Comparison of the effect of N-(2,3-dimercaptopropyl) phthalamidic acid, dl-penicillamine, and dimercaprol on the excretion of tissue retention of mercury in mice

Abstract The effect of N -(2,3-dimercaptopropyl) phthalamidic acid (DMPA) on the elimination and tissue retention of mercury was investigated on male ddY mice and was compared with those of dimercaprol (BAL) and dl -penicillamine ( dl -p). When 75 mg/kg (about a quarter of an LD50) of DMPA and HgCl 2 (0.5 mg Hg/kg) were injected subcutaneously at almost the same time for 5 days, a decrease of the mercury concentration in vital organs and blood and an increase in urinary and fecal elimination of mercury were noted. These effects were greater than those caused by BAL (25 mg/kg) and dl -p (50 mg/kg) injections. DMPA injected after the discontinuation of HgCl 2 dramatically increased the fecal excretion of mercury and inhibited its retention in tissues more effectively than did BAL and dl -p. Approximately the same results were obtained in an experiment using equimolar doses (55 mg/kg for DMPA, 25 mg/kg for BAL, or 30 mg/kg for dl -p) of these compounds. The mechanism involved in the action of DMPA on fecal excretion of mercury was also investigated. DMPA (75 mg/kg) and BAL (25 mg/kg) enhanced the bile flow rate and mercury excretion into bile, the effect of DMPA on the latter being 15% of the body burden and that of BAL, 5.4%, dl -p (50 mg/kg) had no appreciable effect on this. The thiol compounds did not immediately induce the absorption of mercury in bile from the small intestine, but 2 hr later about 8% of the mercury was absorbed in the DMPA group only. The compounds increased slightly the intestinal transit of mercury. An increase of mercury in feces after the injection of DMPA was thus concluded to be due to an increase in biliary excretion.