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FILE NAME Kent KNT DATE 1953 July 4 DOC KNT132 DOCUMENT DESCRIPTION Journal Article - A Study of Cigarettes Cigarette Smoke and Filters - The Journal of the American Medical Association :)* CLINICAL MEITING University ST LOUSItaSte MO Montana DECEMBER 1-4 1953 University : This Issue Exceeds 150,000 Copies N | % 3 wet . . 4 . . American American OF THE Medical Medical Association Association Association ; ORIGINAL ARTICLES EARLY DIAGNOSIS OF PRIMARY MALIGNANT BONE G. Haggart M.D. and J. W. Copel M.D. Boston TUMORS ISONIAZID AND STREPTOMYCIN IN THE TREATMENT OF PULMONARY TUBERCULOSIS . 88 886 Copt F. Fitzpatrick Fitzpatrick W. Tempel Cabe W. M. J. C. Fitzpatrick MC L0.. Major F. U. S. Army and Miller Capt J. H. Sands Weiser , B.S. Denver IMPACT OF MODERN THERAPY MUNICIPAL HOSPITAL .6. 2 ON PULMONARY TUBERCULOSIISN wd Leen as feces A LARGE _ -. W. Weiss M.D. Philadelphia 890 cee bebe ec ccee eee, UTERINE INERTIA : Denver 894 L. C. Heap D. Denver , - OF CIGARETTE SMOKE EFFECT M. T. Friedell M.D. Chicago ON THE PERIPHERAL VASCULAR SYSTEM .897 .901 THE RECORDING OSCILLOMETER IN ORTHOPEDIC PRACTICE .901 be .901 A. Chandler M.D. and P. H. Dickinson M.D. Chicago ANTICOAGULANTS AND SYMPATHETIC NERVE BLOCKS IN THE TREATMENT SYMPATHETIC OF VASCULAR LESTONS G. H. Pratt M.D. New York . ee e ee e ce Sb b eee ne eee 903 CARCINOMA OF THE COLON COMPLICATING CHRONIC ULCERATIVE COLITIS C. Weckesser M.D. and A. B. Chinn M.D. Cleveland .905 CLINICAL NOTES MEDIASTINAL LIPOMA SIMULATING CARDIAC ENLARGEMENT A. M. Gottlieb M.D L. J. Boer M.D. and P. Jordan Jr. M.D. Detroit BENIGN ULCER OF THE ESOPHAGUS ASSOCIATED WITH CHRONIC ACETANILID .908 POISONING ' cence eee teen eect teens W. L. Walton M.D. and M. W. Greenberg M.D. Brooklyn vee te .910 .910 SUBACUTE BACTERIAL ENDOCARDITIS TREATED WITH CHLORAMPHENICOL AND OXYTETRACYCLINE oo : ccc cree ec cence eee .913 .913 G. Lecco M.D. and A. Toto M.D. Lima Peru DERMATITIS DUE TO TRIETHYLENE MELAMINE THERAPY . a .914 M. Frumin M.D. and A. I. Rubenstone M.D. Philadelphio SPECIAL REPORTS WILLIAM BEAUMONT PIONEER PHYSIOLOGIST F. Stenn M.D. Chicago 00.000 - occccecccceee eee. 915 Chemical Laboratory A STUDY OF CIGARETTES CIGARETTE ; SMOKE AND FILTERS 917 Chemistry Council on Pharmacy and Chemistry NEW AND NONOFFICIAL REMEDIES .9 e cee2 eee ee0 e .920 .920 EDITORIALS Incidence of Tuberculosis Among Amer- 922 ican Medical Students .... Fatal Bicycle Accidents in the United States cece United United 923 Industrial Dermatology .923 .923 ORGANIZATION SECTION Federal Medical Legislation 924 State Medical Legislation 924 Medical Articles in Lay Journals .924 The Scientific Exhibit .925 Report of Committee on Awards .926 Registration at the Annual Meeting ... 927 Minutes of the Scientific Sections . 928 REGULAR DEPARTMENTS Medical Medical News 0... 0s... 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Gregg M.D. New York Medicolegal Abstracts York . .963 002, The Leisure Corner 964 Motion Pictures or 965 MedMiceadlical Motion Pictures 965 Medical Literature Abstracts 1... 966 Book Reviews Deere ..... eee e 982 eee ee ee Queries and Minor Notes Warts Treatment for Strongyloidiasis Broken infants Ovalocytosis Ovalocytosi Fossa Palliative Treatment Following Mastectomy Nec- robiosis Diabeticorum Lipoidica enzal Meningitis InfluTreatment of Crypt- Erections oneomal rchidism ImmoIbmmiobliliizzaatitonion of Breasts nation Immobilization Self Trep-.984 Test Self Exam~-- WASHINGTON NEWS Care Medical Non Congress Tax Bills Personnel Miscellaneous . Adv Page 5 National Organizations of Medi- 10 cal interest 2000... . Adv Page Tonics and Sedatives Adv Poge 38 Books Received . Adv Page 50 Nationwide Symposium on Bedside Management Twenty clinically important subjects are dis- cussed in the July Number of the MEDICAL CLINICS OF NORTH AMERICA devoted to a nation- 7 ; , : . wide symposium on Bedside Management Included are such timely topics as Cardiac Emer- gencies Bronchial Asthma Diabetes Acute Burns Anemias Backache and many others The MEDICAL CLINICS bring you every other month a Symposium on some topic of current importance contributions from America's leading medical centers The help they give is minute practical detailed apply the information to your AIVA o--'! This is postgraduate study at you can The Medical Clinics of North _ Issued serially one illustrated America are books volume of about 200 not magazines They are pages every other month ~ . See SAUNDERS Advertisement on next two pages se Vol 151 No. in CHEMICAL LABORATORY 917 In his preface to Experiments and Observations appears a great quotation of medical history " submit a body of facts which cannot be invalidated My opinions may be doubted denied or approved according as they conflict or agree with the opinions of each individual who may read them but their worth will be best determined by the foundation on which they rest incontrovertible facts And again Truth like beauty when unadorned is adorned the most In his notebook now at the Washington School of Medicine St. Louis he wrote Of all the lessons which a young man entering upon the profession of medicine needs to learn this is perhaps the that he should resist the fascination of doctrines and hypotheses till he has won the privilege of such studies by honest labor and faithful pursuit of real and useful knowledge CHEMICAL LABORATORY Following is the first of several reports on cigarettes cigarette smoke and filters by the Chemical Laboratory of the American Medical Association The work was done by the Laboratory at the request of the Advertising Committee of the American Medical Association Many of the technical details of the work which was carried our by Mr. Robert R. Stark of the laboratory staff have been omitted in this presentation and can be obrained upon request from the Chemical Laboratory WALTER WOLMAN PH.D. Director A STUDY OF CIGARETTES Cigarette SMOKE AND FILTERS Alexis St. Martin lived long after the death of his 1. Filter Cigarettes master near Montreal in a state of poverty He had 17 children 4 of whom reached adulthood He displayed his fistula in various parts of the country and had offers to exhibit it in Paris and London When he died in 1880 Sir William Osler attempted to secure the stomach for the Army Medical Museum but the St. Martin family responded by exposing the body to putrefaction and then burying it in an eight foot deep grave The Ethan Allen Beaumont collection is a marvelous store of relics and letters belonging to the great surgeon and his immediate family It was discovered in 1936 by Dr. Arno Luckhardt and bequeathed to the University of Chicago where part of it is on permanent display at Billings Library This added to the precious materials preserved at the Washington University School of Medi- cine constitutes memorabilia that properly should be exhibited like an art treasure everywhere the country Considerable interest has been expressed concerning the effectiveness of filter cigarettes and the called denicotiniz ing process in reducing the amount of nicotine and tars in cigarette smoke Because of the scarcity of published data on the subject the Chemical Laboratory of the American Medical Association has undertaken a study of nicotine and tars in the smoke of filter cigarettes special nicotine cigarettes and re ular cigarettes and the effectiveness of filter holders in removing nicotine and tars from cigarette smoke This first report will deal only with the effect of the filters of the three - . largest selling filter cigarettes They represent the three types of filter on the market namely paper asbestos and cotton During the course of this investigation changes were made in the filters of each of the three brands either to improve the filtering efficiency or to change the smoking char- acteristics of the cigarette The cigarettes with the original filters are designated as A B and C and the cigarettes with modified filters are designated as A B and C in table 1. A regular tobacco cigarette brand D. was also tested These experiments are not designed to interpret such qualities of cigarettes as flavor aroma or smoking character- istics ; to radiate the spirit of a great American physician 1853 W. Polk St. As stated by Bradford Harlan and Hanmer a laboratory smoking process should be sufficiently like human smoking to allow acceptance of the data collected and it must be reproducible Puffing the cigarette by mouth with an absorption Prognosis in Hypertension character or severity of a hypertensive patient's symptoms other of course than those apparatus placed between the cigarette and mouth meets the first requirement but is not reproducible Continuous suction which point to cardiaocr renal failure give little clue to his subsequent fate Headache for example has occured as often to applied the cigarette as employed by Bogen Koperina and others is far from meeting the first requirement as the I in mild as in severe cases Again it might well have been ex- pected that the transient cerebral attack ascribed to angio- spasm would prove to be a curtain for the subsequent length drama of a stroke but this has not been the case intensified heat produced from the long incandescent coal changes the composition of the smoke Constant suction inter- rupted at timed intervals by a stopcock or valve has been employed by Baumberger Bogen Jensen and Haley and others and the incidence of such cerebral episodes was no higher Sas among patients who subsequently had strokes than in those ee who did not Since in addition neither a family history of hypertension nor the existence of a renal basis for the hyper- tension appears to influence prognosis unduly assessment of This method is open to criticism because the volume of puff varies between cigarettes depending on differences in tightness of packing Moreover the volume increases significantly in each cigarette as the smoking proceeds and the air resistance de- creases as the cigarette becomes shorter eassee a hypertensive patient must rest fundamentally upon objective 1. Bradford J. A. Harlan W. R. and Haamer H. R Nature of ler findings Cigaret Smoke Technic of Experimental Smoking Indust Eogin Chem J. Early recognition of the accelerated form of 29 836-839 1936 Joo7 hypertensive disease is particularly desirable since it is in this type of case 2. Bogen .: The Composition of Cigarets and Cigaret Smoke J. A. M. A. 93 110-1114 Oct. 12 1929 . that symapthectomy has most to offer and operation performed in time may completely transform its character Appro- 1. Kopetina A Untersuchung der Stickstod~altigenVerbindungen des Tabakrauches Biochem Zuscht 219 258-276 1930 . priate cases however will not be selected for sympathectomy unless the practice is adopted of submitting every hypertensive patient under the age of 50 to a systematic assessment with the object of establishing how far the disease has already progressed for only by relating this to the age of the patient 4. Baumberger J. P a The Carbon Monoxide Content of Tobacco - Smoke and Its Absorption on Inhalation b The Nicotine Content of Tobacco Smoke c The Amount of Smoke Produced from Tobacco and Its Absorption in Smoking as Determined by Electrical Precipitation J. Pharmacol & Exper Therap 21 23-57 1923 . Jensen C. O. and Haley D. E Studies on the Nicotine Content of Cigarette Smoke J. Agric Res 51 267-275 1935 can it be decided whether been excessive W. D. or not the speed of advance has Leishman D.M. Observations on 6. Pfyl B Zur Bestimmung des Nicouns im Tabakrauch 11 Normung des kunstlichen Verrauchens der Tabakerzeugnisse Zucbr 1. Vatersuch Prognosis in Hypertension British Medical Journal May 23 1953 d Lebensmill 66 501-510 1933 7. Pytika .: Uber die Verteilung des Nicotias berm Rauchen von Zipatetten Chem 39 279 1934 918 CHEMICAL LABORATORY These objections are overcome by a constant volume smoking device such as that described by Pfyl in which the cigarette was puffed by air displacing mercury in a tube as the mercury level was lowered by means of a leveling bulb Pyriki using Pfyl's apparatus to smoke oriental cigarettes to a 15 mm butt taking 40 ml puffs every 30 seconds found 19 to 20 of the nicotine in the mainstream smoke smoke emerging from the puffed end of the cigarettel 37 to 47 in the sidestream Ismoke rising from the burning tipi and 13 to % in the butts with a total recovery of 74 to 85 of the nic tine The remainder of the nicotine is apparently decomposed by the heat of the coal The cigarettes in the present tests were smoked with the Harlan automatic smoking machine described by Bradford and Hanmer This is a constant volume smoking device in which the mercury is replaced by water as the operating fluid The smoke is passed through a glass tube and collected by gravity deposition in a 300 ml flask to which only two up plementary bubblers are attached These are specially designed to reduce the back pressure to about two inches of water LAM.A. July 4 1953 length that is from a 30 mm to a 10 mm butt the nicotine appearing in the smoke of each cigarette increases from 1.3 mg to 3.8 mg These variables may be eliminated by assigning fixed values to each of them The results of the smoking experiments will depend on the values selected but under any given set of conditions comparisons between cigarettes and comparisons in the effectiveness of filter are made possible Laboratory The smoking conditions adopted by the A. M. are those of Bradford and workers In this process 47 mm of each cigarette is smoked thirds of a standard 70 mm cigarette using 35 ml puffs of two seconds duration taken once a minute The size of the puff is considered rea- sonable in view of Pfyl's observation that puffs varied individuals from 27 10 61 ml The time among between puffs is suffi- ciently long to allow the cigarette to return to a free burning state and to prevent the formation of an unnaturally long and hot coal In addition to the variables encountered process certain variables are inherent in the in the smoking cigarettes them- Columna Brand Al Brand A. Brand B.t Brand B. Brand Ll Brand 8 Brand D Table Moisture Nicotine Content and Physical Characteristics of 1 : 3 $ 5 o. Type of Filter . - = Asbestos laminated with paper Asbestos laminated with paper = Cottoo = Cotton ............. Wes teeeeeee Average Date Sample Weight of Cigarette Obtained Gm May 1952 1.003 December 1952 = ADHI 1952 October 1952 1.059 1.011 May 1952 August 1952 February 1953 1.047 1.033 1.094 Aretage Weight of Filter Gm 0.165 0.383 0.159 0.139 0.106 0.173 Total Length Cigarette MT 70.0 39.5 69.5 69.3 69.0 09.0 70.0 Four Brands of Cigarettes 6 Average Length Filter 1.m. 11.0 12.3 10.9 10.9 JG.O 10.0 : Average CircuiD ference of Cigarette um 20.0 20.3 26.7 20.7 25.3 23.3 26.5 S Moisture ja Tobacco % 8.60 9.73 fl' 9.84 9.2 10.77 20.71 > Nicotine to Nicotine Tobacco Moisture Free Basisi 5 1.03 1.92 1.36 1.96 2.34 244 2.02 TABLE Analysis of Smoke from Four Brands of Cigarettes Columa t 3 3 6 : 8 fi 10 Nicotine la Weight of Tobacco Actually : Nicotine Found in Smoked Which is Weight of Tars Found 9% Redue Weight of Average Mainstream Stoke Transferred to in Mainstream Smoke Tobacco Reduc hii: Actually Volume of Mainstream pet Cigarette Mg tloo of Mainstream Smoke % . Nicotine in per Cigarette MG tion of Smoked Smoke per With Mainstream With Nf With Turs 1D = Filter A Mainstream Dry Weight Cigarette Filter With Smoke Filter With Pilter With = 303 Smoke G.D. Removed Filter % Removed Filter Reinoved os tc Filter Brand .. 340 Tip & 0.029 2.85 2.60 Broad ... $ 383833 21 15.9 15.1 3 tts 383833 0.GGO ses eeae 351 0.52 8.43 : 19 16.9 33.9 17 Brand R tenes 329 2.52 1.00 383833 0.095 18 Brand .. 0.591 8 15.0 6.8 BEIE 350 383833 13 Ledada * 2.19 ..... = 16.7 9.1 BEIE Brand .. 0.081 461 3.91 26 20 . 383833 3.38 18.3 Brand ... . . 415 35.6 BEIE 0.055 4.00 2.93 26 383833 18 19.0 15.1 350 bass BEIE Brood D wwe 1635 Cit 21 wees 17.8 an . Placed in this coluina fot comparison with length cigarettes The smoking machine itself consists of a constant res- ervoir that supplies water to a buret equipped with a glass float Four cigarettes are smoked simultaneously by taking a puff from in succession This is accomplished by motordriven valves timed by a clock motor During the puff suction created by the emptying buret draws air through the cigarette The puff is terminated when the falling water level seats the glass float in a ground glass constriction at the bottom of the buret ; In smoking a large number of variables are encountered Six of these listed by Pfyl are rapidity of the puff time of the puff volume of the puft number of puffs duration of smok- ing and the length of the butt The effect of the length of the butt on the nicotine content of the smoke is confirmed by Jensen and Haley who have shown that as a 70 mm cigarette is smoked from sevenths to sevenths of its 8. Wenusch A. Influence of of the Nicotine into the Main Lebensmitt 75 182-184 1938 the Width of the Cuttings on the Passage Smoke Stream Ztschr f Untersuch d 9. Bradford J. A. Harlow E. S Harlan W. and Hanmer Nature of Cigaret Smoke Volatile Bases and Acids J. Indust Chem 29 45-50 1937 H. R Engia selves within a given brand and the results of the experiments will depend to a certain degree upon them Variations in type weight cut and tightness of packing of the tobacco may be expected By careful selection of cigarettes based on their weight some of these variations can be minimized but they cannot be eliminated completely Five cigarettes were smoked for each single determination The smoking of a larger number of cigarettes up to 50 did not produce more reliable or consistent results and the sheer volume of smoke was difficult to collect without losses The average weight of each lot of cigarettes was determined and only those cigarettes weighing within 20 mg of this average were smoked to eliminate gross differences in amount of tobacco and tightness of packing in a room maintained at 77 F - humidity The cigarettes were 25 C and 45 smoked relative The mainstream smoke was collected and the nicotine in the smoke determined by the method of Bradford Harlow Harlan and Hanmer The smoke was collected in a 300 ml Kjeldahl flask containing 5 ml of alcohol and 5 mi of alco holic 0.5 N sulfuric acid The smoke was not bubbled through the solution but the large free space above the solution ered Vol 151. No. 10 CHEMICAL LABORATORY 919 puffs allowed the smoke to settle undisturbed by subsequent The effectiveness of gravity deposition of smoke obviated the need for a long absorption train The two supplementary bubblers filled with glass beads and containing 5 ml of alco- holic 0.5 N acid and mi of aqueous 0.5 N acid respec- tively trapped any nicotine not collected in the flask The smoke solution was rendered alkaline and the nicotine steam distilled into a dilute acid The nicotine was then pre- cipitated as the silicotungstate The nicotine content of the tobaccos of each of the brands of cigarettes smoked was also determined The method used was that of the Association of Official Agricultural Chemists.20 In separate runs tars were determined by again collecting the smoke by gravity deposition over 25 ml of 0.1 V sulfuric acid in the 300 ml Kjeldahl Mask The two bubbler tubes loosely packed with asbestos held in place with cotton plugs were placed between the flask and the smoking machine Upon completion of a run the smoke was allowed to settle 20 minutes and then the smoke tube and bubbler tubes were washed into the flask with chloroform The material in the flask was extracted with chloroform The chloroform was evaporated and the tars were dried for three hours at 100 C. The results of the experiments are given in tables 1 and 2 and in the graph Table | lists the type of filters tested the physical characteristics of the cigarettes and filters and the percentage of moisture and nicotine found in the tobacco Table 2 and the graph give the results obtained from the smoking of the cigarettes If should be noted that the weights of nicotine and tars found in cigarettes and their smoke will vary in different lots of the same brand of tobacco The amount of nicotine in the smoke is a function of the amount of nicotine originally present in the tobacco The nicotine content of tobacco is subject to great variations depending on the position of the leaf on the plant weather conditions during the growing season type of tobacco region of growth and cultural practices The nicotine content of different brands of cigarettes will vary depending on the blend of tobaccos and cigarettes of the same brand may vary considerably if the manufacturer's controls are poor or nonexistent 5 and 10. table 2. for brands B and C if the removed filtertips were replaced by equal lengths of tobacco In the graph the distribution of the nicotine from the 2 smoked portion of the cigarette is shown for the brand of ^/lter and the tobacco cigarette brand D. series Com parisons between brand D and other members of the series are difficult to make when the initial nicotine contents of the smoked portions of the cigarettes are different as shown by differences in the total lengths of the bars A comparison be tween brand D and brand A can be made because the initial cigarettes nicotine contents of the smoked portions of the two are very nearly equal It can readily be seen from the graph that the amount of nicotine in the mainstream smoke from the two cigarettes is almost identical It is also apparent that the amount of nicotine filtered by the tobacco of the butt of cigarette brand D is almost as great as the amount of nicotine filtered by the tobacco remaining in the butt plus the filter of brand A It is interesting to note from the graph that although the total amount of nicotine trapped by the filter of brand C is greater than that trapped by the filter of brand B the percentage efficiency is lower column 5 of table ) This is a direct result of the fact that the tobaczo of brand C has a larger nicotine content in the portion of the cigarette smoked and consequently the concentration of nicotine in the smoke passing through the C filter is greater than that passing through the B filter we Since the amount of nicotine that reaches the smoker's mouth is of primary importance the practical ineffectiveness o ft 2 3 3 6 7 8 9 10 12 NICOTINE NG 14 es 16 In table 2 column 2 the figures are obtained by multiply ing the average number of puffs required to smoke the cigarette to the 47 mm mark by the volume of each puff 35 ml and represent the average volume of smoke sucked into the absorption train This mainstream smoke represents the smoke that presumably would reach the smoker's mouth Columns 3 and 4 of table 2 show the weight of nicotine in this smoke with the filters removed and intact respectively The percentage reduction in nicotine in the mainstream ef- fected by the filter is listed in column 5 and is based on the difference between columns 3 and 4 In columns 8 and 9 of table 2. the weights of the tars appearing in the mainstream smoke per cigarette are given ' without and with the filters attached respectively Column 10 lists the reduction in tars in the mainstream effected by the filter These figures are based on the difference between columns 8 and 9 and are in close agreement with the figures in column 5 The figures on reduction in nicotine and tars in columns figures 5 and 10 favor the filters and are deceptive because the for nicotine and tars in the mainstream smoke listed in columns 3 and 8 from the were obtained from the short cigarettes removal of the filters Tobacco itself is resulting a rather good filter and if the filter were to be replaced by an equal length of tobacco the mainstream smoke from the resulting tobacco cigarettes of brands A. B and C would contain less nicotine and tars than are listed for the shortened cigarettes in column 5 and 10. because the tobacco replacing the filter would remove a certain amount of these sub- stances This laboratory has found that if the paper filter of brand A is replaced by 11 mm of tobacco the additional tobacco will remove B of the nicotine and tars from the mainstream A) NICOTINE IN MAINSTREAM SMOKE NICOTINE REMOVED BY FILTER BB NICOTINE RETAINED BY TOBACCO IN BUTT CF CIGARETTE NICOTINE IN SIDESTREAN AND NICOTINE DESTROYED IN SMOKING PROCESS Distribution of nicotine from smoked portion of four brands of cigarettes of the filter of brand C is demonstrated by the length of the bar that measures the nicotine in the mainstream smoke Brand C contains more nicotine in this portion of the smoke than any other earlier product brand shown in the graph Brand of the same brand name showed C an an even larger amount of nicotine in the mainstream smoke Columns 6 and 7 table 2. show the percentage expressed as the nearest whole number of the total nicotine in the smoked portion of the tobacco that is transferred to the main- stream smoke without and with the filters In column 6 the figures are again shown for the shorter cigarette resulting from the removal of the filter To compensate for the shorter cigarette corrections may again be used here that are based on the substitution of a length of tobacco equal to the length of the filter They are proportional to the corrections that may be applied to columns 5 and 10 and would reduce the figures in column 6 by about % The figures in column 6 show that the proportion of dico- tine transferred from the smoked portion of the cigarette to the mainstream smoke is surprisingly constant If a % cor- cigarettes rection were applied 10 compensate for the shorter the values would range from 19 to 23 These corrected figures would be in close agreement with the work of Brad- ford and workers The values in columa 7 for brands A A C C and D agree closely with one another and with the corrected values for the cigarettes without filters ahah re eral OTeSFP a Tr smoke This is comparable with the % reduction in nicotine and S& reduction in tars effected by the paper filter of brand A.1 Similar reductions might be expected to occur in columns Chemists 10 Association of Official Agricultural Analysis ed 7. Menasha Wis The Collegiate Official Methods of Press George Badta Publishing Company 1950. p 69 920 COUNCIL ON PHARMACY AND CHEMISTRY KA.M.A. July 4 1953 These values and the bars of the graph indicate that the filters are responsible for removing very little of the total nicotine in the smoked portion of the cigarette The bulk of this nicotine about 75 in the case of regular cigarettes is lost in the sidestream or is destroyed by the burning coal On the basis of results obtained in the smoking experiments it can be seen that the over effectiveness of the filters of brands A and C is not significant Indeed it can be seen from column 4 of table 2 and from the graph that the nicotine content of the mainstream smoke of brand C is exceptionally higher than that of regular cigarettes The filter of brand B is the most effective in removing nicotine and tars from the mainstream smoke However the sample of later manufacture brand B is much less effective as the filter is more loosely packed apparently in an effort to improve the smoking qualities In all cases the fraction of nicotine removed by the filter from the smoked portion of the cigarette is small Even io a regular cigarette with no filter only 21 of the total injection over a period of 30 to 60 seconds For muscle relaxa- tion in surgery the average initial dose for adults is 2 to 3 mg If needed 1 to 1.5 mg can be added in 3 to 5 minutes After 45 minutes an additional dose of 1.5 to 2 mg may be administered With ether anesthesia the dose of dimethy tubocurarine chloride should be about third that used with other anesthetic agents For shock therapy and manipulative therapy the average dose is calculated on the basis of 0.025 mg per pound of body weight using I mg less than this diagnostic amount for the initial dose in adults The safe upper limit of dosage is 0.037 mg per pound of body weight As a agent in myasthenia gravis the dose is fortieth to one- tenth of the adult shock therapy dose i e 0.0006 to * 025 mg per pound of body weight administered intravenously The test should always be terminated within 2 or 3 minutes by the intravenous injection of 1.5 mg of neostigmine methylsulfate with 0.6 mg of atropine sulfate The same precautions and contraindications should be observed as with other purified derivatives of curare nicotine reaches the smoker in the mainstream smoke In Tests and Standards recent advertisements calculations have been contrived to ad- Physical Properties tubocurarine chloride is a white odorless claims for vance very low percentages of nicotine in the crystalline powder It decomposes with evolution of gas when heared to mainstream smoke Widely divergent values can be obtained abov 236 It is soluble in water and diluted sodium hydroxide from the same analytical data choosing different bases for SOIL le in alcohol and diluted hydrochloric acid very slightly soslpuabnloeginy the calculations For example an extremely low value can be chloroform and practically insotuble in benzene and ether obtained by basing the calculation on the total weight of the Identity Tests curarine chlord Prepare a solution of about 50 mg of dimethyl in 30 ml of water To 5 ml of the solution add several cigarette Using this stratagem in calculating the figure 0.25 drops of Bitric acid and 1 ml of silver nitrate T.S a curdy white pre- nicotine in the smoke of the regular cigarette brand D is cipitate forms that is soluble in ammonia T.S. presence of chloride The 8 obtained Thus an apparently low figure is obtained from a solution also responds to the second third and fourth ideauty tests in the monograph for dimethyl tubocurarine tubocurarine iodine bts. normal nicotine content The specific rotation 25.b of a solution of 0.25 pm of dimethyl- tubocurarine chloride in 50 ml of water is between 185 and 195 solution ce A 0.005 of dimethyl tubocurarine chloride prepared as directed in the assay in the monograph for tubocurarine iodide stand ex ibits an absorption maximum at about 2800 ^ specific absorbancy % cm about 89 . COUNCIL ON PHARMACY tome, Purity Tests Dry about 0.3 gm of cubocurarine chloride AND CHEMISTRY accurately weighed in a vacuum at 60 over phosphorus pentoxide for 4 oo hours the loss in weight is not more than 14.0 NEW AND NONOFFICIAL REMEDIES The following additional articles have been accepted as conforming to the rules of the Council on Pharmacy and Chemistry of the American Medical Association for admission so New and Nonofficial Remedies A copy of the rules on which the Council bases its action will be sent on application R. T. STORMONT M.D. Secretary Tubocurarine Mecostrin Chloride Squibb . M.W. 723.71 Methyl curarine Dimethyl ether of tubocurarine chloride -The structural formula of tubocurarine chloride may be represented as follows CHYa CH Ct HYCH Cou CH O OCH So GN \ 4 cH -- -- -- CH ce -- oOoNS CH Sr flask tubocurarAine ssay tubcholoc ridue rarine Chloride Transfer 25 mg of dimethyltubocurarine accurately weighed to a 500 ml volumetric and proceed as directed directed in the spectrophotometric for tubocurarine iodide starting hydrochloric acid " spectrophotometric assay in the monograph with ., add to drops of The concentration of the final solution 0.005 in mg = optical density at 2800 ^ - 8.9 The of dimethyl present is not less than 98.0 nor more than 102.0 - tubocurarine chloride Nitrogen Transfer about 0.2 gm of tubocurarine chloride accurately weighed to a semimicro Kjeldahl Bask and proceed as directed in the assay for nitrogen jodide starting with is the monograph for dimethyl digest it with 7 ml of sulfuric acid tubocurarine ad The amount of nitrogen equivalent to not less tubocurarine chloride present is not less than 3.60 than 93.0 nor more than nor more than 3.90 100.8 of dimethyl- Dosage Forms of tubocurarine Chloride SOLUTION Identity Tests The solution responds to the identity tests in dimethyl the monograph for tubocurarine iodide Assay tubocurarine Chloride Transfer to a 50 ml beaker an exactly measured tubocurarine volume of solution equivalent to chloride and proceed as directed about in the 5 mg of assay for tubocurarine iodide evaporate it to dryness solution starting with . . -" The concentration of the and carefully final soluuon 0.005 in me./au = optical density at 2800 ^ ^8.9 The amount of tubocurarine chloride present is not less than 95.0 nor more than 105.0 of the labeled amount E. R. Squibb & Sons Division of Mathieson Chemical Corporation New York Actions and tubocurarine chloride has the same actions and uses as tubocurarine iodide and tubocurarine chloride except that the efficacy of the methylated derivatives in the treatment of spastic diseases has not yet been determined See the monographs on dimethyl arine iodide and tubocurarine chloride Solution Mecostrin Chloride 10 cc vials An isotonic salt solution containing 1 mg of tubocurarine chloride in each cubic centimeter Preserved with 0.9 benzyl alcohol Aluminum Hydroxide U.S.P Remedies 1952 p 306 See New and Nonofficial tubocurarine chloride has approximately the same ratio of potency as tubocurarine iodide when compared with tubocurarine chloride but on the basis of the difference in the molecular weights of the two salis 0.8 mg of tubocurarine chloride provides a dose equivalent to 1 mg of the iodide Like the iodide dimethyltubocurarine chloride is administered only by slow intravenous Physicians Drug & Supply Company Philadelphia Tablets Dried Aluminum Hydroxide Gel 0.3 and 0.65 gm Cortisone Acetate See New and Nonofficial Remedies 1952 p 322 Schering Corporation Bloomfield N. J. Tablets Contogen Acerate 5 mg