Urinary Excretion Of Plutonium Research Articles

URINARY EXCRETION OF PLUTONIUM IN MAYAK WORKERS DURING AND AFTER CA-DTPA ADMINISTRATION.

Chelation therapy is sometimes used after potential exposures to plutonium to increase urinary excretion of the radionuclide to improve the accuracy of bioassay measurements. The purpose of this report is to describe the enhancement of urinary excretion of plutonium during and after the administration of the trisodium salt of calcium diethylenetriaminepentaacetate (Ca-DTPA) daily for 3d to a group of male and female plutonium workers from the Mayak Production Association in Ozyorsk, Russia. One-hundred and two cases (18 females and 84 males) were selected where urinary contents of plutonium, prior to chelation, exceeded the detection threshold. Daily urine collections were obtained during the 3d of Ca-DTPA treatments. In addition, 58 of these cases had urine bioassays at 1-45d after chelation. The daily enhancement over baseline values excretion of plutonium was found to be 50.4×/1.4 (geometric mean and geometric standard deviation); 58.9×/1.2; 72.9×/1.4 in the first, second and third days of Ca-DTPA administration. The mean enhancement for the 3-d period was 60.1×/1.7. The rate of plutonium excretion from 1 to 45d after chelation decreased with a half-period of 3.9d and the chelation enhancement factor (Кenh-i) is described by the function Кenh-i=(0.79±0.24)+(42.9±1.2)×e-(0.18±0.01)×day.

Validation of a system of models for plutonium decorporation therapy.

A recently proposed system of models for plutonium decorporation (SPD) was developed using data from an individual occupationally exposed to plutonium via a wound [from United States Transuranium and Uranium Registries (USTUR) Case 0212]. The present study evaluated the SPD using chelation treatment data, urine measurements, and post-mortem plutonium activities in the skeleton and liver from USTUR Case 0269. This individual was occupationally exposed to moderately soluble plutonium via inhalation and extensively treated with chelating agents. The SPD was linked to the International Commission on Radiological Protection (ICRP) Publication 66 Human Respiratory Tract Model (HRTM) and the ICRP Publication 30 Gastrointestinal Tract model to evaluate the goodness-of-fit to the urinary excretion data and the predictions of post-mortem plutonium retention in the skeleton and liver. The goodness-of-fit was also evaluated when the SPD was linked to the ICRP Publication 130 HRTM and the ICRP Publication 100 Human Alimentary Tract Model. The present study showed that the proposed SPD was useful for fitting the entire, chelation-affected and non-affected, urine bioassay data, and for predicting the post-mortem plutonium retention in the skeleton and liver at time of death, 38.5years after the accident. The results of this work are consistent with the conclusion that Ca-EDTA is less effective than Ca-DTPA for enhancing urinary excretion of plutonium.

Simplified Structure of a New Model to Describe Urinary Excretion of Plutonium after Systemic, Liver or Pulmonary Contamination of Rats Associated with Ca-DTPA Treatments

This study validates, by targeted experiments, several modeling hypotheses for interpretation of urinary excretion of plutonium after Ca-DTPA treatments. Different formulations and doses of Ca-DTPA were administered to rats before or after systemic, liver or lung contamination with various chemical forms of plutonium. The biokinetics of plutonium was also characterized after i.v. injection of Pu-DTPA. Once formed, Pu-DTPA complexes are stable in most biological environments. Pu-DTPA present in circulating fluids is rapidly excreted in the urine, but 2-3% is retained, mainly in soft tissues, and is then excreted slowly in the urine after transfer to blood. Potentially, all intracellular monoatomic forms of plutonium could be decorporated after DTPA internalization involving slow urinary excretion of Pu-DTPA with half-lives varying from 2.5 to 6 days as a function of tissue retention. The ratio of fast to slow urinary excretion of Pu-DTPA depends on both plutonium contamination and Ca-DTPA treatment. Fast urinary excretion of Pu-DTPA corresponds to extracellular decorporation that occurs beyond a threshold of the free DTPA concentration in circulating fluids. Slow excretion corresponds mostly to intracellular decorporation and depends on the amount of intracellular DTPA. From these results, the structure of a simplified model is proposed for interpretation of data obtained with Ca-DTPA treatments after systemic, wound or pulmonary contamination by plutonium.

The development of the plutonium lung clearance model for exposure estimation of the Mayak production association, nuclear plant workers.

The purpose of this study was to develop a biokinetic model that uses urinary plutonium excretion rate data to estimate the plutonium accumulation in the human respiratory tract after occupational exposure. The model is based on autopsy and urinalysis data, specifically the plutonium distribution between the respiratory tract and the remainder of the body, taken from 543 former workers of a radiochemical facility at the Mayak Production Association (MPA) plant. The metabolism of plutonium was represented with a compartmental model, which considers individual exposure histories and the inherent solubility properties of industrial plutonium aerosols. The transport properties of plutonium-containing aerosols were estimated by experimentally defining their in vitro solubility. The in vitro solubilities were found by dialysis in a Ringer's solution. Analysis of the autopsy data indicated that a considerable fraction of the inhaled plutonium is systemically redistributed rapidly after inhalation. After the initial dynamic period, a three-compartment model describes the retention in the respiratory tract. One compartment describes the nuclide retained in the lungs, the second compartment describes a plutonium lung concentration that exponentially decreases with time, and the third compartment describes the concentration in the pulmonary lymph nodes. The model parameters were estimated by minimizing sum squared of the error between the tissue and bioassay data and the model results. The parameters reflect the inverse relationship between plutonium retention in lungs and the experimentally derived aerosol transportability. The model was validated by comparing the autopsy results with in vivo data for 347 cases. The validation indicates that the model parameters are unbiased. This model is being used to estimate individual levels of nuclide accumulation and to compute radiation doses based upon the urinary excretion rates.

Effective Timing of Initial Administration of Ca-DTPA upon Removal of Inhaled Plutonium Nitrate in Rats.

The effective timing of an initial injection of Ca-DTPA and a subsequent early treatment on removal of inhaled plutonium nitrate was determined in rats. Plutonium nitrate inhaled rats received an intraperitoneal injection of Ca-DTPA at a daily dose of 150μmol/kg for 3 days, beginning at 0.5, 1, 2, 6, and 12h after inhalation of plutonium; a second regimen studied was injection at a daily dose of 30μmol/kg (the daily recommended dose for humans), beginning at 1h after plutonium inhalation. One group was served as the control with no treatment. During the experiment, the urine and feces were collected every day; on day 4, the rats were sacrificed and dissected to measure plutonium concentration in blood and various organs. The first administration of Ca-DTPA (150μmol/kg) at 1-6h after inhalation initiated an increase in urinary plutonium excretion during the first 24h following inhalation and also resulted in significant increases of urinary plutonium excretion up to 3 days following the treatment. The increase was measured in comparison to the urinary levels of the other two groups that initiated at 0.5h and 12h. In the group that was given 30μmol/kg Ca-DTPA, the high urinary plutonium excretion was found compared to those of the control group; however, these levels were lower than those of the group that was administered a dose of 150μmol/kg. Although the retention rates in the various organs of Ca-DTPA treatment groups varied to the corresponding organs in the control groups, the changed values were very slight. The results indicate that Ca-DTPA administration within 1-6h after exposure to plutonium is effective to increase the urinary excretion of plutonium in rats.

The Gastrointestinal Absorption and Urinary Excretion of Plutonium in Male Volunteers

The gastrointestinal absorption and urinary excretion of 244 Pu have been measured in five healthy adult males in a two-stage study. Firstly, the volunteers ingested about 10 14 atoms of 244 Pu in citrate solution with a mid-day meal and urinary excretion was measured for the following 7-9 days. After a period of at least six months, the same volunteers were given an intravenous injection of 2 x 10 12 atoms of 244 Pu in citrate solution. Urinary excretion was then measured for the following 7-9 days and subsequently at intervals over periods up to 5-6 years. Fractional absorption of Pu from the gastrointestinal tract, calculated by comparing excretion for the two routes of administration, averaged 6 X 10 -4 , consistent with the ICRP value of 5 x 10 -4 . The results show a positive correlation between increasing age of the subjects, between 36 and 64 years of age, and increasing absorption of ingested Pu from 10 -4 to 10 -3 . In general, results for urinary excretion after injection are consistent with predictions of the current ICRP model although daily excretion after 5-6 years (3 subjects) averaged 0.005% of the administered amount, about twice the predicted value.

On the Use of ICP-MS for Measuring Plutonium in Urine

The analytical protocols currently used to measure plutonium in urinary excretion consist of radiochemical purification, the source preparation by electroplating and alpha spectrometry measurements. Such a procedure is of limited relevance to the individual monitoring of workers exposed to plutonium and mixed oxides. The use of ICP-MS, which takes much shorter counting time, was investigated with the aim of assessing the capabilities of this analytical tool for the determination of urinary excretion of plutonium. It has been shown that the detection level of 1 mBq·1-1 could be achieved after a radiochemical purification process for a standard ICP-MS set-up.

Transfer of Plutonium Across the Human Gut and its Urinary Excretion

The gastrointestinal absorption of 244 Pu(IV) has been measured in three male adult volunteers. The plutonium was in citrate solution and was taken with food. The work was carried out in two stages. The first stage measured urinary plutonium excretion up to 8 or 9 d after the oral intake. The second stage commenced about six months later with an intravenous injection of plutonium citrate and measurements of the urinary plutonium excretion. Results from the two routes of intake were used to calculate the fractional absorption (f 1 ) of ingested plutonium. The f 1 values were in the range (2-9) × 10 −4 . In theory it should be possible to measure the plutonium in the volunteers' urine throughout their lives. Measurements are continuing and the resuls show the excretion pattern up to nearly 2 y for one subject, and 6 months for the other two volunteers

Derivation of a New Expression to Describe the Urinary Excretion of Plutonium by Man

The development of a new urinary excretion function for plutonium is described. Revised human injection study data are utilised which make allowance for chemical recovery losses. Measurement results for a plutonium intake case (AWE-1), obtained over 6500 days post-incident, are included in the derivation of the long-term component of the excretion function. Results suggest that the excretion of plutonium in urine following instantaneous unit uptake to blood is best represented by the equation U(t) = 0.00569exp(−0.658t) + 0.000405exp(−O.0961t) + 0.000137exp(−0.00751t) + 0.0000277exp(−0.00004O5t)

Laboratory Intercomparison of Methods Used for the Assessments of Systemic Burdens of Plutonium

An interlaboratory comparison exercise for estimating systemic uptakes of plutonium is described. Six laboratories participated and four different cases were compared. The data were restricted to urinary excretion of plutonium following acute, chronic or multiple acute intake. The agreement between the laboratories was considered satisfactory, their mean values being within 40% of the overall mean. The differences between laboratories were examined and the two main causes, of roughly equal magnitude, arose from statistical treatment of the data and the use of different metabolic models.

Intracellular plutonium: removal by liposome-encapsulated chelating agent.

Chelating agents, such as ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were successfully encapsulated within lipid spherules (that is, liposomes). Encapsutlated [(14)C]EDTA, given intravenously to mice, was retained longer in tissues that nonencapsulated [(14)C]EDTA. Encapsulated DTPA, given to mice 3 days after pluttonium injection, removed an additional fraction of plutonium in the liver, presumably intracellular, not available to nonencapslulated DTPA. It also further increased urinary excretion of plutonium. Introduction of chelating agents into cells by liposomal encapsulation is a promising new approach to the treatment of metal poisoning

Interpretation of human urinary excretion of plutonium for cases treated with DTPA.

Interpretation of human urinary excretion of plutonium for cases treated with DTPA.

Evaluation of the PUQFUA method of calculating systemic burdens.

Data on urinary excretion of plutonium following pulmonary deposition were obtained from five cases of depositions from plutonium dioxide and from one case of deposition from a mixture of more soluble compounds of plutonium. The PUQFUA system was used to estimate systemic burdens for these cases. An evaluation of the calculated systemic burdens for various time periods after exposure shows an ex-potential movement of plutonium from the lungs to the systemic circulation. The average half-time for the 5 cases was estimated to be 240 days, while the half-time for the exposure from more soluble compounds was 29 days. Systemic burden estimates were made by an integration method and by a lung model urinary excretion curve method. These values agreed with the PUQFUA calculated systemic burdens and justifies the use of the PUQFUA system in calculating systemic burdens received by transfer from the lungs to the systemic circulation.

EXCRETION OF PLUTONIUM FOLLOWING ACCIDENTAL SKIN CONTAMINATION.

An extensive study has been made of the faecal and urinary plutonium excretion from two subjects who sustained high levels of contamination on the uncut skin of the hand from accidental contact with acid plutonium solutions. In one case, where the contaminant was mixed plutonium isotopes in aqua regia and nitric acid, the measurements reported have covered 150 days. In the other case, excretion after contamination with a solution of plutonium in dilute hydrochloric acid containing EDTA and a detergent has been followed for 110 days. The excretion patterns show marked differences from the human experimental data published by LANGHAM, particularly in the high and variable amount of plutonium excreted in faeces relative to urine. The excretion data are supplemented in one case by a series of measurements on the levels of skin contamination, by exploratory body radioactivity measurements and by a few inconclusive blood plutonium analyses. Attempts have been made to estimate the body burdens in various ways. The wide variation of these estimates indicates the uncertainties in predicting body burden from excretion data. The present study gives no indication as to the major site of deposition of the plutonium.

Radioelement Poisoning

Argonne National Laboratory has recently announced important results in the treatment of radioelement poisoning by metal displacement therapy. The treatment, reported by Jack Schubert of the Laboratory's division of medicine, involves injections of a solution of zirconium citrate given to rats which have received previous injections of significant amounts of radioactive materials such as plutonium and yttrium. The zirconium treatment has resulted in at least three‐fourths of the radioactive materials previously injected into rats being removed within six days. The method has been found to cause a great increase in the urinary excretion of plutonium and yttrium and a large decrease in the amount of these elements deposited in the animal's skeleton.