MESO-2,3-DIMERCAPTOSUCCINIC ACID MONOALKYL ESTERS - EFFECTS ON MERCURY LEVELS IN MICE

Seven monoesters of meso-2,3-dimercaptosuccinic acid (DMSA) were evalu ated for relative activities in mobilizing and promoting excretion of mercury in mercury-laden mice. Compounds assessed were the ethyl (M-ED MS), n-propyl (Mn-PDMS), isopropyl (Mi-PDMS), n-butyl (Mn-BDMS), isobu tyl (Mi-BDMS), n-amyl (Mn-ADMS), and isoamyl (Mi-ADMS) esters. 2,3-Dim ercaptopropane-1-sulfonate (DMPS) and DMSA were used as positive contr ols. After the first oral dose of each compound at 0.5 mmol/kg, DMSA a nd DMPS reduced the corporal mercury burden 16% and 24%, respectively, compared to controls, while the monoesters effected reductions of 35% (M-EDMS) to 49% (Mi-ADMS). After the second treatment at the same dos e, the respective reductions produced by DMSA and DMPS were 24% and 38 %, and those conferred by the monoesters ranged from 52% (M-EDMS) to 6 1% (Mn-BDMS). Determination of the comparative dose-response relations hips of DMSA and Mi-ADMS on corporal and renal mercury concentrations revealed the monoester to be more active than DMSA on both parameters at each dose used. The cumulative amount of mercury excreted in urine by control mice over a 3-day period was 7.08 mug; this was increased 2 2%, 85%, and 94% by daily i.p. injections of DMSA, DMPS, and Mi-ADMS, respectively, at a daily dose of 0. 1 mmol/kg. The respective cumulati ve 3-day totals recovered in feces from control mice and from mice tre ated with DMSA, DMPS, and Mi-ADMS were 9.76, 8.2 1, 10.44, and 11.73 m ug. Parallel daily measurements of retained whole body radioactivity f rom Hg-203 in mice were in good agreement with the values calculated f rom the excretion data.