unquestionably a new organic acid for which I propose the name of Toxicodendric Acid," writes Maisch. He further says: "That it is the principle to which poison oak owes its effects on the human system was proved to my entire satisfaction by the copious eruption and formation of numerous vesicles on the back of my hand, on the fingers, wrists, and bare arms while I was distilling and operating with it. Several persons coming into the room while I was engaged with it were more or less poisoned by the vapours diffused in the room; and I even transferred the poisonous effects to some persons, merely by shaking hands with them.

"The diluted acid, as obtained by me, and stronger solutions of its salts, were applied to several persons, and eruptions were produced in several instances, probably by the former, though not always, which was most likely owing to the dilute state of the acid. Whenever this was boiled, I always felt the same itching sensation in the face, and on the bare arms, which I experience on continual exposure of my hands to the juice of the plant."

Toxicodendric acid was thought to be the active principle from the time of Maisch's work until the investigation by Pfaff in 1895.

PFAFF'S WORK.

By far the most valuable work on Rhus toxicodendron is that of Pfaff. From a clinical study of Rhus poisoning, Pfaff came to the conclusion that the poison must be a non-volatile skin irritant. The more volatile the irritant, the quicker is its action on the skin. Formic acid acts very quickly; acetic acid, less volatile than formic, acts more slowly, but still much more quickly than poison ivy, the latent period of which is usually from two to five days. Pfaff thought that the volatile acid obtained by Maisch might have contained some of the poisonous principle as an impurity, but that it would not produce the dermatitis if prepared in a pure state. He therefore prepared a quantity of the acid by distilling the finely divided fresh plant with steam. The yield was increased by acidulating the mixture with sulphuric acid before the distillation. The acid distillate so obtained was freed from a non-poisonous oily substance by shaking the solution with ether. Barium and sodium salts were made by neutralizing the acid, and were purified by crystallization. Analysis showed them to be salts of acetic acid, and they gave the characteristic tests for this acid. The toxicodendric acid of Maisch was thus shown to be acetic acid, and was therefore not the poisonous principle of the plant.

Pfaff obtained the active principle by the following process: The plant was extracted with alcohol, the alcohol was distilled off, and the residue was taken up in ether. The ether solution was washed with water and dilute sodium carbonate solution, and the ether was evaporated. An oily, black, poisonous substance partly soluble in alcohol was obtained. To get the active principle in a pure state, this residue was extracted with alcohol and filtered and the filtrate was precipitated fractionally by lead acetate. The final precipitates consisted of the lead compound of the poison in a pure state. On decomposing the lead compounds with ammonium sulphide, shaking out with ether, and letting the ether evaporate spontaneously, a non-volatile oil was obtained which gave the characteristic skin eruptions. The pure lead compounds made in different preparations were analyzed and assigned the formula C₂₁H₃₀O₄Pb. The oil itself was not analyzed. Pfaff proposed the name Toxicodendrol for the oil. He found that it was not volatile, was decomposed by heat, was soluble in alcohol, ether, chloroform, benzene, etc., but insoluble in water. Its effects upon the human skin were studied in many experiments upon himself and others. It was shown that an exceedingly minute quantity of the poison will produce the dermatitis, even 1/1000 milligram applied in olive oil being active. The oil was given internally to rabbits, its effects being most marked on the kidneys.

The oil obtained by Pfaff from Rhus venenata seemed to be identical with that from Rhus toxicodendron.

EXPERIMENTAL.

The writer's investigation was undertaken with the object of attempting to throw more light on the chemical nature of the poisonous substance found in Rhus toxicodendron. Soon after commencing work, however, it became apparent that the poison could be more intelligently studied if the substances associated with it in the plant were first identified; the scope of the work was therefore extended to an investigation of the other constituents of the plant, and it was hoped that a knowledge of the properties of these constituents would suggest a more economical way of getting the poison than the method of fractional precipitation.

The crude material for this work was prepared by Messrs. Parke, Davis & Co., of Detroit, Mich., according to special instructions submitted to them: 67-1/2 pounds of fresh leaves and flowers of poison ivy were collected near Detroit and carefully inspected by a competent botanist. This material was thoroughly macerated and put into ten-liter bottles with ether. The mass was thoroughly shaken, water being added to make it more mobile. The ether was then separated off and the extraction was repeated three times in the same way to insure complete removal of the toxicodendrol. The ether extracts were combined, thoroughly dried with anhydrous sodium sulphate, and the ether was distilled off, the temperature being kept below 40° C. during the entire distillation. The residue after the removal of the ether was a thick, black, tar-like mass, weighing 3 pounds 11 ounces. In extracting the plant, about twenty-four gallons of ether were used. It is a significant fact in regard to the volatility of the poison that during the process of preparing this material none of the employees engaged in the work were in any way affected, since proper precautions were taken and the utensils were handled with rubber gloves.

The crude ether extract, which will be designated as the "original material," was shipped to Baltimore in August and was kept in a cool place until November when the investigation was begun. When the bottle was opened, there seemed to be an escape of a vapor, and a nauseating odor suggesting crushed green leaves pervaded the atmosphere. Some days later, irregular red patches appeared on the face though a mask of cotton cloth was worn during the work, and the hands were protected by rubber gloves.

Assuming from Pfaff's work that this original material contained the non-volatile oil toxicodendrol, the first experiment was to try to distil it out under diminished pressure. For this purpose, an Anschütze distilling bulb containing ten grams of the tar was connected with a vacuum pump. After a pressure of 2 mm. had been established the bulb was gradually heated in a bath of Wood's metal. Nothing distilled over. The material began to carbonize at a temperature of 140° to 150°.

It was then thought that perhaps the oil could be converted into an ester which might be more volatile and could be distilled out. 20 grams of the original material were dissolved in 100 cc. of absolute alcohol containing 3 grains of hydrochloric acid gas, and the mixture was heated 10 hours on a water-bath under a return condenser. After the heating, the mixture had a delightful ethereal odor. The flask was corked and left