Epidemiology The Case For Metals And Cancer

Numerous epidemiological studies have examined the effects of metals on human cancer. The first epidemiological studies linking metals and human cancer date from the early 1900s.7 Based on available epidemiological data, a number of government agencies— including the U.S. Environmental Protection Agency, the Occupational Safety and Health Administration, the National Institute for Occupational Safety and Health, and the National Toxicology Program, as well as nongovernmental advisory organizations such as the American Conference of Governmental Industrial Hygienists and the International Agency for Research on Cancer—have classified metals with regard to their carcinogenicity in humans. Although there is some disagreement among these organizations as to the carcinogenic potential of specific metal compounds, there is general agreement among them that a given metal (chromium, for example) may occur in carcinogenic forms. Table 3.1 lists the metals and metalloids that have been positively identified as human carcinogens by one or more of these organizations, as well as the metallic form involved, the organ sites they affect, and the relative risk of lung cancer (the most common form of metal-induced cancer) associated with each metal/metalloid.

Relative risk is an epidemiological estimate of the fold increase in risk for a particular disease compared with the general population. Relative risk also serves as a means of comparison among factors associated with a particular disease. Based on current data, the relative carcinogenic potential of the seven metals implicated as human lung carcinogens is as follows: arsenic>chromium> nickel>beryllium and cadmium>lead>cobalt.

One of the greatest difftculties for the epidemiologist studying metal-related cancer is the determination of the risk associated with a single metal or metal compound. Multiple types of metals, or multiple forms of a single metal, are often present in an industrial work environment. For example, welders may be exposed to fumes containing mixtures of iron, chromium, nickel, and manganese, whereas workers in copper or lead smelting plants may also be exposed to significant quantities of arsenic. In addition, persons who work with metals may be exposed to other cancer-causing agents, such as asbestos and cigarette smoke.13 These factors, especially cigarette smoking, may play an additive or synergistic role in cancer causation. It is interesting to note that cigarettes, the major cause of human lung cancer, contain a number of carcinogenic metals, including cadmium, arsenic, nickel, and chromium, and are associated with a five-fold increase in the risk of lung cancer, higher than any single metal.15 The result of these multicarcinogen exposures is that it is generally possible to identify specific metals and metal compounds as human carcinogens, but more difficult to quantify the level of risk associated with a given metal species.

Animal studies have been used to determine the relative carcinogenic potential of various metal species. Because traditional in vitro methods of determining mutagenic or carcinogenic potential, such as Ames testing, do not consistently identify metals as mutagens, animal studies are especially important to determine the relative carcinogenic potentials of metals. An advantage of animal studies is that they allow for the use of single metals or mixtures of known composition and concentration. The disadvantage of animal studies of metal-induced cancer is that they do not always reflect what has been observed in human epidemiological studies. This is especially true for arsenic, which has been associated with human carcinogenesis for more than a century, but which, in animals, does not produce the same lesions

TABLE 3.1 Metal and Metalloid Forms Positively Identified as Human Carcinogens



Forms Considered Human Carcinogens elemental arsenic; inorganic arsenic compounds

Target Organs Relative Lung Cancer Riska lung, skin, kidney, bladder, liver, lymphoma, leukemia

Beryllium Cadmium

Chromium pure metal; alloys lung dust and fumes; carbonate, chloride, lung, prostate fluoroborate, nitrate, oxide, sulfate, and sulfite forms

Cobalt Lead chromium metal; chromite (mineral form); chromic acid; hexavalent (chromate) compounds; carbamate, phosphate, and triacetate forms chromium/cobalt alloys chromate and phosphate compounds lung, nasal passages

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