Maekawa A, Todate A, Onodera H, Matsushima Y, Nagaoka T, Shibutani M, Ogasawara H, Kodama Y, Hayashi Y
Division of Pathology, National Institute of Hygienic Sciences, Tokyo, Japan.
Food Chem Toxicol. 1990 Apr;28(4):235-41. doi: 10.1016/0278-6915(90)90035-l.
The toxicity/carcinogenicity of monosodium succinate, a food additive, was examined in F344 rats. The oral LD50 was greater than 8 g/kg body weight. In a 13-wk subchronic oral toxicity study, the only toxicological finding was suppression of body-weight gain in groups given greater than or equal to 2.5% monosodium succinate in the drinking-water. Histological examination revealed no toxic lesions specifically caused by the compound in any organs of any of the treated rats. The maximum tolerated dose was determined to be 2-2.5% on the basis of body-weight depression. In a long-term (2-yr) toxicity/carcinogenicity study, monosodium succinate was given ad lib. in drinking-water (distilled water) at levels of 0, 1 or 2% to groups of 50 male and 50 female rats. No toxic lesion specifically caused by long-term administration of monosodium succinate was detected. No dose-related increase was found in the incidences of tumours in any organ or tissue except for C-cell tumours of the thyroid gland of females. The incidence of these tumours in females given the 2% dose was higher than that in controls but not significantly so, and a positive trend for this tumour was noted in females. C-Cell tumour is one of the most commonly observed spontaneous tumours in ageing female rats of this strain and occurs at a variable incidence. There was no difference between the female control and treated groups in the incidence of preneoplastic change of the thyroid gland. Furthermore, the incidence of C-cell tumours in the female control group was lower than that in our historical controls. It is concluded that the increase in C-cell tumours in the female high-dose group and the detection of a positive trend for this tumour in females were probably a function of experimental variability and were not related to treatment. The results indicate that monosodium succinate had neither toxic nor carcinogenic activity in F344 rats when it was given continuously at levels of 1 or 2% in the drinking-water for 2 yr.
对食品添加剂琥珀酸二钠的毒性/致癌性在F344大鼠中进行了研究。经口半数致死剂量大于8克/千克体重。在一项为期13周的亚慢性经口毒性研究中，唯一的毒理学发现是饮用水中琥珀酸二钠含量大于或等于2.5%的组体重增加受到抑制。组织学检查显示，在任何接受治疗的大鼠的任何器官中，均未发现该化合物特异性引起的毒性损伤。基于体重下降情况，确定最大耐受剂量为2 - 2.5%。在一项长期（2年）毒性/致癌性研究中，将琥珀酸二钠以0%、1%或2%的水平随意添加到饮用水（蒸馏水）中，分别给予每组50只雄性和50只雌性大鼠。未检测到长期给予琥珀酸二钠特异性引起的毒性损伤。除雌性甲状腺C细胞肿瘤外，在任何器官或组织中均未发现肿瘤发生率与剂量相关的增加。给予2%剂量的雌性大鼠中这些肿瘤的发生率高于对照组，但差异不显著，且在雌性大鼠中观察到该肿瘤有阳性趋势。C细胞肿瘤是该品系老龄雌性大鼠中最常见的自发肿瘤之一，发生率各不相同。雌性对照组和治疗组甲状腺癌前病变的发生率没有差异。此外，雌性对照组中C细胞肿瘤的发生率低于我们的历史对照组。得出的结论是，高剂量雌性组中C细胞肿瘤的增加以及雌性大鼠中该肿瘤阳性趋势的检测可能是实验变异性的作用，与治疗无关。结果表明，当在饮用水中以1%或2%的水平连续给予F344大鼠2年时，琥珀酸二钠既无毒性也无致癌活性。
