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FILE NAME: Smoking (SMOK) DATE: 1953 DOC#: SMOK047 DOCUMENT DESCRIPTION: Journal Article - A Study of Cigarettes, Cigarette Smoke, and Filters CLINICAL MEETING ST. LOUi^MG. - DECEMBER 1-4, 1953 Montana Stale University B077M AN Th s 'ssue Exceeds ,50'0C0 copies- JOURNAL OF THE American Medical Association Volume !52, No. 10 Pu b lis h ed Wcskly at 335 North Oaarborn S tr i t t . Chicago 10. Illinois Subscription. 515. Singlo Copy, 45 conti July 4, 1953 ORIGINAL ARTICLES EARLY DIAGNOSIS OF PRIMARY M A LIG N A N T BONE TUMORS... 883 G. C. H o g g o rt, M .D ., on d J, w . C o p e l, M .D ., Boston ISONIAZIO ANO STREPTOMYCIN IN THE TREATMENT OF PULMONARY TUBERCULOSIS .............................................................................................. 886 C op t. F. W . P itts ; C o l. C . W . Tem po); M o io r F. L. M ille r; C a p t. i. H. Sonds; C o o t. M . J. F ir z o o r n c k . 'M C I , U. S. A rm y , a n d 0 . W e u e r 8.S Denver IM PACT OP MODERN THERAPY ON PULMONARY TUBERCULOSIS IN A LARGE MUNICIPAL H O S P IT A L .................................................................................................. 890 W. W eiss, M .D ., P h ilo d e lp h io UTERINE INERTIA ......................................................................................................... . .894 l. C. Heap, M 0., Denver EFFECT OP CIGARETTE SMOKE ON THE PERIPHERAL VASCULAR SYSTEM............ 897 M .'T . Friedell, M .D .. C h ica g o THE RECORDING OSCILLOMETER IN ORTHOPEDICPRACTICE...................................... 901 f. A. C h an d le r. M .D ., a n d P. H. D ic k in s o n , M .D ., C h ica g o ANTICOAGULANTS AND SYMPATHETIC NERVE BLOCKS IN THE TREATMENT OF VASCULAR LESIONS.......... ............................................................................ 903 G. H. P ra tt. M .O ., N , -- York CARCINOM A OF THE COLON COMPLICATING CHRONIC ULCERATIVE COLITIS .905 E. C. W c c k w je r , M .D ., an d A . B. C h in n , M .D ., C le ve lan d CLINICAL NOTES MEDIASTINAL LIPOMA SIMULATING CARDIACENLARGEMENT................................... 908 A. M. G o ttlie b , M .D .; L. J. Boer, M .D ., ond P. Jordon Jr., M .D ., D etroit BENIGN ULCER OF THE ESOPHAGUS ASSOCIATED WITH CHRONIC ACETANILID POISONING ................................................................................................................... 910 W, l . W otHou, M .O ., an d M . W. G fee n b trg , M .D ., Brooklyn SUBACUTE BACTERIAL ENDOCARDITIS TREATED WITH CHLORAMPHENICOL A N D OXYTETRACYCLINE .............................................................................................913 G. G. le c c a , M .D ., and A . T o la. M .D ., Lim a, Peru DERMATITIS DUE TO TRIETHYLENEMELAMINE THERAPY...................... 914 A . M . Frum in, M .D ., a n d A . I. R u b tn s to n e , M .D ., P h ila d e lp h ia SPECIAL REPORTS W ILLIAM BEAUMONT. PIONEER f . Stenn, M .D., C hicag o PHYSIOLOGIST.......................................................... 915 Chem ical L aboratory A STUDY OF CIGARETTES, CIGARETTE SMOKE, AND FILTERS...................................917 Council on Pharm acy and Chem istry NEW AND NONOFFICIAL REMEDIES.......................................... 920 EDITORIALS Incidence of Tuberculosis Among Amer ican Medical Students....................... 922 Fatal Bicycle Accidents in the United States ................................................ 923 Industrial Dermatology ..........................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 of the Annual Meeting .. . 927 Minutes of the Scientific Sections 923 REGULAR DEPARTMENTS Medicol News .................................... 943 Examinations ond Licensure .. . 950 Meetings ............................................ 951 Deaths ............ .'.................................952 Government Services; A rm y .................. ............................ 956 Public Health Service..........................956 VeteransAdministration .............. 956 Foreign Letters: Chile ............................................. 957 Finland ........................................... 958 Mexico .............................................. 958 Sweden ...............................................959 Correspondence: Worcester Chest X-Ray Survey. Rususcitofion of Newborn infants. Idiopathic Adrenal Apoplexy. Hugh Owen Thomas.960 Miscellany: Note on Military Medicine.................962 A. Gregg, M.D., New York Medicolegal Abstracts ............................963 The Leisure Comer................................ 964 Medical Motion Pictures. ............. 965 Medicol Literature Abstracts................ 966 Book Reviews . . . . . . . ............................. 982 Queries and Minor Notes; Warts. Treatment for Strongyloidiasis. Broken Needle in Tonsillar Fossa. Mea sles in infants. Ovalocytosis. Polliotive Treatment Following Mastectomy. Nec robiosis Lipoidica Diabeticorum. Influ enzal Meningitis. Treatment of Crypt orchidism. Nocturnal Erections. Trep onemal Immobilization Test. Self-Exami nation of the Breasts...........................984 WASHINGTON NEWS Non-Service-Connected Care. Medicol Bills in Congress. Tax Law Amendments. Personnel. Miscellaneous........ Adv. Page 5 National Organizations of Medi cal Interest ......................... Adv. Page10 Tonics and Sedatives................Adv. Page38 Books Received ........................ Adv. Page50 Nationwide Symposium on Bedside Management T w enty clinically im portant subjects are dis cu ssed in the Ju ly N um ber o f the Medical ^Clinics of North A merica (d e v o te d to a n a tio n -w id e symposium on Bedside M anagem ent). In cluded are such tim ely topics as Cardiac Em er g e n c ie s , Bronchial Asthma, Diabetes, Acute Burns, Anemias, Backache, and m any others. T he Medical Clinics bring you, every other month, a Sym posium on som e topic of current im portance-- with contributions from A m erica's leading m edical centers. The help they give you is up-toM he-m inute, practical, d eta iled --you can apply the inform ation to yon' -- '' This is postgraduate study at The Medical Clinics of S o rth America are books, not magazines. They are Issu ed serially , one illu s tra te d volum e o f a b o u t 300 pages every o th e r m onth. See SAUJVDERS A dvertisem ent on next two pages Vol. iS2, No- 11 In his preface to "Experiments and Observations" appears a great quotation of medical history. "I 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-- the incontro vertible 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 first-- 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." Alexis St. Martin lived long after the death of his 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 Osier attempted to secure the stomach for the Army Me'dicl 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 in the country to radiate the spirit of a great American physician. 1853 W. Polk St. Prognosis in Hypertension.--The character or severity of a hypertensive patient's symptoms, other of course than those which point to cardiac or renal failure, give little clue to his subsequent fate. Headache, for example, has occuned as often 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-raiser for the subsequent full-length drama of a stroke: but this bas not been the case, and the incidence of such cerebral episodes was no higher among patients who subsequently had strokes than in those 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 a hypertensive patient must rest fundamentally upon objective findings. Early recognition of the accelerated form of hypertensive disease is particularly desirable, since it is in this type of case that symapthectomy has most to offer, and operation per formed in time may completely transform its character. Appro priate cases, however, will not be selected for sympathectomy unless the practice is adopted of submitting evert' hypertensive patient under the age of 50 to a systematic assessment with the object of establishing how far the disease bas already progressed, for only by relating this to the age of the patient can it be decided whether or not the speed of advance has b e e n excessive.--A. W , D. Lcishman, D.M., Observations on Prognosis in Hypertension. British Medical Journal. May 33, 1953. CHEMICAL LABORATORY 917 CHEMICAL LABORATORY Following is the nrs: O' several reports on cigarettes, ciga rette smoke. and niters t>v 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 or the work, winch was carried our by Mr. Robert R. Stark of the laboratory staff, have been omitted in this presentation and can be obtained upon request from the Chemical Laboratory. W a lter W olman. Ph.D.. Director. A STUDY OF CIGARETTES, AND FILTERS 1. Filter-Tip Cigarettes CIGARETTE SMOKE, Considerable interest has been expressed concerning the effectiveness of filter-tip cigarettes and the so-called denicotinizing process in reducing the amount of nicotine and tars in cigarette smoke. Because of 'he scarcity of published data on the subject, the Chemical Laboratory of the ^American Medi cal Association has undertaken a study of nicotine and tan in the smoke of filter cigarettes, special low-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-tip cigarettes. They represent the three ' types of filter-tips 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-l, B-I, and C-l, and the cigarettes with modified filters are designated as A-2, B-2, and C-2 in table 1. A 'Tegular" all-tobacco cigarette, brand D, was also tested. Puese experiments are not designed to interpret such qualities of cigarettes as flavor, aroma, or smoking character istics. As stated by Bradford, Harlan, and Hanmer.1 a laboratory smoking process should.be sufficiently like human smoking to allow acceptance of the data collected, and it must be repro ducible. Puffing the cigarette by mouth with aa absorption apparatus placed between the cigarette and mouth meets the first requirement, but is not reproducible. Continuous suction applied to the cigarette as employed by Bogen.5 Koperina.1 and others is far from meeting the first requirement as the 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 em ployed by Baumberger,* Bogen,5 Jensen and Haley,* and others. This method is open to criticism because the volume o f 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. 1. Bradford. J. A.; Harlan. W. R,, and Hanmer, H. R.: Mature of Cigaret Smoke: Technic of Experimental Smoking, 1. Indust. Engin. Cbem. S S : If36-839, 1936. 2. Bogen, E.: The Composition of Cigarets and Cigaret Smoke. J. A. M. A. 3 : 1110-1114 (Oct. 12) 1929. 3. Koperina. A.: Untersuchung der SUckstoffhaltigen Verbindungen des Tabakrauches. Biochem. Ztschr. 219:259-276. 1930. 4. Baumberger. J. (a) The Carbon Monoxide Content of Tobacco Smoke and Its Absorption on Inhalation; (S) The Nicotine Content of Tobacco Smoke; t o The Amount of Smoke Produced from Tobacco and Its Absorption in Smoking as Determined by Electrical Precipitation, J. Pharmacol. & Exper. Thcrap. 2 1 : 23-57. 1923. f. Jensen. C. 0-, aod Haley, D. E.: Scudies on the Nicotine Content of Cigarette Smoke. J. Agnc. Res. h i : 267-275. 1935. 6. Pfyl. B.: Zur Bcsommung des Micouns im Tabakrauch: 11: Normuog des kunsUichen V errauchen* der Tabakcrzcugoissc, ZlSChr. f. UOtCrSUClt. d. Lcbensmill. 66: 501-510. 1933. 7. Pynki. C,: Uber die Vcrteilung des Nicotios beira Raucben von Zigaieiteii. Chem.-Zig. 3 3 : 279. 1934. 918 CHEMICAL LABORATORY J.A.M.A., July 4, 1953 'SI These objections sre overcome by a constant volume smoking length, that is from a 30 mm. to a 10 mm. butt, the nicotine device, such as that described by Pfyl.- m which the cigarette w'as puffed by air displacing mercury in a lube as the mercury- appearing in the smoke of each cigarette increases from 1.3 mg. to 3.S mg. These variables may be eliminated by assign level was lowered by means of a leveling bulb. Pyriki.' using Pfyl's apparatus to smoke oriental cigarettes lo a 15 mm. butt, ing fixed values to each of them. The results of the smoking experiments will depend on the values selected, but under taking 40 ml. puffs every 30 seconds, found 19 to 77% of the nicotine in the mainstream smoke ismoke emerging from the puffed end of the cigarettel, 37 to 47% in the sidestream any given set of conditions comparisons between cigarettes and comparisons in the effectiveness of filter-tips are made possible. fsmoke rising from the burning tipi, and 13 to I~Tr in the The smoking conditions adopted by the A. M. A. Laboratory butts, with a total recovery of 74 to 85% of the nic tine. ire those of Bradford and co-workers.: In this process 47 The remainder of the nicotine is apparently decomposed by the heat of the coal. mm. of each cigarette is smoked (two-thirds of a "standard" 70 mm. cigarettel using 35 ml. puffs of two seconds' duration The cigarettes in the present tests were smoked with the taken once a minute. The size of the puff is considered rea automatic smoking machine described by Bradford, Harlan, sonable in view of Pfyl's observation that puffs varied among and Hanmer.1 This is a constant volume smoking device in individuals from 3" to 61 ml. The time between puffs is suffi which the mercury is replaced by water as the operating fluid. ciently long to allow the cigarette to return to a free burning The smoke is passed through a glass tube and collected K state and to prevent the formation of an unnaturally long gravity deposition in a 300 ml. flask to which only two jp- and hot coal. plememary bubblers are attached. These are specially designed In addition to the variables encountered in the smoking to reduce the back pressure to about two inches of water. process certain variables are inherent in the cigarettes them- Calumo Brand Brand A-2 Brand B-l Brand B-2 Brand C-l Brand C-2 Brand O T able 1.--Moisture, Nicotine Content, anti Physical Characteristics of Four Brands o i igarettes 1 Trpe oi Filter Paper ............................................ Fiber ............................................. Asbestos laminated with paper Asbestos laminated with paper C otton ......................................... Cotton ......................................... No Alter ....................................... * 3 Date Sample Obtained l i a r . 1932 December. 1932 April. 1932 October, 1952 Mar. 1952 August, 1932 February, 1953 Average Weight of Cigarette, Gm. 1.0 1.123 1.059 1.011 1.047 1.033 1.094 4 Arerage Weight of Filter-Tip, Gm. 0,165 0.153 0.159 0.159 0.105 0.173- j Total Length o Cigarette. Mm 70.0 09.5 09.5 09.5 09.0 S.0 70.0 0 Average Length of Filter-Tip. Mm. 11.0 11.3 10.9 10.9 1G.0 10.0 . Average Circumfereoec of Cigarette, Mm. 20.0 20.3 20.7 20.7 25.3 25.3 20.5 S Moisture in Tobaeco, r* 6.60 9.75 8.51 9.94 9.27 10.77 10.71 9 Nicotine lo Tobacco 'M ois tu re* Free Basis), % 1.93 1.92 1.5 1.91 2.54 2.44 2.02 T able 2.-- Analysis of Smoke from Four Brands of Cigarettes Column 1 Weight of Average Tobacco Volume of Actually Mainstream Smoked Smoke per (Dry Weight), Cigarette, Gm. Ml. Brand A*l............ ............ 0.029 340 Brand A 2............ 0 .0 0 0 351 Brand B-l............ ............ 0.035 325 Brand B-2............ ............ 0.591 350 Brand C*1............ ............ 0.081 461 Brand C-S............ ............ 0.055 415 Braod D ............ ............ 0 333 350 3 4 Weight of Nicotine Found In Mainstream Smoke per Cigarette. Mg. With FUter-Tip Removed 2.55 2.S2 2.52 2.49 a.si 4.00 W ith Filter-Tip 2.60 2.43 1.00 1.47 3.38 2.93 2.74 * 3 Reduc tion of Nicotine in Mainstream Smoke. *1 9 u 60 41 14 27 6 7 Nicotine In Tobacco Actually Smoked Which ia "Transferred to Mainstream Smoke, % w ith Filter-Tip Removed 24 21 AA 23 25 With Filter-Tip 21 19 9 13 20 18 21 * 6 9 Weight of Tars Found In Mainstream Smoke per Cigarette, Mg. With FIUer-Tlp Removed 15.9 16.3 15.0 16.7 18.5 19.0 w ith Fllter-Tlp 15.1 13.9 6.8 9.4 15.6 15.1 17.8* 10 Reduc tion of Mainstream Smoke, Cc 5 17 55 U 16 23 * Pieced iq this column iot comparison with full-length cigarettes. The smoking machine itself consists of a constant-level res ervoir that supplies water to a buret equipped with a glass float. Four cigarettes are smoked simultaneously by taking a puff from each 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 puff, 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 byJensen and Haley,1 who have shown that as a *0 mm. cig arette is smoked from four-sevenths to six-sevenths of its 8. W enusch, A.: Influence of :he W uJih of the Cuttings cn the Passage o f the Nicotine into the M am Smoice Stream . Ztschr. f. L'ntersuch. d. Lepensmitt. 7 3 :1 8 Z -I8 4 . 1988. 9. Bradford. J. A.; H arlow . E. S.: H arlan. WC. R.. and Hanmer. H. R.; N ature of Cigaret Smoke: V olatile Bases and Acids. J. Indust. Engm. Chem. 2 9 : 45-50. 193". 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. The cigarettes were smoked in a room maintained at 77" F (25 C) and 45% relative humidity" 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 ml. of alco holic 0.5 .V sulfuric acid. The smoke was not bubbled through the solution, but the large free space above the solution Vol. 152. No. 10 CHEMICAL LABORATORY 9.19 allowed the smoke to settle undisturbed by subsequent puffs. 5 and 10. table 2. ior brands B and C if the removed filter- 1 The effectiveness of gravity deposition of smoke obviated ihe tips were replaced by equal lengths of tobacco. need for a tong absorption tram. The two supplementary bubblers filled with glass beads and containing 5 ml. of alco holic 0.5 .V acid and 5 mi. of aqueous U.5 ,V acid, respec tively, trapped any nicotine not collected in the fiask. In the graph, the distribution of the nicotine from the smoked portion of the cigarette is shown for the brand 2 series of niter-tips and the all-tobacco cigarette, brand D. Com parisons netween brand D and other members of the series The smoke solution was rendered alkaline and the nicotine are difficult to make when the initial nicotine contents of the steam distilled into a dilute acid. The nicotine was then pre smoked portions of the cigarettes are different as shown by cipitated as the silicotunestate. differences in the total lengths of the bars. A comparison be 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.1' 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 flask. The two bubbler tubes, loosely packed with asbestos held in place with cotton plugs, were placed between the flask and the smoking machine. L'pon 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 I 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 tween brand D and brand .4-2 can be made because the initial nicotine contents of the smoked portions of the two cigarettes 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 bun 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-2. It is interesting to note from the graph that although the total amount of nicotine trapped by the filler of brand C-2 is greater than that trapped by the filter of brand B-2. the percentage efficiency is lower (column 5 of table 2i. This is a direct result of the fact that the tobacco of brand C-2 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-2 filter is greater than that passjng through the B-2 filter. _ Since the amount of nicotine that reaches the smoker's mouth is of primary importance, the practical Ineffectiveness of nicotine and ta n 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. 'J In table 2, column 2. the figures are obtained by multiply 0 N tCO TIl IN MAINSTREAM SNOW: | g NICOTINE REMOVED BY FILTER ing the average number of puffs required to smoke the cig arette to the 47 mm. mark by the volume of each puff (35 NICOTINE r e t a i n e d BY TOBACCO 3 NICOTINE IN SOESTREAM AM) IN B i m OF CIGARETTE w NICOTINE DESTROYED IK ml.) and represent the average volume of smoke sucked into SMOKING PROCESS the absorption train. This mainstream smoke represents the D istrib u tio n o f n icotin e from sm oked portion of fo u r brands of smoke that presumably would reach the smoker's mouth. c ig a re tte s . 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 of the filter of brand C-2 is demonstrated by the length of the bar that measures the nicotine in the mainstream smoke. Brand C-2 contains more nicotine in this portion o f the smoke difference between columns 3 and 4. than any other brand shown in the graph. Brand C-l, an In columns 8 and 9 of table 2, the weights of the tars earlier product of the same brand name, showed an even appearing in the mainstream smoke per cigarette are given larger amount of nicotine in the mainstream smoke. without and with the filters attached, respectively. Column 10 Columns 6 and 7, table 2, show the percentage, expressed lists the reduction in tars in the mainstream effected by the as the nearest whole number of the total nicotine in the filler. These figures are based on the difference between smoked portion of the tobacco that is transferred to the main columns 8 and 9 and are in close agreement with the figures stream smoke without and with the filters. In column 6 the in column 5. figures are again shown for the shorter cigarette resulting The figures on reduction in nicotine and tars in columns from the removal of the filter. To compensate for the shorter 5 and 10 favor the filters and are deceptive because the figures cigarette, corrections may again be used here that are based for nicotine and tars in the mainstream smoke listed in columns on the substitution of a length of tobacco equal to the length * If 3 and 8 were obtained from the short cigarettes resulting of the filter. They are proportional to the corrections that from the removal of the filters. Tobacco itself is a rather may be applied to columns 5 and 10 and would reduce the ! i. good filter, and. if the filter-tips were to be replaced by an figures in column 6 by about 25. t equal length of tobacco, the mainstream smoke from the The figures in column 6 show that the proportion of nico resulting all-tobacco cigarettes Of brands A. B, and C would tine transferred from the smoked portion of the cigarette to contain less nicotine and tars than are listed for the shortened the mainstream smoke is surprisingly constant. If a 2% cor cigarettes in column 5 and 10. because the tobacco replacing rection were applied to compensate for the shorter cigarettes, tshtaencfeilst.er-tips would remove a certain amount of these sub ftihgeurevsaluweosulwd obueld inracnleoese farogmreem19enttowi2th3%th. eTwheosrek coofrrBecratedd i This laboratory has found that, if the paper filter of brand ford and co-workers.a The values in column 7 for brands A-l is replaced by ! mm. of tobacco, the additional tobacco A-l, A-2. C-K C-2, and D agree closely with one another will rem ove 8% of the nicotine and tars from the m ainstream and w-ith the corrected values for the cigarettes without filters. smoke. This is comparable with the 9% reduction in nicotine and 5% reduction in tars effected by the paper filter of brand A -l. Similar reductions might be expected to occur in columns 10 Association of Official Agricultural^Chemists. Official Methods of Analysis, ed. 7. Mcnasr.a. Wis., The Collegiale Press. .George Banta Publishing C om pany. I90. p. 69. 920 COUNCIL ON PHARMACY AND CHEMISTRY J.A.M.A., July 4, 1953 These values and ihe 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 obtaioed in the smoking experi ments, it can be seen that the over-all effectiveness of the filters of brands A and C is not significant. Indeed, it can be seen from column 4 of tabie 2 and from the graph that the nicotine content of the mainstream smoke of brand C is exceptionally high--higher than that of "regular" cigarettes. The filter of brand B-l is the most effective in removing nico tine and tars from the mainstream smoke. However, the sample of later manufacture, brand B-2, 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 ponion of the cigarette is small. Even in a "regular" cigarette with no filter-tip only 21% of the total nicotine reaches the smoker in the mainstream smoke. In recent advertisements calculations have been contrived to ad vance claims for very low percentages of nicotine in the mainstream smoke. Widely divergent values can be obtained from the same analytical data choosing different bases for the calculations. For example, an extremely low value can be obtained by basing the calculation on the total weight of the cigarette. Using this stratagem in calculating, the figure 0.25% nicotine in the smoke of the "regular" cigarette, brand D, is obtained. Thus an apparently low figure is obtained from a normal nicotine content. COUNCIL ON PHARMACY AND CHEMISTRY NEW AND NONOFFICIAL REMEDIES The following additional articles have been accepted as con forming to the rules of the Council on Pharmacy and Chem istry of the American Medical Association for admission to New and Nonofficial Remedies. A copy of the rules on which the Council bases its action will be sent on application. R. T. Storm o nt, M.D., Secretary. Dimetbyl-Tubocurarine Chloride.--M ecosirin Chloride (Squibb).-- C.*H.CI:N!0.-- M. W. 723.71.--O-Methyl-d-tubocurarine chloride.--Dimethyl ether of d-tubocurarine chloride. --The structural formula of dimethyl-tubocurarine chloride may be represented as follows: Actions and L'ses.--Dimethyl-tubocurarine chloride has the same actions and uses as dimethyl-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-tubocur arine iodide and tubocurarine chloride.) Dosage.--Dimethyl-tubocurarine chloride has approximately the same ratio of potency as dimethyl-tubocurarine iodide when compared with tubocurarine chloride, but on the basis of the difference in the molecular weights of th two salts, 0.8 mg. of dimethyl-tubocurarine chloride provides a dose equivalent to 1 mg. of the iodide. Like the iodide, dimethyltubocurarine chloride is administered only by slow intravenous injection over a period of 30 to 60 seconds. For muscle relaxa tion in surgery, the average initial dose for adults is Z to 3 mg. If needed, I to 1.5 mg. can be added to 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 dimethyltubocurarine chloride should be about one-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 amount for the initial dose in adults. The safe upper limit of dosage is 0.037 mg. per pound of body weight. As a diagnostic agent in myasthenia gravis, the dose is one-fortieth to onetenth of the adult shock therapy dose (i. e., 0.0006 to * *925 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. Tests and Standards.-- Physical Properties: Dimethyl-tubocurarine chloride a a white, odorless, crystalline powder. It decomposes with evolution of gas when heated to abo*. -36*. It is soluble in water and diluted sodium hydroxide; sparingly soil >le m alcohol and diluted hydrochloric acid; very slightly soluble m chloroform; and practically insoluble is betueoe and ether. Identity Tests- Prepare a solution of about 50 mg. of dimethyl-rubo curunne chlondt in 30 ml. of water. To 5 ml. of the solution add several drops of sitric acid and 1 ml. of silver nitrate T.S.: a curdy white pre cipitate forms that is soluble in ammonia T.S. (presence of chloride). The solution also responds to the second, third and fourth identity tests is the monograph for dimethyl-tubocurarine iodine. The specific rotation, (a 125.0. of a solution of 0.25 gm. of dimethyltubocurarine chloride m 50 ml. of water is between 185 and 195*. A 0.0059 soluuoo of dimethyl-tubocurarine chloride, prepared as directed in the assay in the monograph for dimethyl-tubocurarine iodide, exhibits an absorption maximum at about 2800 X (specific absorbancy, col), about 89]. Purity Tests: Dry about 0.3 gm. of dimethyl-tubocurarine chloride, accurately weighed, in a vacuum at 60* over phosphorus peetoxide for 4 hours: the loss in weight is not more than 14.0%. Assay: (Dimethyl-tubocurarine Chloride) Transfer 25 tng. of dimethyltubocurarine chloride, accurately weighed, to a 500 mi. volumetric flask and proceed as directed in the spectrophotomttric assay m the monograph for dimethyl-tubocurarine iodide starting with, M. . . add 10 drops of hydrochloric acid . . The concentration of the final solution (0.005%) in mg./mi. = optical density at 2800 X 8.9. The amount of dimethyl-tubocurarine chloride present is not less than 98.0 nor more than 102.09. (Nitrogen) Transfer about 0.2 gm. of dimethyl-tubocurarine chloride, accurately weighed, to a semimicro Kieldahl flask and proceed as directed in the assay for nitrogen in the monograph for dimetbyl-tubocurarina iodide starting with. . . digest it wish 7 ml. of sulfuric acid . . The amount of nitrogen present is not less than 3.60 nor more than 3.90%, equivalent to not less than 93.0 nor more than 100.8% of dimetbyltubocurarme chloride. Dosage Forms of Dimethyl-tubocurarine Chloride Solution. Identity Tests: The solution respoods to the identity tests in the monograph for dimethyl-tubocurarine Iodide. Assay: (Dimethyl-tubocurarine Chloride) Transfer to * 50 ml. beaker an exactly measured volume of solution equivalent to about 5 mg. of dimethyl-tubocurarine chloride and proceed as directed in the assay for dimethyl-tubocurarine iodide solution starting with, *\ . . and carefully evaporate it to dryness . . The concentration of the final solution (0.005%) in tng./mL = optical density at 2800 X -r- 8.9. The amount of dimethyl-tubocurarine chloride present is not leu than 95.0 nor more than 105-0% of tbe labeled amount. E. R. Squibb & Sods, Division of Mathieson Chemical Cor poration, New York. Solution Mecostrin Chloride: 10 cc. vials. An isotonic salt solution containing l mg. of dimethyl-tubocurarine chloride in each cubic centimeter. Preserved with 0.9% benzyl alcohol. Aluminum Hydroxide Gel-L.'.SJ*. (See New and Nooofiicial Remedies 1952, p. 306). Physicians' Drug & Supply Company, Philadelphia. Tablets Dried Aluminum Hydroxide Gel: 0.3 and 0.65 gm. Cortisone Acetate fSee New and Nonofficial p. 322). Sobering Corporation, Bloomfield, N. J. Tablets Corrogen Acetate: 5 mg. Remedies 1952,