Influence of Site of Subcutaneous Injection upon Toxicity Figures

Abstract

Cupreine (M.W. 310) and quinine, its methyl ether 1 (M.W. 324), were injected subcutaneously in the flank in guinea pigs, chiefly males, in M/4 solutions in HCl to form very nearly the dihydrochlorides. Table I, Series 1, shows the results, deaths with-in 48 hours first, those within 7 days next and in brackets. The 48-hour toxicity curves intersect, although an earlier report 1 assigned to cupreine a toxicity to the guinea pig half that of quinine. With cupreine great irregularity is here seen and late deaths are frequent. Necropsies showed evidence of passage of both bases from the flank site toward or into the abdominal cavity, internal hemorrhage, mesenteric vascular engorgement, intestinal adhesions and necrosis all being noted. It was thought that cupreine might penetrate tissue and reach the peritoneal cavity more readily than quinine, and undergo in this experiment more frequently an accelerated absorption. Later therefore (Series 1 and 2) the site of injection was shifted for half the animals to the dorsum so as to hinder penetration into the abdominal cavity. The toxicity of the cupreine plainly fell (March 16), that of quinine remained of the same order as before. Late deaths became negligible. Further observations (Series 2) indicate that this shift of injection site makes little difference in the 50% lethal dose of quinine but probably doubles that of cupreine. It is clear that in comparative toxicity determinations the use of relatively large numbers of animals on each close may by itself be inadequate to give reliable results; the method must be given close scrutiny.