XI. PHARMACOLOGY 125 



found by siilx-utaiieous injection to be between 0.5 and 1.0 g. per kilo- 

 gram."' '- Dreyfus'-' reported that rabbits are killed by 1 g. per kilogram 

 given rectally or suhcutaneously hut that only 0.11 g. per kilogram is 

 reciuired intravenously. Cats are killed by 24 mg. of choline chloride per 

 kilogram given intra\'enously.'^ The rate of administration is, of course, 

 important. Arai^^ found that if the drug was injected slowly cats could 

 tolerate 15 mg. of choline chloride per kilogram gi\'en intravenously without 

 any obser^'able toxic effect; 30 mg. gi^'en slowly produced a re\'ersible arrest 

 of respiration but 35 mg., even if injected slowly, was lethal. As choline is 

 rapidly destroyed (see below), about 0.8 to 0.9 mg. per kilogram per minute 

 may be injected practically indefinitely into a cat if the concentration is 

 between 0.2 and 0.4%. The MLD for mice (subcutaneously) is 0.7 g. per 

 kilogram. ^^ 



The acute toxicity of choline chloride for both mice and rats has been 

 determined in recent years by using larger numbers of animals and by 

 applying the technique of probit analysis to the data. This permits a more 

 accurate estimate of the dose needed to kill one-half of a given population, 

 i.e., the so-called LD50. Hodge and Goldstein'® injected mice (weighing 18 

 to 20 g.) intraperitoneally with different volumes of 2 % solution of choline 

 chloride. The LD50 was 6.4 mg., or about 300 to 320 mg. per kilogram. The 

 importance of the strength of the solution was shown by Neumann and 

 Hodge^'^ when they found the LDsn in rats given choline chloride by stomach 

 tube to he of the order of 3.4 g. per kilogram when concentrated solutions 

 (670 mg. or 500 mg. per milliliter) were given, but 6.1 g. per kilogram when 

 weaker solutions (400 or 200 mg. per milliliter) were used. McArthur and 

 Lucas^^ obtained a \'alue for the LDso (oral) of choline chloride in rats 

 weighing 150 g. of about 760 mg., i.e., about 5.1 g. per kilogram when 

 the drug was administered in 2 ml. By intraperitoneal or intravenous 

 injection the LD50 in rats is very much less (one-tenth to one-fiftieth, 

 according to preliminary tests, i.e., of about the same order as was found 

 in mice). 



Prolonged ingestion of choline has not revealed any chronic toxicity. 

 Many investigators of lipotropic phenomena have fed rations containing 

 0.1 up to 2 % of choline chloride to rats for periods of from se\'eral weeks to 



1' Brieger, Ueber Ptomaine. Hirschwald, Berlin, 1885-1886. 



'2 Karl Vogt, Sitzber. Abhandl. naturforsch. Ges. {Rostock), Neiv Scr. I, 1 (H)U9): 



quoted by Aral in ref. 15. 

 1^ L. Dreyfus, Compl. rend. soc. hiol. 83, 4S1-483 (1920). 

 '< A. Lohmann, Pfliigers Arch, r/c.s. Phi/sinl. 118, 215-227 (1907). 

 '5 K. Arai, Fflngers Arch. ges. Physiol. 193, ;i59-395 (1922). 



16 H. C. Hodge and M. U. Goldstein, Proc. Soc. Exptl. Biol. Med. 51, 281 2S2 (1942). 



17 N. W. Neumann and H. C. Hodge, Proc. Soc. Exptl. Biol. Med. 58, 87 88 (1945). 

 '8 C. S. McArthur and C. C. Lucas, Biochem. J. 46, 226-231 (1950). 



