material from the ,google ,print project47 ,,some ,,constituents ,,of ,,the ,,poison ,,ivy ,,plant 7,,rhus ,,toxicodendron7 ,,dissertation ,,submitted ,,to ,,the ,,board ,,of ,,university ,,studies ,,of ,,the ,,johns ,,hopkins ,,university ,,in ,,conformity ,,with ,,the ,,requirements ,,for ,,the ,,degree ,,of ,,doctor ,,of ,,philosophy ,,by ,,william ,,anderson ,,syme #aijf #aijf ,,the ,,sun ,,job ,,printing ,,office ,,baltimore ,transcriber's ,note3 ,underscores around words indicates italics while an underscore and curly brackets in an equation indicates a subscript4 ,,contents4 ,acknowledgments #d ,literature #e ,introduction #g ,work of ,khittel #aa ,work of ,maisch #ab ,work of ,pfaff #ac ,experimental #ad ,gallic ,acid #ah ,fisetin #bj ,rhamnose #bc ,the ,poison #bh ,potassium ,permanganate as a ,remedy for ,rhus ,poisoning #ce ,summary #cg ,biography #ch ,,acknowledgments4 ,the author desires to avail himself of this opportunity to tender his thanks to those under whose guidance he has worked while a student at the ,johns ,hopkins ,university1 namely to ,professors ,remsen1 ,morse1 ,jones1 and ,andrews1 and to ,doctors ,acree and ,tingle for instruction in lecture room and laboratory4 ,he is especially indebted to ,dr4 ,s4 ,f4 ,acree1 at whose suggestion this research work was undertaken1 for counsel and assistance in its prosecution4 ,he would also thank ,messrs4 ,parke1 ,davis and ,co41 of ,detroit1 ,mich41 for the preparation of the crude material used in this investigation1 and the ,u4 ,s4 ,department of ,agriculture1 ,washington1 ,d4 ,c41 for electrotypes of figures #ag1 #ah1 and #ai in ,bulletin ,no4 #bj1 ,division of ,botany4 ,,literature4 ,acides ,gummiques1 ,garros 7,dissertation7 #ahie4 ,american ,chemical ,journal4 ,american ,journal of the ,medical ,sciences4 ,american ,journal of ,pharmacy4 ,annalen der ,chemie und der ,pharmacie 7,liebig74 ,annales de ,chimie et de ,physique4 ,berichte der deutschen chemischen ,gesellschaft4 ,biochemie der ,pflanzen 7,czapek7 #aije4 ,brooklyn ,medical ,journal4 ,bulletin de la ,societe ,chimique4 ,bulletins #bj and #bf ,u4 ,s4 ,department of ,agriculture1 ,division of ,botany4 ,chemie der ,zuckerarten1 ,von ,lippmann1 #aijd4 ,chemiker-,zeitung4 ,comptes rendus4 ,industries of ,japan1 ,j4 ,j4 ,rein4 ,journal of the ,chemical ,society4 ,journal of ,experimental ,medicine4 ,les ,sucres1 ,maquenne1 #aijj4 ,manual of ,botany1 #fth ,edition1 ,gray4 ,medical and ,surgical ,reporter4 ,new ,york ,medical ,record4 ,proceedings of the ,american ,pharmaceutical ,association4 ,treatise on ,chemistry1 ,roscoe and ,schorlemmer4 ,ueber ,mategerbstoff1 ,reuchlin 7,dissertation7 #aijd4 ,,some ,,constituents ,,of ,,the ,,poison ,,ivy ,,plant4 7,,rhus ,,toxicodendron7 ,,introduction4 ,plants belonging to the natural order ,anacardiaciae 7,cashew family or ,sumach family7 are found in all the temperate climates of the world and quite frequently in semi-tropical climates4 ,many of these plants play important parts in economic botany1 yielding dye-stuffs1 tanning material1 wax1 varnish1 and drugs4 ,several species are poisonous4 ,at least three poisonous species of the genus ,rhus are found in the ,united ,states4 ,these three are all common and well-known plants1 but confusion frequently arises concerning them on account of the different names by which they are known in different localities4 ,for example1 poison ivy 7,rhus toxicodendron or ,rhus radicans7 probably the best known poisonous plant in ,america1 being found in all the ,states except those in the extreme ,west1 is often confounded with and popularly called poison oak4 ,the true poison oak is the ,rhus diversiloba of the ,western ,states4#a ,the third and most poisonous species of this plant is ,rhus venenata or ,rhus vernix2 it is the ,rhus vernicifera of ,japan1 from which ,japanese lac is obtained4 ,it is popularly known in the ,united ,states as poison sumach1 poison dogwood and poison elder4 ,it grows in swamps from ,canada to ,florida4 ,as the poison ivy is by far the most common of these plants in the ,eastern ,states1 a brief description of it is given here3#b ,a shrub climbing by rootlets over rocks1 etc41 or ascending trees1 or sometimes low and erect2 leaflets #c1 rhombic-ovate1 mostly pointed1 and rather downy beneath1 variously notched1 sinuate1 or cut-lobed2 high climbing plants 7,r4 radicans7 having usually more entire leaves4 ,it is found in thickets1 low grounds1 etc4 ,greenish flowers appear in ,june4 ,illustration3 ,fig4 #a4--,poison ivy 7,rhus radicans or ,rhus toxicodendron74 a1 spray showing aerial rootlets and leaves2 b1 fruit--both one-fourth natural size4 7,chesnut1 ,bulletin ,no4 #bj1 ,division of ,botany1 ,u4 ,s4 ,department of ,agriculture47 ,illustration3 ,fig4 #b4--,poison oak 7,rhus diversiloba7 showing leaves1 flowers1 and fruit1 one-third natural size4 7,chesnut1 ,bulletin ,no4 #bj1 ,division of ,botany1 ,u4 ,s4 ,department of ,agriculture47 ,in the general description of the order ,anacardiaciae1 ,gray#c says3 ,juice or exhalations often poisonous4 ,whether it is contact with some part of the plant1 or with the exhalation from the plant1 that causes the well-known skin eruption has been a topic for discussion ever since its source was known4 ,on account of its intangible nature there has been more speculation than experimental evidence bearing on this question1 although a few investigations have been made with the object of isolating the poison4 ,it is most generally believed that the exhalations are poisonous4 ,dr4 ,j4 ,h4 ,hunt#d states that the exhalations have been collected in a jar and found to be capable of inflaming and blistering the skin of an arm plunged into it4 ,illustration3 ,fig4 #c--,poison sumach 7,rhus vernix71 showing leaves1 fruit1 and leaf-scars1 one-fourth natural size4 7,chesnut1 ,bulletin ,no4 #bj1 ,division of ,botany1 ,u4 ,s4 ,department of ,agriculture47 ,prof4 ,j4 ,j4 ,rein1#e in his treatise on ,lacquer ,work1 describes the poison of the ,japanese lac tree1 ,rhus vernicifera1 as being volatile1 as do also the ,japanese chemist ,yoshida#f and the ,french chemist ,bertrand4#g ,recent work by ,prof4 ,a4 ,b4 ,stevens1#h however1 seems to show that this poison is not volatile1 and is similar to1 if not identical with that obtained by ,pfaff#i from ,rhus toxicodendron and ,rhus venenata4 ,not many cases of internal poisoning by ,rhus toxicodendron are on record in medical literature4 ,two cases of poisoning from eating the fruit of this plant have been described4#aj ,the subjects of these cases were two children who had eaten nearly a pint of the fruit4 ,the symptoms are described in detail1 being in general1 similar to those of alkaloidal poisoning4 ,warm water was given to promote emesis2 afterwards large quantities of carbonate of soda were given in solution under the belief that it was an antidote to the poison4 ,otherwise they were treated on general principles4 ,both children recovered4 ,another case of internal poisoning is the following3#aa ,three children drank an infusion of the root of poison ivy thinking it was sassafras tea4 ,the first of these cases was diagnosed as measles1 but on the appearance of similar symptoms in the sisters of the first patient1 the cause of the trouble was found4 ,all recovered4 ,dr4 ,pfaff#ab explains the few fatal cases that have followed ,rhus poisoning on the assumption that enough of the poison was absorbed through the skin to cause renal complications in persons having chronic kidney trouble4 ,he showed that the poison1 when given internally1 produces a marked effect on the kidneys1 causing nephritis and fatty degeneration of this organ4 ,the irritating action of poison ivy has been attributed at different times to the exhalation1 to a volatile alkaloid1 to a volatile acid1 and to a non-volatile oil4 ,pfaff1#ac who made the most recent investigation of this poison1 obtained from the plant a non-volatile oil having the same action on the skin as the plant itself4 ,he found this oil in all parts of the plant and concluded that it was the active principle1 and that one could be poisoned only by actual contact with some part of the plant4 ,he assumed minute quantities of pollen dust to be in the air to account for the cases of action at a distance so frequently quoted4 ,pfaff says3 ,in my opinion1 it is more than doubtful if ever a case of ivy poisoning has occurred without direct contact with the plant or with some article that has been in contact with the plant4 ,the long latent period of the eruption in some cases may obviously render mistakes extremely easy as to the occasion when contact with the plant really occurred4 ,granting1 however1 that the active principle is practically non-volatile when isolated from the plant1 we cannot say positively that it is not volatile in the juices of the plant1 or under the influence of vital forces4 ,it is quite conceivable that the water transpired by the leaves of the plant may carry with it a quantity of the poison sufficient to produce the dermatitis on a person very susceptible to its action4 ,it is also conceivable that a volatile poison manufactured by a living plant could become non-volatile by changes in it consequent upon the death of the plant4 ,up to the present time1 only three important chemical investigations of the active principle of ,rhus toxicodendron have appeared in medical and chemical literature1 these being the researches of ,dr4 ,j4 ,khittel1 ,j4 ,m4 ,maisch1 a pharmacist1 and ,dr4 ,franz ,pfaff1 of the ,harvard ,university ,medical ,school1 to whose work reference has been frequently made4 ,the chemical work of these investigators and their conclusions are given here in some detail for the sake of completeness4 ,,footnotes3 #a ,chesnut4 ,bull4 ,no4 #bj1 ,u4 ,s4 ,dept4 of ,agr41 ,div4 of ,botany4 #b ,man4 of ,bot41 p4 #aai4 #c ,man4 of ,bot41 p4 #aai4 #d ,brook4 ,med4 ,jour41 ,june1 #ahig4 #e ,rein1 ,the ,ind4 of ,jap41 p4 #cch1 et seq4 #f ,h4 ,yoshida on ,urushi ,lacquer1 ,jour4 ,chem4 ,soc41 #ahhc1 p4 #dgb4 #g ,ann4 de ,chem4 et de ,phys41 ,series ,,vii1 ,vol4 #ab1 p4 #abe1 #ahig4 #h ,amer4 ,jour4 ,pharm4 #gh1 p4 #ec1 ,feb41 #aijf4 #i ,an account of ,pfaff's work will be found in another part of this paper4 #aj ,amer4 ,jour4 ,med4 ,sci4 #ea 7#ahff71 p4 #efj4 #aa ,med4 and ,surg4 ,rep4 #ag1 ,nov41 #ahfg4 #ab ,jour4 ,exp4 ,med4 #b 7#ahig71 p4 #aha4 #ac ,ibid4 ,,khittel',s ,,investigation4 ,the first attempt to find the poisonous constituent of this plant was made by ,khittel in #aheg4 ,his work was published in ,wittstein's ,vierteljahrresschrift fuer praktische ,pharmacie1 ,,vii1 #cdh-cei4ad ,khittel obtained #cg-a_/b ounces of fresh leaves of poison ivy from the botanical garden in ,munich1 dried them1 and got a residue of #i-a_/b ounces which he analyzed4 ,not detecting anything to which the poisonous qualities of the plant could be attributed1 he made another series of experiments which1 as he thought1 showed that a volatile alkaloid is the poisonous constituent4 ,it was obtained by the following process3 #c ounces of the powdered leaves were infused with hot distilled water1 after three days strained1 expressed1 the liquid evaporated to #c ounces1 and with the addition of potassa1 carefully distilled to one-half4 ,the clear1 colorless distillate had an alkaline reaction1 and an odor resembling henbane or hemlock4 ,it was saturated with sulphuric acid1 evaporated1 and treated with a mixture of equal quantities of alcohol and ether which left sulphate of ammonia behind1 the solution was evaporated spontaneously1 distilled with potassa1 the alkaline distillate neutralized with hydrochloric acid1 and a precipitate could now be obtained with chloride of platinum4 ,want of material prevented further experiments4 ,the editor of the ,american ,journal of ,pharmacy inserts the following note3 ,it would have been more satisfactory if the author had given some physiological evidence of the poisonous nature of the alkaloid substance obtained4 ,it is quite interesting to hear that the hitherto intangible venom of this plant has at last been detected4 ,,footnotes3 #ad ,a free translation of this paper is given in ,amer4 ,jour4 ,pharm4 for #aheh1 p4 #edb4 ,,work ,,of ,,maisch4#ae ,the next investigation of this plant was made by ,maisch in #ahfd4 ,he criticizes ,khittel's experiments as follows3 ,it is well known that the exhalations of ,rhus toxicodendron exert a poisonous influence on the human body2 the poisonous principle must1 therefore1 be volatile and1 at the same time1 be naturally in such a loose state of combination as to be continually eliminated and separated with the usual products of vegetable exhalations4 ,it is natural to suppose that during the process of drying1 the greatest portion of the poisonous principle should be lost4 ,the loss must be still greater if the dried leaves are powdered1 a hot infusion prepared from them1 and this infusion evaporated down to the original weight of the dried leaves4 ,it is obvious that ,dr4 ,khittel could not have selected a better method for obtaining the least possible quantity of the poisonous principle1 if1 indeed1 it could be obtained by this process at all4 ,maisch then worked up #h-c_/d ounces of the leaves of the plant in a way to get the alkaloid1 making some improvements on ,khittel's method1 but failed to find it4 ,believing that the poison was a volatile acid1 he enclosed some fresh leaves of the plant in a tin box with several test papers4 ,the blue litmus paper became red showing the presence of an acid4 ,he concluded from this experiment that the exhalations of the leaves contained a volatile organic acid which he thought was the poisonous substance4 ,to determine this point1 he prepared the acid in larger quantity by macerating the leaves with water1 expressing and distilling the expressed juice4 ,he was poisoned in doing this work although he had not been affected by handling the living plant and had considered himself immune4 ,he obtained an acid which investigation showed to be somewhat like formic acid1 more like acetic acid1 but having some reactions different from both4 ,taking all the reactions together1 it is unquestionably a new organic acid for which ,i propose the name of ,toxicodendric ,acid1 writes ,maisch4 ,he further says3 ,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 hand1 on the fingers1 wrists1 and bare arms while ,i was distilling and operating with it4 ,several persons coming into the room while ,i was engaged with it were more or less poisoned by the vapours diffused in the room2 and ,i even transferred the poisonous effects to some persons1 merely by shaking hands with them4 ,the diluted acid1 as obtained by me1 and stronger solutions of its salts1 were applied to several persons1 and eruptions were produced in several instances1 probably by the former1 though not always1 which was most likely owing to the dilute state of the acid4 ,whenever this was boiled1 ,i always felt the same itching sensation in the face1 and on the bare arms1 which ,i experience on continual exposure of my hands to the juice of the plant4 ,toxicodendric acid was thought to be the active principle from the time of ,maisch's work until the investigation by ,pfaff in #ahie4 ,,footnotes3 #ae ,proc4 ,amer4 ,pharm4 ,assn4 #ahfe1 p4 #aff1 and ,amer4 ,jour4 ,pharm4 #ahff1 p4 #d4 ,,pfaff',s ,,work4 ,by far the most valuable work on ,rhus toxicodendron is that of ,pfaff4 ,from a clinical study of ,rhus poisoning1 ,pfaff came to the conclusion that the poison must be a non-volatile skin irritant4 ,the more volatile the irritant1 the quicker is its action on the skin4 ,formic acid acts very quickly2 acetic acid1 less volatile than formic1 acts more slowly1 but still much more quickly than poison ivy1 the latent period of which is usually from two to five days4 ,pfaff thought that the volatile acid obtained by ,maisch might have contained some of the poisonous principle as an impurity1 but that it would not produce the dermatitis if prepared in a pure state4 ,he therefore prepared a quantity of the acid by distilling the finely divided fresh plant with steam4 ,the yield was increased by acidulating the mixture with sulphuric acid before the distillation4 ,the acid distillate so obtained was freed from a non-poisonous oily substance by shaking the solution with ether4 ,barium and sodium salts were made by neutralizing the acid1 and were purified by crystallization4 ,analysis showed them to be salts of acetic acid1 and they gave the characteristic tests for this acid4 ,the toxicodendric acid of ,maisch was thus shown to be acetic acid1 and was therefore not the poisonous principle of the plant4 ,pfaff obtained the active principle by the following process3 ,the plant was extracted with alcohol1 the alcohol was distilled off1 and the residue was taken up in ether4 ,the ether solution was washed with water and dilute sodium carbonate solution1 and the ether was evaporated4 ,an oily1 black1 poisonous substance partly soluble in alcohol was obtained4 ,to get the active principle in a pure state1 this residue was extracted with alcohol and filtered and the filtrate was precipitated fractionally by lead acetate4 ,the final precipitates consisted of the lead compound of the poison in a pure state4 ,on decomposing the lead compounds with ammonium sulphide1 shaking out with ether1 and letting the ether evaporate spontaneously1 a non-volatile oil was obtained which gave the characteristic skin eruptions4 ,the pure lead compounds made in different preparations were analyzed and assigned the formula ,c#ba;,h#cj,o#d,pb4 ,the oil itself was not analyzed4 ,pfaff proposed the name ,toxicodendrol for the oil4 ,he found that it was not volatile1 was decomposed by heat1 was soluble in alcohol1 ether1 chloroform1 benzene1 etc41 but insoluble in water4 ,its effects upon the human skin were studied in many experiments upon himself and others4 ,it was shown that an exceedingly minute quantity of the poison will produce the dermatitis1 even #a_/ajjj milligram applied in olive oil being active4 ,the oil was given internally to rabbits1 its effects being most marked on the kidneys4 ,the oil obtained by ,pfaff from ,rhus venenata seemed to be identical with that from ,rhus toxicodendron4 ,,experimental4 ,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 toxicodendron4 ,soon after commencing work1 however1 it became apparent that the poison could be more intelligently studied if the substances associated with it in the plant were first identified2 the scope of the work was therefore extended to an investigation of the other constituents of the plant1 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 precipitation4 ,the crude material for this work was prepared by ,messrs4 ,parke1 ,davis ,co41 of ,detroit1 ,mich41 according to special instructions submitted to them3 #fg-a_/b pounds of fresh leaves and flowers of poison ivy were collected near ,detroit and carefully inspected by a competent botanist4 ,this material was thoroughly macerated and put into ten-liter bottles with ether4 ,the mass was thoroughly shaken1 water being added to make it more mobile4 ,the ether was then separated off and the extraction was repeated three times in the same way to insure complete removal of the toxicodendrol4 ,the ether extracts were combined1 thoroughly dried with anhydrous sodium sulphate1 and the ether was distilled off1 the temperature being kept below #dj deg4 ,c4 during the entire distillation4 ,the residue after the removal of the ether was a thick1 black1 tar-like mass1 weighing #c pounds #aa ounces4 ,in extracting the plant1 about twenty-four gallons of ether were used4 ,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 affected1 since proper precautions were taken and the utensils were handled with rubber gloves4 ,the crude ether extract1 which will be designated as the original material1 was shipped to ,baltimore in ,august and was kept in a cool place until ,november when the investigation was begun4 ,when the bottle was opened1 there seemed to be an escape of a vapor1 and a nauseating odor suggesting crushed green leaves pervaded the atmosphere4 ,some days later1 irregular red patches appeared on the face though a mask of cotton cloth was worn during the work1 and the hands were protected by rubber gloves4 ,assuming from ,pfaff's work that this original material contained the non-volatile oil toxicodendrol1 the first experiment was to try to distil it out under diminished pressure4 ,for this purpose1 an ,anschuetze distilling bulb containing ten grams of the tar was connected with a vacuum pump4 ,after a pressure of #b mm4 had been established the bulb was gradually heated in a bath of ,wood's metal4 ,nothing distilled over4 ,the material began to carbonize at a temperature of #adj deg4 to #aej deg4 ,it was then thought that perhaps the oil could be converted into an ester which might be more volatile and could be distilled out4 #bj grams of the original material were dissolved in #ajj cc4 of absolute alcohol containing #c grains of hydrochloric acid gas1 and the mixture was heated #aj hours on a water-bath under a return condenser4 ,after the heating1 the mixture had a delightful ethereal odor4 ,the flask was corked and left standing several weeks while other work was in progress4 ,the ester solution was then put in a vacuum desiccator over sulphuric acid and the alcohol evaporated4 ,a black1 tarry1 solid mass was left having the ester odor4 ,it was extracted with warm water and filtered from insoluble tar4 ,the filtrate had a green color and the ethereal odor4 ,it was shaken out with ether2 the ether layer had a blood-red color while the water layer was deep green4 ,the extraction with ether was continued until the water layer was no longer green4 ,the combined ether extracts were evaporated in a desiccator without heat4 ,a black tar-like solid was left very much like the original material1 but it had the ester odor4 ,it was partly soluble in water and readily soluble in alcohol4 ,the alcoholic solution was tested on the skin and found to be not poisonous4 ,the ester1 or mixture of esters1 was not investigated further in this connection1 but was later shown to give the reactions for gallic acid and methyl furfurol4 ,these reactions will be referred to in connection with other experiments4 ,after a few other preliminary experiments1 it became evident that the original material was a complex mixture of substances and that it would have to be fractionated by some means and the fractions studied separately4 ,a portion of the original substance was treated with #ej per cent4 alcohol and was found to be partly soluble in this medium4 ,the solution was filtered from insoluble tar4 ,a portion of the yellow filtrate gave a reddish yellow precipitate with lead acetate4 ,the alcoholic solution was distilled in an ,anschuetze flask under diminished pressure2 a yellow liquid condensed in the arm of the flask while most of the alcohol was collected in a bottle connected with the arm4 ,the yellow liquid was acid to litmus4 ,water was added1 the solution was shaken out with ether and the ether was evaporated4 ,when the small residue was completely dry1 it was a yellow solid soluble in dilute alcohol and acid to litmus4 ,the substance was not volatile enough to justify the use of this method for getting it4 ,chlorophyll could not be removed from the original substance because the solvents for chlorophyll such as alcohol1 ether1 fats1 petroleum1 and carbon bisulphide dissolve large quantities of the mixture4 ,a precipitate obtained by adding lead acetate to a filtered solution of the original substance in #ej per cent4 alcohol was suspended in water1 decomposed by hydrogen sulphide1 shaken out with ether and the ether evaporated4 ,the residue appeared at first to be a yellow oil1 but on complete evaporation of the ether in a desiccator1 a yellow solid was obtained--apparently the same as that obtained by vacuum distillation4 ,a solution of the original material in #ej per cent4 alcohol was filtered through bone-black and the filtrate was colorless4 ,examination showed that everything had been removed by the bone-black and the filtrate was apparently pure alcohol and water4 ,in precipitating an alcoholic solution of the crude material with a solution of lead acetate1 it was noticed that at least two kinds of precipitates were formed4 ,the part that went down first was darker in color than that thrown down later4 ,pfaff used the last fractions in obtaining his oil and stated that these precipitates consisted of the lead compound of the oil in a pure state4 ,it was found by experiment that the darker part was soluble in ether while the lighter part was not4 ,this indicated that the darker part consisted of tarry matter which was brought down mechanically or separated out when the alcoholic solution was diluted by the lead acetate solution1 or was perhaps a lead compound soluble in ether4 ,to test this point an experiment was made as follows3 ,some of the crude material was thoroughly extracted with #ej per cent4 alcohol4 ,the tar insoluble in #ej per cent4 alcohol was then treated with #ie per cent4 alcohol2 most of it dissolved2 the solution was filtered and lead acetate in #ej per cent4 alcohol was added4 ,a greenish colored precipitate was formed which was filtered off and found to be completely soluble in ether and soluble to a considerable extent in strong alcohol4 ,these experiments suggested that the light colored lead compound which was thought to contain the poison could be purified by extraction with ether in a ,soxhlet apparatus more conveniently than by the tedious process of fractional precipitation4 ,further preliminary experiments showed that #ej per cent4 alcohol extracted from the original material all of the substance or substances which gave the light colored precipitate and dissolved only a small amount of the tar4 ,two hundred and eighty-eight grams of the crude material were then extracted several times with #ej per cent4 alcohol and filtered2 the insoluble tar was washed and saved for examination4 ,to the filtrate was added an excess of a solution of lead acetate in #ej per cent4 alcohol4 ,the large precipitate1 which will be designated as precipitate ,a1 was filtered and drained by suction in a ,buechner funnel4 ,the alcoholic filtrate ,a was saved4 ,precipitate ,a was extracted with ether in ,soxhlet extractors until the ether came over practically colorless1 the operation being interrupted from time to time to stir up the precipitate in the thimble4 ,the green colored ether solution was saved for future examination4 ,the lead precipitate1 after extraction with ether and drying1 weighed about #aaf grams4 ,a portion of this lead compound was decomposed by hydrogen sulphide in a mixture of water and ether which was well shaken during the operation4 ,the ether was separated1 filtered1 and evaporated under diminished pressure without heat1 and there remained a yellow oily looking residue having a pleasant odor4 ,when the ether and water were completely removed in a vacuum desiccator1 a hard1 brittle1 yellow resin weighing about #af grams was obtained4 ,it was soluble in alcohol1 had a strong acid reaction and was free from nitrogen#af and sulphur4 ,the nitrogen tests were made by the ,lassaign and soda lime methods1#ag and the sulphur test was made with sodium nitroprusside after fusing the residue with sodium4 ,the main portion of the lead compound was decomposed under alcohol by hydrogen sulphide1 filtered1 and the alcoholic filtrate evaporated in vacuo4 ,the same yellow acid resin was obtained4 ,experiments continuing through several weeks were made in applying solutions of this resin to rats1 rabbits and guinea pigs4 ,finding it to be without effect upon these animals it was tried on the writer and found to be not poisonous4#ah ,in the meantime the resin was being studied in the laboratory4 ,,gallic ,,acid4 ,an alcoholic solution of the resin was just neutralized with potassium hydroxide4 ,during the titration1 the solution rapidly became dark brown4 ,after neutralization it was shaken with ether2 the water solution remained brown while the ether layer was nearly colorless and contained practically no dissolved substance4 ,a portion of the water solution of the potassium salt on being acidified with sulphuric acid and standing over night1 deposited a slight precipitate4 ,the solution of the potassium salt gave a heavy precipitate with lead acetate somewhat similar to the original lead precipitate ,a1 and also slight precipitates with salts of zinc1 mercury1 copper1 and silver 7with reduction74 ,it gave a bluish-black color with impure ferrous sulphate and a dark color with ferric chloride4 ,it reduced ammoniacal silver nitrate and ,fehling solution4 ,these experiments indicated the presence of a tannin compound4 ,an alcoholic solution of the resin gave the same color reactions with iron salts as did the potassium salt4 ,to determine which one of the tannin compounds was present was a matter of some difficulty since the di- and tri-hydroxybenzoic acids have in general the same color reactions4 ,the presence of other plant substances in the solution also interferes with the color tests1 and finally1 a substance which gives a blue color with iron salts and one giving a green color may be found together in the same plant4#ai ,further tests with a solution of the resin in dilute alcohol1 and with a water solution of the acid precipitated by adding sulphuric acid to a solution of the resin in potassium hydroxide1 led to the conclusion that the acid is gallic acid4 ,these tests were the following3 7#a7 ,boiling with an excess of potassium hydroxide gave a black substance 7tauromelanic acid74 7#b7 ,the acid was not precipitated by gelatin4 7#c7 ,on addition of potassium cyanide a transitory red color appeared which reappeared on shaking with air4 ,gallic acid is distinguished from tannic acid by tests 7#b7 and 7#c74 ,at later stages in the work the potassium1 barium1 and sodium salts of gallic acid were obtained1 and finally the pure acid was made by decomposing the sodium salt with sulphuric acid and crystallizing from water4 ,a portion of the acid so obtained was further purified by dissolving in absolute alcohol and pouring into absolute ether4#bj ,the melting point behavior of the acid corresponds with that of gallic acid2 it melted with decomposition at about #bcj deg4 ,for further identification1 some of the acid was converted into an ester by the following process3 it was dissolved in #hj per cent4 alcohol1 hydrochloric acid gas was passed in1 and the solution was heated an hour on the water bath4 ,it was then evaporated to a small bulk1 neutralized with barium carbonate and extracted with ether4 ,the ether1 on evaporation1 left the ester which was crystallized from water and dried in a desiccator over sulphuric acid4 ,the anhydrous ester agreed in melting point 7#aef deg4 to #aei deg47 and other properties with the ester of gallic acid described by ,grimaux4#ba ,for the sake of comparison1 an ester was made from gallic acid obtained from another source and the two agreed in properties4 ,a mixture of the two esters melted within the limits given for the ester of gallic acid4 ,while the tests leading to the identification of gallic acid were being made1 another series of experiments was in progress4 ,eleven and one-half grams of the resin obtained from lead precipitate ,a by decomposition with hydrogen sulphide were treated with #j4a n4 potassium hydroxide added from a burette until the acid was exactly neutralized4 ,all went into solution4 ,on shaking with ether1 some of the potassium salt separated out and was saved for examination4 ,the solution became brown on exposure to air and got darker as the work proceeded4 ,the acid in solution as a potassium salt was precipitated out in four fractions by adding for each fraction one-fourth the amount of #j4a n4 sulphuric acid required to neutralize the potassium hydroxide used4 ,the precipitates were filtered off and examined4 ,the first was small in amount1 gummy and hard to filter4 ,the solution was shaken with ether after each precipitate had been filtered off4 ,the succeeding precipitates were in better condition1 but were not pure4 ,all appeared to be impure gallic acid which had become brown by absorption of oxygen4 ,they were saved1 however1 to be tested for poison4 ,after the last fraction had separated1 the filtrate was shaken several times with ether and saved for further examination1 which will be described under ,rhamnose4 ,this filtrate is designated as ,b4 ,at this stage of the work a portion of the resin obtained from lead precipitate ,a was tested and found to be not poisonous as already mentioned4 ,by this test1 all the substances contained in the lead precipitate ,a after its extraction with ether in the ,soxhlet apparatus1 were eliminated from the possible poisonous substances4 ,the poison must therefore have been extracted by the ether4 ,a fresh portion of the original poisonous material was treated with #ej per cent4 alcohol and filtered from insoluble tar4 ,the filtrate was precipitated in six fractions by lead acetate4 ,the last fractions were lighter in color and apparently much purer than the first4 ,the sixth lead precipitate was decomposed by hydrogen sulphide1 the light-yellow water solution was tested and found to be not poisonous4 ,it gave the characteristic reactions for gallic acid4 ,the poison1 if precipitated at all by lead acetate1 must have gone down in one of the preceding fractions4 ,later experiments showed that it is brought down partly mechanically and partly as a lead compound in the first precipitates4 ,,fisetin4 ,having identified gallic acid1 and not finding any other phenol derivative in the lead precipitate1 some of the original material was extracted with hot water to remove gallic acid and filtered from tar while hot4 ,the filtrate had a deep yellow color4 ,on cooling over night1 an olive green precipitate separated out which was dried and found to be a light powder4 ,it was practically insoluble in cold water1 soluble with great difficulty in boiling water from which it separated in yellow flakes1 slightly soluble in ether and in acetic acid1 but readily soluble in alcohol4 ,the solutions were not acid to litmus1 gave a dark color with ferric chloride1 an orange-red precipitate with lead acetate which was easily soluble in acetic acid1 and an orange-yellow precipitate with stannous chloride4 ,these properties and reactions indicated that the substance was the dye-stuff fisetin and that it occurs in the free state in this plant though it is usually found as a glucoside of fisetin combined with tannic acid4 ,a compound of this kind was found in ,rhus cotinus and named fustin-tannide by ,schmid#bb4 ,he showed that the fustin-tannide could be decomposed by acetic acid into tannic acid and a glucoside1 fustin ,c#df;,h#db,o#ba4 ,fustin1 on heating with dilute sulphuric acid1 gave fisetin and a sugar supposed to be rhamnose4 ,fisetin was also found as a glucoside compound in ,rhus rhodanthema by ,perkin4#bc ,the yellow substance which separated from the boiling water solution was further purified by dissolving in a small quantity of hot alcohol and adding hot water4 ,on cooling1 the yellow substance separated out in a flocculent condition4 ,examined under the microscope1 the flakes appeared to be made up of masses of fine crystals4 ,an alcoholic solution of the substance gave a black color with ammonia which became red on addition of more ammonia4 ,concentrated acids intensified the yellow color of the alcoholic solution4 ,fehling solution and ammoniacal silver nitrate were reduced by it4 ,potassium hydroxide added to an alcoholic solution gave at first a deep red color accompanied by a green fluorescence which disappeared1 leaving a yellow liquid4 ,with an excess of caustic potash1 the red color returned and was permanent4 ,these reactions are characteristic for fisetin4#bd ,furthermore1 fisetin should give protocatechuic acid and phloroglucinol by fusion with caustic potash under proper conditions4#be ,the experiment was carried out as follows3 #b grams of fisetin were gently heated in a nickel crucible with #f grams of caustic potash dissolved in #f cc4 water4 ,an inflammable gas1 apparently hydrogen1 was evolved during the fusion4 ,the pasty mass was dissolved in water1 acidified with sulphuric acid1 and filtered4 ,the filtrate was shaken out with ether containing one-fourth its volume of alcohol4 ,the ether was evaporated and the residue was extracted with warm water and filtered4 ,lead acetate was added to the filtrate to precipitate protocatechuic acid1 while phloroglucinol remained in the filtrate from this precipitate4 ,the lead precipitate was suspended in water1 decomposed by hydrogen sulphide1 filtered1 and evaporated to obtain protocatechuic acid4 ,that the substance obtained was protocatechuic acid was shown by the following characteristic tests3 7#a7 ,it gave a greenish brown color with ferric chloride2 on addition of one drop of a dilute solution of sodium carbonate1 the color became dark blue2 on adding more sodium carbonate the color became red4 7#b7 ,a violet color was obtained when a solution of the acid was treated with a drop of sodium carbonate solution and then with a drop of ferrous sulphate4 7#c7 ,it reduced ammoniacal silver nitrate4 7#d7 ,it did not reduce ,fehling solution4 ,the filtrate supposed to contain phloroglucinol was treated with hydrogen sulphide to remove lead1 filtered1 and shaken with ether4 ,the residue left on evaporating the ether was taken up in water4 ,this solution gave the following reactions characteristic for phloroglucinol3 7#a7 ,it reduced both silver nitrate and ,fehling solution4 7#b7 ,it colored pine wood moistened with hydrochloric acid red4 7#c7 ,it gave a red color with vanillin and hydrochloric acid1 and 7#d7 ,a deeper red color with oil of cloves and hydrochloric acid1 becoming purple on standing4 7#e7 ,it gave a violet color with ferric chloride4 ,the substance is then1 without doubt1 fisetin4 ,the formula#bf of fisetin is supposed to be ,c#ae;,h#aj,o#f4 ,,rhamnose4 ,it was stated above that ,schmid obtained a sugar solution by the decomposition of a fisetin-glucoside from ,rhus cotinus1 and ,perkin obtained the same from a glucoside in ,rhus rhodanthema4 ,these investigators thought that the sugar was isodulcite or rhamnose1 but they did not isolate it on account of the small quantities of material at their disposal4 ,moreover1 the sugar is very hard to crystallize in the presence of other soluble substances and is not found in large quantity in plants4 ,maquenne#bg could obtain only #ae to #bj gm4 of rhamnose by working up #a kilogram of the berries of ,rhamnus infectorius4 ,assuming that the free fisetin found in poison ivy leaves had its origin in the decomposition of a fisetin-glucoside by natural processes1 it was reasonable to suppose that the sugar would also be found in the free state1 although1 according to ,roscoe and ,schorlemmer3#bh ,isodulcite does not occur in the free state in nature1 but is found as a peculiar ethereal salt belonging to the class of glucosides4 ,on boiling with dilute sulphuric acid1 this splits up into isodulcite and other bodies4444 ,the more recent works on the sugars and on plant chemistry#bi mention the occurrence of rhamnose only in the glucoside form1 with one possible exception4 ,the exception referred to is the occurrence of a free sugar1 supposed to be rhamnose1 in a certain palm-wine4#cj ,czapek says3#ca ,the well-known methyl pentoses do not occur in the free state in plant organisms so far as we know4 ,since rhamnose forms a lead compound1 the sugar1 if present1 should be found in the first lead precipitate1 ,a1 and also in filtrate ,a in case it is not completely precipitated in the presence of acetic acid and alcohol4 ,the filtrate ,a 7about two liters7 was examined first4 ,it had a light yellow color1 contained an excess of lead acetate1 and was acid from the acetic acid liberated in the precipitation of the lead compound ,a4#cb ,this filtrate was evaporated to dryness under diminished pressure to remove alcohol1 water1 and acetic acid4 ,the clear distillate had a peculiar odor suggesting both tea and amyl formate4 ,it was saved for examination and was found to be not poisonous4 ,the residue in the dish after evaporation was a tough reddish brown1 gummy mass which could be drawn out into fine threads4 ,it had a pleasant sweet odor4 ,it was extracted several times with hot water1 each portion being filtered4 ,a brownish yellow powder remained undissolved and was saved4 ,the combined filtrates deposited more of the yellow solid on standing4 ,this powder will be referred to later as ,p4 ,the filtered liquid was freed from lead by hydrogen sulphide4 ,the solution then had a lemon yellow color1 a sweet odor and was acid from acetic acid4 ,on concentrating the solution by evaporation and making a small portion of it alkaline with sodium hydroxide1 the yellow color came out very intense#cc4 ,the alkaline solution reduced ,fehling solution and ammoniacal silver nitrate1 indicating the presence of a sugar4 ,another portion of the solution gave a slight precipitate with phenyl hydrazine in the cold4 ,the remainder of the solution was evaporated to dryness1 extracted with water1 filtered1 and again evaporated4 ,a dark sticky syrup was left which was only partly soluble in water4 ,this was treated with water1 filtered1 and the filtrate was evaporated1 the water being replaced from time to time to remove acetic acid4 ,finally the liquid gave the following tests for rhamnose1 besides those already mentioned3 7#a7 ,with alpha-naphthol#cd and sulphuric acid1 a purple violet color4 7#b7 ,with thymol#ce and sulphuric acid1 a red color4 7#c7 ,with resorcinol#cf and sulphuric acid1 red color4 7#d7 ,with orcinol#cg and hydrochloric acid1 red color4 7#e7 ,with ammonium picrate and sodium picrate1 yellowish red color4 7#f7 ,with phloroglucinol and hydrochloric acid1 red color4 7#g7 ,it decolorized an alkaline solution of potassium ferricyanide4 7#h7 ,it gave a white precipitate with lead acetate4 ,the filtrate ,b 7p4 #bj7 from which gallic acid was precipitated by sulphuric acid in four fractions was saved to examine for sugar4 ,to remove gallic acid completely1 and other vegetable matter1 it was shaken out several times with ether1 and was kept at a low temperature with salt and ice for a long time4 ,it was left standing for several weeks1 during which time more brown matter separated out and was filtered off4 ,the filtrate was evaporated to a small bulk1 cooled1 and filtered from crystals of potassium sulphate4 ,the filtrate was evaporated to dryness1 the residue taken up in water and filtered through bone-black4 ,addition of alcohol caused complete precipitation of potassium sulphate4 ,the solution then gave the above mentioned characteristic tests for rhamnose4 ,all attempts to get the osazone of the sugar by the method of ,fischer#ch failed1 probably on account of the small quantity of the sugar present4 ,the plant1 it will be remembered1 was originally extracted with ether in which rhamnose is practically insoluble4 ,the above described tests1 however1 can leave no doubt as to the identity of the sugar4 ,additional evidence that the sugar is rhamnose was obtained by a method described by ,maquenne#ci as follows3 ,the production of methyl furfurol in the dehydration of isodulcite furnishes a very simple means of characterizing this sugar in mixtures which contain it2 it is sufficient1 for example1 to distil #ej gm4 of quercitron wood with as much sulphuric acid and about #aej gm4 of water1 then to rectify the liquid obtained in order to get several drops of the crude furfurol1 which on addition of alcohol and concentrated sulphuric acid gives immediately the green coloration characteristic of methyl furfurol4 ,this procedure is applicable to extracts as well as to entire plants1 and has the advantage that it does not require the separation of isodulcite1 the crystallization of which is often very slow and at times impossible when it is mixed with other very soluble substances4 ,the experiment was tried with the crude ether extract of the plant according to the directions of ,maquenne1 and the green color with alcohol and sulphuric acid was obtained from the thicker oily portion of the distillate4 ,this test can be made with hydrochloric acid#dj as well as with sulphuric4 ,therefore the color test was tried with the ester mixture prepared in one of the early experiments by boiling the original plant material with hydrochloric acid and alcohol4 ,methyl furfurol was found here also1 this method indeed giving better results than that of ,maquenne4 ,the presence of free rhamnose has thus been shown in the original material1 in the first precipitate by lead acetate1 and in the filtrate from this precipitate4 ,experiments to be described under ,the ,poison showed that the ether extract from the ,soxhlet apparatus contained a substance which yielded rhamnose when hydrolyzed by dilute sulphuric acid4 ,the presence of free gallic acid1 fisetin1 and rhamnose in the plant can be readily explained by a series of assumptions for which there is a considerable amount of experimental evidence4 ,there is reason to believe that tannin-like bodies are formed at the expense of chlorophyll1#da that complex tannin bodies can be broken down by acetic acid 7also found in ,rhus toxicodendron7 into a tannic acid and a glucoside 7for example1 the fustin-tannide mentioned above yields tannic acid and fisetin-glucoside72 and finally that the glucoside can be hydrolyzed by acids or enzymes giving1 in the sumach plants1 fisetin and rhamnose4 ,nitrogenous ferments which can effect the hydrolysis of glucosides and give rise to sugars are frequently found in plants1 for example1 emulsin in almonds1 myrosin in mustard1 and erythrozym in madder4 ,acree and ,hinkins#db found that diastase1 pancreatin1 and a number of other enzymes cause hydrolysis of triacetyl glucose with the formation of glucose and acetic acid4 ,stevens#dc obtained a nitrogenous oxidizing enzyme from ,rhus vernicifera4 ,the close relationship between the poisonous species of ,rhus would lead us to suppose that the same soluble ferment exists in poison ivy1 though it was not detected in the original material used in these experiments1 probably because the plant was extracted with ether in which the enzyme is insoluble4 ,the existence of such a soluble ferment would explain the presence of free sugar and free fisetin4 ,,evidence ,,of ,,the ,,presence ,,of ,a ,,fatty ,,acid ,,in ,,filtrate ,a4 ,the brown substance ,p1 obtained from filtrate ,a by evaporation and extracting the residue with hot water1 was suspended in warm water and dilute sulphuric was added4 ,a white precipitate was formed and a strong fatty acid odor was developed4 ,after the mixture had been heated for some hours on the water bath a small portion was made alkaline and it reduced ,fehling solution4 ,the main solution was filtered and the precipitate supposed to be a fatty acid was saved4 ,the filtrate was neutralized with barium carbonate1 filtered1 evaporated1 freed from caramel1 and the solution then gave the tests mentioned above for rhamnose4 ,a portion of the precipitate supposed to be a fatty acid was ignited in a porcelain spoon4 ,it fused1 carbonized1 and burned4 ,the remainder was heated with alcoholic potash and reprecipitated with hydrochloric acid4 ,the precipitate was washed and heated with alcohol4 ,part of it dissolved4 ,the insoluble part was found to be a lead compound4 ,on boiling it with hydrochloric acid and cooling1 lead chloride crystallized out4 ,this was confirmed by dissolving the lead chloride in hot water and precipitating as lead sulphide4 ,these experiments were not carried farther on account of the small quantity of material1 but they show that the gummy substance obtained from filtrate ,a contained rhamnose 7either as a lead compound of free sugar or as a lead compound of a rhamnoside71 and also1 most probably1 the lead compound of an organic acid4#dd ,,the ,,fragrant ,,distillate4 ,several times in the course of this work1 extracts of the original plant material in alcohol and in water were distilled under diminished pressure for the purpose of concentrating the solutions4 ,the distillate1 in every case1 had an ethereal odor suggesting amyl formate in very dilute solution1 but was more fragrant4 ,the distillate from a water extract was examined4 ,it was a clear liquid1 a little darker than pure water1 was not poisonous1 was neutral to litmus paper1 gave no color with ferric chloride1 reduced ammoniacal silver nitrate1 but not ,fehling solution1 and gave a faint red color with dilute ammonium hydroxide and with sodium carbonate4 ,a small quantity of a finely divided black precipitate separated out from the water distillate on standing4 ,the substance with the fragrant odor was extracted by shaking the distillate with ether and letting the ether evaporate spontaneously4 ,a very small quantity of a yellow solid was deposited on the sides of the dish4 ,this substance had a strong and persistent odor1 so sweet as to be almost nauseating4 ,not enough was obtained for examination or analysis4 ,this fragrant residue was difficultly soluble in water and the solution reduced silver nitrate in ammonia4 ,a steam distillate of the original plant material had the same fragrant odor as the distillate from a water extract4 ,,the ,,poison4 #bhh grams of the original poisonous material were extracted with #ej per cent4 alcohol1 and this alcoholic solution was precipitated with lead acetate in the manner already described 7p4 #ag74 ,the lead precipitate so obtained was extracted with ether in ,soxhlet extractors and after the extraction was found by test to be free from poison4 ,therefore the poison1 if precipitated by the lead acetate1 must have been extracted by the ether4 ,this ether solution had a dark green color1 and was acid from acetic acid brought down in the lead precipitate4 ,the ether was evaporated in a vacuum desiccator without heat and there remained a small quantity of an acid mixture of water and a soft tar2 the watery part was colored green1 showing that the tar was soluble to some extent in dilute acetic acid4 ,the mixture had the peculiar odor of the original material4 ,a small drop of the green watery part was applied to the wrist1 allowed to remain a few minutes and was then removed by absorbent paper1 but the spot was not washed4 ,itching and reddening of the skin commenced within twenty-four hours4 ,at the end of forty-eight hours1 there was a well developed case of poisoning4 ,how this was cured will be described in another place4 ,a small portion of the poisonous mixture was dissolved in alcohol1 and this solution was divided into three parts4 ,the first part was treated with ferric chloride1 but it gave no color reaction4 ,another portion of the alcoholic solution was diluted with water4 ,it became turbid4 ,the third portion gave a dirty-green precipitate with lead acetate1 which seemed to come down more readily when the solution was diluted with water4 ,the main portion of the poisonous mixture was then dissolved in #ie per cent4 alcohol and lead acetate in #ej per cent4 alcohol was added4 ,the precipitate was filtered1 washed1 and decomposed by hydrogen sulphide in a mixture of water and ether4 ,the ether solution was filtered and evaporated4 ,the residue was a tar which1 on standing in a desiccator for some time1 became dry enough to break into sticky lumps4 ,an alcoholic solution of this substance gave a dark color with ferric chloride and a light colored precipitate with lead acetate4 ,to get more of the poisonous tar for study1 #bcc grams of original material were extracted with #ie per cent4 alcohol4 ,strong alcohol was used in order to dissolve as much of the tar as possible4 ,the solution had a dark greenish color1 but was somewhat yellow in thin layers4 ,the undissolved tar was filtered off and extracted twice again in the same way4 ,the tar left after the third extraction was only slightly soluble in alcohol1 and its solution was not poisonous4 ,the three filtrates from these three extractions were precipitated separately by lead acetate in #ej per cent4 alcohol4 ,the first precipitate was largest1 darkest in color1 and carried down more tarry matter4 ,the second was light green1 and the third was quite small1 black1 and was not a lead compound at all1 but some of the tar which separated out on diluting the strong alcohol with the weaker grade containing lead acetate4 ,it was soluble in ether and less soluble in alcohol4 ,the alcoholic solution of this third lot gave no precipitate with hydrogen sulphide4 ,the first and second lead precipitates were filtered by suction and washed with water4 ,they were kept a day or two in a desiccator over sulphuric acid1 but did not become completely dry4 ,the weight of these two moist precipitates together was #agb grams4 ,they were combined and extracted with ether in ,soxhlet extractors which were kept in operation during work hours for three days4 ,in the meantime the alcoholic filtrates from these lead precipitates were combined and concentrated on the water bath by distilling off two liters of alcohol4 ,the alcohol obtained had the peculiar odor of the original material1 but was not poisonous4 ,after a long extraction of the lead precipitate in the ,soxhlet extractors1 the green ether solutions were combined and washed by shaking them with water to remove lead acetate and acetic acid in case any should have been held in the lead precipitate4 ,the ether was distilled off at a low temperature and there remained a soft tar1 a portion of which was not completely soluble in #ie per cent4 alcohol4 ,the alcoholic solution had a greenish yellow color and was poisonous4 ,the tar was also partly soluble in acetic acid1 and this solution was found to contain lead4 ,thinking that the lead acetate had not been completely washed out1 the main part of the tar was dissolved in ether and shaken with water4 ,the wash water continued to give a test for lead as long as the washing was continued4 ,this indicated probably the hydrolysis of an unstable lead compound4 ,hydrogen sulphide was passed into the ether solution mixed with water to remove the lead4 ,lead sulphide was filtered off1 and the ether was evaporated4 ,a small portion of the tar residue in alcoholic solution gave a color reaction with ferric chloride4 ,as this may have been due to traces of lead gallate dissolved in the extraction with ether and afterwards decomposed by hydrogen sulphide1 the main portion of the tar was redissolved in ether and shaken with water until it no longer reacted with ferric chloride4 ,the ether was then evaporated and a soft1 black1 poisonous tar or gum of uniform consistency was left which was shown by tests to be free from gallic acid and lead4 ,these experiments showed that some of the poison was precipitated as a lead compound soluble in ether and some was brought down mechanically in the free state4 ,to see if the extraction with ether in the ,soxhlet apparatus was complete1 the residue in the thimbles was decomposed by hydrogen sulphide and shaken with ether4 ,the dark colored ether solution was freed from gallic acid by shaking with water and dilute sodium carbonate solution1 and was evaporated4 ,a small quantity of tar was obtained which was added to the main portion4 ,a solution of the poisonous tar in #ie per cent4 alcohol did not reduce ,fehling solution and did not give a precipitate with lead acetate except the separation of a small quantity of tar1 which was not a lead compound4 ,the lead compound of the poison was apparently soluble in #ie per cent4 alcohol as well as in ether1 for it would not precipitate in this medium1 although it was found in the original precipitate by lead acetate4 ,the alcoholic solution of the tar became turbid on diluting with water4 ,in order to see if the poison is volatile with vapor of acetic acid1 since this acid is found in the plant and it is thought by some that the poison is volatile1 a portion of the tar was distilled under diminished pressure with acetic acid4 ,it was soluble to some extent in the acid4 ,the temperature did not go higher than #ee deg4 during the distillation4 ,a tube containing cotton wet with sweet oil was placed between the receiver and the water suction so that the uncondensed vapors would have to pass through the cotton4 ,this cotton was rubbed on the skin and was not poisonous4 ,the yellow distillate collected in the receiver was also tested and was not poisonous4 ,,hydrolysis ,,of ,,the ,,poison4 ,about #e grams of the poisonous tar free from gallic acid and sugar was dissolved in alcohol1 and dilute 7#b per cent47 sulphuric acid was added4 ,some of the tar separated out on diluting the alcohol with the acid4 ,the mixture was heated on a water bath during work hours for four days4 ,a purple and green fluorescent solution was formed1 though much tar was left apparently unchanged4 ,the alcohol was evaporated off and the solution was filtered from tar4 ,the fluorescent filtrate was shaken with ether1 by which the green substance was removed1 leaving the solution purple4 ,the ether left1 on evaporation1 a small quantity of a green substance having a pleasant ester odor4 ,it was not further examined4 ,a portion of the purple solution was exactly neutralized with sodium carbonate4 ,this solution gave a blue-black color with ferric chloride which became red on addition of another drop of sodium carbonate1 indicating gallic acid4 ,it also reduced ,fehling solution4 ,another portion of the purple solution was made alkaline with sodium carbonate4 ,a reddish-brown flocculent precipitate was formed and was filtered off4 ,the filtrate did not give any color with ferric chloride1 but it reduced ,fehling solution4 ,it also gave the test for rhamnose with alpha-naphthol4 ,the main portion of the purple solution was made alkaline with sodium carbonate2 the precipitate was filtered off and dissolved in acetic acid4 ,this solution was yellow and gave a reaction with ferric chloride similar to that of gallic acid4 ,the filtrate from the precipitate by sodium carbonate was concentrated by evaporation until sodium sulphate began to crystallize out4 ,alcohol was added to precipitate the sodium sulphate completely1 the mixture was heated and filtered4 ,the alcoholic filtrate was concentrated to a syrup which reduced ,fehling solution and gave the characteristic tests for rhamnose already described4 ,by this hydrolysis1 the tar was split up into rhamnose and some form of gallic acid which could be precipitated by sodium carbonate4 ,this compound1 whose acetic acid solution was yellow1 probably contained fisetin also4 ,the reason for this last statement will appear from the following experiment3 ,,decomposition ,,of ,,the ,,poison ,,with ,,acetic ,,acid4 ,a portion of the poisonous tar was heated in an open dish with strong acetic acid4 ,the tar seemed to be decomposed to some extent1 giving a yellow substance4 ,acetic acid was added from time to time as it evaporated4 ,after several evaporations1 water was added1 the mixture was heated to boiling and filtered4 ,this filtrate ,no4 #a will be mentioned later4 ,the residue in the dish consisted of undecomposed tar and an olive-green flaky substance4 ,this substance was heated with a fresh portion of glacial acetic acid4 ,water was added1 and the mixture was boiled and filtered4 ,the filtrate had a deep yellow color suggesting fisetin4 ,it was shaken out with ethyl acetate which became colored yellow4 ,a portion of the ethyl acetate solution gave an orange red precipitate with lead acetate showing the presence of fisetin4 ,the ethyl acetate was removed from the remainder of the solution by evaporation and the yellow residue was taken up in alcohol4 ,this alcoholic solution gave the characteristic reactions for fisetin with stannous chloride1 with potassium hydroxide1 with ferric chloride and with ,fehling solution4 ,filtrate ,no4 #a obtained by heating the poisonous tar with acetic acid and hot water as described above was investigated as follows3 ,a portion of it gave a reddish colored precipitate with sodium carbonate as in the case when the tar was hydrolyzed with sulphuric acid4 ,the remainder was nearly neutralized with sodium carbonate and lead acetate was added in excess to remove gallic acid4 ,the excess of lead was removed by sulphuric acid1 and the sulphuric acid was removed by barium carbonate4 ,the solution on evaporation reduced ,fehling solution to some extent1 but a white precipitate was also formed4 ,in this experiment1 gallic acid and fisetin and probably sugar were formed by decomposition of the poisonous gum with acetic acid1 the acid found in the plant by ,pfaff4 ,the presence of free gallic acid1 fisetin and rhamnose in the plant can therefore be explained by the natural hydrolysis of a complex gum or tar or a constituent thereof4 ,the poisonous property is lost in the general rearrangement which takes place during hydrolysis4 ,the poisonous tar was not hydrolyzed by boiling with a dilute solution of sodium carbonate4 ,it was found1 as has been stated elsewhere1 that the lead compound of the poison could not be precipitated in #ie per cent4 alcohol4 ,further experiments1 however1 showed that on extracting the poisonous gum with #ej per cent4 alcohol1 a portion of it dissolved1 and this solution gave a precipitate with lead acetate which was a true lead compound4 ,the remainder of the purified tar 7about #aj gm47 was treated with #ej per cent4 alcohol and filtered4 ,very little dissolved in alcohol of this strength1 but on addition of lead acetate in #ej per cent4 alcohol to the solution1 a light colored precipitate was formed1 which became dark on standing4 ,it was filtered off1 washed free from lead acetate1 decomposed by hydrogen sulphide1 and shaken out with ether4 ,the ether left1 on evaporation1 a yellow resinous substance having a faint odor like garlic4 ,by drying in a desiccator1 a small quantity of a solid yellow resin was obtained which was completely soluble in alcohol4 ,a very small drop of this solution applied to the skin on the end of a glass rod which had been drawn out to a point caused an eruption in about thirty-six hours4 ,following the nomenclature used by ,maisch and ,pfaff1 this substance will be designated as ,toxicodendrin1 the ending in indicating its glucoside nature4 ,the filtrate from the lead precipitate just described was freed from the excess of lead acetate by hydrogen sulphide1 was tested for poison1 and was found to be poisonous1 showing that the precipitation by lead acetate was not complete even in #ej per cent4 alcohol4 ,on spontaneous evaporation of the solution1 a yellow1 sweet smelling resin was left4 ,a portion of the alcoholic solution of the toxicodendrin gave a dark coloration with ferric chloride1 did not reduce ,fehling solution and was slightly acid to litmus4 ,to see whether the toxicodendrin could be hydrolyzed1 the remainder was dissolved in alcohol and dilute sulphuric acid was added4 ,a fine1 white precipitate was formed at once which rose to the surface on standing as a light flocculent substance4 ,the mixture was heated for several days on a water bath1 filtered from unhydrolyzed resin and the filtrate was neutralized and concentrated in the way already described4 ,the solution obtained reduced ,fehling solution4 ,not enough was obtained for further sugar tests1 but all the hydrolysis experiments point to the conclusion that the poisonous substance is a rhamnoside1 and is the source of the sugar in the plant4 ,the reaction with ferric chloride observed whenever a lead compound of the poison is decomposed by hydrogen sulphide may be explained by the formation of traces of gallic acid or fisetin through the action of the weak acids present4 ,the supply of purified poisonous tar having been exhausted in the preceding experiments1 further study of the active principle is postponed until more can be prepared4 ,it is highly desirable to investigate the white precipitate formed by addition of sulphuric acid to an alcoholic solution of the toxicodendrin4 ,,oxidation ,,of ,,the ,,purified ,,tar ,,with ,,nitric ,,acid4 ,when the purified poisonous material 7p4 #cb7 was extracted with #ej per cent4 alcohol1 only a small quantity was dissolved as was stated above4 ,the insoluble residue was treated with fuming nitric acid4 ,violent reaction took place at once with copious evolution of red fumes and heat4 ,when the reaction was over1 a sticky red gummy mass was left which was slightly soluble in cold water and readily soluble in warm alcohol4 ,the water extract was yellow1 and the alcoholic solution was red4 ,that the water extract contained picric acid was shown by the following experiments3 7#a7 ,a portion was gently warmed with a few drops of a strong solution of potassium cyanide and two drops of sodium hydroxide4 ,the red color of potassium isopurpurate was formed4 7#b7 ,a portion of the water solution was heated with glucose and a few drops of sodium hydroxide4 ,the deep red color of picraminic acid was produced4 7#c7 ,a few drops of an ammoniacal solution of copper sulphate was added to the water extract4 ,a yellow-green precipitate was formed4 7#d7 ,the water extract dyed silk1 but did not dye cotton cloth4 ,,distillation ,,of ,,the ,,tar ,,with ,,soda ,,lime4 ,about #be gm4 of the tar left after extracting the original material with hot water was dissolved in ether and poured into a glass retort containing soda lime4 ,the ether was distilled out1 leaving the tar intimately mixed with the soda lime4 ,the retort was then gradually heated4 ,vapors and liquid were given off1 both of which turned red litmus blue and had a strong odor like tobacco smoke4 ,no odor of ammonia was detected4#de ,at the high temperature of the triple burner1 a semi-solid1 red1 greasy substance collected in and closed the condenser tube4 ,this substance had the same powerful odor as the liquid portion of the distillate4 ,the clear1 watery portion of the distillate was separated from the thicker parts1 and was found to contain pyrrol and pyridine derivatives by the following characteristic tests3 7#a7 ,wood moistened with hydrochloric acid was turned red by it4 7#b7 ,colorless fumes were formed when brought near hydrochloric acid2 mixed with hydrochloric acid1 a red insoluble substance was formed4 7#c7 ,it precipitated the hydroxides of iron1 gave a light blue precipitate with copper sulphate1 and a white precipitate with mercuric chloride4 ,the greasy1 semi-solid mass was extracted with #aj per cent4 hydrochloric acid and filtered4 ,on addition of a solution of mercuric chloride to the red filtrate1 a brown flocculent precipitate was formed4 ,it was filtered off and distilled with caustic soda1 but the distillate did not contain pyridine4 ,,potassium ,,permanganate ,,as ,a ,,remedy ,,for ,,rhus ,,poisoning4#df ,in the early stages of this work some experiments were made to see if potassium permanganate could be used to purify the lead precipitate by oxidizing the tar brought down in precipitation4 ,it was found that the permanganate attacked the lead precipitate as well as the other organic matter in the vessel4 ,this fact and the well-known value of permanganate in treating skin diseases1 its use as an antidote for some kinds of alkaloid poisoning1#dg as an antidote given to cattle poisoned by plants1#dh and as an antidote for snake bites1#di suggested its use as a remedy for ,rhus poisoning4 ,maisch#ej mentioned that he had used it with success1 but it never came into general use1 probably on account of its staining the skin and clothing4 ,in carrying out this work abundant opportunities for testing its value as a remedy for the dermatitis caused by poison ivy were afforded by many cases of accidental and intentional poisoning4 ,the best example of the latter was obtained with the ether solution from the extraction of the lead precipitate in the ,soxhlet apparatus 7page #bh74 ,after removing the ether1 a small drop of the residue was applied to the wrist as described4 ,an itching red spot about the size of a dime was noticed in thirty-six hours1 and it steadily increased in size4 ,nearly two days after the application of the poison1 a dilute solution of potassium permanganate containing a little caustic potash was rubbed into the spot until the pimples were destroyed4 ,a little black spot was left wherever there had been a pimple1 showing that the permanganate had been reduced to oxide in the skin4 ,the place was washed and nothing more was thought of it until the morning following1 when it was noticed that the wrist had commenced to swell during the night1 and the characteristic watery secretion was running from the poisoned spot4 ,more permanganate solution was applied without potash and the wrist was bandaged1 thinking that this would prevent the spreading of the eruption1 but it really facilitated spreading by becoming saturated with the poisonous fluid and keeping it in contact with a larger surface of skin4 ,in the meantime the swelling and inflammation had extended nearly to the elbow4 ,the arm now had the appearance of having been bitten by a snake4 ,to reduce the swelling it was immersed in hot water4 ,this seemed to bring out the eruption very quickly and the blisters were treated with permanganate as fast as they appeared4 ,the swelling was reduced1 but returned during the night4 ,on the evening following1 the forearm was immersed in a bowl of hot permanganate solution containing a little caustic potash4 ,the solution was kept as hot as could be borne for about half an hour4 ,after this bath1 the poison was completely oxidized1 for the swelling was reduced and did not return1 nor was there any fresh eruption4 ,what appeared to be a severe case of poisoning was thus cured very quickly4 ,the use of hot water not only reduces the swelling1 but also helps to destroy the poison4 ,the action of permanganate is also more rapid at high temperatures4 ,the oxidizing power of permanganate1 as is well known1 is greater in acid solution than in alkaline1 five atoms of oxygen being available in the former and three in the latter1 according to these equations3 #b ,k,mn,o#d #c ,h#b,,so#d ,k#b,,so#d #b ,mn,s,o#d #c ,h#b,o #e ,o4 #b ,k,mn,o#d ,h#b,o #b ,mn,o#b #b ,,koh #c ,o4 ,permanganate was used as a remedy in some cases mixed with dilute sulphuric acid1 and in others1 with zinc sulphate2 also with lime water4 ,it was found to be satisfactory whether used alone or with any of the substances mentioned1 provided it was well rubbed into the skin4 ,the concentration of the solution used was varied according to the location and condition of the eruption4 ,where the skin was thin or already broken1 dilute solutions 7one per cent47 were used4 ,in one case1 the eruption appeared in the palm of the hand where the skin was so thick that it was necessary to open it before the remedies could reach the poison4 ,the difficulty of getting the remedy in contact with the poison in the skin is the reason why the eruption is hard to cure4 ,the remedy most commonly used for this eruption is an alcoholic solution of lead acetate4 ,this remedy is unsatisfactory for the reason that its action consists in depositing an unstable lead compound of the poison in the skin where the conditions of moisture and temperature are favorable for its decomposition1 liberating the poison with all its irritant properties4 ,moreover1 alcoholic preparations should not be used because the alcohol dissolves the poison and1 on evaporation1 leaves it spread over a larger surface like a varnish4 ,potassium permanganate1 however1 oxidizes the poison completely4 ,the only objection to the use of permanganate of which the writer is aware is that it stains the skin4 ,the stain can be removed by vigorous scrubbing with soap1 or it will wear off gradually in a few days4 ,it can be removed at once by certain acids1 but these should not be used by persons not familiar with their action4 ,with the knowledge of the facts mentioned1 many solutions were tested for poison by applying them to the skin1 and when an eruption appeared1 it was cured quickly and permanently by rubbing in a permanganate solution1 usually mixed with dilute sulphuric acid4 ,,footnotes3 #af ,nitrogen was found very readily by the soda lime test in the tar left after extracting the original material with #ej per cent4 alcohol1 but was not found by the ,lassaign test4 #ag ,stevens4 ,amer4 ,jour4 ,pharm4 #gg1 #bee1 ,june1 #aije4 #ah ,whenever it is stated in this paper that a solution was poisonous or not poisonous1 the test was made by the writer upon himself4 #ai ,liebig's ,annalen1 ,,cxi1 p4 #bae4 #bj ,ueber ,mategerbstoff1 p4 #bj4 #ba ,bull4 ,soc4 ,chim4 7,,ii71 ,vol4 #b1 #ie 7#ahfd74 #bb ,berichte #ai1 #agce 7#ahhf74 #bc ,jour4 ,chem4 ,soc4 #ga1 #aaid 7#ahig74 #bd ,berichte #ai1 #agdj4 #be ,ibid4 #agdg2 ,annalen1 #aab1 #ig4 #bf ,biochem4 ,pflan4 ,,ii1 #eba4 #bg ,ann4 de ,chim4 et de ,phys41 #fth ,series1 ,,xxii1 #gf 7#ahia74 #bh ,treatise on ,chem41 ,vol4 ,,iii1 ,pt4 ,,iii1 #dib4 #bi ,les ,sucres2 ,chem4 der ,zuck42 ,biochem4 der ,pflan4 #cj ,chem4 ,zeit4 #bc1 ,rep4 #agg4 #ca ,loc4 cit4 #a1 #bji4 #cb ,on standing several weeks1 a small quantity of tar separated out on the walls of the vessel1 also a brown precipitate which was filtered off1 suspended in water1 and hydrogen sulphide was being passed in when an accident occurred and it was lost4 #cc ,by warming with alkalies or barium hydroxide1 rhamnose is colored yellow4 ,chem4 der ,zuck4 ,i1 #agg4 #cd ,ibid4 #ahh4 #ce ,ibid4 #cf ,rayman1 ,sur ,l',isodulcite1 ,bull4 ,soc4 ,chim4 #dg1 #ffh 7#ahhg74 #cg ,acides ,gummiques4 #ch ,berichte ,,xx1 pp4 #ajhi1 #ajia1 #aahh1 #beff4 #ci ,ann4 de ,chim4 et de ,phys4 7#f7 ,,xxii1 #ic 7#ahia74 #dj ,biochem4 der ,pflan4 ,i1 #baj4 #da ,comptes rendus ,,cxv1 #hib4 #db ,amer4 ,chem4 ,jour4 #bh1 #cgj4 #dc ,amer4 ,jour4 ,pharm4 #gg1 #bee 7,june1 #aije72 #gh1 #ec 7,feb41 #aijf74 #dd ,a wax obtained from ,rhus succedanea was shown by ,stahmer to contain palmitic acid and glycerol in the form of glycerol palmitate4 ,annalen #dc1 #cdc1 7#ahdb74 #de ,see ,amer4 ,jour4 ,pharm4 #gg1 #bef4 #df ,this section is added in the hope that it may be of use to others who are subject to this form of poisoning4 #dg ,moor1 ,n4 ,y4 ,med4 ,rec4 #de 7#ahid71 #bjj4 #dh ,bull4 ,no4 #bf1 ,u4 ,s4 ,dept4 ,agr41 ,div4 of ,bot4 #dg4 #di ,lacerda1 ,comptes rendus #ic 7#ahha7 #dff-dfi4 #ej ,amer4 ,jour4 ,med4 ,sci4 #eb 7#ahff71 #bhe4 ,,summary4 ,leaves and flowers of the poison ivy plant were extracted with ether and the ether was removed by evaporation4 ,in the residue1 the following substances were found and studied3 gallic acid1 fisetin1 the sugar rhamnose1 and a poisonous tar1 gum1 or wax4 ,the lead compound of the poison was soluble in ether2 this fact gave a means of separating the poisonous substance from the non-poisonous matter in one operation4 ,the poison was not volatile with vapor of acetic acid1 or with vapor of alcohol4 ,the poisonous tar or wax was decomposed by acids and yielded gallic acid1 fisetin1 and rhamnose1 showing the probable source of these compounds in the plant1 and indicating that the poison is a complex substance of a glucoside nature4 ,it was found that a portion of the poisonous substance could be precipitated by lead acetate from a solution of the purified tar in #ej per cent4 alcohol4 ,all cases of poisoning developed on the writer were easily cured with potassium permanganate4 ,the following method is suggested for obtaining the poisonous substance from the plant3 ,extract the plant with alcohol1 filter1 and precipitate at once with lead acetate4 ,wash the precipitate1 dry1 and extract with ether in ,soxhlet extractors 7loosely filled74 ,combine the ether extracts1 mix with water1 and pass in hydrogen sulphide4 ,separate the water and the ether solution1 and filter the latter4 ,wash the ether solution thoroughly by shaking with water1 and then evaporate at a low temperature4 ,,biography4 ,william ,anderson ,syme1 the author of this dissertation1 was born in ,raleigh1 ,n4 ,c41 on ,july #aa1 #ahgi4 ,he was prepared for college at the ,raleigh ,male ,academy1 entered the ,north ,carolina ,college of ,agriculture and ,mechanic ,arts in #ahif1 and was graduated in #ahii with the degree ,b4 ,s4 ,he was an ,instructor in ,chemistry at the same ,college from ,january #ast1 #aijj1 until ,june1 #aijc1 when he received the degree ,m4 ,s4 for graduate work4 ,in ,october following1 he entered ,johns ,hopkins ,university as a graduate student in ,chemistry1 and was awarded one of the ,north ,carolina ,scholarships4 ,his minor subjects are ,physical ,chemistry and ,biology4