Strain dependent rate of Li+ elimination associated with toxic effects of lethal doses of lithium chloride in mice.

Strain differences in response to the administration of two lethal doses (700 and 900; mg/kg) of lithium chloride were studied in eight week old males from six genetic strains of mice. Two parameters were considered; (a) toxicity (time to death) and (b) hypothermia. Lithium distribution in the body (blood, seven tissues, excreta and urine) were evaluated for each strain following IP injection of 200 mg/kg dose of LiCl. The strain differences were significant for toxicity. The order of susceptibility of the strains was 129/ReJ greater than S.W. greater than C3H/S greater than DBA/2 = Balb/c greater than C57/6J with a 15-fold difference between the most susceptible and the least susceptible strain at the 900 mg/kg dose. Strain differences for hypothermic response at both doses were not significant. Significant strain differences were also observed for lithium distribution in different parts of the body, excreta and urine. The concentration of Li+ found in urine and excreta was positively correlated with resistance (time to death at 900 mg/kg LiCl) to the toxic effect of lithium. The lithium concentration in blood, muscle and lung on the other hand reflected a negative correlation with toxicity. The susceptibility of a strain could be characterized by its inherent lithium excretory ability, particularly through urine. It may suggest an involvement of membrane transport mechanisms in determining toxicity to lithium compounds.