Toxicity study of europium chloride in rats

EuCl3.6H2O was administered by gavage for 28 consecutive days to groups of 10 male and 10 female rats (Slc:Wistar strain) at doses of 0, 40, 200, or 1000 mg/kg/day. Additional groups of male and female rats receiving the 0 and 1000 mg/kg doses were used to assess recovery after 14 days subsequent to cessation of compound administration. Body weights and food consumption were measured, and hematological, clinical biochemistry, and histopathological examination were performed. The concentrations of europium (Eu) and of essential elements in organs were determined by ICP-MS or ICP-AES. In the rats of each sex dosed at 200 and 1000 mg/kg, the body weight gain significantly decreased because of reduction in food consumption. Hyperkeratosis of the forestomach and eosinocyte infiltration of the stomach submucosa were found in both sexes receiving the 1000 mg/kg dose group, suggesting an irritation effect by EuCl3.6H2O. The Eu levels increased dose dependently in the liver, kidneys, spleen, and femurs, and the accumulated volume of Eu in these organs was estimated to be about 1/100,000 of the total dosed amount. The administration of EuCl3.6H2O increased the serum iron concentration in males and the serum total iron binding capacity in each sex and decreased cholinesterase activity in females in the 1000 mg/kg dosed group. Iron concentrations in the spleen and strontium concentrations in the femurs of rats of both sexes dosed at 1000 mg/kg were significantly decreased. We concluded that the no-observed-effect level is 200 mg/kg/day. Our investigation demonstrated that elemental analyses of organs is a useful approach to toxicological study.