Gio Batta Gori

Analytical cigarette yields as predictors of smoke bioavailability

The smoke intake of 865 undisturbed smokers of over 10 cigarettes per day was measured using plasma nicotine and cotinine, and expired carbon monoxide (CO) as markers. While nicotine yields, according to Federal Trade Commission (FTC) analytical standards, varied 16-fold from 0.1 to 1.6 mg/cigarette, the corresponding plasma nicotine values varied from around 25 to 45 ng/ml, and estimated mean nicotine intake of smokers varied from around 0.75 to 1.25 mg/cigarette. Expired CO and plasma cotinine values also varied in similar proportion, but mean daily cigarette consumption was independent of the FTC nicotine yield of the cigarettes smoked. The results indicate that pharmacodynamic satiation causes behavioral regulation, and that smokers of very high yield brands compensate downward, and vice versa. The ratio of tar yield to nicotine yield usually increases with increasing tar yield; therefore tar intake is likely to increase at higher tar yields, even though the increment of nicotine intake is small. It follows that FTC analytical determinations are poor predictors of relative intake of nicotine, CO, or tar, while rankings based on mean tar-to-nicotine ratio of a brands smoke could be more meaningful. Moreover, the considerable variation of individual smoking behavior suggests that precise numerical rankings of cigarettes are not justified. An analogic ranking of cigarettes into a few broad classes would better reflect the realities and expectations of average consumers.

Mouth versus deep airways absorption of nicotine in cigarette smokers

Nicotine from the alkaline smoke of cigars is absorbed through the buccal mucosa, but such absorption from the more acidic smoke of American cigarettes has not been reported. Forty-one male and 52 female smokers were studied under normal ventilation and smoking conditions, and under high ventilation and controlled smoking conditions that restricted intake to the mouth only, with no inhalation. The major finding is that there is virtually no intake of nicotine through the buccal mucosa while smoking American cigarettes. Confirming prior reports, plasma nicotine and expired CO levels showed no correlation with the analytical yields of nicotine and CO of the cigarettes smoked. Fifteen nonsmokers (7 male, 8 female) participated in this study as controls. Data from these subjects provided additional information regarding absorption of nicotine and carbon monoxide during passive smoking. Within the highly ventilated environment, there was no significant change of CO and nicotine levels of nonsmokers. However, within the normally ventilated environment, there was minimal increase in both substances, statistically significant only for nicotine. These results suggest that nicotine may be a better indicator of exposure to second-hand smoke than carbon monoxide.

Mainstream and environmental tobacco smoke

Environmental tobacco smoke (ETS) is derived from cigarette smoldering and active smoker exhalation. Its composition displays broad quantitative differences and redistributions between gas and respirable suspended particulate (RSP) phases when compared with the mainstream smoke (MSS) that smokers puff. This is because of different generation conditions and because ETS is diluted and ages vastly more than MSS. Such differences prevent a direct comparison of MSS and ETS and their biologic activities. However, even assuming similarities on an equal mass basis, ETS-RSP inhaled doses are estimated to be between 10,000- and 100,000-fold less than estimated average MSS-RSP doses for active smokers. Differences in effective gas phase doses are expected to be of similar magnitude. Thus the average person exposed to ETS would retain an annual dose analogous to the active MSS smoking of considerably less than one cigarette dispersed over a 1-year period. By contrast, consistent epidemiologic data indicate that active smoking of some 4-5 cigarettes per day may not be associated with a significantly increased risk of lung cancer. Similar indications also obtain for cardiovascular and respiratory diseases. Since average doses of ETS to nonsmoking subjects in epidemiologic studies are several thousand times less than this reported intake level, the marginal relative risks of lung cancer and other diseases attributed to ETS in some epidemiologic studies are likely to be statistical artifacts, derived from unaccounted confounders and unavoidable bias.

Smoker intake from cigarettes in the 1-mg federal trade commission tar class

Cigarette yields measured by the standard analytical procedures of the U.S. Federal Trade Commission (FTC) may not be sufficiently informative to smokers of low-yield brands because actual intake is likely to depend mainly on the aggressiveness of personal behavior. This study determined intake in smokers of 1-mg FTC tar class cigarettes, as they switched brands. Plasma cotinine levels, used as a marker of intake, spanned over a similar range of values from nondetectable to about 800 ng/ml in all brands tested. Pharmacokinetic considerations suggest that smokers of these brands--as a group--intake nicotine in excess of posted FTC values. However, mean values across smokers for each brand, as well as the brand differences in individual smokers, were closely proportional to the analytical differences of FTC nicotine yields for each brand smoked. Thus, standard analytical values may not predict absolute intake of smoke, but they appear to inform about the relative intake smokers can expect from different brands in the 1-mg FTC tar class.

Consumer Perception of Cigarette Yields: Is the Message Relevant?

Over 1200 randomly selected subjects from the U.S. and key European countries were interviewed by telephone, to establish how consumers perceive the meaning and relative value scale of tar yields of commercial cigarettes. Some 50% of respondents interpreted numerical tar yields as being precise quantitative predictors of intake related to health effects. A less precise quantitative intuition is shown by 20-30% of respondents. The remaining respondents had little or no interest in, or understanding of, tar yield meaning. Despite local differences, the aggregate responses from the U.S. were analogous to European responses and were not significantly affected by age, sex, or socioeconomic status. The results show that consumers expect a cigarette grading message predictive of actual intake from different brands. The current message based on standard analytical yields does not meet this requirement and needs modification. Cigarette ratings based on the tar-to-nicotine ratio of standard yields could offer the basis for an acceptable message.

Adjudicating cancer causation: Scientific, political, and legal confilicts

Lawsuits concerning cancer causation resort to scientific argumentation. Yet, the apparent ambiguities of science confuse the courts, the juries, and the public. This is especially so with regard to official regulatory definitions of cancer causation that carry the weight of law. At the heart of this problem is a prevailing misunderstanding of science and the scientific method, and of the limits of current scientific knowledge about cancer. Moreover, current regulatory policies encourage the public to perceive official cancer risk assessments as if they were scientifically derived and accepted, even though official fine print readily admits they are not. Some recent court decisions have begun to recognize these difficulties with a body of precedent, and this may result in future rulings influenced more by objective appraisals than by reliance upon official but contingent assumptions.

Economics and extended longevity: A case study☆

Preventive and therapeutic advances have brought life expectancy in the United States to well over 70 years and have shifted mortality causes from acute to chronic diseases, the determinants of which are genetics, lifestyle, the environment, and aging itself. Plausible approaches to chronic disease prevention are likely to increase longevity further, with some foreseeable effects on demographic and economic projections. Primarily, longevity advances would swell forecasts of population size, and would thus have to be met by production advances in order to maintain or improve living standards. This study, a restricted example, considers the probable demographic and economic consequences of a limited prevention program in the context of the Ford Motor Company, based on actual experience and certain expectations up to the year 2000. According to the results, prevention would reduce outlays for life insurance, disability, and health care, but would also generate the higher costs of extending pension plans. Undoubtedly, prevention will continue to be highly ranked in societys pursuit of happiness, and society must prepare to meet its effects with appropriate social and economic policies.

Open letter to the European Commission : scientifically unfounded precaution drives European Commission's recommendations on EDC regulation, while defying common sense, well-established science, and risk assessment principles

We, the undersigned editors of journals of pharmacology and toxicology, are drawing your attention to the imminent decisions by the European Commission to enforce a regulatory framework for so-called endocrine-disrupting chemicals (EDCs).1 The currently drafted framework is based on virtually complete ignorance of all well-established and taught principles of pharmacology and toxicology, of opinions raised by the European Commission’s own competent expert authority (European Food Safety Authority (EFSA 2013), and of critical statements made by member countries, while avoiding asking for support from the European Commission’s own scientific expert committees.

How sick a patient?: Report of a Workshop on Cancer Risk Assessment Rapporteurs

A report by the U.S. Government Office of Management and Budget (OMB) criticized the way health, safety, and environmental regulation of potential cancer causing substances is conducted by federal agencies, especially the Environmental Protection Agency. Cancer risk assessment--this report indicates--is governed by arbitrary policy assumptions and procedures improperly disguised as scientific and is designed to overestimate risk. Unwarranted economic burdens of ensuing regulation may then adversely affect standards of living and ultimately the very health and longevity that regulation is presumed to safeguard. An interdisciplinary workshop generally agreed with the OMB position and sharpened criticism of the procedures and scientific pretensions in the regulation of potential carcinogens. Various options for change were discussed, although it was felt that the success of detailed remedies would require a wider political, administrative, and scientific discourse.A report by the U.S. Government Office of Management and Budget (OMB) criticized the way health, safety, and environmental regulation of potential cancer causing substances is conducted by federal agencies, especially the Environmental Protection Agency. Cancer risk assessment--this report indicates--is governed by arbitrary policy assumptions and procedures improperly disguised as scientific and is designed to overestimate risk. Unwarranted economic burdens of ensuing regulation may then adversely affect standards of living and ultimately the very health and longevity that regulation is presumed to safeguard. An interdisciplinary workshop generally agreed with the OMB position and sharpened criticism of the procedures and scientific pretensions in the regulation of potential carcinogens. Various options for change were discussed, although it was felt that the success of detailed remedies would require a wider political, administrative, and scientific discourse.

Cancer risk assessment : the science that is not

Regulators have adopted the assumption of low dose linearity in cancer risk assessment, variously justified as scientifically correct and as responsible public health policy. Corollary assumptions are the one-molecule-one-hit hypothesis, the exclusion of no-effect thresholds, and the equivalency of response in experimental rodents and man. While our understanding of the carcinogenesis process remains tentative, these generalizations are not sustained by the limited scientific evidence available, not even as interim working hypotheses. In this light, they reflect a facile bureaucratic response to pragmatic demands borne of political perceptions, rather than the recognition of a complex and still opaque reality.