STUDIES ON THE TOXICITY AND PHARMACOLOGICAL ACTION OF p-DIMETHYLAMINOBENZENEDIAZO SODIUM SULFONATE (DAS)

¹ University of Chicago Toxicity Laboratory and the Department of Pharmacology, University of Chicago, Chicago, Illinois

1. Measurement of the toxicity of p-dimethylaminobenzenediazo sodium sulfonate (DAS) administered intraperitoneally gave the following approximate LD50 values in mgm./kgm.: albino rats 15; albino mice 70, guinea pigs 30, rabbits 10-20, and dogs 5-10. The oral LD₅₀ for albino rats was about 55 mgm./kgm.

2. No tolerance to DAS was observed in rats and the rodenticide was acceptable and produced high mortality of rats when placed in the diet at concentrations of 0.5 per cent and 1.0 per cent.

3. Toxicity measurements on N,N-dimethyl-p-phenylenediamine given intraperitoneally gave the following LD₅₀ values in mgm./kgm.: albino rats 21, mice 25, guinea pigs 45, rabbits 100, and dogs 10-20. The differences in species susceptibility to this compound and DAS suggest that the latter substance does not undergo cleavage at the azo linkage before exerting its toxic effect.

4. DAS caused a generalized depression in all species, degeneration of the kidney tubules, hyperemia of the intestine and liver, a fall in blood pressure and respiratory paralysis.

5. Hyperglycemia followed by hypoglycemia occurred in animals poisoned by DAS. The extent of these changes was dependent upon the dose of DAS and the species susceptibility to the agent. The hyperglycemia could be prevented by insulin or by adrenal-demedullation but survival of the animals was not influenced by these treatments. The hypoglycemic convulsions could be terminated or prevented by glucose which prolonged the survival time but did not prevent ultimate death of the animals.

6. A depletion of liver and muscle glycogen of rats was observed after administration of DAS and the animals were unable to deposit liver glycogen from injected glucose; this indicated that DAS exerts an inhibitory action on glycogen synthesis.