L-甲基叶酸钙(L-5-MTHF-Ca;CAS号151533-22-1)是叶酸的来源,也是叶酸的替代品,用于人类食品和食品补充剂。通过遗传毒性测试评估L-5-MTHF-Ca的安全性,亚慢性和产前发育毒性。在体外测定中,L-5-MTHF-Ca不致突变并且不诱导其它染色体事件。此外,L-5-MTHF-Ca在体内微核试验中没有遗传毒性,也没有诱导大鼠肝细胞的DNA损伤。在一项亚慢性毒性研究中,通过口服管饲法给予高达400mg/kgbw/天的L-5-MTHF-Ca的大鼠13周没有治疗相关的死亡率,没有发现与治疗相关的行为影响,体重,食物消费,眼科,血液学,或器官重量。未观察到治疗相关的宏观或组织病理学发现。钙和钠水平随着剂量的增加而增加,然而,轻微的增加在历史控制范围内,并且在恢复期后是可逆的。L-5-MTHF-Ca既不致畸也不具有胚胎毒性。根据体外和体内研究的结果,支持L-5-MTHF-Ca作为食品成分的安全使用.未观察到的不良反应水平是亚慢性毒性研究中的最高剂量,即雄性和雌性大鼠400毫克/千克体重/天。
Calcium L-methylfolate (L-5-MTHF-Ca; CAS Number 151533-22-1) is a source of folate and an alternative to folic acid for use in human food and food supplements. The safety of L-5-MTHF-Ca was evaluated by testing for genotoxicity, subchronic and prenatal developmental toxicity. In in vitro assays L-5-MTHF-Ca was not mutagenic and did not induce other chromosomal events. Additionally, L-5-MTHF-Ca was not genotoxic in the in vivo micronucleus test nor did it induce DNA damage in rat liver cells. In a subchronic toxicity study, rats administered up to 400 mg/kg bw/day of L-5-MTHF-Ca via oral gavage for 13 weeks had no treatment-related mortalities, and no treatment-related effects were identified on behaviour, body weight, food consumption, ophthalmology, haematology, or organ weights. No treatment-related macroscopic or histopathological findings were observed. Calcium and sodium levels increased with increasing dosage, however the slight increases were within historical control ranges and reversible after the recovery period. L-5-MTHF-Ca is neither teratogenic nor embryotoxic. Based on the results of the in vitro and in vivo studies, the safe use of L-5-MTHF-Ca as an ingredient in foods is supported. The no observed adverse effect level was the highest dose in the subchronic toxicity study, i.e. 400 mg/kg bw/day for male and female rats.