The Toxic Principle of Poison Ivy and Other Related Plants DAVID WASSERMAN and CHARLES R. DAWSON Columbia University, New York City
M . .
OST people who have made the acquaintance of polson ivy can recall the occasion without much effort. The occasion is generally clearly marked in their memory by the fact that it was soon followed by a period of great personal discomfort. The painful irritation, inflammation, and blistering of the skin that follows the slightest contact with most parts of the plant is an experience that many people suffer every year. This is particularly true in the spring, when most parts of the plant are rich in an oily substance that is responsible for the toxicity. Likewise, the danger of contact is probably greatest at this time, for it is in the spring and early summer months that many people turn to the woods and fields to view the wonders of nature. Poison ivy is probably the most widely known of all American poisonous plants, being found in nearly all parts of the United States and Canada. After contact with the plant, and in the absence of proper first aid treatment, poison ivy dermatitis may develop to a severity that requires hospitalization. There are three varieties of the species Rhus toxicodendron that are responsible for the majority of poisonivy-like dermatitis cases in this country. They are poison ivy (R. toxicodendran radicans), poison oak (R. toxicodendron diwersilobum), and poison sumac (R. toxicodendron werniz). Poison ivy is a shrubby vine that grows best in places which lend support to the vine, and along with the other two varieties of the Rhus genus, can be found in nearly all parts of the country that support vegetation. Because the vine is covered with hairlike rootlets which enable it to cling to any convenient support, it is often found growing on fences, trees, buildings, and stones. I t is readily recognized in the spring and early summer months by its characteristic smooth light green leaves arranged in a cluster of three leaflets per stem. I t has inconspicuous yellowish green flowers which are followed in the late summer and autumn by a cream-colored fruit about the size of a cherry stone. This fruit, arranged in small clusters, often remains on the plant through the winter. Poison oak is similar to poison ivy, but usually grows without support as a bush. Its leaves are similar in shape to oak leaves. The poison sumac bush or tree has smooth grayish bark on the trnnk and older branches, whereas the young new branches are reddish brown. There are seven to fourteen leaves on each stalk, and the fruit is similar to that of poison ivy and poison oak. The reader is referred elsewhere (1,2) for a more complete and illustrated description of these plants. The ~oisonis present in the leaves, flowers, fruits,
bark, and roots of the poison ivy plant, but not in the wood, hairs, or pollen, according to Muenscher (3). During the past decade the chemical nature of the oily mixture responsible for the toxicity of poison ivy has become known. A highly toxic material has been isolated, and its structural skeleton established. I t is to be hoped that this experimental progress will be followed by a better understanding of the causes and prevention of poison ivy dermatitis. G. A. Hill and coworkers at Wesleyan University in 1934 (4) were the investigators who finally succeeded in isolating and identifying the toxic principle of poison ivy. They showed that the vesicant oil was "urushiol," a material isolated from the sap of the Japanese lac tree in 1909 by Riko Majima (5). The story of the detection, isolation, and identification of "wshiol" by Majima is an interesting one. Many wooden articles manufactured in Japan are lacquered with a vesicant material from the sap of the Japanese lac tree (R. wernici&u). This material, upon exposure to air oxidation, leaves a beautiful, resistant, black coating. The vesicant nature of the material presents, however, a serious handicap. The workers are often incapacitated by very bad rashes and blistered skins caused by the irritant in the lacquer. About the turn of the century, Majima became interested in the problem and started a chemical investigation in 1906 which continued until 1922. The sap from the lac tree was collected on a plantation near Yokohama, and extracted with alcohol. After filtration and removal of the alcohol by distillation, the residue was extracted with petroleum ether. After removal of solvent, the residue was distilled in a vacuum to give a yellow oil with acidic properties, which was first misnamed "urushic acid." The oil gave the typical chemical reactions associated with catechol type compounds, i. e., reduction of ammaniacal silver solution, a white precipitate of the lead salt with lead acetate, and a dark green to black color with ferric chloride. Upon dry distillation, a distillate containing a long chain hydrocarbon, some catechol, along with degradation products of these two, was obtained (6). This indicated to Majima that the toxic oil contained a catechol compound carrying a long hydrocarbon chain attached to the ring. He therefore renamed it "urushiol" to indicate that it was a phenolic compound, rather than a carboxylic acid. In the next few years, structural studies, including ozonolysis, and oxidative degradations, (7, 8, 9, 10,11, 12, 13) led Majima to conclude that urushiol was probably a mixture of four compounds, which he could
Further proof that "urushiol" from poison ivy is a mixture was given by Mason and Schwartz (14) when they separated four phenolic components from the toxic oil by chromatographic adsorption using a column packed with alumina. The four compounds were indicated by fluorescent bands under ultraviolet light. The chemical structure of these compounds was not investigated. During the past year a method of synthesis for compounds of the urushiol type has been proposed by the authors (21). The method makes possible the location of double bonds in the side chain at desired positions. Such synthetic compounds should help to elucidate the chemical nature of the toxic oil, firH2),,cH8 @~~wH=cH(cmcH. by serving as comparison models, when the pure components of the oil have been isolated. (2) (l) OH The fact that these catechol compounds are very sensitive to oxidative destruction by air, and also that they are present in the poison ivy plant originally in very low concentration, 0.04 to 0.07 per cent by weight of the bark, makes the problem of isolation and determination of the chemical strncture of the pure components a difficult task. In addition, the fact that they are powerful vesicants, and must therefore (4) be handled with great care, further complicates the However, a recent investigation (14) uncovering the problem. Apparently the vesicant activity of the molecule is possibility of the presence of unsaturated impurities in the toxic oil, as isolated by Majima, makes it ad- dependent upon two factors, first, its fat-like quality visable to view the above structures with some reserve, which enables it to penetrate the epidermis, and second, particularly in regard to the exact position of the the presence of the catechol nucleus which provides the irritant action. The long hydrocarbon side chain double bonds. Long before Majima had started his investigation enhances its solubility in the oils of the skin, and apin Tanan.. several American investieators had at- parently the double bonds serve only to increase this tempted to isolate the irritant responsible for poison property of the molecule. This is borne out by the fact ivy dermatitis. The earliest recorded work is that of that on catalytic hydrogenation the urushiol mixture Khittel in 1858 (15) who thought the poison was a yields a single white solid compound, tetrahydrourushvolatile alkaloid, but could not identify it with a pure iol, which is a slightly less active vesicant than urushiol chemical compound. Maisch in 1866 (16) steam dis- itself. The difference in activity can probably be tilled a volatile acid out of the plant, hut the physiologi- attributed to the fact that the solid tetrahydrourushiol cal evidence that this was the poison was not definite. would be expected to penetrate the epidermis less In fact, Pfafl in 1897 (17) showed that the volatile acid readily than wshiol. Other homologs that have been shown to exhibit was impure acetic acid containing traces of the poison. Acree and Syme (1906) (18) used an alcoholic extract vesicant activity are 3-methyl catechol (22), 3-n-propyl of the leaves from which they precipitated the poison catechol(23), 3-tetradecyl catechol (24), 3-aUyl catechol with lead acetate, and came to the conclusion that it (25), and 3-geranyl catechol (26). The degree of was a glycoside. However, this was later refuted by vesicant activity of these catechols varies with the McNair in 1916 (19), as the result of his studies on length and unsaturated character of the side chain, poison oak. McNair succeeded in isolating the active both of which effect the fat-like qualities of the molepoison in impure form in 1921 (20) and showed that cule. As previously mentioned, dermatitis-producing it was a catechol derivative. He could not, however, identify it. As previously mentioned, the toxic plants like poison ivy and poison sumac are found in principle was finally isolated in sufficiently pure form many parts of the world. The majority of these by Hill and coworkers in 1934 (4) to enable them to plants belong to the anacardiaceae family, many of whose members are noted for the production of acrid identify it with urushiol. The identification of poison ivy "urushiol" with and vesicant juices. The most dangerous are the Japanese lac urushiol was based mainly on a com- members of the Rhus genus of anacardiaceae, because parison of certain derivatives of the hydrogenated side the poison is found in many parts of the plant, i. e., chain compound, hydrourushiol. The possibility there- bark, sap, leaves, flowers, and roots. Among the fore exists that the positions of the double bonds in most prominent of this species outside the United the side chain of poison ivy "urushiol" may differ from States and Canada are the Chinese and Japanese lac trees (R. werniciflua L.) and the Yunnan, Fortheir positions in the Japanese lac variety.
not separate by distillation. On the basis of the degradation products, and the fact that the toxic oil had an average of two double bonds of aliphatic nature, he postulated that urushiol was a mixture of four catechols differing in the number of double bonds in a normal 15-carbon side chain in position (3) of the benzene nucleus. He showed that one of the compounds carried a completely reduced side chain. Majima proposed the following structures for the four components of the toxic oil:
UJ~CH~)~CH=CH(C,H~)CH=CH~
