VIII. PHARMACOLOGY 



443 



when given to rats daily for 30 days. The growth rate of rats was found by 

 Hatton and associates'^ to be diminished if 0.3 % of the diet was menadione; 

 when the concentration was raised to 0.8 %, depression of growth was severe 

 and was accompanied by anemia and splenomegaly. Sublethal doses of 

 menadione derivatives (but not of phytyl menadione) have induced anemia 

 in dogs,'^ rats,'^ and rabbits,'^ but occasionally polycythemia has been 



TABLE VI 

 LDso OF Menadione Derivatives Administered in Single Doses to Animals 



Rabbit 



15-20 



98 



250 



91 



Dose in mg. per kg. body weight. 



^ No toxicity with 6 g. phytyl menadione per kg. body weight when administered subcutaneously or 

 with 25 g. per kg. given orally. 



"-' No toxicity with 25 g. phytyl menadione per kg. body weight when administered orally. 



"* Esters of menadiol were progressively less toxic, in order: diacetate, dipropionate, di-n-valerate, di- 

 n-butyrate, di-isovalerate; this last one was not lethal in doses of 18 g. per kg. when administered orally. 



" Compounds administered: 1, phthioool: 2, menadione; 3, menadione bisulfite; 4, menadiol disucci- 

 nate; 5, menadiol. 



observed in the same animals,^' apparently the result of chronically de- 

 creased oxygen consumption.'^ Excess menadione has been found to cause 

 methemoglobinemia;'^ Cannava" has duplicated the hemoglobin change 



95 E. H. Hatton, A. Dodds, H. C. Hodge, and L. S. Fosdick, J. Dental Research 24, 



283 (1945). 

 9« F. Roller, Schweiz. vied. Wochschr. 69, 1159 (1939). 



" A. Cannavd and L. Untersteiner Occhialini, Boll. sac. iial. biol. sper. 23, 1041 

 (1947). 



98 K. Fromherz, Z. Vitaminforsch. 11, 65 (1941). 



99 A. Cannavd, Boll. soc. Hal. biol. sper. 24, 593 (1948). 



