292 PYRIDOXINE AND RELATED COMPOUNDS 



is detected within 1 hour by colorimetric tests as pyridoxine in the urine ;^^'^ 

 recovery of pyridoxine in the urine after ingestion of 8 to 100 mg. ranged 

 from 4 to 8%.^^'^'^^ Negligil)le amounts of pyridoxine appear m the 

 sweat. ^^ Microbiological assays which differentiate between pyridoxine, pyri- 

 doxal, and pyridoxamine have shown that normally only minute amounts 

 of any of the three forms of vitamin are found in urine. "^^ 4-Pyridoxic 

 acid,'-^ the main metabolic product of pyridoxine and also of pyridoxal and 

 pyridoxamine, accounts for 70 to 90 % of the excretion products measured 

 after ingestion of either form of vitamin Be in man.^^- ^'^' " It has also been 

 found in the urine of rats, but not of dogs.-^ Ingestion of large amounts of 

 pyridoxine leads to increased excretion of pyridoxal and also of pyridoxa- 

 mine. On the other hand, no evidence could be obtained showing the con- 

 version of pyridoxal or pyridoxamine to pyridoxine.^" 



Median lethal doses of pyridoxine hydrochloride have been determined 

 in animals as follows: on intravenous injection in mice (545 mg. per kilo- 

 gram) and in rats (657 mg. per kilogram) f^ on subcutaneous injection in rats 

 (3.7 g. per kilogram); and on oral administration in rats (5.5 g. per kilo- 

 gram).^ Tonic convulsions precede death in mice and rats. Doses larger 

 than 1 g. per kilogram administered to rats, rabbits, and dogs caused in all 

 three species characteristic manifestations which began w^ith marked im- 

 pairment of coordination and of righting reflexes within two or three days, 

 progressing to severe tonic convulsions and death in the stage of paralysis.^ 

 Autopsies showed enlargment of the adrenals with occasional hemorrhages 

 into the cortex. Neurohistologic examination of dogs and rats treated with 

 2 to 6 g. of pyridoxine per kilogram revealed degeneration of the posterior 

 columns of the spinal cord and in some cases also a w^ell-marked degenera- 

 tion of the posterior roots, posterior ganglia, and peripheral nerves.-^ 



Prolonged daily administration of pyridoxine to rats (25 mg. per kilo- 

 gram), dogs (20 mg. per kilogram), and monkeys (10 mg. per kilogram) 

 failed to cause any toxic manifestations or pathologic changes in the tissues.* 

 Rats receiving 2.5 mg. per kilogram daily were raised through three genera- 

 tions. Mice tolerated repeated intravenous injections of 100 mg. per kilo- 

 is J. V. Scudi, K. Unna, and W. Antopol, J. Biol. Chem. 135, 371 (1940). 

 i« T. D. Spies, R. K. Ladisch, and W. B. Bean, /. Am. Med. Assoc. 115, 839 (1940). 

 1' J. Flexner and M. R. Chassin, /. Clin. Invest. 20, 313 (1941). 



18 M. Swaminathan, Indian J. Med. Research 29, 561 (1941). 



19 B. C. Johnson, T. S. Hamilton, and H. H. Mitchell, /. Biol. Chem. 158, 619 (1945). 



20 J. C. Rabinowitz and E. E. Snell, Proc. Soc. Exptl. Biol. Med. 70, 235 (1949). 



21 J. W. Huff and W. A. Perlzweig, J. Biol. Chem. 155, 345 (1944). 



22 H. Linkswiler and M. S. Reynolds, /. Nutrition 41, 523 (1950). 



23 J. W. Huff and W. A. Perlzweig, Science 100, 15 (1944). 



24 C. G. Wcigand, C. R. Eckler, and K. K. Chen, Proc. Soc. Exptl. Biol. Med. 44, 147 

 (1940). 



25 W. Antopol and I. M. Tarlov, J. Ncuropathol. Exptl. Neurol. 1, 330 (1942). 



