The effect of the administration of salvarsan in combination with various colloid substances on its toxicity

Abstract

In some unpublished articles it has been shown that the ill effects following salvarsan administration may be divided into two types; first, an immediate reaction from which the animal dies suddenly in a convulsive seizure as a result of embolism of its agglutinated red cells, and second, a late death occurring in from two days to as many weeks, which is the result of degenerative lesions in the kidneys and liver. As the former has been shown to be the effect of the physical properties of the salvarsan solution, while the later is the result of its chemical constitution, we have suggested the terms “physical” and “chemical” toxicity for these two types of ill effects. We have also studied the protective action of various colloids on the process of agglutination of red cells in vitro and found that there is a marked inhibition of the agglutination from salvarsan by certain of these substances. 1

Recently the effect of the administration of salvarsan in mixture with these protective colloids has been studied. An almost complete removal of the physical toxicity of salvarsan has been found. Under our standard conditions an animal rarely survives the injection of more than .27 gram per kilo of 2 per cent. disodium salvarsan. Yet we have repeatedly given doses of .40 gram per kilo of a similar preparation mixed in a 3 per cent. solution of gelatin with no immediate ill effects. Such animals die from the late chemical toxicity of this tremendous dose in the course of a few days.

The late chemical toxicity of salvarsan is also lessened. Under the conditions of our experiments the maximum tolerated dose of salvarsan was found to be .og gram per kilo, the majority of animals receiving such a dose surviving two weeks.