Approximate lethal dose versus median lethal dose in acute toxicity testing of pharmaceuticals. A retrospective study.

The relation between approximate lethal doses (ALD, i.e. the lowest dose at which mortality occurs) and the corresponding median lethal doses (LD50) was investigated in 231 acute toxicity studies in mice and rats. The ALD values were divided into four classes (less than 5 mg/kg, 5-50 mg/kg, 50-500 mg/kg, 500-2000 mg/kg) and the LD50/ALD factors were calculated. In intravenous studies the LD50 values were higher than the ALD values by mean factors of 1.27-1.61 in mice and 1.25-2.84 in rats. In oral studies the LD50 values were higher by mean factors of 1.46-2.5 in mice and 1.59-2.1 in rats. Only in 20 cases (8.7%) did the LD50 values differ by factors higher than 2.