Cancer and the Workplace
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CA Cancer J Clin 1996;46:70-92 Cancer and the Workplace Jeanne Mager Stellman, PhD Steven D. Stellman, PhD, MPH Introduction makes to the total cancer burden, recog- Although occupationally related cancers nition and concern for cancers related to make up only a small fraction of all can- workplace exposures have been central cers, many environmental carcinogens themes in control of environmental car- have first been discovered in occupation- cinogens. There are several good reasons al settings. The estimate typically found for this. One is the unique nature of the in the scientific literature is that about workplace, which serves as a focal point two to eight percent of all human cancers in which large numbers of people may are of occupational origin.1 However, by be exposed to high concentrations of averaging the unexposed population in chemicals or other hazardous situations. with the exposed, such estimates tend to Another is that the very nature of work obscure the heavy toll that occupational creates a cohort for the kinds of epidemi- cancer can take on specific populations of ologic studies described below that can exposed workers. Among persons actual- help establish a cause-effect relationship ly exposed to carcinogens at work, risk es- between an environmental exposure and timates are much higher. For instance, cancer. It is because of the exposures to Morabia et al2 have put the attributable large doses and the opportunities to im- risk for lung cancer at 9.2 percent for men plement effective procedures for risk as- employed in occupations characterized sessment and control in the workplace by exposure to established carcinogens. that the study of occupational cancer For bladder cancer, the population attrib- plays so important a role in the control of utable risk from occupational exposures cancer in general. may exceed one case in five for men3 and Finally, perhaps the most important one in ten for women.4 reason to identify occupational carcino- Indeed, despite the relatively small gens and to elucidate their role in cancer “contribution” that occupational cancer causation is that occupational cancers are, for the most part, entirely pre- Dr. Jeanne Stellman is an Associate Professor of ventable through appropriate engineer- Clinical Public Health in the Division of Health ing, personnel practices, and strict gov- Policy and Management in the School of Public ernmental protective legislation. Health at Columbia University in New York, New The ultimate goal of collecting, eval- York. uating, and disseminating data on car- Dr. Steven Stellman is Chief of the Division of cinogenicity of occupational exposures is Epidemiology at the American Health Foundation in New York, New York. to develop strategies for prevention of disease. The most efficient strategy relies This work was supported in part by National Cancer Institute grants CA-17613, CA-63021, CA-68384, on primary prevention, that is, identifica- and CA-32617. tion and elimination of sources of expo- 70 Ca—A cancer Journal for Clinicians CA Cancer J Clin 1996;46:70-92 sure. Secondary prevention through timately presented as monographs, each screening of asymptomatic illness plays a of which contains a critical evaluation of lesser role, but may still be valuable in the carcinogenicity of one or more target specific workplaces. Recent advances in exposures. The evaluations take into ac- molecular biology have led to identifica- count many different types of informa- tion of tests that can identify workers ex- tion, including data from epidemiology, posed to various carcinogens. Such tests, experimental studies on rodents and oth- however, are at present extremely expen- er laboratory animals, in vitro studies sive, and their predictive value is no where appropriate, and other relevant greater than that of traditional industrial data including toxicity, metabolism, hygiene workplace evaluations. Occupa- genotoxicity, and metabolic studies. tional screening may have its greatest According to the IARC, “Each usefulness as a tool for educating workers monograph consists of a brief description to potential hazards in the workplace. of the chemical and physical properties of the agent; methods for its analysis; a description of the methods and volumes Identifying Human Carcinogens of production and use; data on occur- Despite the fact that more than six mil- rence and human exposure; summaries lion chemicals have already been identi- of case reports and epidemiologic studies fied and registered with the Chemical of cancer in humans; summaries of ex- Abstracts Service and more than 50,000 perimental carcinogenicity tests; a brief are estimated to be regularly used in com- description of other relevant biologic merce, probably fewer than 1,000 chemi- data, such as toxicity and genetic effects, cals or exposure situations have been that may indicate its possible mechanism scrutinized as to their potential for cancer of action; and an evaluation of its car- causation.5 Even so, the literature on cinogenicity.”6 Because the IARC peri- evaluation of cancer risks for even this odically revises its evaluations to reflect small fraction of known exposures is mas- accumulation of new data and evolution sive and not altogether consistent for of methods of assessment, the informa- many specific substances. Estimation of tion in these monographs is generally actual cancer risks to humans requires current and forms the basis of the sum- careful sifting and evaluation of large mary tables in this paper. quantities of data from many different studies. Since the early 1970s, an exten- Categories of Carcinogenicity to sive effort has been made to systematize the available data on cancer risks. A com- Humans prehensive methodology for assessment The IARC classifies the evidence for car- of human cancer risks has been devel- cinogenicity of specific exposures into oped by the International Agency for Re- four categories: sufficient, limited, or in- search on Cancer (IARC) that draws on adequate evidence of carcinogenicity or data from a variety of disciplines. evidence suggesting lack of carcinogenici- The IARC methods, which are ty. Sufficient evidence of carcinogenicity widely regarded as definitive, rely on the implies that a causal relationship has judgment of internationally recognized been established between exposure to the experts. Groups of scientists with exper- agent, mixture, or exposure circumstance tise in various disciplines are convened to and human cancer and that chance, bias, discuss and summarize the literature on and confounding have been ruled out individual carcinogens, groups of related with reasonable confidence. carcinogens, or in some cases entire in- Limited evidence of carcinogenicity dustries. These critical evaluations are ul- implies that a positive association has Vol. 46 No. 2 March/April 1996 71 Cancer and the workplace been observed between exposure to the vided into Group 2A, probably carcino- agent, mixture, or exposure circumstance genic to humans, and Group 2B, possibly and cancer for which a causal interpreta- carcinogenic to humans. These catego- tion is considered to be credible, but rizations take explicit note of the rele- chance, bias, or confounding cannot be vance of animal studies to human cancer ruled out with reasonable confidence. risk and are most often used to classify Inadequate evidence of carcino- substances for which human data may be genicity means that the available studies limited or inadequate but where animal are of insufficient quality, consistency, or data are deemed sufficient and mechanis- statistical power to permit a conclusion tically relevant to humans (Group 2A) or regarding the presence or absence of a less than sufficient but strongly support- causal association or that no data on can- ive of existing human data (Group 2B). cer in humans are available. The seemingly large number of Evidence suggesting lack of carcino- agents denoted as carcinogenic or proba- genicity means that there are several ade- bly carcinogenic (Groups 1 and 2A, quate studies covering the full range of N=117) is a reflection of the selection exposure levels that human beings are process for inclusion in the monographs. known to encounter that are mutually Agents are generally evaluated only when consistent in not showing a positive asso- substantial data bases already exist. These ciation between exposure to the agent data bases, in turn, have usually evolved and the studied cancer at any observed over a period of years in response to con- level of exposure. cerns of industry, workers, or the public. Tables 2 and 3 present the IARC Mono- Criteria for Evaluating graph groupings of known and probable Carcinogenicity Based on Total human carcinogens (Groups 1 and 2A) and typical uses or occurrences.7 Table 4 Evidence summarizes occupational exposure situa- A set of criteria analogous to those for as- tions that have been classified as falling sessing risk in human studies is used to into Groups 1, 2A, and 2B. classify cancer risk even when definitive human data are not available. This Some Examples of Exposures and process takes into account information from carcinogenesis bioassays and other Controls in Health Care experimental studies of animals along The history of occupational cancer identi- with toxicity and other biologic data. The fication and control has been recounted expert committee deliberations take into by many authors.8 The potential for account epidemiologic, animal, and other work-related cancers has been recog- types of data, including in vitro and meta- nized at least since the work of Ramazzini bolic studies where appropriate, from in the sixteenth century, and in fact our which an overall assessment of carcino- modern understanding of the influence of genicity to humans is synthesized within a environmental factors on human cancer scheme that consists of four broad is due in large measure to occupational groups. To date, 61 volumes of IARC studies, ironically many of them drawn Monographs have been published, and from the exposures of people in the 782 agents or exposure circumstances health care professions.