Role of metals in carcinogenesis. Problems of epidemiological evidence.

Abstract

Problems associated with the use of epidemiological evidence to evaluate the carcinogenicity of metals are, in the main, those associated with epidemiological enquiry in general. There are, however, some additional difficulties that arise from the variety of ways in which exposure to metals can occur, the variety of metal species and compounds, and the frequency of mixed exposure. We shall, therefore, review some of these problems, and the ways in which they can be overcome, before reviewing the evidence relating to individual elements.One of the greatest difficulties is to obtain a population for study that is large enough to distinguish the effects of a specific hazard from the effects of the random variation of small numbers or alternatively to be confident that no material risk exists, when negative results are obtained (the problem of statistical power and its relation to sample size). These cannot always be overcome by increasing the size of the population, as the number of people exposed to high concentrations of the agent may be small and extension of the study to include larger numbers will only dilute the results, if the additional subjects have not been intensively exposed. In studies of cancer, there is also the problem that the first ten years after exposure to a carcinogen seldom provide much evidence of risk. Longer periods, even 30 years or more, may be required before the existence of a risk can be properly assessed, and the inclusion of large numbers of subjects who have been observed for only a short period will serve to dilute the results still further. The analysis should, therefore, be identified whenever possible, both by intensity of exposure and by length of time since exposure began.The exact nature of past exposure at the workplace is often difficult to determine and, in the case of exposure to metals, may be quite complex. Little * This section was prepared by a Workgroup chaired by Sir Richard Doll (University of Oxford, England). Other members of the workgroup were:

Squamous cell carcinoma of the palm in Nigeria

“…[ 16 ] On considering the problems associated with the use of epidemiological evidence with respect to chemical exposures, Doll et al . who dealt with the carcinogenicity of metals, stated that “there is a need to study dose-response relationships for arsenic in water and skin cancer.”[ 17 ] To our knowledge, such research is not being carried out in Nigeria.…”

Occupational health assessment of chromite toxicity among Indian miners

“…Hexavalent chromium compounds have been confirmed to be carcinogenic on the basis of epidemiologic investigations of workers and of experimental studies with animals. [ 26 27 ] Continuous inhalation of hexavalent chromium compounds increases the risk of lung cancer,[ 28 ] with the amount of hazard depending on the particular salts and their solubility under biological circumstances, and on long-term exposure to inhaled tobacco smoke from cigarettes. [ 29 ] Epidemiologic studies conducted in the USA 40 years ago, demonstrated a 10 to 30 fold- increased risk of lung cancer among workers of the chromate industry compared to the general population.…”