Acute toxicity of some silver salts of sulfonamides in mice and the efficacy of penicillamine in silver.

The silver salt of 2-metanilamido-5-chloropyrimidine (AgMCP) and the sodium, amminosilver and trimethylphosphite-silver salts of 3',5'-dichlorobenzenesulfonanilide (NaDBS, AgNH3DBS and AgP(OCH3)3DBS were synthesized as possible antibiotic of antiparasitic drugs. All the organosilver compounds were extremely water-insoluble. For animal studies these, and other reference compounds, were given as fine suspensions in an Emulphor-safflower oil mixture. The ip LD50's in mice in mmol/kg were: 1.67 for NaDBS, 0.22 for silver acetate (AgAc), 0.15 for AgP(OCH3)3DBS, 0.13 for AgMCP and 0.10 for AgNH3DBS. When given by mouth, 15 mmol AgAc/kg produced a high mortality, but none of the organosilver compounds caused death in maximal doses (1.9 to 2.6 mmol/kg) that could be given based on considerations of total volume and stability of the suspension. All the silver compounds, including AgAc, produced a similar toxic syndrome with initial hyperexcitability, ataxia, central nervous depression, labored breathing, loss of righting reflex and death. Most deaths occurred between 12 and 24 hours after dosing. In contrast, animals given NaDBS often died within 3 hours although the major signs were very similar to those produced by the silver compounds. When given ip as a single dose 30 minutes after AgAc, D-penicillamine was effective in reducing mortality, but it had no effect on the mortality of the organosilver compounds. Histological studies revealed similar patterns of silver deposition, especially in the liver and kidneys, at 6, 18 and 24 hours after the organosilver compounds and after AgAc. We conclude that the presence of silver contributes significantly to the acute toxicity of these sulfonamides although they may dissociate free silver less readily than does AgAc.