126 CHOLINE 



several months with no evidence of any toxic el'fects, other than some sUght 

 decrease in food intake at the higher concentrations. 



Hodge'^ administered rekxtively large amonnts of choline chloride to rats 

 for a period of 4 months, to some in their food, to others in the drinking 

 water. Prolonged consumption of diets or drinking water containing 1 % 

 choline chloride produced no evidence of toxicity. Food intake was low and 

 growth poor when the diet contained over 2.7%; no deaths occurred in 

 those given 5 % choline chloride in the ration. Those given 10 % lost weight, 

 and three out of five died, but no histological evidence of damage was 

 detectable. When the drinking water contained 2.7 % choline chloride a 

 40 % reduction in growth occurred; when it was increased to 4 % no growth 

 took place and all the rats (five out of five) died within 3 months. 



Davis-" has claimed that administration of choline chloride to dogs by 

 stomach tube (10 mg. per kilogram of body weight, once or twice daily) 

 produces hyperchromic anemia. Howe\'er, when Clarkson and Best'-^ main- 

 tained dogs on a good ration under controlled conditions for a period suffi- 

 cient to stabilize the blood picture (satisfactorily constant basal values for 

 red cell counts and hemoglobin concentrations) and then added to the diet 

 extra choline chloride (up to 30 mg. per kilogram of bod}^ weight per day), 

 no evidence whatever of macrocytic anemia could be detected. On the 

 contrary, the condition of the dogs given choline chloride, either m the diet 

 or by stomach tube, improved steadily, probably owing to the general 

 excellence of the diet rather than to the added choline. 



Roth and Allison-'- fed rats of the Sherman strain a diet containing 

 1.35% choline chloride for 20 days. The rats were fed the same weight of 

 food as was consumed by another group given an excess (4.8 %) of methio- 

 nine in the diet. The animals in both groups lost about 35 % of their body 

 weight in the 20-day period. Although the food intake is not given, it would 

 appear from the data for ingested nitrogen that the rats (250 g.) obtained 

 only 6.7 g. of the ration (12 % casein) per day. Restriction of food intake 

 rather than toxicity of choline chloride appears to explain the loss in w^eight 

 observed in this study. 



The fate of choline in the organism has not been fully elucidated. Choline 

 is destroyed in the body with considerable speed. -^ When injected it dis- 



'3 H. C. Hodge, Proc. Soc. Exptl. Biol'. Med. 58, 212-215 (1945j. 



20 J. E. Davis, Am. J. Phijsiol. 142, 213-215, 402-406 (1944); 147, 405-411 (1946); 

 Science 105, 43-44 (1947); J. E. Davis and D. E. Fletcher, J. Pharmacol. Exptl. 

 Therap. 88, 246-253 (1946); J. E. Davis and J. B. Gross, A)n. J. Physiol. 144, 444- 

 446 (1945). 



21 M. F. Clarkson and C. H. Best, Science 105, 622-623 (1947). 



22 J. S. Roth and J. B. Allison, J. Biol. Chem 183, 173-178 (1950). 



23 H. von Hoesslin, Beitr. chem. Phijsiol. Pathol. 8, 27-37 (1906); quoted by Fuchs, 

 ref. 31. 



