Dithiocarbamates and cadmium metabolism: further correlations of cadmium chelate partition coefficients with pharmacologic activity

N,N-bis(beta-Hydroxyethyl)dithiocarbamate (DHDC), N-methyl-N-hydroxyethyldithiocarbamate (MHDC), and N-ethyl-N-hydroxyethyldithiocarbamate (EHDC) were compared for their relative efficacies in promoting organ mobilization and excretion of metallothionein-bound cadmium (Cd). An attempt was made to correlate certain aspects of their pharmacodynamic properties with the octanol/aqueous partition coefficient of each Cd-dithiocarbamate complex. All compounds assessed were effective in mobilizing renal, intestinal, and testicular Cd. Those analogs with slightly greater lipid than aqueous solubility were more effective in this regard (DHDC less than MHDC less than EHDC). However, those analogs with higher lipid solubility (log10P greater than 0) promoted redistribution of Cd to liver. Only DHDC, with the lowest lipid solubility (log10P = -0.3 to -0.6), promoted Cd excretion. None of the congeners effected any redistribution of Cd to brain. Methods of preparation of the sodium salts of these analogs are described in detail.