XI. PHARMACOLOGY 391 



can be cured by riboflavin."* Vascular networks of the iris were markedly 

 improved after only 2 days of riboflavin supplementation. 



Kruse and colleagues'-^' '-* reported corneal vascularization in forty-five 

 of fort^^-seven patients Avith riboflavin deficiency. Proliferation and en- 

 gorgement of the bulbar conjunctival capillaries of the limbar plexus were 

 considered by them to be the earliest and most common sign of aribo- 

 flavinosis. As a consquence of many controversial reports,'''^''^' the signifi- 

 cance of these observations is not clear. No evidence of corneal vasculariza- 

 tion was noted by the Elgin group''- despite frequent slit-lamp examinations 

 of subjects before, during, and after experimental riboflavin deficiency. 



XI. Pharmacology 



M. K. HORWITT 



The low solubility of riboflavin may be responsible for its relative innocu- 

 ousness. Unna and Greslin' found that oral administration of 10 g. per 

 kilogram to rats and 2 g. per kilogram to dogs produced no toxic effects. 

 Giving 340 mg. per kilogram to mice intraperitoneally, which is 5000 times 

 the therapeutic dose, or the equivalent of 20 g. per day for a man, had no 

 apparent effect.-'* The rat LD50 for riboflavin following intraperitoneal ad- 

 ministration was 560 mg. kilogram.' Death, which was due to kidney con- 

 cretions, occurred in 2 to 5 days. Similar results were obtained by Antopol^ 

 after intraperitoneal administration of 125 to 500 mg. per kilogram of the 

 sodium salt. In addition, cytological changes were noted in the heart, 

 pancreas, and pituitary gland, and the adrenals were markedly congested. 



Since crystalline concretions of riboflavin were readily detectable in the 

 ureter and bladder within a few hours after a saturated solution of riboflavin 



1" H. S. Stannus, Trans. Ophthalmol. Soc. United Kingdom 62, 65 (1942). 



"5 J. B. Youmans, E. W. Patton, W. D. Robinson, and R. Kern, Trans. Assoc. Am. 



Physicians 57, 6 pp. (1942). 

 >^6 H. R. Sandstead, Public Health Repts. (U.S.) 57, 1821 (1942). 

 '••^ D. Vail and K. W. Ascher, Am. J. Ophthalmol. 26, 1025 (1943). 

 i« F. F. Tisdall, J. F. McCreary, and H. Pearce, Can. Med. Assoc. J. 49, 5 (1943). 

 "9 J. F. McCreary, J. V. V. Nicholls, and F. F. Tisdall, Can. Med. Assoc. J. 51, 106 



(1944). 

 "0 H. S. Stannus, Brit. Med. J. II, 103 (1944). 

 >" J. G. Scott, J. Roy. Army Med. Corps 82, 133 (1944). 



1 K. Unna and J. G. Greslin, ./. Pharmacol. Exptl. Therap. 76, 75 (1942). 



2 R. Kuhn and P. Boulanger, Z. physiol. Chem. 241, 233 (1936). 

 3R. Kuhn, Klin. Wochschr. 17, 222 (1938). 



* V. Demole, Z. Vitaminforsch. 7, 138 (1938). 



6 W. Antopol, /. Med. Soc. New Jersey 39, 285 (1942). 



