390 THE BIOCHEMISTRY OF B VITAMINS 



autonomic ganglia. By vagal stimulation it slows and weakens the heart 

 and causes a drop in blood pressure. Choline increases salivary, lacrimal, 

 and other secretions and both gastroc and intestinal peristalsis. Doses of 

 600 mg in 240 ml physiological saline may be slowly administered intra- 

 venously (15-20 minutes) without great danger. 



Levels of 1, 2, and 4 per cent choline in chick diets produce retarded 

 growth but no other apparent ill effects. In rat diets, 2.7, 5, and 10 per 

 cent choline decreases rat growth by 20, 45, and 100 per cent, respec- 

 tively. When 1 per cent choline, corresponding to 500 mg/kg/day is 

 used, it is not effective. The 2.7 per cent level corresponds to 1350 

 mg/kg/day. Drinking water containing 1 per cent choline decreases 

 growth, the dose being 750 mg/kg/day. 105 The LD 50 of choline given 

 intraperitoneally to mice is 320 mg/kg, and the oral LD 50 for rats is 6.7 

 gm/kg. Other studies have reported the oral LD 50 for rats to vary from 

 3.4 to 6.1 gm/kg depending upon the solution concentration used. 106, 109 

 It has been pointed out that the same toxicity applied to man would mean 

 that minimum effects would occur at 15-70 gm/day and the LD 50 dose 

 would be about 200-400 gm. 107 



Pyridoxine. The lethal dose (LD 50) of pyridoxine for rats by sub- 

 cutaneous injection is about 3.1 gm/kg. 108 The oral LD 50 is 4. gm/kg. 

 Toxic symptoms involve tonic convulsions some 24 hours after dosing, 

 the hind limbs being stretched away from the body. These convulsive 

 attacks continue for from several days to three weeks unless death inter- 

 venes. At lethal doses death occurs in from 36 to 72 hours. The closeness 

 of the subcutaneous and oral toxic doses is of course a reflection of the 

 delayed nature of the symptoms. Autopsy of these animals reveals adrenal 

 enlargement with occasional cortical hemorrhage. In man pyridoxine is 

 said to have a sedative effect. Daily feeding of 10 mg/kg to rats, dogs, 

 and monkeys for a period of three months produces no significant change, 

 and 20 mg/kg given to cats intravenously is ineffective, as are single 

 doses up to one gram. 110 



Riboflavin. There is little or no information available regarding the 

 toxicology and pharmacology of riboflavin. Five thousand times the 

 therapeutic dose for mice (i.e.: 340 mg/kg) is not effective in producing 

 any observable action and it has been estimated that on this basis 20 gm 

 per day for a 70-kg man should be harmless. 111-113 



Folic Acid. Folic acid is relatively nontoxic, judging by the limited 

 available data. The intravenous LD 50 in mg/kg is 600 for the mouse, 

 500 for the rat, 410 for the rabbit, and 120 for the guinea pig. Death is 

 apparently caused by the obstruction of the renal tubules as the result 

 of precipitation of folic acid. Taylor and Carmichael 116 have recently 

 found a high sex differential in the toxicity of folic acid for dba mice, 



