Tobacco Documents Online

CTR HN 026372

I r F I I on November 15, 1°oi I I L L ~ L ..., r _ . - PHILIP MORRIS Ii\'COR.PORSTED TOBACCO AND HEALTH-R~D APPROACH Presentation to R & D Corr,mittee by Dr. H. Wakeham at meetL'iq held in New York Off_ce CONF 1DEhl1 Al.. c L r~ ~ ~ - .~ ~ yurr . .. • • . ~ . . . ~ . ~ . .. .b.J~J . ~ti.. ~ ~v L qq CTR HN 026373 i

c I TOBrXCO AND HEALTH - R& D hPPROACH P_ = I. Chemistry of Cigarette Smoke ......................... 1 I r r Composition of Mainstream Smoke................. 2 Major Constituents of Mainstream Particulate Phase ........................ 3 Flavor and Irritation Studies ....................... 4 II. The Cancer Controversy..•.••••.•...••......•..•.•... 5 Evidence Linking Cancer and Tobacco ........ . . . . . • 6 The Problem of Carcinogen Identification........... 7 Relative Potency of Carcinogens to the S'.Ln of Mice; Comparison of Different Systems of Grading .............................. 8 I' I Ii Partial List of Compounds in Cigarette Smoke also Identified as Carcinogens.......... .. 0 Cancer Promoting Agents in Cigarette Smoke....... 10 Phenols in Cigarette Smoke ................. 11 Anti- Carcinogens. ............................ ... 12 Smoking and Cardiovascular Diseases ................. 13 IV. R & D Program Leading to a Medically Acceptable . Cigarette .............. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 - , Reduction of Irritating Factors in Smoke ........... 15 Controlled Nicotine in Filler and Smoke............ 16 Reduction of Carcinogens in Smoke ................ 17 The Production of Polycyclic Hydrocarbons from Tobacco vs. Cigarette Paper........ 18 Polycyclic Hydrocarbons from Tobacco Constituents••••12 Some Possible Ways to Reduce Carcinogens in Tobacco Smoke..••.••.•.•...••••.•••• 20 I I V. I Siljllmary ................... . .... . . . .... .. .. . . . . ... 21 COigFIDEW'AL ....r...... ...~w.......l~f.I:A.."~l4~1..J'RA.J'.~...~t....~.. ,..~..+N C `' R h N 0 r„ ~ ~_ _

CTR HN 026375

COMPOSITION OF MAINSTREAM SMOKE Ethane Pentenes Methyl fu.nn Toluene Benzene Acetaldehyde . 1.4 0.7 0.4 0.8 0.7 0.7 0.8 0.2 0.2 0.1 1.0 Water • : 5 mg. :' Bases ` 4 -- Humectants 3 Hydrocarbons • :1 Carbonyls 1 Organic Acids 2 * - Phenols 0.3' •• • Esters • , Trace ' + 15 - 20 mq. of substancea : ..-- not quantitatively established : CTR HN 0283ef 6 'Air 444 mg. Carbon dioxide 55 Carbon monoxide 10 Water 11 Nitrogen oxides 0.03 Ammonia Organic vapors .. Trace p ; Isoprene Methyl chloride _..gexenes Acetone Methanol

MAJOR CONSTITUENTS : OF M.AINSTR.EAM PARTICULATE PHASE 'Acetic Lactic 8ucc•inic Proplonic Formic ~ Butyric 2-Aminobutyric aluiimic Lialoaic Wlic Oalic Valeric 0.8 mg. Nicotine 0.3 Anabasine 0.2 Nornicotine 0.2 Myoamine 0.1 Nicotyrine 0.1 Nornicotyrine 0.1 Analabine 0.1 0.1 0.05 0.05 0.05 gARBONYL COMPOUNDS Biacetyl (butanedione) Butyraldehyde Diethyl ketone olyoul . . Fvrfurs.1 gydroxy methyl turfural Methyl furiural Pyridyl ketones, 0.2 mg. 0.3 0.2 0.2 0.1 . HYDROCARBONS Para.ifin Waxes ..• ~ 0.3 mq. Neophytadrene 0.2 Toluene : - 0.1 Dipentene (d-limonene).. 0.1 _ Xylenea Trace Ethyl toluenes - Naphthalene Mthrscene CONF/DENTIat_ COPYi . CTR HN 02837'7

[ FLAVOR AND IRRITATION STUDIES . . Independent Evaluations at Cigarette Smcke Concentrations Flavor IntO -10 Methanol 0.8 Methy1 Acetate 1.1 Propyne (acetylene) 5.1 CoNF11DEKT1al- C CTR mH 026378

C A R C I N O M A - a malignant growth arising from , t TUMOR a substance which applied to the tissue of a test animal gives rise to tumor , formation. In tests for carcinogens It is assumed that tumors ultimately lead to cancerous growths and that a_ carcinogen so demonstrated in test a.zimals is dangerous to man. • . . . ., P R O M O T E R -. a substance which by Itself does not . : show carcinogenic activity but which .. .' applied before or concurrently with a carcinogen enhances the effect of the : 1 latter. ANTICARCINOGEN- a substance which Inhibits the normal activity of a carcinogen in a test animal. CTR HN 0~'€~~~{~ epithelial tissue (skin, gastric or intestinal nnucosa, lungs, etc. ) a malignant growth arising from connective or muscle tissues (muscles, blood vessels, cartilage, bone, ' - : lymph, etc. ) ~ 1

Based on two main points EVIDENCE LINKIN3 CANCER AND TOBACCO a S t a t i s t i c a 1 evidence that certain diseases are more prevalent among smokers than non-smokers. Lung cancer : Bladder cancer ~ Cardiovascular diseaaes produce lung cancer. causative factor. - These associations suggest that smokin9 may be a 2. PhYsioloqical tests in which animals treated with smoke condensates, extracts, or compounds therefrom, sutfer from increased tumor frequency. Most testie '• involve skin peinting or in jections on special strains of - mice. Smoke inhalation experiments have failed to COPY ! Ct Rt t N 028.~ 20

. M3ny factors need to be considered In studying carcinogenesis. ~'AE PROBLEM OF CARCINOGEN IDENTIFICATION_ - alone but is % lanctlon vf the iollowing factors: (a) The dosage, the nature of the vehicle, the mode and length of ttme of sdmtnistration of the agent; (b) The strain, the species, the sex, and the age of the test antmais; J. P. Greensteln, Biochemistry of Cancer - "The carcinogenic potency of an aqsnt does not reside in the nature of the agent (c) The site of application, the presence of coincornitant ; _ factors aach as the level of essential dietary constituents and the numbar of aalrnals kept in a caye." 2 One in five of all randomly performed chronic toxicity tests reveals the presenee of a carcinogen. 8artwell,. 8urvej of Compounds Which Have Been Tested for arcinooen.c Accivity, U. S. Public Health Service - About one-hall 8 oi the new carcinogens belongs to five chernicai classes as follvars: 1 a s e ., New Compounds Carcinogens Allphatic Casbaao,atea 18 15 Tricyclic Aminofluorenes 14 12 Tetracyclic Cyclopentenophenanthrenes 14 8 Azo compounds 88 38 Heterocyclic Benzacridine 22 14 154 83 CO~F10EN~lAL 7 Ci9R HN 026361