Effects of physico-chemical properties of actinide oxides on tumour induction after inhalation exposure in rats

This review described results obtained with new methods in authors' laboratory to measure dissolution parameters of inhaled actinide oxides and the distribution of α-delivered dose within lungs in relation to their tumor induction in rats. The oxides were industrial PuO2 (>50% of α, due to 238Pu), 237NpO2 and 2 different (U, Pu)O2 containing about 5% industrial Pu. The aerodynamic median activity diameter of their aerosols with authors' specific device measured with a cascade impactor were similar to each other (1.7-3.6 μm σg). Their chemical composition was characterized using scanning transmission electron microscopy by energy dispersive X-ray spectrometry on alveolar macrophages which had phagocytosed them. Measurements of dissolution parameters after inhalation exposure in the rat and after in vitro incubation respectively revealed that the fr values were in the range of 2 x 10-2-1 x 10-4, indicating oxides behaved as a type S compound, and that the values were quite different from those above, suggesting Ss should be considered as a variable for dose calculation, depending on time after inhalation. An autoradiographic method using solid tract detector and lung frozen sections revealed that aggeregations involving interstitial macrophages were often associated with fibrosis and/or preneoplastic lesions, which was explainable of a threshold in the dose-effect relationship for lung cancer occurrence. Results showed that, on inhalation of the oxides, risk assessment for lung tumor induction at low doses can not be extrapolated from that at high doses. (K.H.)