基)戊酸钠/钾]以5000、15000或35000 ppm的剂量喂饲Crl:CD(SD)大鼠两代。在所有剂量水平下均观察到体重减轻。在F0和F1代亲代动物中，35000 ppm剂量对体重增加有持续影响，这与较低的饲料效率、软便以及着床部位数量略有减少有关。35000 ppm剂量下出生的幼崽数量和存活窝仔数较低被认为是由于母鼠着床部位数量略少所致。F0和F1代的生精终点、发情周期、生殖性能、平均妊娠期和分娩均未受影响。对F1和F2代的出生后存活没有影响。35000 ppm剂量下断奶前幼崽体重减轻导致研究结束时F1和F2代体重降低。F1代后代青春期标志略有延迟被认为是幼崽体重降低的继发结果。基于受试物对体重和食物效率的影响、母体着床部位略有减少以及相应的存活窝仔数减少，以及35000 ppm剂量下断奶前幼崽体重降低，全身、生殖和新生儿效应的未观察到有害作用水平(NOAEL)为15000 ppm。
