硝酸镧致突变性及致畸性评价  

Toxicological experiments-based evaluation on mutagenicity and teratogenicity of lanthanum nitrate

作　　者：肖倩倩 刘青云 康陈萍 孟庆贺 蒋建军[1,2] 杨晓华 尚兰琴[1,2] 郝卫东 XIAO Qianqian;LIU Qingyun;KANG Chenping;MENG Qinghe;JIANG Jianjun;YANG Xiaohua;SHANG Lanqin;HAO Weidong(Department of Toxicology,School of Public Health,,Peking University,Beijing 100191,China;Key Laboratory of Toxicological Research and Risk Assessment for Food Safety,Beijing 100191,China)

机构地区：[1]北京大学公共卫生学院毒理学系,北京100191 [2]食品安全毒理学研究与评价北京市重点实验室,北京100191

出　　处：《中国公共卫生》2023年第10期1304-1310,共7页Chinese Journal of Public Health

基　　金：国家重点研发计划(2017YFC1600203)。

摘　　要：目的评价硝酸镧的致突变性和致畸性,为稀土元素的安全使用提供科学依据。方法根据硝酸镧对ICR小鼠的半数致死剂量(LD50),分别设高、中、低(雄性为875、437.5、218.75 mg/kg·BW;雌性为1015、507.5、253.75 mg/kg·BW)3个剂量组,对ICR小鼠(每组10只,雌雄各半)进行骨髓细胞微核试验,观察硝酸镧对小鼠骨髓微核细胞率的影响;根据硝酸镧对CHL细胞的半数抑制浓度,分别设高、中、低(不加S9混合液时为1×10^(-3)、1×10^(-4)、1×10^(-5)mol;加S9混合液时为5×10^(-3)、2.5×10^(-4)、1.25×10^(-5)mol)3个剂量组,进行体外哺乳动物细胞(接种至25 mL细胞培养瓶中对数分裂期生长良好的CHL细胞,1×10~6个/瓶)染色体畸变试验,观察硝酸镧对哺乳动物细胞染色体畸变率的影响;设硝酸镧5个剂量组(分别为5、1、0.2、0.04、0.008 mg/皿),在S9代谢活化系统存在或不存在的条件下进行鼠伤寒沙门氏菌(TA97、TA98、TA100、TA102、TA1535)回复突变试验,观察硝酸镧对鼠伤寒沙门氏菌回复突变的影响。设硝酸镧3个剂量组(分别为9、36、144 mg/kg·BW),通过对SD孕鼠(每组至少15只)的致畸试验,观察硝酸镧对孕鼠生长和着床能力、胎仔体重和身长情况及对胎鼠骨骼畸形率、各脏器畸形率及总内脏畸形率的影响。结果小鼠骨髓细胞微核试验结果显示,硝酸镧各剂量组的微核细胞率与阴性对照组比较,差异无统计学意义(P>0.05)。体外哺乳动物细胞染色体畸变试验结果显示,在不加S9混合液的条件下,硝酸镧在1×10^(-5)M时可导致染色体畸变细胞率升高(χ^(2)=12.109,P<0.01),但畸变细胞率<5%,可能不具有生物学意义;在加S9的条件下,硝酸镧各剂量组的染色体畸变细胞率与阴性对照组比较,差异无统计学意义(P>0.05)。鼠伤寒沙门氏菌回复突变试验结果显示,在S9代谢活化系统存在或不存在的条件下,硝酸镧各剂量组的回复突变菌落数与阴性对照组比较�Objective To evaluate mutagenic and teratogenic effects of lanthanum nitrate for providing evidence to safe use of the rare earth element.Methods The mutagenicity of lanthanum nitrate was evaluated by micronucleus assay on mouse bone marrow cells,in vitro chromosome aberration test,and Salmonella typhimurium strains bacterial reverse mutation test and the teratogenic effect of lanthanum nitrate was assessed with teratogenicity test in rats.The micronucleus assay on mouse bone marrow cells was performed in three groups of ICR mice(10 in each group,half male and half female)administrated with lanthanum nitrate at concentrations(mg/kg·BW)of 875,437.5,218.75 for the male mice and 1015,507.5,253.75 for the female mice according to the median lethal dose(LD50)of lanthanum nitrate for the mice.The chromosome aberration test of mammalian cells in vitro was conducted on Chinese hamster lung(CHL)cells(with good growth during logarithmic division and inoculated into 25 mL cell culture bottle,1×10^(6) cells per bottle)treated with lanthanum nitrate at concentrations of 1×10^(-3),1×10^(-4),1×10^(-5)mol(without S9 mixture)and 5×10^(-3),2.5×10^(-4),1.25×10^(-5)mol(with S9 mixture)based on the median inhibition concentration(IC50)of lanthanum nitrate on CHL cells.Five lanthanum nitrate dose groups(5,1,0.2,0.04,0.008 mg/dish,respectively)were set up to carry out Salmonella typhimurium(TA97,TA98,TA100,TA102,TA1535)strains bacterial reverse mutation test in the presence or absence of S9 metabolic activation system.In teratogenicity test on pregnant Sprague-Dawley(SD)rats(at least 15 in each group),three lanthanum nitrate dosages of(9,36,144 mg/kg·BW)were determined and the growth and implantation ability and the offspring rats′weight and length,rate of skeletal malformation,rate of organ malformation and total rate of viscera malformation were oberserved.Results In micronucleus assay,the micronucleus formation rates of bone marrow cells in each lanthanum nitrate dose group were similar with that of vehicle control group(

关 键 词：硝酸镧 致突变性 致畸性 安全性评价 

分 类 号：R114[医药卫生—卫生毒理学]