Bioassay of metals for carcinogenesis: whole animals

Metals have been evaluated as potential carcinogens by administering pure elements or compounds by a large variety of routes. These include mixing the agent in the food, dissolving the test compound in the drinking water, or administering the material by gavage. The respiratory tract routes tested include inhalation, intratracheal instillation, the direct injection of particulates into the pleural cavity, or the implantation of hooks by surgical intervention. The parenteral routes used were intravenous injection, intraperitoneal injection, subcutaneous implantation, as well as intrafemoral and intramuscular injection. This latter route is the most commonly used. There are major objections to the subcutaneous implantations route, and data generated from these experiments are difficult to interpret for the foreign body reaction may give rise also to fibrosarcomas. This then is a nonspecific reaction. Exotic routes tested include intrarenal, intratesticular, and intracranial injections. The endpoints of the carcinogenic reactions are, in the main, sarcomas of certain types with fibrosarcomas predominating. Rhabdomyosarcomas are the next most frequent cancer found, and squamous cell carcinoma may account for less than 2% of the cancers reported. Much more research is necessary to clarify the nature of metal carcinogenesis. Dose-response information is almost nonexistent; the divided dose problem has not been studied adequately, and very little information is available on interspecies reactions. More work is needed to help interpret the mechanism of action.