Tobacco Documents Online

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Prioe $25.00 +. Copyright © 1978 b}American Medical Association Education and Research Foundation LC 78-52881 Reprints of published research reports are not available through the Publisher. Please contact each author directly. Grantee's name is in bold face type in abstract. r American Medical Association Education and Research Foundation 535 North Dearborn Street Chicago, Illinois 60610

q "A Research Study on Tobacco and Health - devoted to the study of human ailments that may be caused or aggravated by smoking, the particular element or elements that may be the causal or aggravating agents and the mechanisms of their action."' V

® Contributors x American Brands, Inc. Brown and Williamson Tobacco Corporation Liggett Group Inc. Lorillard, A Division of Loews Theatres, Inc. Philip Morris Incorporated R. J. Reynolds Industries, Inc.

Contents Preface Contributors Committee Membership Committee Statement Section I Absorption, Distribution, Metabolism, Excretion, Toxicology 1 Summary 3 Abstracts 52 6 Section VI Reproduction Summary Abstracts 47 263 265 266 Section II Carcinogenesis Summary Abstracts 45 25 29 31 Section VII Respiratory System Summary Abstracts 172 285 291 298 Section III Cardiovascular System 49 Authors Index 359 Su m mary 59 Abstracts 262 77 Section IV Central and Autonomic Participating Institutions Index 367 Nervous System 171 Summary 177 Abstracts 145 182 Section V Gastrointestinal Tract 231 Summary 235 Abstracts ~ 72 237 vli

Dedication This book is dedicated to Maurice H. Seevers, M.D., Ph.D., who served as Chairman of the AMA-ERF Committee for Research on Tobacco and Health from the time of its inception in 1964 until his death in May 1977. Doctor Seevers was Professor and Chairman of the Department of Pharmacology at the University of Michigan Medical School from 1942 until his retirement. He distinguished himself as an authority on drug and drug abuse not only at the medical school level but as a consultant to state, federal and foreign governments, private industry, medical publications, the American Medical Association and health organizations around the world. During his career, he served as a member of the Surgeon General's Committee on Smoking and Health, the President's Committee on Marihuana and Drug Abuse, the White House Conference Drug Abuse Panel on Narcotics and Drug Abuse, the National Research Council's Committee on Problems of Drug Abuse, the AMA Committee on Alcohol and Drug Dependence, the AMA Council on Drugs, and as. a consultant on Drug Abuse to Japan, Thailand, Australia and the United States. The AMA-ERF Committee for Research on Tobacco and Health is pleased to have had the privilege of serving with Doctor Seevers and herewith dedicates this publication to his memory as a physician, scientist, educator, leader and humanitarian. Richard J. Bing, M. D. Stuart Bondurant, M. D. Earl A. Evans, Ph. D. Robert ). Hasterlick, M. D. Paul Kotin, M. D. Marvin Kuschner, M. D. Paul S. Larson, Ph. D. Richard D. Remington, Ph. D. Ira Singer, Ph. D. a . !

1%. TOBACCO AND HEALTH Compiled by the AMA-ERF Committee for Research on Tobacco and Health 1978 Amprican Medical Association Education and Research Foundation

The AMA-ERF Committee for Research on Tobacco and Health wishes to thank the many individuals both in this country and abroad who participated in the research which resulted in this publication. Special thanks goes to Edward Domino, M.D., Professor of Pharmacology, University of Michigan Medical School, who assisted the Committee in summarizing Section IV, Central and Autonomic Nervous System, following the death of Doctor Seevers. We also wish to thank Dr. John C. Ballin and Dr. Ira Singer who served as scientific secretaries to the Committee, and Mr. Leo E. Brown who provided the final stimulus for the production of this publication. Special appreciation is due Ms. Barbara Newkirk, Mrs. Susan Remley, and Mrs. Shirley Sullivan of the AMA secretarial staff, and to the personal secretaries of our Committee members. To Mr. Ralph Linnenburger, Director, and to Ms. Irene Parks Foster, Production Editor of the AMA Department of Creative Services, and Mr. Joseph Giacalone, we are indebted for the design and the typography of this publication. O v'%

AMA-ERF COMMITTEE FOR RESEARCH ON TOBACCO AND HEALTH (Appointed June 1964 - Richard J. Bing, M. D. 1964-1977 Professor of Medicine University of Southern California Director of Cardiology and Intramural Medicine Huntington Memorial Hospital Stuart Bondurant, M. D. 1970-1977 President and Dean Albany Medical College of Union University Paul S. Larson, Ph.D. 1964-1977 Haag Professor of Pharmacology Chairman Emeritus, Department of Pharmacology Medical College of Virginia Charles LeMaistre, M. D. 1964-1966 Chancellor University of Texas Southwestern Medical School, Dallas, Texas Earl A. Evans, Jr., Ph.D. 1969-1977 Richard D. Remington, Ph.D. 1969-1977 Professor and Chairman Emeritus Department of Biochemistry University of Chicago Dean, School of Public Health University of Michigan Robert J. Hasterlik, M. D. 1966-1977 Maurice H. Seevers, M.D., Ph.D.** La Jolla, California CHAIRMAN 1964-1977 ohn B. Hickam, M. D.* 1964-1970 Professor Emeritus Department of Pharmacology University of Michigan Chester M. Southam, M. D. 965-1966 Chairman, Department of Internal Medicine University of Indiana Paul Kotin, M. D. 1966-1977 Vice President, Health, Safety and Environment Johns-Manville Chairman, Dept. of Oncology Jefferson Medical College of Thomas Jefferson University AMA Staff Secretaries John C. Ballin, Ph.D. 964-1965 Greenwood Plaza Marvin Kuschner, M. D. 1969-1977 American Medical Association Ira Singer, Ph.D. 1966-1977 Dean, School of Medicine Health Science Center State University of New York at Stony Brook American Medical Association * Deceased February 9, 1970 ** Deceased April 29, 1977 xi

pref ace In January of 1964, the American Medical Association Educ.ation and Research Foundation (AMA-ERF) entered into a five year agreement with six tobacco companies' to conduct a comprehensive program of research on Tobacco and Health. The research was to be devoted to the study of human ailments that may be caused or aggravated by smoking, the particular element or elements that may be the causal or aggravating agents and the mechanisms of their action. The six participating tobacco companies pledged to contribute a total of ten million dollars to the AMA-ERF to finance this five-year research effort. The AMA-ERF Board of Directors appointed an eminently qualified Scientific Committee2 to develop guidelines and suggestions on research policies and procedures, identify significant areas of research and screen applications for research grants. The agreement was renewed in 1969 for another five years, terminating in December 1973. On July 18, 1972, it was altered to eliminate industry's financial commitment in 1972 and 1973 with no new grant applications being accepted in 1973 although grants funded in 1972 were continued to com- pletion. Between 1964 and 1975, 844 researchers in 85 United States and 13 foreign -.research institutions produced 795 publications and reports on the relation- ships of tobacco and health on (1) Absorption, Distribution, Metabolism, Excretion and Toxicology; (2) Carcinogenesis; (3) Cardiovascular System; (4) Central and Autonomic Nervous System; (5) Gastrointestinal Tract; (6) Re- production; and (7) Respiratory System. The content of this publication includes a summary of the research projects conducted in each of the above sections, abstracts of the research projects and the names of the participating researchers and institutions. It is hoped that this information will stimulate additional research in the field of tobacco and health. The American Medical Association and its Education and Research Foundation wish to express its gratitude to the Tobacco Industry for its financial support, the members of the Scientific Committee, the participating institutions and the 196 researchers without whose dedication and intellect this book would not have been possible. . ' see page x 2 see page xi James H. Sammons, M. D. Executive Vice President American Medical Association Education and Research Foundation ix