Biomedical subjects
G B Gori
Publications and source records attributed to G B Gori.
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.
How sick a patient? Report of a workshop on cancer risk assessment.
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.
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.
Are animal tests relevant in cancer risk assessment? A persistent issue becomes uncomfortable.
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Adjudicating cancer causation: scientific, political, and legal conflicts.
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.
Time for cigarette reclassification?
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Of Lucy, diet, fiber, and white horses...
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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.
Cigarette classification as a consumer message.
Cigarette yields of tar, nicotine, and carbon monoxide, obtained by standard smoking machine procedures, have been adopted as official consumer information throughout the world. However, real-life dynamics of cigarette puffing and inhalation are not standard, but follow widely fluctuating individual behavior. In addition, smokers inhale after puffing, an event that standard smoking machines do not address. Clearly then, analytical cigarette yields alone are insufficient as quantitative predictors of smoke intake valid for all smokers. Bioavailability studies show that virtually all cigarettes, regardless of analytical yield, can satisfy the nicotine demand of any smoker. On the other hand, tar intake and nicotine intake are related according to the tar-to-nicotine ratio of the smoke, which varies with brands. Thus, while a generalized message predictive of quantitative individual intake is not feasible, tar-to-nicotine ratios of standard analytical yields tell any smoker about expectations of proportional tar intake from different brands, and should be adopted as the preferred consumer message.
Epidemiology and the concept of causation in multifactorial diseases.
Unlike infectious diseases of the past, diseases prevalent in modern industrialized societies have multifactorial origins whose complexity so far has defied an integrated scientific understanding. Their epidemiologic investigation suffers from the conceptual inability of formulating plausible causal hypotheses that mimic a complex reality, and from the practical difficulties of running elaborate studies controlled for multifactorial confounders. Until biomedical research provides a satisfactory understanding of the complex mechanistic determinants of such diseases, epidemiology can only field reductionist causal hypotheses, leading to results of uncertain significance. Consensual but rationally weak criteria devised to extract inferences of causality from such results confirm the generic inadequacy of epidemiology in this area, and are unable to provide definitive scientific support to the perceived mandate for public health action.
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.
Decline of U.S. cancer mortality rates: expert estimates of past underreporting.
Regulatory and public health policies in the United States are predicated on the uncritical acceptance of an alleged explosion in cancer mortality rates. In reality, several studies offer evidence that cancer mortality went underreported as one goes back in time, due to progressive deficiencies in diagnostic and registration practices. Because the absence of historical records precludes a comprehensive direct verification, a group of experts were polled to estimate the impact of this bias on U.S. cancer mortality statistics. The nature of this exercise speaks against a numerical interpretation of the results; however, their broad analogic meaning suggests that age-adjusted mortality and probably the incidence of leading cancers have significantly declined for decades, with the major exception of respiratory tract cancers.
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 brand's 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.
Development of less hazardous cigarettes.
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Dietary and nutritional implications in the multifactorial etiology of certain prevalent human cancers.
It has been estimated that 80--90% of the cancer rate in the U. S. can be attributed to environmental factors. For the last 20 years the role of smoking has been recognized by the scientific community. However it is only recently that the role of diet, i.e., food and beverages in carcinogenesis has begun to be recognized. It is likely that diet is more important than smoking in cancer causation. Both human and animal studies support this assumption. The study of special populations in the U. S. such as the Mormons and the Seventh Day Adventists also point to the potential of reducing U. S. cancer rates and individual risk factors through the modification of dietary habits. The major hypotheses of the role of dietary and nutritional factors in cancer etiology are examined in light of current scientific knowledge. General guideline for the reduction of risk from the major chronic diseases are also discussed.
Reduction of carbon monoxide in cigarette smoke.
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