X. TOXICITY 49 



'I'ho fate of PABA in tlic kidney lias Ween stiulicd l)y Jjiiiukiuist,'-'* usinj>; 

 tlu' tot'hiii<nu's ot" modern renal pliysiolojiiy. It was concluded that PABA 

 is secreted by the tubules in addition to being filtered by the glomerulus. 

 Unfortunately, here, too, PABA was determined by tlie Bratton-Marshall 

 colorimetiic method which does not difTerentiate between PABA and 

 /;-aminohippuric acid (PAHA). Since it is well known that PAHA is 

 secreted by the tubules, the significance of Lundquist's conclusions may 

 be questioned. Similarly, Terp's conclusions-^^ that PABA is eliminated by 

 tulndar secretion in the dog and rabbit is open to question because the 

 method employed in the determination of PABA does not differentiate 

 P.\BA from PAHA. 



Beyer et al?'' have studied PABA clearance in the dog, utilizing the 

 Cohen and McGilvery^^ method involving ether extraction at pH 3.95 for 

 the separation of PABA from PAHA. Extremely low clearance ratios for 

 PABA were found, thus indicating tubular reabsorption. Although com- 

 parisons between the human being and the dog with respect to renal phys- 

 iology are not always warranted, it would be surprising, indeed, if clearance 

 studies of PABA in the human subject, utilizing a specific method for the 

 determination of PABA, did not show low renal clearance for PABA, 

 indicativ^e of tubular reabsorption. 



PABA is excreted dermallj^ to the extent of about 0.24 7 per 100 ml. of 

 sweat, according to Johnson el alP Their results were based on microbio- 

 logical assays with Acetohacter suboxydans. 



X. Toxicity 



LEMUEL D. WRIGHT and PETER A. TAVORMINA 



A. IN LABORATORY ANIMALS 



The acute toxicity of PABA and its sodium salt has been determined 

 in animals by Scott and Robbins.^ The results are summarized in ^fable 

 VIII. 



Orally, acute toxic signs in mice consist at first only of weakness and 

 loss of normal posture, death occurring in several hours. Mild chronic 



" F. Lundquist, Acta Pharmacol Toxicol. 1, 307 (1945). 

 36 P. Terp, Acta Pharmacol. Toxicol. 7, 259 (1951). 



" K. H. Beyer, E. K. Tillson, H. F. Russo, G. S. Schuchardt, and A. A. Pitt, Federa- 

 tion P roc. 11, 13 (1952). 

 38 P. P. Cohen and R. W. McGilvery, J. Biol. Chem. 166, 261 (1946). 

 " B. C. Johnson, H. H. Mitchell, and T. S. Hamilton, J. Biol. Chem. 161, 357 (1945). 

 ' C. C. Scott and E. B. Rol)hins, Pmc. Soc. Expll. Biol. Med. 49, 184 (1942). 



