[en] Curium isotopes are major by-products in irradiated nuclear reactor fuel and comprise a significant fraction of the alpha-emitting radionuclide inventory. Although little use is currently being made of purified Cm sources, such usage is possible if reprocessing of spent fuel becomes feasible. Because little information is available on the biokinetics and dosimetry of inhaled Cm compounds, a study was conducted in which adult beagle dogs received a single inhalation exposure to either a monodisperse aerosol of 244Cm2O3 (1.4 micron activity median aerodynamic diameter [AMAD]; sigma g = 1.16) or a polydisperse aerosol of 244Cm (NO3)3 (1.1 micron AMAD; sigma g = 1.74). At times ranging from 4 h to 2 y after exposure, animals were sacrificed and their tissues analyzed for Cm content. The data describing the uptake and retention of 244Cm in the different organs and tissues and the measured rates of excretion of these dogs formed the basis on which a biokinetic model of Cm metabolism was constructed. This Cm model was based on a previously published model of the biokinetics of 241Am that was shown to be applicable to data from human cases of inhalation exposure to 241Am aerosols. This Cm model was found to be adequate to describe the biological distribution of Cm in dogs and was also applied to the sparse data from humans. Reasonable agreement was found between the model predictions for lung retention of Cm and for urinary excretion patterns in humans

[en] 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

[en] The subject matter for this 26th Annual Hanford Life Sciences Symposium evolved from the deliberations of a Task Group on Modeling for Scaling to Humans, which was established in January 1986 through the efforts of the Office of Health and Environmental Research of the Department of Energy (OHER/DOE). Several laboratories that utilize animals in radiobiological research sponsored by the OHER/DOE were extensively reviewed in the spring of 1985, and, as a result, OHER recommended establishment of eight task groups designed for selected purposes. The current membership of the Task Group on Modeling for Scaling to Humans is presented. Dr. James A. Mewhinney of the Lovelace Inhalation Toxicology Research Institute has been Chairman since these Task Groups were established. Ms. Judy Mahaffey of Battelle. Pacific Northwest Laboratories served as chairperson for this symposium, and the Task Group membership has served as the Program Committee. The OHER/DOE thanks all of them for their work as members of the Task Group as well as for their arranging such a potentially productive and informative meeting

[en] Data were obtained from the literature for gonad and body weights and for the Pu or Ce content of the gonads and body at death for several laboratory animal species, five human Pu injection cases, and 731 human adults exposed environmentally to Pu in fallout. Data for Pu concentration in gonads, liver, and bone samples of 59 male and five female occupational Pu cases (including four completely analyzed whole bodies) were obtained from the U.S. Transuranium Registry. A logarithmic function was used to relate fractional Pu or Ce concentration in testes and ovaries to body weight of the animals and to predict fractional Pu or Ce concentrations in human gonads, [Pu]G . PuB-1 = aBWb, where [Pu]G or [Ce]G is the nuclide concentration in gonads (Bq g-1 of wet weight), PuB or CeB is the nuclide content of the body at death, and BW is body weight (kg). The fractional Pu and Ce concentrations in both the testes and ovaries are inverse and nearly linear functions of body weight. The regression lines of fractional Pu or Ce concentration in testes and ovaries have similar slopes (b = -1.07 +/- 0.14); however, the nuclide concentrations (coefficient a) in ovaries are six times greater than in testes. Extrapolation of the animal data yielded fractional Pu concentrations in human testes and ovaries that agree with those calculated for the occupational cases and those recommended by the International Commission on Radiological Protection. The good agreement between the fractional concentrations of Pu and Ce in the testes and in the ovaries suggests that these data can be substituted in metabolic models of chemically similar elements for which gonadal data are scarce

[en] Concentrations and organ distribution patterns of alpha-emitting isotopes of U (238U and 234U), Th (232Th, 230Th, and 228Th), and Pu (239,240Pu) were determined for beagle dogs of our colony. The dogs were exposed to environmental levels of U and Th isotopes through ingestion (food and water) and inhalation to stimulate environmental exposures of the general human population. The organ distribution patterns of these radionuclides in beagles are compared to patterns in humans to determine if it is appropriate to extrapolate organ content data from beagles to humans. The results indicated that approximately 80% of the U and Th accumulated in bone in both species. The organ content percentages of these radionuclides in soft tissues such as liver, kidney, etc. of both species were comparable. The human lung contained higher percentages of U and Th than the beagle lung, perhaps because the longer life span of humans resulted in a longer exposure time. If the U and Th content of dog lung is normalized to an exposure time of 58 y and 63 y, median ages of the U and Th study populations, respectively, the lung content for both species is comparable. The organ content of 239,240Pu in humans and beagles differed slightly. In the beagle, the liver contained more than 60%, and the skeleton contained less than 40% of the Pu body content. In humans, the liver contained approximately 37%, and the skeleton contained approximately 58% of the body content. This difference may have been due to differences in the mode of intake of Pu in each species or to differences in the chemical form of Pu. In general, the results suggest that the beagle may be an appropriate experimental animal from which to extrapolate data to humans with reference to the percentage of U, Th, and Pu found in the organs

[en] The sensitivity testing of an age-related dosimetric model and its application to the dosimetry of ²³⁹Pu are described. The model is used to calculate the committed dose received by the skeleton and liver to age 70 y, following intakes of ²³⁹Pu by an adult aged 20 y and by children aged 0 and 10 y. The model is biologically based and takes account of the age-dependent transfer of Pu between the different organs of the body and between the different components of the skeleton. It consists of 22 compartments, 16 of which are skeletal, each connected by transfer pathways defined by age-dependent rate constants. The sensitivity of the predictions of the model, as applied to adults, to changes in the assumed values of rate constants were tested. The results of the tests applied suggested that the age-related model is relatively robust and is not particularly sensitive to changes in the assumed values of many of the rate constants used

[en] Improved lung models provide a more accurate assessment of dose from inhalation exposures and, therefore, more accurate dose-response relationships for risk evaluation and exposure limitation. Epidemiological data for externally irradiated persons indicate that the numbers of excess respiratory tract carcinomas differ in the upper airways, bronchi, and distal lung. Neither their histogenesis and anatomical location nor their progenitor cells are known with sufficient accuracy for accurate assessment of the microdosimetry. The nuclei of sensitive cells generally can be assumed to be distributed at random in the epithelium, beneath the mucus and tips of the beating cilia and cells. In stratified epithelia, basal cells may be considered the only cells at risk. Upper-airway tumors have been observed in both therapeutically irradiated patients and in Hiroshima-Nagasaki survivors. The current International Commission on Radiological Protection Lung-Model Task Group proposes that the upper airways and lung have a similar relative risk coefficient for cancer induction. The partition of the risk weighting factor, therefore, will be proportional to the spontaneous death rate from tumors, and 80% of the weighting factor for the respiratory tract should be attributed to the lung. For Weibel lung-model branching generations 0 to 16 and 17 to 23, the Task Group proposes an 80/20 partition of the risk, i.e., 64% and 16%, respectively, of the total risk. Regarding risk in animals, recent data in rats indicate a significantly lower effectiveness for lung-cancer induction at low doses from insoluble long-lived alpha-emitters than from Rn daughters. These findings are due, in part, to the fact that different regions of the lung are irradiated. Tumors in the lymph nodes are rare in people and animals exposed to radiation.44 references

[en] The primary goal of this paper is to consider factors that affect the availability and transport of actinides from maternal blood, through the placenta, to the conceptus. These factors, of particular importance in scaling results from animals to man, include the route and temporal pattern of administration, the mass and physicochemical state of material administered, metabolism of the pregnant animal and fetal organs or tissue, and species-specific changes in placental structure relative to stage of gestation at exposure. Preliminary concepts for descriptive and kinetic models are proposed to integrate these results, to identify additional information required for developing more comprehensive models, and to provide a basis for scaling to human pregnancies for purposes of radiation dosimetry

[en] A code, DOSEDAY/DOSEYEAR, was developed as a research tool for calculating dose in humans from internally deposited radionuclides, using the International Commission on Radiation Protection (ICRP) Publication 30 compartmental scheme as a framework and ICRP Publication 30 values for default compartmental rate constants. This framework can be varied to investigate new rate constants, fractionation, recycling pathways, and other metabolic information. The compartmental model described in ICRP Publication 30 cannot easily be solved analytically; approximate solutions are generally used. The code calculates the numerical solution to a system of 70 simultaneous, stiff differential equations describing the compartmental model. Step sizes for numerical integration were determined internally by the code to insure stability, and a material balance was calculated for comparison with inputs, which provided a self-contained verification system. The code contains modules for calculating activity and decay in each compartment and for converting these values to dose. Using numerical integration techniques allowed researchers to use recycling compartments (i.e., as proposed for I) and to calculate dose over any time period. DOSEDAY/DOSEYEAR calculates dose for inhalation, ingestion, and injection intake pathways. Chronic intake may also be calculated, using a selected equational form to describe intake (i.e., sinusoidal, representing diurnal Rn exposure; linear, representing 1-d exposure to a constant source; etc.). The code is operational on any personal computer which supports compiled BASIC and thus provides researchers with a readily implemented problem-solving tool to investigate metabolic models

[en] The interaction of biochemical processes and radiation damage appears to play a major role in determining long-term biological effects. It is responsible for both the removal of radiation-induced alterations in macromolecules and for the time-dependent changes in survival of irradiated cells. Restoration of macromolecules by such means as the rejoining of strand breaks in DNA suggests a variety of possible mechanisms which could lead to the observed enhancement of cell survival. However, even though a number of molecular repair mechanisms have been identified, specific links between any such mechanisms and a subsequent modification of cell survival have proved difficult, if not impossible, to demonstrate. Models of cellular response provide a means of attempting to establish this connection. Although details of radiation chemistry, chromatin structure, enzymatic repair, molecular genetics, and cell cycle kinetics are generally simplified, each individual model incorporates features based on a set of assumed mechanisms. For example, one group of models assumes that all damage is potentially lethal, while another assumes that part of the damage is sublethal. Using split-dose, dose-rate, and delayed-plating techniques, we have demonstrated two distinct components of repair in plateau-phase Chinese hamster ovary cells. One process has a characteristic time of about 1 h; the other, about 18 h. In both cases, the reaction rates and the fractions of damage repaired appear to be independent of the initial amounts of damage produced. These observations suggest that none of the simpler models adequately describes cell inactivation; i.e., reproductive death is inconsistent with all assumptions regarding any of them. Consequently, more-complex models involving combinations of sublethal and potentially lethal damage or multiple-step damage processes may be required