Contribution to the toxicological study of inhaled cadmium compounds at the rat

Our period of probation was performed in the Experimental Cancerology Laboratory which is a laboratory depending from the Life Sciences Directory from French Atomic Commission. The role of this laboratory is to characterize the short, middle and long term effects of irradiation acting alone or associated with exposure to airborne pollutants. This period of probation allowed us to approach different aspects of animal experimentations, cytological and histological techniques and Atomic Absorption Spectrometry especially applied in short and long term assays. Long term studies were performed on Sprague Dawley male rats which showed several advantages; first, similar pattern of spontaneous tumors compared to human; second, low incidence of spontaneous lung tumors (<1 %); third, because the high frequency of radio-induced mammary tumors in female rats and their metastases to the lungs, male rats were only studied. Animals were whole body irradiated by exposure to fission neutrons (0.6 Gy). Irradiated or unirradiated rats were exposed to cadmium chloride (0.7 mg/m³, 5 days a week, 6 hours a day, during 5 weeks). One group corresponded to cadmium exposed animals which was treated by repeated intramuscular injections of 5-6 benzoflavone (25 mg/Kg, 6 injections at 2 weeks interval). The last groups were rats administrated cadmium hydroxide (10 and 50 mg/Kg) by intramuscular injection in the posterior leg. Our participation was limited to animal care, autopsy and necropsy, tissue sampling and processing until paraffin embedding. Preliminary results show no carcinogenic or co-carcinogenic effect of cadmium excepted after its intramuscular administration. Short term studies have concerned metabolism and toxicity of different inhaled cadmium compounds. Chloride, oxide and sulfide have shown a different biological behaviour. Oxide was readily solubilized and transferred to other parts of the organism as many as five times more than the chloride soluble form. Such phenomenon was observed at subtoxic doses and transfer from oxide decreased for toxic doses as the initial lung deposit increased. Macrophages were not a site for retention of inhaled cadmium under the chloride or oxide forms. A mixed behaviour was observed for cadmium sulfide. About half of the initial lung deposit was readily solubilized and the other half remained mostly as particles in alveolar macrophages. Most of these results were obtained from Atomic Absorption Spectrometry measurements. Cytological studies have shown that the minimal initial lung deposit inducing inflammatory reaction was higher for chloride than for oxide. Alveolar macrophages toxicity decreased gradually from oxide to sulfide and chloride, and was visualized by the appearance of multinucleated cells, micronuclei and cytoplasmic alterations. Particles were only observed after sulfide exposure and even 24 hours after inhalation, many free particles were observed associated to macrophage necrosis. A huge increase of macrophage proliferation was induced by cadmium and was observed for oxides doses which were not associated with any inflammatory reaction. This results suggest that cadmium alone could induce an increased cell proliferation. Target organs for toxic effects appear to be the lungs and the kidney after exposure to chloride and oxide respectively. However, alveolar macrophage is the main target cell after oxide or sulfide inhalation. These data were obtained by using cytological and immunocytological methods. (author)