50 P-AMINOBENZOIC ACID 



convulsions with death in 5 to 10 minutes result from intravenous lethal 

 doses in mice and rats. In dogs, 1 to 2 days elapse before death occurs. 

 Toxic signs are tremor, listlessness, and weakness. Toxic and chronic 

 convulsions were observed in one dog receiving 3.0 g. per kilogram. Au- 

 topsies in the animals which received lethal doses show acute gastroenteritis 

 with hemorrhages apparently of capillary origin in the small intestine. 

 Acute necrosis of the liver occurred in the dogs given the two highest 

 dosages. In chronic toxicity trials of 28 days' duration, growing rats re- 

 ceiving up to 1.4 g. of PABA per kilogram orally per day made as good 

 gains as the controls. At autopsy none of the rats receiving the drug showed 

 evidence of toxicity. 



Richards^ studied the toxicity of sodium /^-aminobenzoate at pH 6.0 in 

 a number of species. Only 30 % of a group of rats died after intravenous 

 injections of 4 g. per kilogram. The symptoms consisted of comailsions and 



TABLE VIII 

 Acute Toxicities of PABA and Its Sodium Salt 



respiratory paralysis that might be due to the high osmotic pressure of 

 the solution. On a dose of 4 g. per kilogram given intraperitoneally, 40% 

 died within a few hours. No deaths occurred after oral dosages unless at 

 least 6 g. per kilogram was fed daily for 3 successive days. The LD50 in 

 rabbits is approximately 2 g. per kilogram, given intravenously. The blood 

 pressure of dogs and cats is raised slightly by doses of 100 mg. of PABA 

 per kilogram, but this rise was found to depend upon the rate of injection 

 of the drug. No change in respiration occurs. 



Chronic intraperitoneal toxicity of PABA in growing rats at the single 

 level of 7.5 mg. per day has been studied by Sullivan and Archdeacon.* 

 After 48 days of treatment, rats receiving PABA show distinct s3anptoms 

 of toxicity. Prominent evidences of toxicity are depressed growth, bloated 

 abdomens, diarrhea, and increased weight of the adrenals. 



Chronic oral toxicity of PABA in growing rats at a level of 3 % of the 

 diet was studied by Gordon et al} PABA feeding causes a significant in- 



2 R. K. Richards, Federation Proc. 1, 71 (1942). 



•^ C. D. Sullivan and J. W. Archdeacon, Endocrinologij 41, 325 (1947). 



" A. S. Gordon, E. 1). Goldsmith, and H. A. Charipper, Endocrinologij 37, 223 (1945). 



