54 P-AMINOBENZOIC ACID 



caused no toxic reactions when the substance was administered as a single 

 dose by stomach tube. In mice, 50 mg. subcutaneously was without effect, 

 although larger amounts caused temporary excitation followed by pa- 

 ralysis.^" EUinger and Hensel^ noted that 1 g. subcutaneously produced 

 death in some rabbits, but HenseF^ subsequently found that doses up to 

 2 g. subcutaneously per day for 4 days were apparently non-toxic. 



Tadpoles could withstand a 0.5% solution for 3 days, when death oc- 

 curred.-- A dose of 1 g. per kilogram was tolerated by dogs but 10 g. per 

 kilogram caused emesis. In humans, 5 g. produced nausea and ^'omiting, 

 although this dose is now commonly exceeded. Toxic symptoms in mam- 

 mals were similar to those following aniline, namely, fall of body tempera- 

 ture, marked muscular weakness, accelerated respirations, cardiac depres- 

 sion, tetanic cramps, and finally death from respiratory standstill. 



According to Selbie,-^ the oral lethal dose in mice was 100 to 200 mg. 

 Scott and Robbins'-^ found PABA to be more toxic to mice and dogs than 

 to rats. In dogs, single oral doses larger than 1 g. per kilogram caused death 

 in some instances, with acute gastroenteritis and hemorrhage into the 

 small bowel. Acute necrosis of the liver resulted from doses of 2 g. per kilo- 

 gram. Rats, however, tolerated a daily oral dose of 1.4 g. per kilogram for 

 4 weeks without inhibition of growth or appearance of pathologic changes. 

 Intravenous injection of 4 g. per kilogram was lethal to 30% of rats, mani- 

 festations of toxicity being convulsions and respiratory paralysis.^* Given 

 intraperitoneally, this dose killed 40 % of the animals within 4 hours. 

 Given orally, no deaths occurred unless at least 6 g. per kilogram was fed 

 daily for 3 consecutive days. The LD50 intravenously in rabbits was ap- 

 proximately 2 g. per kilogram. Young rats injected with 200 to 500 mg. 

 per kilogram daily for 21 days grew slightly faster than controls. No ab- 

 normalities in the blood or urine were noted. After receiving 600 mg. per 

 kilogram intraperitoneally, rats showed a slight increase of oxygen con- 

 sumption. 



On feeding 1 % PABA in the diet of female rats, Ershoff-^ could find no 

 adverse effect on growth, reproduction, or lactation. Adult male rats which 

 ate a diet containing 3 % PABA gained weight normally, and the blood 

 picture did not change.'-^ On the other hand, Sullivan and Archdeacon'* 



20 H. Hildebrandt, Beitr. Chem. Physiol. Pathol. 3, 365 (1903). 



21 M. Hensel, Z. phijsiol. Chem. 93, 401 (1915). 



-2 A. Oswald, Chemische Konstitution und Pharmakologische Wirkung. Gebriider 

 Borntrager, Berlin, 1924. 



23 F. R. Selbie, Brit. J. Exptl. Pathol. 21, 90 (1940). 



24 C. C. Scott and E. B. Robbins, Proc. Sac. Exptl. Biol. Med. 49, 184 (1942). 



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



2« B. H. Ershoff, Proc. Soc. Exptl. Biol. Med. 63, 479 (1946). 



27 A. S. Gordon, E. D. Goldsmith, and H. A. Charipper, EndocrinoUujy 37, 223 (1945). 



28 C. D. Sullivan and J. W. Archdeacon, Endocrinology 41, 325 (1947). 



