Long-Term Effects of Combined Exposure to Fission Neutrons and Inhaled Cadmium Chloride in Rats

Abstract

The results of several epidemiologic studies in the U.S.A. (Thun et al., 1985), Sweden (Elinder et al., 1985) and the U.K. (Kazantzis et al., 1992; Kazantzis and Blanks, 1992) have shown a significant excess of lung cancer in workers exposed to cadmium and its inorganic compounds, but only the study of Stayner et al. (1992) shows clear evidence of a dose-response relationship. Moreover, in some groups heavily exposed in the past to cadmium at indoor airborne levels of about 1 mg m~, only marginal or no excess of lung cancer were observed, despite marked nephrotoxicity. Long-term carcinogenesis studies following inhalation exposure to different cadmium inorganic compounds in different laboratory rodents showed some conflicting results according to animal species. All the experiments carried out in rats demonstrated an excess of lung cancer for cadmium oxide dust, cadmium sulphide, cadmium chloride and cadmium sulfate (Glaser et al., 1990), but two experiments using cadmium oxide fumes were negative. A significant excess of lung tumours was observed in mice exposed to cadmium oxide fumes and cadmium oxide dust, but not in those exposed to cadmium sulphide (Heinrich, 1992). By contrast, all experiments following inhalation exposure in hamsters failed to demonstrate any increased occurence of lung cancer (Heinrich et al., 1989), whatever the cadmium compound. The aim of the experiment reported here was to show whether cadmium chloride (CdCl2) acted, either as a complete lung carcinogen when inhaled alone during a short exposure period at dose levels similar to that encountered in industry in a recent past, or as a lung co-carcinogen in rats previously exposed to fission neutrons, irradiation acting then as an initiator, or as a lung co-carcinogen in rats exposed to cadmium chloride and treated after the end of inhalation by intramuscular injections of 5-6 benzoflavone (PNF) which has been previously demonstrated to be a specific promotor of experimentally induced squamous cell lung cancers in Sprague-Dawley rats (Morin et al., 1978).