RESULTS: First, Ames tests were carried out using strains TA1535, TA100, TA1538, and TA98 and their nitroreductase-deficient strains YG7127, YG7128, YG7129, and YG7130. The results showed that mutagenic activity was reduced by about 50% in the nitroreductase-deficient strains, indicating that part of the mutagenic activity shown in Ames test was due to bacterial metabolism. Second, in vivo genotoxicity tests were conducted, including the one that had not been developed in 1970\'s. Both a micronucleus test and a gene mutation assay using transgenic mice were negative. Third, assuming it is a genotoxic carcinogen, the virtual safety dose of 550 μg/day was calculated from the TD50 in rats with a probability of 10-5.
CONCLUSIONS: AF-2 has been shown to be carcinogenic to rodents and has previously been indicated to be genotoxic in vitro. However, the present in vivo genotoxicity study, it was negative in the forestomach, a target organ for cancer, particularly in the gene mutation assay in transgenic mice. Considering the daily intake of AF-2 in the 1970s and its virtually safety dose, the carcinogenic risk of AF-2 could be considered acceptable.
结果:首先,使用菌株TA1535,TA100,TA1538和TA98及其硝基还原酶缺陷型菌株YG7127,YG7128,YG7129和YG7130进行了Ames测试。结果表明,硝基还原酶缺陷型菌株的诱变活性降低约50%,表明Ames试验中显示的部分诱变活性是由于细菌代谢所致。第二,进行了体内遗传毒性试验,包括1970年代没有开发的。使用转基因小鼠的微核试验和基因突变测定均为阴性。第三,假设它是基因毒性致癌物,根据大鼠的TD50计算出550μg/天的虚拟安全剂量,概率为10-5.
结论:AF-2已被证明对啮齿动物具有致癌性,并且先前已被证明在体外具有遗传毒性。然而,目前的体内遗传毒性研究,前胃是阴性的,癌症的靶器官,特别是在转基因小鼠的基因突变分析中。考虑到20世纪70年代AF-2的每日摄入量及其几乎安全的剂量,AF-2的致癌风险可被认为是可接受的.