Two-generation reproductive and developmental toxicity assessment of dietary N-acetyl-L-aspartic acid in rats

Two-generation reproductive and developmental toxicity assessment of dietary N-acetyl-L-aspartic acid in rats
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DOI:
10.1016/j.fct.2011.08.025
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发表时间:
2011-12-01
影响因子:
4.3
通讯作者:
Delaney, Bryan
Delaney, Bryan
中科院分区:
农林科学2区
文献类型:
--
作者:
Karaman, Sule;Barnett, John, Jr.;Delaney, Bryan

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N-乙酰-L-天冬氨酸(NM)是哺乳动物中枢神经系统(CNS)的一种成分,也已在许多食物中发现。本文报告了在Sprague-Dawley(R)大鼠中进行的NM生殖毒理学研究的结果。以100、250和500 mg/kg体重/天的目标剂量向饲料中添加NM,并连续给药两代。载体对照组给予不添加NAA的饮食,比较对照组给予天冬氨酸(ASP),NM的组成氨基酸,目标剂量为500 mg/kg体重/天。该研究评价了OECD 416项生殖性能变量和其他部分,以评估潜在的发育影响、神经行为和眼科功能以及脑和血浆中NM或ASP的浓度。在任何生殖反应变量、神经行为试验、眼科检查、体重、摄食量或器官重量方面均未观察到生物学显著差异。此外,未观察到供试品相关死亡或不良临床、神经组织病理学或组织病理学结果。在本研究条件下,NM的最高目标剂量500 mg/kg体重/天代表了Sprague-Dawley大鼠生殖和全身毒性以及神经毒性的无明显不良作用水平(NOAEL)。(C)2011爱思唯尔有限公司版权所有。
N-acetyl-L-aspartic acid (NM) is a component of the mammalian central nervous system (CNS) that has also been identified in a number of foods. This paper reports the outcome of a reproductive toxicology study conducted with NM in Sprague-Dawley (R) rats. NM was added to diets at target doses of 100, 250 and 500 mg/kg of body weight/day and administered for two consecutive generations. A carrier control group was administered diet with no added NAA and a comparative control group was given aspartate (ASP), the constituent amino acid of NM, at a target dose of 500 mg/kg of body weight/day. The study evaluated OECD 416 reproductive performance variables and additional segments to assess potential developmental effects, neurobehavioural and ophthalmologic function, and the concentrations of NM or ASP in brain and plasma. No biologically significant differences were observed in any reproductive response variables, neurobehavioural tests, ophthalmologic examinations, body weights, feed consumption, or organ weights. Further, no test substance related mortalities or adverse clinical, neurohistopathologic or histopathologic findings were observed. Under the conditions of this study, the highest target dose of NM, 500 mg/kg of body weight/day, represents the no-observed-adverse-effect-level (NOAEL) for reproductive and systemic toxicity, and neurotoxicity for Sprague-Dawley rats. (C) 2011 Elsevier Ltd. All rights reserved.