Metabolism of americium-241 in man: an unusual case of internal contamination of a child and his father.

The metabolism of americium-241 has been studied during an 8-year period in an adult male and his son who, at the ages of 50 and 4 years, respectively, were accidentally and unknowingly contaminated within their home by means of inhalation. Chelation therapy with calcium trisodium pentetate was more effective in enhancing the removal of americium-241 from the child than from the father.

Failure of interferon to inhibit plutonium-induced osteosarcomas in mice.

The injection of murine interferon three times weekly in dose levels of 1,250, 5,000, or 20,000 U produced no significant antitumor effect against primary 239Pu-induced osteosarcomas in C57BL/6J mice. The interferon treatment was begun 94 days after the plutonium injection, which is well before the radiographic or microscopic appearance of neoplasia, and was continued until the moribund state or death. The average radiation dose accumulated by the skeleton at the time of first treatment was approximately 300 rad. The largest dose of interferon studied, 20,000 U/injection, was approximately 3 X 10(6) U/m2 of body surface, or 10(6) U/kg body weight.

Incidence of plutonium-induced bone cancer in neutered mice.

The incidence of bone cancer, after a single i.p. injection of monomeric 239Pu citrate, is significantly higher in female than in male mice. To evaluate the role of the gonads in this sex-related difference, male and female C57BL/Do (albino) mice were castrated at 40 days of age. Fifty days later, they were given injections of 239Pu. After castration, the frequency of bone sarcomas in the two sexes was approximately equal. This resulted from an increased incidence in the castrated males and a decreased incidence in the ovariectomized females as compared to the intact plutonium-treated mice.

Effect of age on the efficacy of Zn-diethylenetriaminepentaacetic acid therapy for removal of Am and Pu from beagles.

Decorporation of intravenously injected monomeric 241Am and 237+239Pu by the administration of 30 mumole Zn-diethylenetriaminepentaacetic acid (DTPA)/kg each day beginning 2 weeks after radionuclide injection was compared in beagles entered into the experiment when 3 months (juveniles). 1.9 years (young adults), or 10 years (mature adults) old and studied for about 5 months. DTPA therapy was most effective in the juvenile dogs and least effective in the mature adults. Retention of 241Am in the liver decreased from a pretreatment value for adults of about 50% of the injected activity to about 10% in the mature adults and less than 1% in the young adults at 140 days of treatment, while the liver retention of juveniles decreased from pretreatment values of about 16% to undetectable levels by 28 days of treatment. Plutonium retention in the liver decreased from adult pretreatment levels of about 30% of the injected activity (corrected for radioactive decay) to near 10% in the mature adults and 6% in the young adults at 140 days of treatment, while juvenile liver retention decreased from pretreatment values near 15% to undetectable levels by 56 days of treatment. Nonliver Am retention (mainly skeleton) decreased in mature adults from pretreatment values of about 45% of the injected activity to near 25%, in young adults from 35 to 20%, and in juveniles from roughly 70 to 9% by 140 days of DTPA administration. Nonliver Pu retention decreased from pretreatment values of about 50% of the injected activity (corrected for radioactive decay) for mature and young adults to about 30% by 140 days and from 75 to 16% in juveniles over the time period.

Retention and dosimetry of injected 241Am in beagles.

Equations have been derived, from the results of total-body and partial-body counting and gamma-ray counting of individual bones and soft tissues, which describe the retention of injected 241Am in the liver, in the nonliver tissue (including skeleton), and in the skeleton of young adult beagles. Retention was found to be dependent upon injection level, and different sets of equations were developed for dogs given about (a) 2.8 microCi/kg (b) 0.9 microCi/kg (c) 0.3 microCi/kg, and (d) 0.1 microCi/kg and less. Liver rention, RL, was characterized by a single exponential equation of the form RL = ce-beta t, with c = 0.49 +/- 0.04 and beta = a function of injection level. Nonliver tissue was assigned a retention equation of the form RNL = d + alpha + J(l - e-mt), with d = 0.102 +/- 0.024 e-1.22t, alpha = 0.41 +/- 0.04, and both J and m as a function of injection level. Skeletal retention was found to be about 0.885 +/- 0.037 of nonliver retention with no significant dependence upon either injection level or time after 241Am injection. Dosimetry equations based on these retention expressions were derived. Individual bones of 55 beagles were assayed at death for their 241Am content for a determination of 241Am distribution within the skeleton.

Determination of alpha-emitting uranium isotopes in soft tissues by solvent extraction and alpha-spectrometry.

A radiochemical procedure has been developed for the determination of alpha-emitting isotopes of uranium ((238)U, (235)U and (234)U) in soft tissues. Known amounts of sample are spiked with (232)U internal tracer and wet-ashed. Uranium is co-precipitated with iron hydroxide as carrier, and extracted into 20% trilaurylamine solution in xylene after dissolution of the precipitate in 10M hydrochloric acid. The uranium, after stripping into an aqueous phase, is electro-deposited onto a platinum disc and counted by alpha-spectrometry. The radiochemical recovery ranges from 60 to 85% for bovine liver samples. The average radiochemical recoveries for human tissues vary from 53 to 78%.

Determinations of actinides in biological and environmental samples.

This paper summarises the radiochemical procedures utilised in our laboratory to determine U, Th and Pu in different sample matrices, including soft tissues, bones, urine, faeces, soil, water, air-filters, lichen, and building materials such as granite, phosphate and concrete. Sample preparation, depending upon the matrix of the sample, includes either dry ashing and/or wet ashing with a mixture of HNO3 and H2SO4 or HNO3 alone with occasional additions of a few drops of HNO3 and H2O2. Uranium, Th and Pu are either co-precipitated with Fe carrier as hydroxides or with Ca as oxalates. Solvent extractions are performed from 2M HNO3, 4M HNO3 or 10M HCl depending upon the actinide or combination of actinides to be determined. The techniques have been very successful for most samples, with radiochemical recoveries exceeding 70%. However, radiochemical recoveries of Th from soil samples have been very poor (10-30%). Attempts are being made to improve these recoveries.

Reducing radon exhalation from covered tailings: optimization or cost effectiveness?

Reduction of radon exhalation from uranium tailings as a function of the number of radon diffusion lengths in cover materials is discussed, based on dimensionless mathematical functions. Cost effectiveness is examined to determine the least expensive cover with a preselected number of radon diffusion lengths (i.e., a preselected level of radiation protection), and to find the maximum attainable reduction in radon flux with a predetermined cost (i.e., a fixed amount of money). Cost effectiveness rather than optimization through cost benefit analysis can be used advantageously in these cases.

Localization of vanadium-containing particles in the lungs of uranium/vanadium miners.

Several geological formations of the Utah-Colorado mining region mined for uranium ore during and after World War II had been mined earlier for vanadium. Therefore, most miners and millers from that region were exposed to those metals' ores or tailings at one time or another. Preliminary investigation to determine uranium and vanadium retained in the lungs of a former uranium miner and miller from this region, who died of lung cancer (mesothelioma), showed a high nonuniform distribution of vanadium. This observation led to the hypothesis that the vanadium content in the lungs could be associated with inhaled particles. Further examination of spectra of characteristic X-rays obtained by scanning particle-induced X-ray emission (microPIXE) of an autopsy sample of this lung indicated that vanadium was indeed present in localized sites within the 20-µm spatial resolution of the proton beam. This work points out that the microPIXE-RBS (Rutherford backscattering) test for vanadium can be used for site localization of inhaled particles retained in the lungs. Further studies are in progress to: (i) locate uranium-bearing particles in lung tissues of former uranium miners and millers; and (ii) evaluate the local doses of alpha radiation received from these particles.

Is the beagle dog an appropriate experimental animal for extrapolating data to humans on organ distribution patterns of U, Th, and Pu?

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.

Uranium and thorium isotopes and their state of equilibria in lungs from uranium miners.

Radiochemical analysis of seven lungs obtained at autopsy show that concentrations ranged between 6 and 63 pCi/kg for 238U and 6-66 pCi/kg, for 234U. Similarly, 230Th ranged from 17 to 54 pCi/kg, two orders of magnitude higher than 230Th observed in the lungs of the general population from the Western mining region. For individual lungs, 238U and 234U were close to equilibrium with an average ratio of 238U/234U of 0.94 and a range of 0.80-1.02. Surprisingly, 230Th was close to equilibrium with 234U with a 230Th/234U ratio of 1.1 and a range from 0.54 to 2.6. Equilibrium between U and Th isotopes is in contrast to the disequilibrium reported in beagles which chronically inhaled carnotite, where the 230Th/234U ratio was observed to range from 5.4 to 7.4 with an average of 6.3. The average radiation dose rate to lung from each of the three radionuclides was calculated as follows: D = 18.7 CE where D = dose rate in mrad/year, C = activity concentration in tissue in pCi/g and E = energy absorbed per disintegration in MeV. The combined radiation dose rate (at death) due to three long-lived radionuclides 238U, 234U and 230Th varied from 2.5 to 14.2 mrad/yr with a mean of 9.6 mrad/yr. The concentration of 226Ra and daughters in the lung was not determined. An upper limit to the dose rate from the whole chain, calculated assuming 226Ra through 210Po are in equilibrium with 238U, 234U and 230Th, would be 30 mrad/yr.

Concentrations of 210Pb and its states of equilibrium with 238U, 234U and 230Th in U miners' lungs.

The concentrations of 210Pb and its states of equilibrium with 238U, 234U and 230Th in U miners' lungs obtained at autopsy are reported. The concentration of 210Pb ranged from 0.63 to 123 Bq/kg wet weight with an average of 32.7 Bq/kg. The 210Pb concentrations were almost seven times higher than the concentrations of 238U, 234U and 230Th. The radiation dose rates to U miners' lungs from 210Po alone ranged from 0.017 to 3.30 mGy/y with an average of 0.88 mGy/y. The dose rates from 238U, 234U and 230Th combined ranged from 6.8 X 10(-3) to 7.2 X 10(-1) mGy/y with an average of 2.9 X 10(-1) mGy/y. The dose rates from all alpha-emitting members of the 238U series, excluding 210Po, varied from 1.1 X 10(-2) to 2.2 mGy/y with an average of 7.5 X 10(-1) mGy/y.

Plutonium concentration in human tissues: comparison to thorium.

The concentration of 238Pu, and 239,240Pu, and of 228Th, 230Th, and 232Th were measured in 10 sets of human tissues from Washington, DC, and 12 sets from Grand Junction, CO. The tissues were collected at autopsy by qualified pathologists from normal healthy persons most of whom died suddenly. The subjects had acquired plutonium from fallout of global nuclear testing and burnup of a space nuclear generator utilizing 238Pu. The median concentration of 239,240Pu was 0.08 pCi/kg in lung, 0.46 pCi/kg in tracheobronchial lymph nodes, 0.60 pCi/kg in liver, 0.02 pCi/kg in kidney and 0.17 pCi/kg in bone in Washington, DC subjects. Similarly, the concentration of 239,240Pu in Grand Junction subjects was found to be 0.17 pCi/kg in lung, 0.68 pCi/kg in lymph nodes, 0.55 pCi/kg in liver, 0.03 pCi/kg in kidney, 0.22 pCi/kg in bone and 0.08 pCi/kg in spleen. The median concentration in four gonads was 0.02 pCi/kg; the concentration in one thyroid was 0.01 pCi/kg. 238Pu was below the limit of detection in most organs except the liver where it ranged from 0.02 to 0.17 pCi/kg with a median concentration of 0.06 pCi/kg. The organ distribution pattern shows that most of the plutonium was accumulated in bone and liver with 54-60% in bone and 34-43% in liver. Only 3-6% was found in lung including lymph nodes; kidney, spleen, thyroid and gonads together contained around 1%. The analytical results show three major differences between plutonium and thorium concentrations and organ distributions: (1) for plutonium the liver is a major locus for storage (approximately 40% of that found in the total body), whereas little thorium is accumulated in the liver (around 4%); (2) the relative amounts of 230Th and 232Th are much higher in lung and lymph nodes (10-28%) than currently for plutonium (3-6%); (3) the ratio of throium concentrations in lymph nodes to lung is significantly higher than the ratio of plutonium concentration in lymph nodes to lung showing thereby that fallout plutonium is more soluble than natural thorium.

Concentrations of alpha-emitting isotopes of U and Th in uranium miners' and millers' tissues.

The concentrations of alpha-emitting isotopes of U (234U, 235U, and 238U) and Th (228Th, 230Th, and 232Th) were determined in soft tissues and bones of three deceased U miners and two deceased U millers. The soft tissues generally included lung, liver, kidney, spleen, gonad and heart. The concentrations of U isotopes in the miners' lungs varied up to a factor of 18, suggesting that the accumulations of U in lungs at the time of death varied drastically. The concentrations of 230Th in the miners' lungs were similar to the concentrations of 234U and 238U. The concentrations of U isotopes and 230Th in millers' lungs also differed by a factor of almost 10. The most noticeable difference between the concentrations of U isotopes (238U and 234U) and 230Th was in the skeleton of U miners and millers. The 230Th/234U concentration ratios were as high as 94 in bones of miners and as high as 23 in millers. These results suggest that the fraction of Th transferred from blood to bones is much higher than the fraction of U transferred, and that the residence time of Th in skeleton is much higher than the residence time of U as suggested in ICRP Publication 30.

Macro-distribution of naturally occurring alpha-emitting isotopes of U in the human skeleton.

Argonne National Laboratory (ANL) exhumed the remains of two individuals who had received Pu by intravenous injection, performed Pu analysis on these remains, and then sent portions of individual bones to our laboratory. We analyzed these bone samples to determine the macro-distribution of naturally occurring alpha-emitting isotopes of U (234U and 238U). We found that the sacrum contained the highest concentrations of 234U and 238U (4.9 +/- 0.3 mBq g-1 of bone ash). Different ribs contained varying concentrations of 234U and 238U ranging from 0.26 +/- 0.2 to 1.6 +/- 0.4 mBq g-1 of bone ash for 234U, and from 0.16 +/- 0.1 to 1.5 +/- 0.4 mBq g-1 ash for 238U. The upper and lower values differ significantly at p = 0.001. Concentrations of 234U and 238U in vertebral bodies were lower than in left ribs numbers 1 and 2, but were similar to the concentrations in the other left ribs. The concentration of 235U was below the detection limit in each bone (lower limit of detection (LLD) = 4 X 10(-4) Bq per sample). The results indicate that the distribution of U isotopes is not uniform throughout the skeleton. Thus, the skeletal burden of U estimated from determinations in an individual bone sample may be quite erroneous until the fraction of total skeletal U contained in each bone is known.

Utilization of femoral head for estimating the skeletal burden of U and Pu in humans.

Uranium and Pu were determined in vertebrae, ribs and femoral head samples obtained from the same population. Vertebrae and rib samples were obtained at autopsy and femoral head samples were obtained from persons undergoing hip surgery. The results indicate that there was no statistically (p less than or equal to 0.05) significant difference between the mean concentration of 239,240Pu in vertebrae and ribs. Also, there was no significant difference between the mean concentration of 239,240 Pu in ribs and femoral head. Also, statistical tests were performed to see whether the mean concentrations of 238U and 234U in three different bones differ from each other. The results suggest that there was no statistically significant difference between vertebrae and ribs, vertebrae and head of the femur nor between ribs and femoral head. These results indicate that femoral head may be an appropriate substitute for vertebrae or ribs, the most commonly used bone for inferring the skeletal burden of U and Pu in human. Femoral head samples can be obtained from living persons undergoing hip surgery, while vertebrae and ribs are obtained only at autopsy.

Thermoluminescence measurements of gamma-ray doses attributable to fallout from the Nevada test site using building bricks as natural dosimeters.

During the 1950's, the U.S. Government conducted an intensive atmospheric nuclear testing program in Nevada. Fallout from these atmospheric tests was measured throughout the U.S. with some of the heaviest concentrations to populated areas falling east of the test site in Washington County, UT. External exposures from 6.5 x 10(-4) C kg-1 to 26 x 10(-4) C kg-1 (2.5-5.0 R) were reported for this region. This study provides an independent measurement of fallout radiation doses to selected communities in Utah using a thermoluminescence technique originally developed for the dating of ancient pottery. The application of the predose thermoluminescence technique to fallout dosimetry is described. A mean dose of 38 +/- 15 mGy (4.4 +/- 1.7 R), attributed to fallout radiation, was measured in quartz grains extracted from the outer centimeter of bricks removed from six communities in Washington and Kane Counties in Utah.

Thorium concentration in human tissues from two U.S. populations.

The concentrations of natural alpha-emitting isotopes of thorium (228Th, 230Th and 232Th) have been determined in 22 sets of human tissue samples obtained at autopsy from Grand Junction, CO and in 10 sets from Washington, DC. Tissues included lung, pulmonary lymph nodes, liver, kidney, bone, a few gonads, spleen and thyroid. Personal data on each individual's age, sex, smoking history and occupation were obtained whenever possible. The concentrations of 228Th, 230Th and 232Th were highest in lymph nodes for both populations with 2.6 and 5.1 pCi/kg of 228Th, 4.60 and 11.10 pCi/kg of 230Th, and 2.8 and 7.8 pCi/kg of 232Th in Washington, DC and Grand Junction, CO, respectively. The order of concentrations of all three isotopes in all other organs for both populations was as follows: (formula; see text) The data suggest that the non-mining residents who lived in the vicinity of uranium mine tailings do not have elevated 230Th concentrations in their lungs, when compared to the residents of Washington, DC who are not exposed to such tailings. However, 230Th concentration in bone of Grand Junction subjects was just significantly higher (at p less than 0.1) than that for Washington, DC subjects after suitable age adjustments. The data also suggest that 230Th is more available for accumulation in skeleton than would be supposed from its relative geochemical abundance.

Cancer incidence and lifespan vs. alpha-particle dose in beagles.

Young adult beagles were injected with graded activities of 239Pu, 241Am, 228Th, 228Ra or 226Ra and observed throughout their lifespans. The vast majority of the dose was from alpha particles. The lifetime incidence of bone sarcoma increased with average skeletal dose, more or less linearly up to high incidence for 239Pu, 241Am, 228Th and 226Ra, but sigmoid fashion for 228Ra. Based on average skeletal dose, the toxicity of the emitters relative to 226Ra = 1.0 was 239Pu = 16.6 +/- 4.5, 241Am = 5.4 +/- 1.6, 228Th = 8.5 +/- 2.3 and 228Ra = 2.0 +/- 0.5. At the lowest doses, the average lifespans were 97% +/- 3% of that in the controls. If beneficial effects occurred, they may have been overwhelmed by the destructiveness of the densely ionizing alpha particles. A cell nucleus 5 micron in diameter receives a mean dose of about 1 Gy (100 rad) when traversed by a single alpha particle. We found no evidence that alpha-particle doses suppressed cancer or lengthened lifespan in beagles.

The beagle: an appropriate experimental animal for extrapolating the organ distribution pattern of Th in humans.

The concentrations and the organ distribution patterns of 228Th, 230Th and 232Th in two 9-y-old dogs of our beagle colony were determined. The dogs were exposed only to background environmental levels of Th isotopes through ingestion (food and water) and inhalation as are humans. The organ distribution patterns of the isotopes in the beagles were compared to the organ distribution patterns in humans to determine if it is appropriate to extrapolate the beagle organ burden data to humans. Among soft tissues, only the lungs, lymph nodes, kidney and liver, and skeleton contained measurable amounts of Th isotopes. The organ distribution pattern of Th isotopes in humans and dog are similar, the majority of Th being in the skeleton of both species. The average skeletal concentrations of 228Th in dogs were 30 to 40 times higher than the average skeletal concentrations of the parent 232Th, whereas the concentration of 228Th in human skeleton was only four to five times higher than 232Th. This suggests that dogs have a higher intake of 228Ra through food than humans. There is a similar trend in the accumulations of 232Th, 230Th and 228Th in the lungs of dog and humans. The percentages of 232Th, 230Th and 228Th in human lungs are 26, 9.7 and 4.8, respectively, compared to 4.2, 2.6 and 0.48, respectively, in dog lungs. The larger percentages of Th isotopes in human lungs may be due simply to the longer life span of humans. If the burdens of Th isotopes in human lungs are normalized to an exposure time of 9.2 y (mean age of dogs at the time of sacrifice), the percent burden of 232Th, 230Th and 228Th in human lungs are estimated to be 3.6, 1.3 and 0.66, respectively. These results suggest that the beagle may be an appropriate experimental animal for extrapolating the organ distribution pattern of Th in humans.