Oral toxicity of the cyclic polyethers—12-crown-4, 15-crown-5, and 18-crown-6—in mice

The acute and chronic oral toxicities of a homologous series of three crown ethers in mice have been studied. The LD50 values and the partition coefficients (octanol/water) of the compounds have been determined. The LD50 values are as follows: 12-crown-4, 3.15 g/kg; 15-crown-5, 1.02 g/kg; and 18-crown-6, 0.71 g/kg. The compounds follow a general trend of increasing toxicity with increasing ring size and water solubility. There appears to be no cumulative effect of daily ingestion of small amounts (one-half to one-third the LD50 value) of the compounds over a 2-week period.