The toxicity of three gold compounds in laboratory animals.

Abstract

Compounds of gold have been used in the treatment of human rheumatoid arthritis for several decades, and their effectiveness is generally accepted. The compounds currently used (Myochrysine@ and Solganal? are poorly absorbed by the gastrointestinal tract and consequently are administered by deep intramuscular injection. The toxic effects of these two drugs in laboratory animals are not well known; there are no published reports of studies by currently accepted procedures. The series of papers which follow is intended to provide a profile of the toxicology of gold-containing compounds used in the treatment of arthritis. They are based on our studies of 2 gold-containing compounds that are effective after oral administration in the suppression of adjuvant-induced arthritis in rats,'. and on Myochrysine, which is given parenterally. Throughout the reports in this series of papers the doses are given as amount of compound, followed by the gold content in parentheses. Comparisons between doses of the three compounds dealt with are not appropriate. This is obviously so where the routes of administration and frequency of dosing differ. However, it also applies to the two orally administered compounds, because of differing percentages of absorption, excretion and tissue distribution; there may be other, unknown differences as well. Only qualitative comparisons are appropriate. For both the oral and injectable gold compounds ionic gold, Ag, is being administered and not molecular gold, Ag2. The effects of molecular gold (e.g., as used in dental restorations) are not considered herein. Comprehensive monitoring of many parameters, typical of toxicity studies of pharmaceutical agents, was done. To have included the raw data or comment on parameters that were not significantly altered would have obscured the major features of the toxicologic profiles which emerged from the studies. Some small changes of minor interest are mentioned only once, although they occurred in subsequent similar studies. Furthermore, some entire studies are not reported at all since no significant compound-related effect occurred. Despite the omission herein of the many details submitted in the dossiers to governments, considerable repetition of findings from