The author is Chairman of the European Independent Working Group on Environmental Tobacco Smoke and Lung Cancer whose report was released in May 1996. The report addresses the possible association between exposure to environmental tobacco smoke (ETS) and lung cancer in nonsmokers. The expertise within the Group was directly relevant to carcinogenesis, spanning molecular, genetic, biochemical, nutritional, statistical and clinical disciplines. The entire report is intended as a risk assessment, combining the analysis of hazard identification, exposure assessment, statistical associations and biological endpoint evaluation. The report of the Working Group is intented to add to the debate, in the hope that it will stimulate further research in this important area of science.The Working Group attempted to unify knowledge regarding exposure to ETS by drawing on as broad a base of scientific literature and scientific experience as possible. In this way a mature judgement can be made regarding an evaluation of the risk of lung cancer in populations exposed to ETS. The principal conclusions of the Working Group were: Exposure to ETS cannot be equated to active smoking. Ageing of ETS, adsorption onto surfaces and ventilation all operate to alter the composition of ETS. Mainstream tobacco smoke contains ~ 4000 chemical components, whilst ~ 50 have been detected in ETS. Extrapolation from active smoking to ETS exposure is therefore a fruitless exercise. Exposure to ETS should be regarded as a low-level exposure to a chemical mixture. The Working Group considered the 28 chemical constituents of ETS whose human exposure in the workplace is regulated by a threshold judgement. These constituents fall 10 to 1,000,000 times below occupational exposure thresholds for concern regarding health and safety. Lung cancer is not a single disease, but a multiplex of discrete histological diagnoses, with differential distributions by race and gender and differing treatment opportunities and clinical outlooks. These multiple diseases are likely to have multiple causes. Genetic susceptibility and refractiveness almost certainly play a role. The epidemiological studies, upon which previous risk assessments have largely been based, are of mixed quality. The Working Group reviewed the occupational, childhood and spousal exposure studies. The findings of the Working Group are entirely consistent with there being no elevated risk of lung cancer by exposure to ETS at work or in the home, either from a smoking parent or a spouse. Diet has a significant impact upon lung cancer risk, especially the consumption of fruits and vegetables which are rich in antioxidants. A poor diet is an important risk factor for many cancers, including lung cancer. Diet may also be a confounder in epidemiological studies of ETS and lung cancer and must be adjusted for to avoid artificially high relative risks. A plethora of dietary, psychosocial and behavioural factors differ between smoking and nonsmoking households which, if not adjusted for, will disguise the true relative risk of ETS for lung cancer. All nucleated mammalian cells possess an array of mechanisms for disposing of damaged genomes, including cell cycle arrest, apoptosis and DNA repair. Some common human cancers are associated with deficient DNA repair and thus optimal DNA repair may be essential for preventing cancer induction. Most animal carcinogen bioassays have been carried out using doses of genotoxic agents some 100 to 10,000 times greater than human exposure levels. Evidence suggests that DNA repair is more efficient at low levels of genotoxicity and, moreover, repair processes are commonly more efficient in human cells compared with rodents. Evidence is accumulating with several genotoxic agents that a nonlinear threshold model best describes the dose-response relationship. Low dose exposure to chemicals and chemical mixtures such as ETS shares much in common with low-level radiation exposure, for which the latter provides an appropriate model. Studies on the Japanese atom bomb survivors and on nuclear industry workers provides compelling evidence of hormesis, the beneficial effects to health of low doses of an agent which is harmful at high doses. Based upon this and other evidence, there have been moves to modify radiation protection regulations by the introduction of threshold radiation doses and a "zero equivalent point" for triage in nuclear disasters. Other types of genotoxic agents, such as chemicals, should in principle display hormesis. Chemical hormesis, by definition, implies a threshold in the dose-toxic response relationship. The Working Group considered that the concentration of the chemical constituents of ETS is below a threshold for lung cancer, a finding consistent with the epidemiological data. Whilst strongly endorsing the need to protect public health, the Working Group wished to see a sensible policy towards chemical hazard regulation based upon new paradigms for risk evaluation which take account of the burgeoning data on host defence mechanisms and of both the experimental and epidemiological investigation of low-level chemical exposures, i.e. the weight of evidence. It is both fruitless and frivolous to continue restating that all animal carcinogens are carcinogenic to man, no matter how low the dose. The public interest may be better served by the evolution of regulatory systems which take account of the contemporary data.Having unified the data from a broad area of science, the Working Group made an assessment of the risk of lung cancer from exposure to ETS as follows: There is insufficient evidence from the epidemiological studies performed to date that ETS is a human lung carcinogen. There is insufficient evidence from animal studies that ETS is a lung carcinogen in animals. There is insufficient evidence that the chemical constituents of ETS which are lung carcinogens when administered at high doses to animals reach concentrations sufficient to cause excess mortality from lung cancer in humans. There is insufficient evidence that the relatively small number of known ETS constituents, at the concentrations in which they are found in ETS, adds significantly to the toxic burden of the huge number of environmental chemicals to which human populations are exposed through the diet, fragrance chemicals, agrochemicals, drinking water and outdoor air pollution. Having considered the weight of evidence, it was the judgement of the Working Group that environmental tobacco smoke is not a primary lung carcinogen.