Inhalation and Intravenous Studies of UF6/UO2F2 in Dogs

Nineteen UF6/UO2F2 inhalation studies were undertaken in purebred, female beagle dogs (N = 16) to examine inter alia, (a) the possible relations of exposure, whole body, lung and renal uranium levels to excretion rates; (b) the threshold U6+ dose and renal concentration for renal injury; (c) the distribution and retention functions for U6+ in major tissues; (d) biochemical indicators of renal injury; and (e) aspects of U-induced tolerance. Each of these issues was investigated in the context of the chemical toxicity of U6+ following brief exposures to 235UO2F2 in the presence or absence of HF (the decomposition products of 235UF6). Both gamma-(235U) and alpha-(234U) counting methods were applied. In nine studies on 5 dogs, UO2F2 was administered intravenously. The major findings from both types of studies include: (1) UO2F2 retention time in the lungs is shorter than for UO3 or uranyl nitrate, viz. greater than 80% translocated with T 1/2 of less than 20 min; (2) the urinary elimination of U6+ follows closely to the ICRP excretion equation; (c) an absorbed dose of approximately 10 micrograms U6+ kg-1 body weight appears to be effective in producing renal injury; (d) a renal concentration of 0.3 micrograms g-1 kidney is close to a threshold concentration for renal injury; and (e) urinary and blood biochemical changes and histopathologic data were acquired and evaluated in both novice and tolerant animals. This report, considers all of these objectives and findings: Those involving biochemical indices and uranium-induced tolerance will be more fully reported elsewhere. In general, the dog studies attest to the usefulness of the intravenous human studies for certain U6+ dose-response data and interface well with new retention data on intravenous uranyl citrate in dogs by Stevens et al.