目的 研究不敏感含能材料2,2',4,4',6,6'-六硝基二苯基乙烯(HNS)的急性经口毒性、急性眼刺激性、皮肤刺激性、皮肤致敏毒性,为HNS的职业健康防护提供理论指导.方法 根据《化学品毒性鉴定技术规范》,采用SD大鼠、豚鼠、日本大耳白兔进行急性经口毒性、皮肤致敏毒性、急性眼刺激性和皮肤刺激性试验.结果 急性经口毒性采用最大限量法一次性染毒,14 d观察期内大鼠无死亡,大体解剖无异常;急性眼刺激性试验,兔染毒0.1 g HNS后,眼刺激性总积分平均值为0分,未发现损伤作用;皮肤刺激性试验,兔染毒0.5 g HNS后,皮肤刺激性总积分平均值为0分,未观察到腐蚀性和刺激性;皮肤致敏试验,20只豚鼠染毒0.4 ml HNS,诱导浓度为1000 mg/ml,激发浓度为500 mg/ml,激发接触24 h后共有5只豚鼠皮肤出现轻微红斑或水肿,48 h后染毒组皮肤反应恢复正常.染毒组阳性致敏率与阴性对照组比较,差异有统计学意义(P＜0.05).结论 根据毒性分级标准进行判定,HNS低毒,无眼刺激性和皮肤刺激性,具有轻度致敏性.

在非代谢活化(-S9)和代谢活化(+S9)条件下,以1,1-二氨基-2,2-二硝基乙烯(FOX-7)处理小鼠淋巴瘤L5178Y细胞和中国仓鼠肺CHL细胞,进行体外哺乳动物细胞TK基因突变试验和染色体畸变试验.结果 显示,分别以500、250、125 μg/ml浓度的FOX-7处理L5178Y细胞,各剂量组突变频率与溶剂对照组相比,差异有统计学意义(P＜0.05),且具有剂量相关性;分别以300、200、100 μg/ml浓度FOX-7处理CHL细胞,各剂量组染色体畸变细胞率与溶剂对照组比较,差异无统计学意义(P＞0.05).提示FOX-7可能对小鼠淋巴瘤L5178Y细胞TK基因具有致突变性,对中国仓鼠肺CHL细胞染色体无致突变性.

Objective: To evaluated the potential developmental toxicity and teratogenicity of ammonium dinitroamide (ADN) by micromass test (MM Test) and embryonic stem cell test models. Methods: In September 2018, rat embryos were isolated and limb bud cells were collected. The limb bud cells were treated with different concentrations of ADN (0, 312.50, 625.00, 1250.00, 2500.00, 5000.00, 10000.00 μg/ml) . Half proliferation inhibitory concentration and half differentiation inhibitory concentration were calculated and the teratogenic effects were evaluated according to the criteria. For the embryonic stem cell test, the effects of different concentrations of ADN (0, 39.06, 78.13, 156.25, 312.50, 625.00, 1250.00, 2500.00 μg/ml) on the differentiation of mouse embryonic stem cells (mESCs) into myocardial cells and the cytotoxicity of mESCs and 3T3 cells were detected. The embryonic toxicity was evaluated according to the criteria. In this study, both 5-fluorouracil (5-FU) , a known strong embryonic toxic drug, and penicillin-G (P-G) , a non-embryonic toxic drug, were used to verify the effectiveness of the model, and the validated test model was applied to evaluate the embryonic toxicity of ADN. Results: In the MM Test, the inhibition rates of proliferation and differentiation of limb bud cells in ADN groups were higher than that in control group (P<0.05) . And the half proliferation inhibitory concentration and half differentiation inhibitory concentration of ADN on limb bud cells were 7480.32 and 4526.09 μg/ml, respectively. ADN was determined to be non-teratogenic by standard. In the embryonic stem cell test, the inhibition rates of mESCs proliferation in ADN groups were higher than that in control group, and the inhibition rates of 3T3 cells in 156.25, 312.50, 625.00, 1250.00, 2500.00 μg/ml ADN groups were higher than that in control group (P<0.05) . The half proliferation inhibitory concentration and half differentiation inhibitory concentration of ADN on mESCs were 1851.73 and 1796.39 μg/ml, respectively, and the half proliferation inhibitory concentration on 3T3 cells was 3334.35 μg/ml. ADN was determined to be non-embryotoxic by standard. Conclusion: After evaluation by MM Test and embryonic stem cell models, ADN has no embryo toxicity and is a non-teratogenic substance.