Salvarsan. 



305 



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 pro- 

 tective 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 com- 

 plete 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 .09 gram per kilo, the majority of 

 animals receiving such a dose surviving two weeks. When ad- 

 ministered in 3 per cent, gelatin solution, the maximum tolerated 

 dose was found to be .14 gram per kilo. Administration in 

 acacia solution and in serum was found much less effective in 

 reducing the toxicity, the maximum tolerated dose in the former 

 case being .10 gram per kilo. 



Repeated injections of large doses are also better tolerated if 

 the salvarsan is administered in gelatin solution. In some 

 previous experiments animals were given .10 gram per kilo every 

 three days. All the animals died, the majority after the second 

 injection, and on microscopic examination showed marked necrosis 

 of their kidneys. Three rabbits receiving the same dose in gelatin 

 solution withstood 4, 6 and 7 doses and lived 9, 16 and 24 days 

 respectively. The kidneys of these animals showed in the first 

 case a slight parenchymatous degeneration with some necrosis, 

 while in the other two no definite lesions were found. 



1 These articles will appear in an early number of the Journal of Pharmacology and 

 Experimental Therapeutics. 



