PHYSIOLOGY, PHARMACOLOGY, AND TOXICOLOGY 391 



the males being much more resistant. Thus, whereas 600. mg/kg. pro- 

 duced a 100 per cent mortality in females, 1600 mg/kg. did not kill any- 

 male mice. Five mg/kg intraperitoneal^ does not affect rats or rabbits 

 when administered daily over long periods, but doses of 50 to 75 mg/kg 

 do have some slight effects. All efforts to demonstrate any pharmacologi- 

 cal activity have been unsuccessful. 114 



Pantothenic Acid, Biotin, p-Aminobenzoic Acid, and Inositol. Little 

 is known concerning the pharmacology of pantothenic acid. Intravenous 

 doses as high as 100 mg have been given to man without apparent 

 effects" (p. 422). Monkeys have been fed as high as one gram per day 

 and rats have also been given one gram per rat per day without apparent 

 harmful effects. Biotin, p-aminobenzoic acid and inositol are also known 

 to be relatively nontoxic but have been little studied in this regard. A 

 number of esters of p-aminobenzoic acid (the ethyl ester, "Benzocaine," 

 and the butyl ester, "Butesin") have however been widely used as local 

 anaesthetics. 



Summary of Relationships 



It is apparent that the B vitamins play certain physiological roles in 

 the higher animals that differ from their maintenance functions in cellular 

 metabolism, and these roles occur by virtue of the existence of differen- 

 tiated physiological functions in the higher animals. In these cases the 

 vitamins undoubtedly act in the same type of reaction, but the process in 

 which the reaction occurs is not one characteristic of all living cells. The 

 fact that only a few such relationships can be demonstrated lucidly at 

 present is probably the result of the state of our learning rather than an 

 indication of a limitation to the number of "special cases." It seems 

 entirely reasonable to expect that in the evolutionary scale, increased 

 morphological complexity would demand an increased complexity in 

 catalyst functions, and this view should receive considerable elucidation 

 in the years ahead. 



The symptoms of vitamin deprivation, and physiological and phar- 

 macological levels of B vitamin administration, apparently bear little 

 relationship to one another. To some extent, this may be a reflection upon 

 the present status of knowledge. It is also apparent however that closely 

 similar structural analogues may have vastly different pharmacodynamic 

 properties. Of considerable theoretical and practical interest in this regard 

 is the allergic reaction to thiamine, since the symptoms in hypersensitivity 

 bear little or no relationship to the structure of the causative reagent. The 

 implications of this situation in regard to future plans for high vitamin 

 therapy are of the greatest significance, and it may be anticipated that 

 similar sensitivities will appear for other B vitamins. One cannot but 



