Ruthenium-106 is a fission product radionuclide present in nuclear fuel cycles and has potential for release as ruthenium tetroxide. Ruthenium tetroxide is a vapor, diffuses rapidly in air and through porous barriers and is rapidly reduced to the dioxide form when in contact with organic compounds. The current ICRP model for inhaled particles does not predict respiratory tract deposition and clearance for inhaled vapors. This study provides data needed to assess radiation doses to humans exposed to IMRu tetroxide. Rats were given a nose-only exposure to IMRuO4 vapor to determine the subsequent distribution and retention. Initial whole-body activity ranged from 4.1 to 15 pCi of IMRu. Fifty-four per cent was in the upper respiratory tract, less than 1% was in the pulmonary region, the remaining 45% was external contamination. Clearance of l ' Ru from the body was predominately through the gastrointestinal tract to feces. A simulation model was developed to describe retention and translocation of inhaled IMRu04 and to provide estimates of radiation doses to internal organs. Current ICRP recommendations consider lung and gastrointestinal tract as critical organs for inhaled particles of radioactive ruthenium. This study indicated that the nasopharynx should be considered a critical region for vapor forms of radioactive ruthenium in human inhalation exposures.

The effectiveness of repeated bronchopulmonary lavage for removing inhaled l4We fused clay particles from the lungs of Beagle dogs was investigated. Twelve Beagle dogs were exposed to a 144Ce fused clay aerosol resulting in initial lung burdens ranging from 47-64 pCi/kg body weight. Eight received 10 saline lavage treatments, five on each lung over a 56-day period. At the end of each lavage, they also received 50 mg of calcium diethylenetriaminepentaacetic acid (DTPA) intravenously. Four dogs received no treatment. A second group of four dogs was exposed to an aeorsol of fused clay only and given 10 lung lavages over a 56-day period. I n the eight treated dogs, an average of 44% of initial lung burden was removed by the 10 lavage procedures. Recovery from two of these eight dogs was considerably lower, 23 and 27%, than the average of the remaining 6, 51%. The reason for this has not been established. Examination of the urinary excretion showed that although the DTPA injections increased urinary excretion 10 fold, this difference between the treated and untreated dogs accounted for only 1.6% of the initial lung burden. Thus, for 144Ce inhaled in this form, the lavage procedure was 28 times more effective in removing '44Ce from the body than were the DTPA injections. The reduction in initial lung burden over a 56-day treatment period resulted in a decrease of the cumulative radiation dose to the lung, at 90 days and infinity, to 53 and 57%, respectively, of that found for the untreated dogs. No significant clinical changes due to treatment were observed in these animals. All of the dogs in this study were alive at 90 days post-exposure and are now under observation in the colony.

In the absence of adequate data exclusively from studies of inhaled particles in people, the results of inhalation studies using laboratory animals are necessary to estimate particle retention in exposed people. To make accurate projections from animal studies and the limited human data, it is necessary to consider species similarities and differences in lung retention and accumulation patterns for inhaled materials. This paper reviews species similarities and differences in pulmonary retention and clearance for inhaled particles, with emphasis on animal species most commonly used in inhalation toxicology research (rats, guinea pigs, dogs, and nonhuman primates). Simulation models for these four species and for humans were used to compare projected lung burdens which would be accumulated during chronic inhalation exposures. These simulation models project an eightfold difference among these species in the lung concentration of particles per gram of lung after a 2-y chronic inhalation exposure to the same aerosol for 8 h d-1, 5 d wk-1. The largest lung accumulation would occur in guinea pigs, the smallest in rats. To reach the same target lung concentration of particles in the lungs of both animals would therefore require about an eightfold difference in air concentration of the exposure material. These comparisons are useful for selecting appropriate laboratory animal species to study as surrogates for humans, for setting aerosol concentrations to use in inhalation studies, and for making approximations of lung burdens that would result from defined exposure scenarios.

Chronic inhalation of insoluble particles of low toxicity that produce substantial lung burdens of particles, or inhalation of particles that are highly toxic to the lung, can impair clearance. This report describes model calculations of accumulations in lung of inhaled low-toxicity diesel exhaust soot and high-toxicity Ga2O3 particles. Lung burdens of diesel soot were measured periodically during a 24-mo exposure to inhaled diesel exhaust at soot concentrations of 0, 0.35, 3.5, and 7 mg m-3, 7 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y after a 4-wk exposure to 23 mg Ga2O3 m-3, 2 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y both studies using inhaled radiolabeled tracer particles. Simulation models fit the observed lung burdens of diesel soot in rats exposed to the 3.5- and 7-mg m-3 concentrations of soot only if it was assumed that clearance remained normal for several months, then virtually stopped. Impaired clearance from high-toxicity particles occurred early after accumulations of a low burden, but that from low-toxicity particles was evident only after months of exposure, when high burdens had accumulated in lung. The impairment in clearances of Ga2O3 particles and radiolabeled tracers was similar, but the impairment in clearance of diesel soot and radiolabeled tracers differed in magnitude. This might have been related to differences in particle size and composition between the tracers and diesel soot. Particle clearance impairment should be considered both in the design of chronic exposures of laboratory animals to inhaled particles and in extrapolating the results to people.

Research directed toward developing an improved understanding of the biomedical consequences of inhaling transuranic elements was initiated at the Lovelace Foundation in 1968, recognizing the need for additional information on these radionuclides as well as the opportunity to obtain data for comparison with those previously collected and being collected on fission product radionuclides. The research is being performed to develop information that will assist in predicting potential effects in man from inhaled transuranic elements, and to provide the data necessary for establishing realistic radiation protection guides. Recognizing the need for quantitative data on the influence of particle size on the toxicity of inhaled alpha emitters, a major, and successful, effort has been directed toward the production of monodisperse aerosols of respirable particles. Studies on the metabolism and toxicity of 23gPu, 241Am, 244Cm and 262Cf have been performed or are under way in mice, Chinese hamsters, Syrian hamsters, rats and Beagle dogs. The effectiveness of bronchopulmonary lavage for removing inhaled radioactivity, including 239Pu, is also being studied. This study, in part, provided the basis for the use of bronchopulmonary lavage to recently treat an individual who accidentally inhaled 23DPu.