THE AMERICAN JOURNAL OF PHARMACY NOVEMBER, 1907 POISON SUMAC. By A. B. STEVENS AND L. E. WARREN.* Rhus vernix Linne (Rhus venenata De Candolle) (Fam. Anacardiacea), known by various names, such as Poison sumac,' Poison dogwood, Poison elder,' Poison-tree, Poison wood, Poison ash,3 Swamp sumac3 or Swamp dogwood,3 is a small shrub or tree, six to eighteen or occasionally twenty-five feet in height, which attains a diameter of from three to six or even ten inches. It is found in swamps widely scattered over the eastern portions of North America, from Canada to Florida, and west to Minnesota and Louisiana. The bark is mottled-gray or brownish-gray, smooth on the branches and young shoots, but somewhat roughened on the trunks of the older trees. The leaves are compound, each leaf stalk bearing five to thirteen nearly sessile, ovate, obovate, or oval, beautiful green leaflets, each of which is acute at the apex and smooth at the edges. In autumn the colors of the foliage become extremely brilliant, scarlets, oranges and yellows predominating. In consequence of its attractive appearance at this season many collectors, ignorant of its venomous properties, are poisoned by it each year. The small, * Holder of Frederick Stearns & Co. Fellowship of Pharmaceutical Chemistry. 1" Silva of N. Am." C. S. Sargent, III, 23-24. "Trees and Shrubs of Mass." G. B. Emerson, II, 575. 3" Plant Names, Scientific and Popular.” A. B. Lyons, 321. "Silva of N. Am." C. S. Sargent, III, 23. 5 "Trees of New Eng." Dame and Brooks, 136. 6 "Silva of N. Am." C. S. Sargent, III, 23. 7 "Trees of New Eng." Dame and Brooks, 187; also "Silva of N. Am." C. S. Sargent, III, 24. greenish-yellow flowers, which appear late in June or early July, are borne on long, loose panicles from the axils of the leaves. The sterile and the fertile flowers are borne on separate plants. The fruit is a drupe, 4 to 6 mm. in diameter, unequal sided and somewhat flattened. At maturity in September the outer coat is thin, more or less striated, grayish-white and lustrous; the stone is pale yellow in color and noticeably grooved. ance. The fruit remains on the tree until spring. On wounding the trees, a pale cream-colored, thick, poisonous juice exudes in abundThis begins to darken at once and finally becomes black. Very little work has been done upon the chemistry of the poison of Rhus vernix. A number of chemists, however, have worked upon the poisonous constituents of Japanese lac (Rhus vernicifera) and of poison ivy (Rhus radicans), and, as clinical observation has established that the dermatitis caused by any one of the venomous species of Rhus is similar in appearance to that from the others, it is now generally believed that the poisons from all these plants are identical. We give below a brief digest of the results that have been obtained by previous investigations of the constituents of these plants. In 1815 Dr. Bigelow experimented upon the juice of Rhus vernix, and showed that it possessed varnish-forming properties similar to the juice from Japanese sumac. He says: "A quantity of the juice was boiled alone, until nearly all the volatile oil had escaped, and the remainder was reduced almost to the state of a resin. In this state it was applied while warm to several substances, which, after cooling, exhibited the most brilliant, glossy, jet black surfaces. The coating appeared very durable and firm, and was not affected by moisture. It was elastic and perfectly opaque, and seemed calculated to answer the purposes of both paint and varnish." Dr. Bigelow seems to have done no further work upon the chemistry of the juice. In 1859 J. Khittel worked upon poison ivy. He attributed the poisonous properties of this plant to a volatile alkaloid. He did not. succeed in isolating any alkaloids, however, so that his results were of but little value. 8 "Medical Botany," J. Bigelow, I, 101-102. 9 Wittstein's Vierteljahresschrift für praktische Pharmacie, 7, 348–59 ; abstract AM. J. PHARM., 1858, 542-4. In 1865 J. M. Maisch1o denied the presence of a volatile alkaloid in poison ivy, but announced the discovery of a new volatile acid to which he ascribed the poisonous properties of that plant, and to which he gave the name "toxicodendric acid." He prepared salts of this acid, and stated that its properties were somewhat similar to those of formic acid and acetic acid, but more nearly like the latter The conclusions of Professor Maisch remained unverified for thirty years, and standard works on pharmacology quoted them without question until Dr. Pfaff investigated the subject in 1894–96. Dr. Pfaff" proved that the "toxicodendric acid" of Maisch was acetic acid, and that the real poison of ivy (and sumac) existed in an oily substance which he named "toxicodendrol," and which was completely non-volatile. He states that he prepared this oil by repeated fractional precipitations of its lead salt from alcoholic solution by means of alcoholic solution of lead acetate. The free oil was obtained from its lead compound by decomposing the latter with ammonium sulphide. He found the poisonous oil in all parts of the plant— stems, branches, roots, leaves and fruit. It was present in both ivy and sumac, but more abundant in the latter. Dr. Pfaff does not state whether the "toxicodendrol" was obtained from the green or the ripened fruit, an omission to which we will again refer. According to this author, "toxicodendrol" is soluble in ether, alcohol, chloroform and similar solvents, but is insoluble in water. It is easily decomposed by heat and is partially converted into resin on long standing. None of its other physical or chemical properties or constants were determined. The fruit of Rhus toxicodendron contained 3.6 per cent. of crude oil (i. e., active oil contaminated with resinous matter and with oil not precipitated by lead acetate), the leaves 3.3 per cent. and the stems and branches 1.6 per cent. Rhus vernicifera, the Japanese varnish tree, exhibits poisonous properties similar to the American sumac. The milk juice, which exudes when the plant is wounded, forms the Japanese lac of Oriental commerce. Several chemists have investigated the prop 10 Proc. Am. Pharm. Assoc., 1865, 166. erties of this juice. The earliest was Ishimatsu, who reported13 that the lac had a sweetish odor, an irritating taste, that it burned with a luminous flame, which emits dense black smoke, and that it mixes with fixed oils in all proportions. He found that the lac consisted of a substance soluble in alcohol, a gum soluble in water, a residue insoluble in alcohol or water, and small quantities of water and "volatile poison." His method of separation was to extract the milk-juice with absolute alcohol, evaporate the solvent and dry the dissolved portion at 100° to constant weight. The portion insoluble in alcohol was extracted with hot water, filtered, the filtrate evaporated and the residue dried at 100° and weighed as gum. The residue insoluble in water was dried at 100° and weighed. Water and volatile matter were determined by difference. He found that the fresh lac yielded 58-24 per cent. of substance soluble in alcohol. This alcohol-soluble substance was brownishblack in color and had the same odor as the original; however, it never dries to a varnish as that does. Lead salts of this compound were prepared and analyzed, from which the formula CHO2 was calculated. No experimental proof that the poisonous constituent was volatile was offered. 14 30 In 1883 H. Yoshida, employing Ishimatsu's method of separation, found 85.15 per cent. of alcohol-soluble substance in fresh lac of known purity. He called this soluble substance urushic acid (from Ki-urushi, Japanese lac). He states that the gum is identical with gum acacia, and reports the portion insoluble in alcohol or water as diastatic matter. He proved that the hardening of the lac was due to an oxidizing enzyme acting in the presence of moisture. Like the previous investigator, Yoshida believed that the poisonous constituent of the lac was volatile, but offered no experimental proofs for this supposition. Yoshida found that urushic acid was soluble in benzin, ether and carbon disulphide; less easily soluble in amyl alcohol and petroleum of high boiling point; insoluble in water; sp. gr. 09851 at 23°. It remains unchanged at 160°, but slowly decomposes with carbonization at 200°. From the alcoholic solution of urushic acid many salts were prepared, most of which were slightly soluble in alcohol, but insoluble in water. From the analy 13 Manchester Lit. and Philos. Soc. [3] 1882, 249. 1 J. Chem. Soc., 1883, 472. 18 2 sis of its lead salt Yoshida calculates the formula C1,HO2 for urushic acid. By oxidizing urushic acid with chromic acid and analyzing the product obtained, he concluded that this acid takes up one atom of oxygen to form oxyurushic acid, CH1O3. He prepared and analyzed a bromine derivative of urushic acid, to which he ascribed the formula C1,H12BrO2. 12 In 1905 Tschirch and Stevens15 showed that the volatile principle of Japanese lac was acetic acid and that the poisonous constituent was a resinous substance which was non-volatile. This resinous substance was obtained by extracting the lac with alcohol and evaporating the filtrate (as Ishimatsu and Yoshida had done), taking up the residue with petroleum-benzin (b. p. below 65°) and pouring the solution into a large excess of fresh petroleum-benzin. A non-poisonous, semi-fluid resin was precipitated, while the poisonous substance remained in solution and was obtained as a dark, brownish-red oil on decanting and evaporating the solvent. By agitating the benzin-soluble portion with ethyl alcohol and petroleum-benzin in immiscible proportions, the poisonous principle remained in the alcoholic layer on separation. An oily, non-poisonous, brownishred residue was left on evaporating the benzin layer, while the alcoholic layer gave a poisonous resin of similar appearance. Three fractions were thus obtained, but one of which was poisonous. Analyses of these will be referred to later. All were soluble in alcohol and all gave black precipitates with alcohol-soluble salts of mercury, iron, copper and silver. Lead acetate gave a gray precipitate, which became darker on standing. By oxidation all of the resinous substances gave a brown insoluble substance which the authors called oxyurushin, and to which they gave the formula C102 H138N2O19 16 Gum and diastatic matter were also obtained from the lac, but the authors were unable to separate them. By using Ishimatsu's method of separation Tschirch and Stevens found the following results for Japanese lac :17 Soluble in alcohol. Soluble in water. Insoluble residue Water and volatile matter 15 Arch. Pharm., 243, 516. 16 Arch. Pharm., 243, 524. 17 Arch. Pharm., 243, 515. Per Cent. |