The costly illusion of regulating unknowable risks.

Uncommon but alarming man-made toxic episodes have occasioned regulation to ensure the safety of novel and commonly used substances and foremost to control agents that may cause cancer. However, the safety or harm of novel entities has no durable record of human use, and hence is virtually unknown. Compelled to act, regulators have chosen animal tests to forecast human cancer risks. To this end, animal data are filtered through a series of preconceived assumptions that are presumed to overcome a host of human/animal differences of biology, exposure, and statistics-differences that in reality are insurmountable. Asked for authoritative opinion, the National Academy of Sciences repeatedly found this regulatory approach without factual or scientific justification and, by implication, arbitrary and irrational. On these grounds, such a regulatory process appears vulnerable to scientific, legal, and constitutional challenges. Although it cannot provide credible assurance that an agent may be safe or harmful, the process has been a prime reason for an annual regulatory burden that exceeds the combined after-tax profits of all U.S. industrial activity. It is argued here that better use of national resources would come from a rational approach based on trade-off considerations, where a substance would be regulated depending on its socio-economic utility and on scientific evidence of proved relevance to human safety.

Presentation: Epidemiology and public health: is a new paradigm needed or a new ethic?

Public health militancy has been increasingly frustrated by what many perceive as the marginally fertile studies of risk factors operating at the individual level, whose causal underpinnings are often and inevitably weakened in multifactorial situations. As a remedy, leading advocates propose a refocusing of epidemiology and public health on socioeconomic, cultural, and political studies, and on broad interventions at population level. This new "paradigm" would be aided by a relaxation of evidentiary standards of causality, away from scientific criteria and more toward dialectic (rhetorical) precepts derived in a humanistic and sociologic tradition. It is countered here that such proposals would further reduce the objectivity and thus likely weaken rather than strengthen epidemiology and the justification of public health action. Instead, a realistic appraisal finds that multifactorial epidemiology raises warning signals of varying influence, and that the usefulness of epidemiology and public health could be enhanced by conceiving of methods to score the relative strength and priority of such warnings.

Science, imaginable risks, and public policy: anatomy of a mirage.

Experimental predictivity, qualified by probability criteria, is the test that enables scientific inferences of causality and objective statements of fact. Yet, especially during this century the rational discipline of science has been assailed as arrogant by a rising fashion of intellectual laissez faire. In this ambiguous climate, health risk claims that are void or extremely weak in factual content are represented as if scientifically objective and forced at all levels of policy deliberations, especially in cancer risk assessment. Such pretensions deny essential guarantees of public fairness and undermine the credibility of science.

Environmental tobacco smoke and coronary heart syndromes: absence of an association.

Concerns about possible cardiovascular and especially coronary effects of environmental tobacco smoke (ETS) derive from the reported effects of active smoking. Despite similarities, however, ETS has composition and physical characteristics different from the mainstream smoke (MS) that active smokers inhale and appears relatively more chemically inert and less biologically active. ETS doses to nonsmokers are small and often below the sensitivity of detection technologies. They are several orders of magnitude less than MS doses in active smokers. Numerous epidemiologic studies report that the active smoking of less than 10 cigarettes/day is not associated with measurable risk of coronary heart disease (CHD). Thus, even assuming that ETS and MS have equivalent biologic activities, conceivable ETS doses to nonsmokers are far below apparent no-effect thresholds for active smoking. Hence, it is no surprise that epidemiologic reports are inconclusive about a possible association of ETS exposure and CHD, some suggesting a slight elevation, others a reduction of risk. Often, the elevations reported are higher than the CHD risk values associated with active smoking. Such equivocations likely result from the presence of contrasting protective or aggravating confounders, of which more than 200 have been reported in the literature--confounders that were not and could not be adequately controlled by any epidemiologic study. By scientific standards, the weight of evidence continues to falsify the hypothesis that ETS exposure might be a CHD risk factor.

Environmental tobacco smoke: experimental facts and societal issues.

Involuntary exposure to environmental tobacco smoke (ETS) in public or in working places is considered to be a serious risk to human health. This symposium addressed several issues of toxicological interest that are associated with exposure to ETS. Epidemiologic evidence obtained in human studies suggests that "passive smoking" increases the risk of developing lung cancer in nonsmokers and favors the development of respiratory tract infections in children. Comparatively few data are available from animal studies that provide experimental support of the observations. Exposure of pregnant or neonate rats to cigarette sidestream smoke (SS) affects developmental patterns of drug metabolizing enzymes that may persist up to 90 days. In young roosters, SS accelerates the development of arteriosclerotic plaques. On the other hand, exposure of adult rats for up to 90 days induces only transient signs of damage in the nasal passages, but not in the deep lung, and this only at extremely high concentrations of ETS. So far, experimental toxicology has provided comparatively few data on the correlation between exposure to ETS and adverse health effects. yet, such data are needed, particularly since many conclusions drawn from the epidemiological studies remain open to criticism and questions.

Science, policy, and ethics: the case of environmental tobacco smoke.

The successful campaign against smoking will long be celebrated as a landmark achievement of public health. Recently, a prominent component of this campaign has been the portrayal of environmental tobacco smoke as a major health risk. To this day, however, the scientific basis for this later contention remains speculative. The elevation of heuristic hypotheses into official precepts raises an intriguing ethical question: Should a claim of best intentions justify representing conjecture as scientific knowledge in public policy formulation?

Whither risk assessment? An overall perspective.

Major regulatory initiatives in health and safety are increasingly viewed as too costly, not objectively justified, and thus failing in their mandate to ensure a fair social distribution of rights and burdens. Official but arbitrary assumptions in cancer risk assessment and open-ended statutory language encourage regulatory agencies to overregulate. Also, institutional self-serving motivations of regulatory agencies add incentives to expand regulation. Mitigation of the current regulatory crisis may come from curbing these selfish incentives, and from requiring that regulation be justified on the basis of strict scientific standards of evidence, rather than on arbitrary assumptions and conjectures.

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.