Special Report
The Food and Drug Administration's Regulation of Tobacco Products
N Engl J Med 1996; 335:988-994September 26, 1996
- Article
On August 23, the Food and Drug Administration (FDA) issued a regulation restricting the sale and distribution of cigarettes and smokeless tobacco to children and adolescents.1 This regulation, known as a rule, is the most far-reaching measure ever instituted to reduce the use of tobacco by young people. This article describes the investigation that led the FDA to assert its jurisdiction over cigarettes and smokeless tobacco and the policy considerations that shaped the final rule.
The FDA announced on February 25, 1994, that it was considering regulating tobacco products under the authority of the Federal Food, Drug, and Cosmetic Act.2 Under the act, the decision to regulate tobacco products as drug-delivery devices for nicotine would depend on whether the products were “articles (except for food) intended to affect the structure or any function of the body.” After its announcement, the agency extensively reviewed the effects of nicotine on the structure or function of the body and investigated whether cigarettes and smokeless tobacco are “intended” to deliver nicotine to consumers. The agency also investigated the effect of advertising and marketing by the tobacco industry on children and adolescents.
Eighteen months later, on August 10, 1995, President Bill Clinton announced that the agency's evidence and analysis supported a finding, subject to public comment, that the nicotine in cigarettes and smokeless-tobacco products is a drug and that these products are drug-delivery devices under the terms of the act.3 Citing evidence that smoking begins in childhood as a “pediatric disease,” the FDA proposed a regulatory program that would reduce the use of cigarettes and smokeless tobacco by young people by limiting their advertising and sale.4
The FDA received more than 700,000 comments on its finding of jurisdiction and on the proposed regulations — more comments than had been received about any other federal rule in history. These comments included 2500 pages of text and nearly 50,000 pages of exhibits from the cigarette and smokeless-tobacco industries alone. Among the hundreds of public health organizations, physicians, and other health professionals expressing views, virtually all agreed that cigarettes and smokeless tobacco should be regulated by the FDA. (The supporting documentation for this report can be found in the August 10, 1995, Federal Register and the administrative record supporting that publication; these documents, including both unpublished industry reports and scientific studies, are available for review at FDA headquarters.)
These tobacco regulations are historic for their importance to the public health, for the depth of the President's commitment, and for the extent of public support. They are aimed at protecting American children from a lifelong addiction that often leads to a premature death.
The Investigation of Tobacco
In 1994, the FDA began an investigation to determine whether the pharmacologic effects of nicotine were “intended” by tobacco manufacturers. If they were, cigarettes and smokeless tobacco would fall within the agency's jurisdiction. At that early stage, agency officials understood very little of what the tobacco industry knew about its products or how it designed them. Piece by piece, a clearer picture emerged. Documents from the industry showed that it has known for decades that tobacco products have powerful pharmacologic effects, including addiction to nicotine. Moreover, the evidence revealed that tobacco manufacturers design their products to provide consumers with pharmacologically active doses of nicotine. The inevitable consequence has been to keep consumers addicted to these products.
Early Developments
Two developments prompted the FDA inquiry into whether the pharmacologic effects of cigarettes and smokeless tobacco were intended and should therefore be regulated under the authority of the Food, Drug, and Cosmetic act. First, by the early 1990s, a scientific consensus had emerged that the nicotine in tobacco products is addictive and that the market for such products is based largely on this addiction.5-11 The scientific definitions of addiction place their primary emphasis on the presence of highly controlled or compulsive use (despite a desire to quit or repeated attempts to do so); psychoactive effects produced by the action of the drug on the brain; and drug-seeking behavior caused by the “reinforcing” effects of the psychoactive substance.12
Second, the tobacco industry was introducing new products whose composition showed that the manufacturers could control the amount of nicotine delivered to the user or even remove the nicotine entirely. In 1988, for example, the R.J. Reynolds Tobacco Company introduced Premier, a novel product that heated, rather than burned, tobacco to deliver a carefully controlled dose of nicotine.13 One year later, Philip Morris test-marketed Next, a cigarette that contained no nicotine.14
In the spring of 1994, the FDA observed a trend that strongly suggested that the tobacco industry manipulated and controlled the levels of nicotine in conventional cigarettes. Tobacco companies are required to report the levels of nicotine and tar in their products to the Federal Trade Commission. When FDA investigators analyzed those reports, they found that the amount of nicotine delivered has been increasing since 1982, with the greatest increases in the lowest-tar cigarettes (Figure 1Figure 1
Changes in Mean Levels of Nicotine and Tar in Smoke from All Brands of Cigarettes, 1982–1991, as a Percentage of 1982 Levels.).15 These increases occurred without parallel increases in the delivery of tar, directly contradicting the industry's claim that “nicotine follows the tar level” in “a near perfect correlation.”16 It seemed unlikely that the delivery of nicotine could increase independently of the delivery of tar unless the manufacturers had made deliberate design decisions.The agency's suspicions grew when FDA scientists learned that certain cigarettes advertised as having the lowest tar content actually contained the blends of tobacco richest in nicotine. For example, tests of three varieties of Merit cigarettes — one delivering the regular amount of tar, one low in tar, and one with ultra-low levels of tar — showed that the ultra-low-tar variety had the highest concentration of nicotine in its tobacco blend.17 This suggested that the manufacturers were compensating for the effects of filtration and ventilation, the principal variables in design used to reduce the delivery of tar, by using high-nicotine tobacco in the blends of their lowest-tar products.
A review of tobacco-industry patents also showed that since the early 1960s the industry has been conducting extensive research on methods of controlling the precise amount of nicotine a cigarette delivers.18 As one patent stated, “maintaining the nicotine content at a sufficiently high level to provide the desired physiological activity, taste, and odor . . . can thus be seen to be a significant problem in the tobacco art.”19
Inside the Tobacco Companies
The FDA's first important insights into the internal knowledge and actions of the tobacco companies came in the spring and summer of 1994. In April 1994, Victor DeNoble and Paul Mele, two former Philip Morris scientists, testified before Congress about that company's efforts in the early 1980s to find an analogue of nicotine that would “mimic nicotine's effect in the brain” but not have “cardiovascular liability.”20 The scientists explained that to identify the pharmacologic effects of nicotine on the brain, Philip Morris used “exactly the same tests” that the National Institute on Drug Abuse uses to determine whether a drug has a potential for abuse.21 The company's experiments showed that rats would both self-administer nicotine and develop tolerance to it — two key properties of an addictive substance.22 The experiments in rats also showed that nicotine served as a discriminative stimulus,23 a finding predicting that a substance will have mood-altering effects in humans — another defining trait of addictive compounds.24 Thus, it appeared that at least one tobacco company had knowledge of nicotine's potential for addiction.
In May 1994, further evidence of the industry's knowledge of nicotine's addictiveness emerged when The New York Times published an article describing confidential documents obtained from the Brown and Williamson Tobacco Corporation, the nation's third-largest tobacco company, and its British parent, BAT Industries, formerly the British–American Tobacco Company.25 The documents showed that in the 1960s senior company officials had explicitly acknowledged that “smoking is a habit of addiction”26 and stated that “we are, then, in the business of selling nicotine, an addictive drug.”27 The Brown and Williamson documents also showed that the companies had conducted dozens of studies of the drug-like properties of nicotine, leading company researchers to conclude that nicotine is “pharmacologically active in the brain”28 and “an extremely biologically active compound capable of eliciting a range of pharmacological, biochemical, and physiological responses.”29
The FDA investigators also discovered that Brown and Williamson had created a new variety of tobacco grown in Brazil, code-named Y-1, with twice the normal level of nicotine.30 Most important, company executives stated that Y-1 was intended as a “blending tool” to permit the design of cigarettes lower in tar but not in nicotine.31 Company officials, however, said that they did not use it as such.
The next piece of evidence arrived anonymously in the mail — part of one company's handbook on leaf blending and product development. From it the agency learned that tobacco companies used chemical additives to affect the delivery of nicotine; for example, they added ammonia compounds to “liberate free nicotine from the blend, which is associated with increases in impact and `satisfaction' reported by smokers.”32
The Emerging Picture
The FDA investigation also revealed that for at least three decades manufacturers have conducted and funded extensive research into the pharmacokinetics of nicotine, its pharmacodynamics, and methods of delivery.33 Through research, the industry learned that nicotine has potent pharmacologic effects on the brain, that that is the primary reason consumers use tobacco products, and that nicotine delivery can be manipulated and controlled through a wide array of methods, including the blending of tobacco, selective filtration and ventilation, and chemical manipulation.
In late July and early August 1995, shortly before the President announced the FDA's proposed tobacco regulations, important information became available about Philip Morris, the nation's largest tobacco company, when the contents of hundreds of pages of confidential company documents were disclosed to Congress.34,35 These and other company documents showed that as early as 1969, Philip Morris researchers had told the company's board of directors that “the ultimate explanation for the perpetuated cigarette habit resides in the pharmacological effect of smoke upon the body of the smoker.”36 Throughout the 1970s, Philip Morris laboratories had conducted extensive research into both the pharmacology of nicotine and methods of nicotine manipulation.37 Philip Morris researchers also “systematically manipulated tar and nicotine parameters of cigarettes . . . to predict nicotine/tar ratios for optimal cigarette acceptability.”38 In one 1972 document that emerged in a court case,39 a senior Philip Morris researcher actually conceived of the cigarette as “a dispenser for a dose unit of nicotine.”40
Numerous documents were submitted to the FDA during the period of public comment that followed the President's August 1995 announcement. According to one tobacco-company document, in the 1970s, R.J. Reynolds researchers stated that “the confirmed user of tobacco products is primarily seeking the physiological `satisfaction' derived from nicotine”41 and that “without any question, the desire to smoke is based on the effect of nicotine on the body.”42 In another document, William Farone, the former director of applied research at Philip Morris, informed the agency that “product developers and blend and leaf specialists at Philip Morris were responsible for manipulating and controlling the design and production of cigarettes in order to satisfy the consumer's need for nicotine.”43
More Than Just Cigarettes
FDA laboratories and investigators also examined how manufacturers of smokeless tobacco manipulate the delivery of nicotine. The FDA learned that manufacturers of smokeless tobacco adjust the pH of their products to produce intentionally graduated nicotine deliveries.44 The industry's “starter” products for new users have a low pH and consequently deliver a low level of “free” nicotine, limiting the absorption of the compound in the mouth. Smokeless-tobacco products intended for users who have already acquired a tolerance to nicotine have a high pH and consequently deliver a high level of free nicotine, increasing the amount of nicotine available for absorption. Indeed, internal documents from the United States Tobacco Company, the nation's largest smokeless-tobacco manufacturer, refer to an explicit “graduation process” designed to encourage users to progress from low-nicotine brands to high-nicotine ones.45
Asserting Jurisdiction
The agency's task in determining whether the FDA has jurisdiction over tobacco products has been part scientific inquiry and part detective work. Like investigators trying to solve a mystery, we examined the evidence from several perspectives. In the end, the evidence converged remarkably.
Under the Food, Drug, and Cosmetic Act, the agency can establish in several ways that a product is “intended to affect the structure or any function of the body” and hence that it meets the criteria for a drug or device subject to FDA jurisdiction. The agency may show that a reasonable manufacturer would foresee that the product will be used for pharmacologic purposes, that consumers actually use it for such purposes, or that the manufacturer expects or designs the product to be used in such a manner.
The agency's analyses of the intended use of cigarettes and smokeless tobacco according to these three independent legal standards all led to the same conclusion: that cigarettes and smokeless tobacco are delivery devices for the drug nicotine. Although evidence meeting any one of these standards would suffice to establish the FDA's jurisdiction over cigarettes and smokeless tobacco, the evidence met all three standards to support such a finding.
The Regulation of Tobacco
The agency's investigation and its finding that the FDA has regulatory jurisdiction over cigarettes and smokeless tobacco raised a difficult question: What is the most appropriate way to regulate these products? To answer this question, we considered the public health consequences of tobacco consumption and the pattern of tobacco use in the United States.
Tobacco affects the public health profoundly. More than 50 million Americans smoke cigarettes,46 and experts estimate that 77 to 92 percent of them are addicted to nicotine.47-49 Tobacco use is the leading preventable cause of death in the United States.50 Tobacco-related disease kills more than 400,000 Americans annually,50 more people than die from AIDS, car accidents, alcohol, homicides, illegal drugs, suicides, and fires combined.51
The death and disease caused by tobacco use occur primarily in adulthood, but nicotine addiction usually begins in adolescence or before. Consequently, the addiction begins as a “pediatric” disease. Eighty-two percent of adults with any history of smoking had their first cigarette before the age of 18, and more than half of them had already become regular smokers by that age.52
New smokers and smokeless-tobacco users come primarily from the ranks of the young. Approximately 3 million American adolescents already smoke, and an additional 1 million adolescent boys use smokeless tobacco.53 Nearly 3000 young people start smoking each day, or more than a million each year.54 Despite a decline in adult smoking, adolescent smoking is on the rise, and studies show that children begin smoking at earlier and earlier ages.55-57 Even more alarming, approximately one of every three such young smokers will die prematurely from a tobacco-caused disease.58
Given the level of addiction already present among adults, an outright ban would not be effective in preventing the use of tobacco. Instead, the FDA has decided to focus on breaking the cycle of addiction to nicotine. There is convincing evidence that the right policy is to stop children and adolescents from using tobacco in the first place.
Restricting Access to Tobacco
Each year young people purchase tobacco products worth an estimated $1.26 billion.59 Despite laws in all 50 states that prohibit tobacco sales to minors, numerous studies show that adolescents have little difficulty purchasing these products. The 1994 report of the surgeon general examined 13 studies of over-the-counter sales and determined that approximately 67 percent of the time minors can buy cigarettes illegally.60 Moreover, substantial numbers of young people successfully purchase smokeless tobacco as well, with 90 percent of such users in junior high and high school saying they buy their own smokeless tobacco.61
Studies show that minors who purchase cigarettes and smokeless-tobacco products in stores are infrequently asked for identification. In addition to over-the-counter sales, vending machines are a principal source of cigarettes for children. The 1994 surgeon general's report examined studies of vending-machine sales and found that children and adolescents were successful in purchasing cigarettes in that manner 88 percent of the time.60 In addition, surveys show that vending machines are most popular with the youngest smokers. According to a study by the vending-machine industry itself, 22 percent of 13-year-olds who smoke purchase cigarettes from vending machines, as compared with 2 percent of 17-year-olds.62
Self-service displays also give young people easy access to cigarettes and smokeless-tobacco products, because they permit them to obtain these products quickly, easily, and independently. A study by the Institute of Medicine found that more than 40 percent of grade-school students who smoked daily had at some time shoplifted cigarettes from self-service displays.63 Young people also obtain tobacco products by redeeming coupons for free or discounted cigarettes through the mail. As part of an investigation by his office, the attorney general of Massachusetts had 30 minors mail in coupons to manufacturers for free samples of smokeless tobacco. Virtually all of them received the samples.64 Children and adolescents often obtain free samples of cigarettes that are distributed on street corners, at shopping malls, and at festivals, concerts, and other places frequented by youngsters. Despite the tobacco industry's voluntary code prohibiting the distribution of free samples to children, a number of surveys and reports demonstrate that young people can obtain them easily. Finally, “kiddie” packs, which typically contain 5, 10, or 15 cigarettes, are inexpensive and easy for young people to hide.
To limit young people's easy access to tobacco products, the FDA's rule prohibits the sale of tobacco products to anyone under 18 years old and requires retailers to check photographic identification, such as a driver's license, for everyone 26 or under. In addition, the access provisions of the rule prohibit tobacco vending machines and self-service displays, except in facilities, such as certain nightclubs, where the management ensures that no one under 18 will be present at any time. It also prohibits free samples, kiddie packs, and most sales of single cigarettes. And while permitting mail-order sales, it prohibits coupons for cigarettes or smokeless tobacco from being redeemed through the mail.
Reducing the Appeal of Advertising
Tobacco products are among the most heavily advertised and promoted commodities in this country. In 1993, tobacco companies' expenditures for advertising and promotion exceeded $6 billion.65-67 Studies show that advertising substantially influences young people's smoking and use of smokeless tobacco.
Two reports on tobacco and young people, one by the surgeon general68 and the other by the Institute of Medicine,69 studied how advertising affects young people's use of tobacco and concluded that it was an important factor. Officials at the FDA reviewed scores of other reports examining the psychological and social factors affecting tobacco use. Collectively, the studies showed that young people are widely exposed to cigarette advertising, aware of it, and influenced by it. One study found that 30 percent of three-year-olds and 91 percent of six-year-olds could identify Joe Camel as a symbol of smoking.70 Other studies have shown that young people's exposure to cigarette advertising is correlated with their smoking behavior and their intention to smoke. Still others suggest that cigarette advertising helps young people decide what behavior is normal or socially acceptable and that those who are led to overestimate the prevalence of smoking seem more likely to begin smoking and progress to regular smoking. Finally, such advertising appears to be particularly effective with children and adolescents. The three most heavily advertised brands are smoked by 86 percent of young smokers; by contrast, adults are far more likely to choose one of the “generic” brands, which are advertised less and are less expensive.71
Billboards are one of the most effective means of reaching young people with tobacco advertising. A survey conducted by BKG Youth for Advertising Age showed that 46 percent of children 8 to 13 years old said they most often saw cigarettes advertised on billboards, more than in magazines.72 Furthermore, the billboard industry's own marketing materials emphasize the unavoidability of billboards, as in this statement: “Outdoor is right up there. Day and night. Lurking. Waiting for another ambush.”73
Promotional items — such as T-shirts, caps, sporting goods, and other items displaying tobacco brand names or other types of product identification — have become particularly popular with young people. A Gallup survey found that about half of adolescents who smoke and one quarter of adolescents who do not smoke owned at least one such item.74
Lastly, studies show that sponsorship by cigarette and smokeless-tobacco companies associates the use of their products with events young people perceive as exciting, glamorous, or fun, such as car races and rodeos. Such sponsorship provides an opportunity for advertising to create a “friendly familiarity” between tobacco and sports enthusiasts, many of whom are children and adolescents. The leading source of data on television viewership estimates that motor vehicle sports are watched 64 million times a year by those under 18.75 Whereas print advertisements are typically seen for only a few seconds, the brand name is viewed for hours at a time during sponsored events.
The many types of advertising and promotion of tobacco — billboards, printed advertisements, direct mail, promotional items, and sponsored events — give children and adolescents the misperception that the large majority of their peers and adults use tobacco. Children are constantly exposed to this message, which is funded by $6 billion in advertising and promotional expenditures. Teenagers look at Rolling Stone and see a cardboard Joe Camel pop out of the center of the magazine holding concert tickets in his hand.76 Children walking home from school pass under billboards showing appealing images related to tobacco products. When they attend a car race or watch one on television, they see the bright-red Marlboro car and posters around the racetrack bear the brand name and its associated colors. On their friends' caps and T-shirts they see yet more ads for tobacco.
For these reasons, the regulation limits tobacco advertising in the media to a black-and-white, text-only format. This restriction preserves the textual information for adult smokers while at the same time eliminating the colorful imagery that makes advertising appealing and compelling to children and adolescents. There are a few exceptions. Advertising in publications read primarily by adults or that appears in places frequented only by adults is exempt from restrictions. In contrast, outdoor advertising within 1000 feet of schools or playgrounds is prohibited.
Tobacco companies will not be permitted to sell or distribute promotional items, such as T-shirts, caps, and sporting goods, that carry the brand name or logo of a tobacco product. Similarly, tobacco companies that sponsor sporting or other events, race cars, athletic teams, or the like will be restricted to using their corporate names only.
Educating Children about Tobacco
Young people are generally aware of the link between tobacco use and a variety of diseases. However, studies show that those who smoke do not usually see these long-term risks as applying to them personally and that, furthermore, they tend to discount the risks. For example, only half of high-school seniors who smoke, but three quarters of those who do not smoke, report that smoking a pack or more of cigarettes per day constitutes a serious health risk.77
In addition, although young people say that nicotine is addictive, there is evidence that those who begin to smoke do not believe that they themselves will become addicted. One study found that senior-high-school students' expectations about their own future smoking bore little relation to their actual smoking practices. Of students who smoked at least one pack a day and said they would probably or definitely not be smoking in five years, only 13 percent did in fact quit. More than 72 percent continued to smoke at least one pack a day.78
For these reasons, the FDA intends to require a national program of education, relying primarily on television messages, to help young people understand the health risks to which they are subjecting themselves if they use tobacco. Such messages proved effective in the late 1960s, when broadcasters were required to air them to counter the advertising for cigarettes that was then permitted on television. After the publication of this rule, the agency plans to notify the major cigarette and smokeless-tobacco companies that it will begin discussing a requirement that they fund an educational program in the mass media.
These regulations will be implemented over the next two years. The goal is to cut the use of tobacco among young people by half over a seven-year period. This reduction will improve the public health in general because as these children grow up, fewer and fewer adults will be addicted to nicotine.
In financial terms alone, the rule is expected to yield substantial health-related benefits ranging from $28 billion to $43 billion each year. The FDA estimates that implementing the rule will entail a one-time cost of $174 million to $187 million and annual operating costs of $149 million to $185 million. These economic benefits were calculated by estimating the number of adolescents who will not start smoking because of the rule and then, from existing risk data, predicting how much sickness and death caused by tobacco products will be prevented. These cost estimates were based on the public comments and on extensive economic analyses by the affected industries.
Conclusions
This new FDA regulation presents a historic opportunity, giving the United States a chance to reduce the consumption of a product that kills more Americans each year than die from any other preventable cause. The approach is focused in the right place: sparing children and adolescents a lifetime of addiction to tobacco.
Source Information
From the Food and Drug Administration, Office of the Commissioner, 5600 Fishers Ln., HF-1, Rockville, MD 20857, where reprint requests should be addressed to Dr. Kessler.
- References
References
1
Department of Health and Human Services 2
Kessler DA. Agency's response to Coalition on Smoking OR Health's outstanding petitions. Rockville, Md.: Food and Drug Administration, February 25, 1994.
3
Department of Health and Human Services, Food and Drug Administration 4
Department of Health and Human Services, Food and Drug Administration 5
Department of Health and Human Services, Office on Smoking and Health. The health consequences of smoking: nicotine addiction: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1988:13-4. (DHHS publication no. (CDC) 88-8406.)
6
Benowitz NL. Clinical pharmacology of inhaled drugs of abuse: implications in understanding nicotine dependence. In: Chiang CN, Hawks RL, eds. Research findings on smoking of abused substances. NIDA research monograph 99. Washington, D.C.: Government Printing Office, 1990:12-29.
7
Diagnostic and statistical manual of mental disorders. 3rd ed. rev. Washington, D.C.: American Psychiatric Association, 1987:159-60, 176-8.
8
Ethyl alcohol and nicotine as addictive drugs. In: 1993 AMA policy compendium. Chicago: American Medical Association, 1993:35.
9
World Health Organization. The ICD-10 classification of mental and behavioral disorders: clinical descriptions and diagnostic guidelines. Geneva: World Health Organization, 1992:76.
10
Health and Welfare of Canada, Health Protection Branch. Tobacco, nicotine, and addiction: a committee report. Ottawa: Royal Society of Canada, 1989:v-vi.
11
MRC Field Review of Drug Dependence. London: Medical Research Council, 1994:11.
12
Department of Health and Human Services, Office on Smoking and Health. The health consequences of smoking: nicotine addiction: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1988:7-8. (DHHS publication no. (CDC) 88-8406.)
13
Chemical and biological studies: new cigarette prototypes that heat instead of burn tobacco. Winston-Salem, N.C.: R.J. Reynolds Tobacco, 1988.
14
Dagnoli J. PM's denic may get more nicotine. Advertising Age. February 12, 1990:31.
15
Kessler DA. Statement. In: Regulation of tobacco products. Part 1. Hearings before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce, House of Representatives. Washington, D.C.: Government Printing Office, 1994:Chart T. (Serial no. 103-149.)
16
Spears AW. Testimony. In: Regulation of tobacco products. Part 1. Hearings before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce, House of Representatives. Washington, D.C.: Government Printing Office, 1994:143-4. (Serial no. 103-149.)
17
Department of Health and Human Services, Food and Drug Administration 18
Regulation of tobacco products. Part 1. Hearings before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce, House of Representatives. Washington, D.C.: Government Printing Office, 1995:Charts B–D. (Serial no. 103-149.)
19
Bavley A, Air D, Robb E II. Additive-releasing filter for releasing additives into tobacco smoke. 1966. (U.S. Patent No. 3,280,823.)
20
DeNoble VJ. Statement. In: Regulation of tobacco products. Part 2. Hearings before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce, House of Representatives. Washington, D.C.: Government Printing Office, 1994:33. (Serial no. 103-153.)
21
Regulation of tobacco products. Part 2. Hearings before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce, House of Representatives. Washington, D.C.: Government Printing Office, 1994:17. (Serial no. 103-153.)
22
Regulation of tobacco products. Part 2. Hearings before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce, House of Representatives. Washington, D.C.: Government Printing Office, 1994:17-8. (Serial no. 103-153.)
23
Regulation of tobacco products. Part 2. Hearings before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce, House of Representatives. Washington, D.C.: Government Printing Office, 1994:6. (Serial no. 103-153.)
24
Department of Health and Human Services, Office on Smoking and Health. The health consequences of smoking: nicotine addiction: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1988:274-5. (DHHS publication no. (CDC) 88-8406.)
25
Hilts PJ. Tobacco company was silent on hazards. New York Times. May 7, 1994.
26
Ellis C. The smoking and health problem. In: Smoking and health — policy on research. Southampton, England: BATCO Research Conference, 1962:4.
27
Yeaman AY. Implications of Battelle Hippo I and II and the Griffith filter. Southampton, England: BATCO Research Conference, July 17, 1963:4.
28
Minutes of the BATCO Group R&D Conference on Smoking Behaviour, Southampton, England, October 11 and 12, 1976. (BW-W2-02145.)
29
Minutes of the BATCO Group R&D Conference on Method of Nicotine and Cotinine in Blood and Urine, Southampton, England, May 21, 1980:2.
30
Federative Republic of Brazil, Ministry of Industry, Commerce and Tourism, National Institute for Industrial Property. Genetically stable tobacco variety and tobacco plant. Louisville, Ky.: Brown & Williamson Tobacco, 1993. (Publication no. PI 9203690A.)
31
Department of Health and Human Services, Food and Drug Administration 32
Regulation of tobacco products. Part 3. Hearings before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce, House of Representatives. Washington, D.C.: Government Printing Office, 1995:21. (Serial no. 103-171.)
33
Department of Health and Human Services, Food and Drug Administration 34
Waxman HA. Remarks. Congressional Record (Daily ed.) 1995;141:H7470.
35
Waxman HA. Congressional Record (Daily ed.) 1995;141:H8007.
36
Wakeham H. Smoker psychology research. In: Presentation to the Philip Morris board of directors. Richmond, Va.: Philip Morris, November 26, 1969:240.
37
Dunn WL. Plans and objectives — 1979. Congressional Record (Daily ed.) 1995;141:H7668-70.
38
Dunn WL. Smoker psychology/April 1–30, 1974. Memorandum, May 9, 1974. Congressional Record (Daily ed.) 1995;141:H8132.
39
Cipollone v. Liggett Group, Inc., et al. Civil Action No. 83-2864, U.S. District Court for the District of New Jersey.
40
Dunn WL. Motives and incentives in cigarette smoking. Richmond, Va.: Philip Morris, 1972:5.
41
Teague CE. Memorandum. Research planning memorandum on the nature of the tobacco business and the crucial role of nicotine therein. Winston-Salem, N.C.: R.J. Reynolds Tobacco, April 14, 1972.
42
Senkus M. Some effects of smoking. Winston-Salem, N.C.: R.J. Reynolds Tobacco, 1976/1977:4.
43
Department of Health and Human Services, Food and Drug Administration 44
Department of Health and Human Services, Food and Drug Administration 45
Africk J. Interview. Executive vice president of U.S. Tobacco Company and president of the international division. Up to Snuff. Winter 1986:2.
46
Department of Health and Human Services. National household survey on drug abuse: population estimates 1993. Rockville, Md.: Substance and Mental Health Services Administration, 1994:89, 95. (DHHS publication no. SMA 94-3017.)
47
Cottler LB . Comparing DSM-III-R and ICD-10 substance use disorders. Addiction 1993;88:689-696
CrossRef | Web of Science | Medline48
Hughes JR ,Gust SW ,Pechacek TF . Prevalence of tobacco dependence and withdrawal. Am J Psychiatry 1987;144:205-208
Web of Science | Medline49
Woody GE ,Cottler LB ,Cacciola J . Severity of dependence: data from the DSM-IV field trials. Addiction 1993;88:1573-1579
CrossRef | Web of Science | Medline50
Department of Health and Human Services, Centers for Disease Control
Medline51
Institute of Medicine. Growing up tobacco free — preventing nicotine addiction in children and youths. Washington, D.C.: National Academy Press, 1994:3.
52
Department of Health and Human Services. Preventing tobacco use among young people: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1994:65. (S/N 017-001-00491-0.)
53
Department of Health and Human Services. Preventing tobacco use among young people: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1994:5. (S/N 017-001-00491-0.)
54
Pierce JP ,Fiore MC ,Novotny TE ,Hatziandreu EJ ,Davis RM . Trends in cigarette smoking in the United States: projections to the year 2000. JAMA 1989;261:61-65
CrossRef | Web of Science | Medline55
Cigarette smoking among adults -- United States, 1993
Medline56
Johnston LD, O'Malley PM, Bachman JG. National survey results on drug use from the Monitoring the Future Study 1975–1993. Vol 1. Secondary school students. Rockville, Md.: National Institutes of Health, 1994:9, 19, 79, 80, 101. (NIH publication no. 94-3809.)
57
Smoking rates climb among American teen-agers, who find smoking increasingly acceptable and seriously underestimate the risks. Ann Arbor: University of Michigan News and Information Service, July 17, 1995.
58
Ericksen MP. Tobacco mortality estimates from the Centers for Disease Control and Prevention. CDC Fact Sheet. August 7, 1995.
59
DiFranza JR ,Tye JB . Who profits from tobacco sales to children? JAMA 1990;263:2784-2787
CrossRef | Web of Science | Medline60
Department of Health and Human Services. Preventing tobacco use among young people: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1994:249. (S/N 017-001-00491-0.)
61
Department of Health and Human Services, Office of Inspector General. Youth use of smokeless tobacco: more than a pinch of trouble. Washington, D.C.: Government Printing Office, 1986:4. (Publication no. P-06-86-0058.)
62
Response Research. Findings for the study of teenage cigarette smoking and purchasing behavior. Chicago: National Automatic Merchandising Association, June/July 1989. (Exhibit 22.)
63
Institute of Medicine. Growing up tobacco free — preventing nicotine addiction in children and youths. Washington, D.C.: National Academy Press, 1994:215.
64
Harshbarger S. Comment. In: Proposed regulations restricting the sale and distribution of cigarettes and smokeless tobacco products. Rockville, Md.: Food and Drug Administration, 1996. (Docket 95N-0253. No. C29885.)
65
Federal Trade Commission. Report to Congress for 1993: pursuant to the Federal Cigarette and Advertising Act. Washington, D.C.: Government Printing Office, 1995:Table 3D.
66
Federal Trade Commission. Report to Congress: pursuant to the Comprehensive Smokeless Tobacco Health Education Act of 1986. Washington, D.C.: Government Printing Office, 1995:25-35.
67
Teinowitz I. Add RJR to list of cigarette price cuts. Advertising Age. April 26, 1993:3, 46.
68
Department of Health and Human Services. Preventing tobacco use among young people: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1994. (S/N 017-001-00491-0.)
69
Institute of Medicine. Growing up tobacco free — preventing nicotine addiction in children and youths. Washington, D.C.: National Academy Press, 1994.
70
Fischer PM ,Schwartz MP ,Richards JW Jr ,Goldstein AO ,Rojas TH . Brand logo recognition by children aged 3 to 6 years: Mickey Mouse and Old Joe the Camel. JAMA 1991;266:3145-3148
CrossRef | Web of Science | Medline71
Changes in the cigarette brand preferences of adolescent smokers -- United States, 1989-1993
Medline72
Levin G. Poll shows Camel ads are effective with kids; preteens best recognize brand. Advertising Age. April 27, 1992:12.
73
Outdoor: it's not a medium, it's a large. Washington, D.C.: Outdoor Advertising Association of America.
74
Teen-age attitudes and behavior concerning tobacco — report of the findings. Princeton, N.J.: George H. Gallup International Institute, 1992:17, 59.
75
Slade J. Tobacco product advertising during motor sports broadcasts: the quantative assessment. Paris: 9th World Conference on Tobacco and Health, 1994.
76
Advertising supplement between pages 12 and 13. Rolling Stone. March 7, 1996:12, 13.
77
Department of Health and Human Services. Preventing tobacco use among young people: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1994:80. (S/N 017-001-00491-0.)
78
Department of Health and Human Services. Preventing tobacco use among young people: a report of the Surgeon General. Washington, D.C.: Government Printing Office, 1994:86. (S/N 017-001-00491-0.)
- Citing Articles (50)
Citing Articles
1
M. Estivals, J.-C. Dubus, S. Porcher, P. Auquier, A. Dieudonné-Loundou, I. Missotte, L. Besson-Leaud, S. Laumond-Barny. (2011) Tabac et cannabis chez l’adolescent scolarisé de Nouméa. Revue des Maladies Respiratoires 28:5, 636-646
CrossRef2
David P. Kennedy, Joan S. Tucker, Michael S. Pollard, Myong-Hyun Go, Harold D. Green. (2011) Adolescent romantic relationships and change in smoking status. Addictive Behaviors 36:4, 320-326
CrossRef3
S. Negriff, L. D. Dorn, B. Huang. (2010) Pubertal timing and smoking initiation in adolescent females: Differences by race. Nicotine & Tobacco Research 12:7, 748-755
CrossRef4
Jennifer K. Ibrahim. (2010) The Tobacco Tug-of-War: Advertising and Counteradvertising Tobacco Products to Youth. Pediatric Allergy, Immunology, and Pulmonology 23:2, 105-111
CrossRef5
C. Chen, L.M. Isabelle, W.B. Pickworth, J.F. Pankow. (2010) Levels of mint and wintergreen flavorants: Smokeless tobacco products vs. confectionery products. Food and Chemical Toxicology 48:2, 755-763
CrossRef6
Daniel K. Cortese, M. Jane Lewis, Pamela M. Ling. (2009) Tobacco Industry Lifestyle Magazines Targeted to Young Adults. Journal of Adolescent Health 45:3, 268-280
CrossRef7
Jorge Rivera, Jennifer Oetzel, Peter deLeon, Mark Starik. (2009) Business responses to environmental and social protection policies: toward a framework for analysis. Policy Sciences 42:1, 3-32
CrossRef8
Jeffrey I. Seeman, Richard A. Carchman. (2008) The possible role of ammonia toxicity on the exposure, deposition, retention, and the bioavailability of nicotine during smoking. Food and Chemical Toxicology 46:6, 1863-1881
CrossRef9
Masuma Novak, Anne Hammarstrom, Christina Ahlgren. (2007) Inequalities in smoking: Influence of social chain of risks from adolescence to young adulthood: A prospective population-based cohort study. International Journal of Behavioral Medicine 14:3, 181-187
CrossRef10
Amit Bhargava, M.E. Greiss. (2007) Effects of smoking in foot and ankle surgery—An awareness survey of members of the British Orthopaedic Foot & Ankle Society. The Foot 17:3, 132-135
CrossRef11
Mustafa Erat, Mehmet Ciftci, Kenan Gumustekin, Mustafa Gul. (2007) Effects of nicotine and vitamin E on glutathione reductase activity in some rat tissues in vivo and in vitro. European Journal of Pharmacology 554:2-3, 92-97
CrossRef12
Arbay O. Ciftci, Ibrahim Sanlıalp, F. Cahit Tanyel, Nebil Büyükpamukçu. (2007) The Association of Pulmonary Lymphangioleiomyomatosis with Renal and Hepatic Angiomyolipomas in a Prepubertal Girl: A Previously Unreported Entity. Respiration 74:3, 335-337
CrossRef13
C CALLICUTT, R COX, F HSU, R KINSER, S LAFFOON, P LEE, K PODRAZA, E SANDERS, J SEEMAN. (2006) The role of ammonia in the transfer of nicotine from tobacco to mainstream smoke. Regulatory Toxicology and Pharmacology 46:1, 1-17
CrossRef14
E.W. Willems, B. Rambali, W. Vleeming, A. Opperhuizen, J.G.C. van Amsterdam. (2006) Significance of ammonium compounds on nicotine exposure to cigarette smokers. Food and Chemical Toxicology 44:5, 678-688
CrossRef15
Jack Henningfield, David Burns, Erik Dybing. (2005) Guidance for research and testing to reduce tobacco toxicant exposure. Nicotine & Tobacco Research 7:6, 821-826
CrossRef16
Kimberly M. Thompson. (2005) Addicted Media: Substances on Screen. Child and Adolescent Psychiatric Clinics of North America 14:3, 473-489
CrossRef17
Kenan Gumustekin, Mehmet Ciftci, Abdulkadir Coban, Sayit Altikat, Omer Aktas, Mustafa Gul, Handan Timur, Senol Dane. (2005) Effects of nicotine and vitamin E on glucose 6-phosphate dehydrogenase activity in some rat tissues in vivo and in vitro. Journal of Enzyme Inhibition and Medicinal Chemistry 20:5, 497-502
CrossRef18
Jacques Cosnes. (2004) Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice. Best Practice & Research Clinical Gastroenterology 18:3, 481-496
CrossRef19
Lisa Henriksen, June A. Flora, Ellen Feighery, Stephen P. Fortmann. (2002) Effects on Youth of Exposure to Retail Tobacco Advertising1. Journal of Applied Social Psychology 32:9, 1771-1789
CrossRef20
H. A. Washington. (2002) Burning Love: Big Tobacco Takes Aim at LGBT Youths. American Journal of Public Health 92:7, 1086-1095
CrossRef21
Tracy Meis, Martha Gaie, Suzanne Pingree, Eric W. Boberg, Christi A. Patten, Kenneth P. Offord, Kelly L. Berry, David H. Gustafson. (2002) Development of a Tailored, Internet-based Smoking Cessation Intervention for Adolescents. Journal of Computer-Mediated Communication 7:3, 0-0
CrossRef22
Kazim Husain, Benjamin R. Scott, Sathya K. Reddy, Satu M. Somani. (2001) Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system. Alcohol 25:2, 89-97
CrossRef23
Cheryl Alexander, Marina Piazza, Debra Mekos, Thomas Valente. (2001) Peers, schools, and adolescent cigarette smoking. Journal of Adolescent Health 29:1, 22-30
CrossRef24
Myers, Matthew L., . (2000) Protecting the Public Health by Strengthening the Food and Drug Administration's Authority over Tobacco Products. New England Journal of Medicine 343:24, 1806-1809
Full Text25
Peggy M. McCarthy, Nadine C. Jelsing. (2000) An advocacy perspective on screening and early diagnosis of lung cancer. Cancer 89:S11, 2510-2514
CrossRef26
Gary M. Strauss, Lorenzo Dominioni. (2000) Perception, paradox, paradigm. Cancer 89:S11, 2422-2431
CrossRef27
Peggy M. McCarthy, Nadine C. Jelsing. (2000) An advocacy perspective on screening and early diagnosis of lung cancer. Cancer 89:S11, 2510-2514
CrossRef28
Gary M. Strauss, Lorenzo Dominioni. (2000) Perception, paradox, paradigm. Cancer 89:S11, 2422-2431
CrossRef29
Peggy M. McCarthy, Nadine C. Jelsing. (2000) An advocacy perspective on screening and early diagnosis of lung cancer. Cancer 89:S11, 2510-2514
CrossRef30
Gary M. Strauss, Lorenzo Dominioni. (2000) Perception, paradox, paradigm. Cancer 89:S11, 2422-2431
CrossRef31
Peggy M. McCarthy, Nadine C. Jelsing. (2000) An advocacy perspective on screening and early diagnosis of lung cancer. Cancer 89:S11, 2510-2514
CrossRef32
Gary M. Strauss, Lorenzo Dominioni. (2000) Perception, paradox, paradigm. Cancer 89:S11, 2422-2431
CrossRef33
Peggy M. McCarthy, Nadine C. Jelsing. (2000) An advocacy perspective on screening and early diagnosis of lung cancer. Cancer 89:S11, 2510-2514
CrossRef34
Gary M. Strauss, Lorenzo Dominioni. (2000) Perception, paradox, paradigm. Cancer 89:S11, 2422-2431
CrossRef35
John E. Calfee. (2000) The Historical Significance of Joe Camel. Journal of Public Policy & Marketing 19:2, 168-182
CrossRef36
Jack E. Henningfield, Tula Michaelides, Steve Sussman. (2000) Developing Treatment for Tobacco Addicted Youth–Issues and Challenges. Journal of Child & Adolescent Substance Abuse 9:4, 5-26
CrossRef37
William G. Shadel, Saul Shiffman, Raymond Niaura, Mark Nichter, David B. Abrams. (2000) Current models of nicotine dependence: what is known and what is needed to advance understanding of tobacco etiology among youth. Drug and Alcohol Dependence 59, 9-22
CrossRef38
JACK E. HENNINGFIELD, REGINALD V. FANT, JOSEPH GITCHELL, SAUL SHIFFMAN. (2000) Tobacco Dependence: Global Public Health Potential for New Medications Development and Indications. Annals of the New York Academy of Sciences 909:1, 247-256
CrossRef39
David T. Sweanor. (1999) Policy Options to Reduce Tobacco-Caused Mortality. Journal of Addictive Diseases 18:3, 1-11
CrossRef40
L C An, P M O'Malley, J E Schulenberg, J G Bachman, L D Johnston. (1999) Changes at the high end of risk in cigarette smoking among US high school seniors, 1976-1995.. American Journal of Public Health 89:5, 699-705
CrossRef41
Jack Henningfield, Reginald Fant. (1999) Tobacco use as drug addiction: The scientific foundation. Nicotine & Tobacco Research 1:1, 31-35
CrossRef42
Gary Giovino. (1999) Epidemiology of tobacco use among US adolescents. Nicotine & Tobacco Research 1:0, S31-S40
CrossRef43
J L Forster, D M Murray, M Wolfson, T M Blaine, A C Wagenaar, D J Hennrikus. (1998) The effects of community policies to reduce youth access to tobacco.. American Journal of Public Health 88:8, 1193-1198
CrossRef44
Jean L. Forster, Mark Wolfson. (1998) YOUTH ACCESS TO TOBACCO: Policies and Politics. Annual Review of Public Health 19:1, 203-235
CrossRef45
Jack E. Henningfield, Lakshmi Gopalan, Saul Shiffman. (1998) Tobacco dependence. Current Opinion in Psychiatry 11:3, 259-263
CrossRef46
Martin J. Jarvis, Gay Sutherland. 1998. Tobacco Smoking. , 645-674.
CrossRef47
S L Tomar, G A Giovino. (1998) Incidence and predictors of smokeless tobacco use among US youth.. American Journal of Public Health 88:1, 20-26
CrossRef48
K Atwood, G A Colditz, I Kawachi. (1997) From public health science to prevention policy: placing science in its social and political contexts.. American Journal of Public Health 87:10, 1603-1606
CrossRef49
(1997) The Food and Drug Administration's Regulation of Tobacco Products. New England Journal of Medicine 336:12, 880-882
Full Text50
Annas, George J., . (1996) Cowboys, Camels, and the First Amendment — The FDA's Restrictions on Tobacco Advertising. New England Journal of Medicine 335:23, 1779-1783
Full Text
- Letters
