July 15, 1921] 



SCIENCE 



55 



SPECIAL ARTICLES 



THE PREDICTION OF THE PHYSIOLOGICAL 

 ACTION OF ALCOHOLS' 



CosrpARATrvELY few laws are known connect- 

 ing the chemistry of various substances with 

 their physiological effects; such a condition is 

 natural because of the complexity of many 

 of the compounds used in therapeutics. In 

 seeking for generalizations it is therefore ad- 

 visable to direct our attention at first to com- 

 pounds possessing rather simple structures. 



In connection with the testing of the 

 toxicity of various normal primary alcohols 

 upon Paramecia the writer noticed the almost 

 quantitative application of a simple numerical 

 rule. Methyl alcohol, as was expected from 

 its structure, exhibited an abnormajity, but 

 beginning with ethyl alcohol and expressing 

 its action as unity the acute toxicities of 

 ihe successive members subjected themselves 

 to numerical expression, particularly when 

 the quantity of alcohol used was exjnressed 

 in moles and not in grams. 



In an homologous series of this kind the 

 molar toxicity of any given member is three 

 times that of the preceding member. The 

 rule is expressed numerically by the geomet- 

 rical progression : 



1: 3: 3= : 3=: 3": 3'> . . . . 



The value of this generalization, originally 

 presented by Traube on the basis of surface 

 tension experiments, lies in the fact that it 

 may be appplied not merely to unicellular or- 

 ganisms, but to mammals as well. Its applica- 

 tion is shown best by a few examples. 



EXAMPLE I 



The toxic concentration of ethyl alcohol 

 for a given strain of paramecia was found by 

 experiment to be 4.5 per cent. Wlrat concen- 

 tration of ?i-octyl alcohol will prove equally 

 toxic to the same strain of organisms ? 



Solution: 1X3x3x3x3x3x3 = 729. 

 4.5% X 2.8* 2 



729 



= 0.02% = calculated concentration. 



The observed value was found to be 0.03 per 

 cent. 



1 Article No. 4, Chemical Researcli Department, 

 Parke, Davis & Co. 



EXAMPLE II 



If a mouse is killed within a few hours by 

 inti-aperitoneal administi-ation of 12 mg. of 

 ethyl alcohol per gram of body weight, what 

 will be the corresponding toxic dose of n-amyl 

 alcohol ? 



Solution: 1X3X3X3 = 27. 



12 mg. X 1.9* 

 27 



= 0.84 mg. 



The observed value was found to be very close 

 to 1.0 mg. per gram of body weight. 



EXAJIPLE m 



The toxic dose of ethyl alcohol when in- 

 jected- into the blood stream of the cat was 

 found by Macht^ to be 5.0 c.c. per kilo. The 

 administration time was 50 minutes. Under 

 exactly similar experimental conditions what 

 will be the toxic dose (a) of ra-propyl alcohol, 

 (6) of w-amyl alcohol? 



Solution : (a) 1 X 3 = 3. 



5.0 c.c. Xl.3* „,., 

 s = 2.17 c.c. 



= 2.14 c.c. corrected for sp. gr. 



The experimental value was found by Macht 



to be 2.0 c.c, although in this case the toxic 



amount of liquid was administered during 20 



minutes. 



Solution: (b) 1 X 3 X 3 X 3 = 27. 

 5.0 X 1.9* 



27 



0.35 c.c. (uncorrected for sp. gr.). 



The experimental value was found to be 0.15 

 c.c, which is a very satisfactory result in 

 view of the fact that the toxic material was 

 administered during seven minutes. When 

 administered over an interval of from 30 to 

 50 minutes the observed value would no doubt 

 approach the calculated value. 



A more detailed discussion of the present 

 work is appearing in a series of reports in the 

 J. Am. Pharm. Association. 



Oliver Kamm 



2 The values marked with the asterisk are molecu- 

 lar weight ratios which serve to convert the pre- 

 dicted values from moles to grams. 



3 J. Pharmacol, 16, 1 (1920). 



