Carcinogenicity of cadmium in animals: What is the significance for man?

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Abstract
The carcinogenic potency of cadmium injected into rats and mice has been demonstrated 20 years ago. In contrast, chronic dietary intake of cadmium‐containing food by laboratory animals did not induce any tumors. With regard to inhalation of aerosols of different cadmium compounds, there is now an extensive data base which shows that inhaled cadmium does induce lung tumors in laboratory rats. Even the highly insoluble CdS was found to induce lung carcinomas in rats, although it appears at a first glance that higher inhaled concentrations of CdS are needed to give the same pulmonary carcinogenic response as inhaled CdCl2 or CdO dust. In fact, an exposure concentration‐lung tumor relationship for the rat can be established which can be transformed into a dose (in terms of cadmium per gram lung tissue)‐response curve for the rat by applying lung dosimetric principles. However, the question arises as to whether and how the results of the rat studies should be extrapolated to humans since chronic inhalation exposure of mice and hamsters to cadmium aerosols did not lead to a significant increase in lung carcinomas, and since the evidence of a pulmonary carcinogenic effect of inhaled cadmium in humans was termed limited. Such extrapolation to humans can be done by applying species specific (rat and man) pulmonary deposition and retention data for inhaled cadmium. Results from this extrapolation modeling show that the risk to humans for lung cancer from inhaled environmental cadmium is very low, but will increase significantly for highly polluted areas and at the workplace without protective measures. The question, however, of whether the human respiratory tract reacts more like that of a rat or that of a hamster and mouse is not answered by such extrapolation modeling. In order to answer this, more research about the carcinogenic mechanisms of cadmium is needed. Future studies may, therefore, include: the influence of Superoxide and hydroxyl radicals; the importance of metallothionein induction in cells of the respiratory tract; inhibition of DNA repair by cadmium; alteration of DNA‐protein interaction and gene expression; activation of oncogenes. In particular, the mechanism underlying the interesting finding of zinc‐cadmium antagonism in the pulmonary carcinogenesis of cadmium needs further attention. However, lacking the results of such mechanistic studies it is only prudent at present to regard all inhaled cadmium compounds as being carcinogenic for the human respiratory tract.