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

  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 × 106 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 (P > 0.05) . In vitro chromosome aberration test, the rate of cells with chromosome aberration in 1 × 10 ^{– 5} M lanthanum nitrate group significantly increased in the absence of S9 compared to that of the control group (χ² = 12.109, P < 0.01); however, the proportion of cells with chromosome aberration was less than 5%, indicating a biological insignificance; in the presence of S9, there was no significant difference in chromosome aberration the between each lanthanum nitrate dose group and the control group (all P > 0.05). The results of Salmonella typhimurium strains bacterial reverse mutation test showed that there were no significant differences in the mutagenicity among lanthanum nitrate dose groups and the control group in both the presence and absence of S9 mixture. The results of teratogenic test showed that there were no significant differences in the growth and the implantation ability of pregnant rats among all dose groups and the vehicle group; lanthanum nitrate at concentration of 144 mg/kg BW inhibited fetal body weight and length significantly (both P < 0.05) and increased skeletal malformation of fetal rat compared with those of the vehicle group (χ² = 9.939, P < 0.05). However, there was no significant difference in organ-specific and total visceral malformation among the dose groups (P > 0.05 for all).

  Conclusions  The mutagenic effect of lanthanum nitrate was not observed under the conditions of this study and the study resulted in a no observable adverse effect level (NOAEL) of 36 mg/kg BW for lanthanum nitrate (15.38 mg/kg BW in terms of lanthanum).