Nature of the Vesicating Constituent of Croton Oil. 241 



it for medical use, strictly according to this same process. It is a 

 thick oil, possessing very powerful vesicating properties. In the first 

 instance the substance was distilled with steam but nothing passed 

 over, and the oil was apparently unchanged. Distillation under the 

 ordinary pressure produced entire decomposition. Distillation under 

 reduced pressure gave no better results. A liquid began to distil 

 near 200° C. (50 mm.), but this was evidently a product of decom- 

 position, the quantity of which increased as the temperature rose 

 gradually to 250° C. None of the fractions exhibited vesicating power, 

 and the residue was also inactive. 



F factional precipitation of the lead salt of the acid was next 

 adopted, in order to ascertain whether the substance was homo- 

 geneous. A solution of lead acetate in alcohol was added to an alcoholic 

 solution of the crotonoleic acid. Water was then mixed with the 

 clear solution, until a permanent turbidity resulted. The oily lead 

 salt which soon settled was removed and decomposed with dilute 

 hydrochloric acid, and then the free crotonoleic acid was extracted 

 with ether. The alcoholic mother liquor was precipitated a second 

 time with lead acetate and water, and the acid similarly regenerated 

 from the lead salt. Since a third fraction could not be obtained from 

 the alcoholic solution, this was decomposed and the acid recovered 

 from the dissolved lead salt. Since our object was to ascertain whether 

 the original material was homogeneous and consisted entirely of the 

 vesicating constituent of croton oil, and as there is no chemical test 

 for the presence of the active substance, we were obliged to fall back 

 on a physiological method of detecting it and indicating approxi- 

 mately the extent to which the active substance was contained in 

 different specimens of material. The plan adopted was to dissolve 

 equal weights of the substances in the same weight of oleic acid, and 

 then to apply a single drop of each solution to the arm; the extent 

 of the blistering which ensued being carefully noted. This we have 

 found to be the only method readily available for gauging approxi- 

 mately the vesicating power of different specimens. When the three 

 specimens, fractionated from the original crotonoleic acid, were tested 

 in this manner, the first was found to be quite inactive, the second to 

 be nearly inactive, whilst the third and smallest fraction proved to 

 be a violent vesicant, far exceeding in power the original crotonoleic 

 acid. A number of these fractionation experiments were performed, 

 always with the same result, thus conclusively proving that croton- 

 oleic acid is a mixture for the most part composed of non- vesicating 

 material. When the original substance is fractionally precipitated 

 with lead acetate the non- vesicating constituents are precipitated 

 first, leaving nearly all the active material in solution. It therefore 

 seemed probable that by taking advantage of this difference in the 

 solubility of the lead salt in dilute alcohol we might be able to isolate 



