Radionuclide biokinetics database (RBDATA-EULEP): an update.

The main activity of the RBDATA-EULEP project is the development of an electronic database of information on the biokinetics of radionuclides after intake by inhalation, ingestion or injection. It consists of linked tables of publications and experiments, with details and comments on the materials, procedures and results. By March 2004 it contained information on more than 1600 experiments from 600 publications. It will be extended and Internet access will also be provided.

A local approach to reduce industrial uranium wound contamination in rats.

The aim of this work is to develop a new approach to partially decontaminate wounds after industrial uranium contamination, during the interval of time between contamination and transfer of the patient to the infirmary. A wound dressing and a paste mixed or not with uranium-chelating ligands, ethane-1-hydroxy-1,1-bisphosphonate (EHBP) and carballylic amido bis phosphonic acid (CAPBP), were tested in vitro on muscles and in vivo on rats after deposit of uranium oxide compounds. The dressing and the paste, composed of carboxymethylcellulose-based hydrocolloids known to be highly absorbent, were applied on simulated wounds a few minutes after the contamination. The incorporation of chelating ligands did not improve the efficacy of the dressing or paste, and the best results were obtained with the dressing. In vivo, after 1 h of contact with the wound, the dressing absorbed about 30% and 60% of a UO4 compound deposited intra- and intermuscularly, respectively. After intramuscular deposit, the efficacy of the dressing was not reduced if the contact time decreased from 1 h to 15 min. Therefore, this wound dressing could be a practical option to treat uranium-contaminated wounds, but its efficacy depends on the localization of the uranium deposit.

Efficacy of 3,4,3-LI(1,2-HOPO) for decorporation of Pu, Am and U from rats injected intramuscularly with high-fired particles of MOX.

This study aimed to assess the efficacy of 3,4,3-LI(1,2-HOPO) for reducing uranium, plutonium and americium in rats after intramuscular injection of (U-Pu)O2 particles (MOX). Sixteen rats were contaminated by intramuscular injection of a 1 mg MOX suspension and then treated daily for 7 d with LIHOPO (30 or 200 micromol kg(-1)) or DTPA (30 micromol kg(-1)). LIHOPO was inefficient for removing Pu, Am and U from the wound site. However, it reduced Pu retention in carcass and liver by factors of 2 and 6 respectively, and Am retention in carcass and liver by factors of 10 and 30. In contrast, the effect of LIHOPO on U was to decrease the retention in kidneys by a factor of 75. These results confirm that LIHOPO is a good candidate for use after contamination with MOX, in combination with localised wound lavage or surgical treatment aimed at removing most of the contaminant at the wound site.

Characterisation and dissolution of depleted uranium aerosols produced during impacts of kinetic energy penetrators against a tank.

Aerosols produced during impacts of depleted uranium (DU) penetrators against the glacis (sloping armour) and the turret of a tank were sampled. The concentration and size distribution were determined. Activity median aerodynamic diameters were 1 microm (geometric standard deviation, sigma(g) = 3.7) and 2 microm (sigma(g) = 2.5), respectively, for glacis and turret. The mean air concentration was 120 Bq m(-3), i.e. 8.5 mg m(-3) of DU. Filters analysed by scanning electron microscopy (SEM) and X ray diffraction showed two types of particles (fine particles and large molten particles) composed mainly of a mixture of uranium and aluminium. The uranium oxides were mostly U3O8, UO2.25 and probably UO3.01 and a mixed compound of U and Al. The kinetics of dissolution in three media (HCO3-, HCl and Gamble's solution) were determined using in-vitro tests. The slow dissolution rates were respectively slow, and intermediate between slow and moderate, and the rapid dissolution fractions were mostly intermediate between moderate and fast. According to the in-vitro results for Gamble's solution, and based on a hypothetical single acute inhalation of 90 Bq, effective doses integrated up to 1 y after incorporation were 0.54 and 0.56 mSv, respectively, for aerosols from glacis and turret. In comparison, the ICRP limits are 20 mSv y(-1) for workers and 1 mSv y(-1) for members of the public. A kidney concentration of approximately 0.1 microg U g(-1) was predicted and should not, in this case, lead to kidney damage.

Effect of DTPA on the nephrotoxicity induced by uranium in the rat.

The only treatment proposed after human contamination with MOX (mixed oxide of uranium and plutonium) is diethylenetriaminepentaacetic acid (DTPA), because plutonium is considered to be the major risk. However, both DTPA and uranium are nephrotoxic at high dosages and DTPA has been shown to increase in vitro the cytotoxicity induced by uranium on cultured epithelial tubular cells. This work aimed to test this effect in vivo. Rats were injected with subtoxic (57 microg kg(-1)) to toxic (639 microg kg(-1)) amounts of uranium as nitrate at 0 h, they received two DTPA injections (30 micromol kg(-1)) at 2 min and 24 h and were euthanased at 48 h. The nephrotoxic effects were evaluated by measurement of the body weight gain, food and water intake, measurement of biochemical parameters in urine and blood, and histological examination of one kidney. The main result was that DTPA did not increase the nephrotoxicity induced by uranium in the range of concentrations tested, which was inconsistent with the in vitro results.

RBDATA-EULEP: providing information to improve internal dosimetry.

The overall aim of the concerted action RBDATA-EULEP is to provide information to improve the assessments of intakes of radionuclides and of the resulting doses. This involves a review of the behaviour of radionuclides following intake, and the transfer of expertise on methodology by organising small training workshops. The main activity is the development of an electronic database, effectively an annotated bibliography, but the electronic format used facilitates extension, updating and information retrieval. It consists of linked tables of references and experiments, with details and comments on the materials, procedures and results. By June 2002 it contained information on 524 inhalation, 282 ingestion and 164 injection experiments from 391 references. It will be extended, and Internet access provided. Prospective users include groups developing standards for internal dosimetry, scientists conducting research on radionuclide biokinetics and health physicists assessing the consequences of accidental intakes.

Determination of the physical and chemical properties, biokinetics, and dose coefficients of uranium compounds handled during nuclear fuel fabrication in France.

The introduction of new ICRP recommendations, especially the new Human Respiratory Tract Model (HRTM) in ICRP Publication 66 led us to focus on some specific parameters related to industrial uranium aerosols collected between 1990 and 1999 at French nuclear fuel fabrication facilities operated by COGEMA, FBFC, and the CEA. Among these parameters, the activity median aerodynamic diameter (AMAD), specific surface area (SSA), and parameters describing absorption to blood f(r), s(r) and s(s) defined in ICRP Publication 66 were identified as the most relevant influencing dose assessment. This study reviewed the data for 25 pure and impure uranium compounds. The average value of AMAD obtained was 5.7 microm (range 1.1-8.5 microm), which strongly supports the choice of 5 microm as the default value of AMAD for occupational exposures. The SSA varied between 0.4 and 18.3 m2 g(-1). For most materials, values of the absorption parameters f(r), s(r), and s(s) derived from the in vitro experiments were generally consistent with those derived from the in vivo experiments. Using average values for each pure compound allowed us to classify UO2 and U3O8 as Type S, mixed oxides, UF4, UO3 and ADU as Type M, and UO4 as Type F based on the ICRP Publication 71 criteria. Dose coefficients were also calculated for each pure compound, and average values for each type of pure compound were compared with those derived using default values. Finally, the lung retention kinetics and urinary excretion rates for inhaled U03 were compared using material-specific and default absorption parameters, in order to give a practical example of the application of this study.

Effect of absorption parameters on calculation of the dose coefficient: example of classification of industrial uranium compounds.

In the Human Respiratory Tract Model (HRTM) described in ICRP Publication 66, time-dependent dissolution is described by three parameters: the fraction dissolved rapidly, fr, and the rapid and slow dissolution rates sr and ss. The effect of these parameters on the dose coefficient has been studied. A theoretical analysis was carried out to determine the sensitivity of the dose coefficient to variations in the values of these absorption parameters. Experimental values of the absorption parameters and the doses per unit intake (DPUI) were obtained from in vitro dissolution tests, or from in vivo experiments with rats, for five industrial uranium compounds UO2, U3O8, UO4, UF4 and a mixture of uranium oxides. These compounds were classified in terms of absorption types (F, M or S) according to ICRP. The overall result was that the factor which has the greatest influence on the dose coefficient was the slow dissolution rate ss. This was verified experimentally, with a variation of 20% to 55% for the DPUI according to the absorption type of the compound. In contrast, the rapid dissolution rate sr had little effect on the dose coefficient, excepted for Type F compounds.

Reduction of uranium transfer by local chelation in simulated wounds in rats.

The aim of the paper is to develop a new approach to treat uranium-contaminated wounds. The efficacy of a local uranium chelator, carballylic amido bis phosphonic acid (CAPBP) was assessed using two different uranium compounds. Rats were contaminated by intramuscular injections of uranyl nitrate or an industrial U04 compound to simulate wound contamination. CAPBP was injected intramuscularly (i.m.) or intraperitoneally (i.p.) at a dosage of 30 micromol kg(-1). In one experiment, the local administration of CAPBP was combined with a systemic administration of ethane-1-hydroxy-1,1-biphosphonate (EHBP). The local CAPBP treatment resulted in increased retention of uranium at the wound site: about 30% for uranyl nitrate or U04 after the first day and about 15% of UO4 after the third day. Consequently, it reduced uranium translocation into the blood and deposition in the kidneys and bone. The combined treatment reduced the uranium deposits in the kidneys, bone and carcass to about one-half of those observed in controls 3 days after U04 contamination. The local CAPBP treatment increased the interval of time between contamination and uranium deposit in the target organs. Thus, it can increase the efficacy of nonspecific local treatments or specific systemic treatments. It could be given rapidly through spray or gel after an accident.

Efficacy of ethane-1-hydroxy-1,1-bisphosphonate (EHBP) for the decorporation of uranium after intramuscular contamination in rats.

PURPOSE: To obtain compounds that will effectively reduce the fixation of uranium in its main target organs: bone and kidney. There is an urgent need for a chelating agent that is suitable and available for human use. MATERIALS AND METHODS: The efficacy of ethane-1-hydroxy-1,1-bisphosphonate (EHBP), already in use as a therapeutic agent, was investigated in animal experiments. The effect of different treatment regimens was investigated on rats (EHBP: 50-100 micromol kg(-1); ligand/uranium ratio 2500 to 5000). RESULTS: The present study shows that one prompt injection of EHBP reduced uranium deposition in kidneys by a factor of five after acute intramuscular contamination in rats. At the same time, the total body uranium in the treated animals was 70% of controls. When the treatment was delayed 30 min after contamination, the kidney content was still reduced by a factor of two. CONCLUSIONS: EHBP has the advantage of clinical acceptance as a therapeutic agent for other purposes and its toxicity has been well studied. It therefore has a role in the treatment of human contamination with uranium.

Review and critical analysis of available in vitro dissolution tests.

The procedures recommended in Publications 30 and 66 by ICRP for calculating radiation doses from inhaled or ingested radionuclides include classification of material on the basis of different parameters, among which transportability plays a major role, The allocation of transportable Classes or absorption Types should, whenever possible, be based on animal or human data. However, when such in vivo data are unavailable, it becomes appropriate to consider the use of other approaches, among which in vitro dissolution techniques are reasonable alternatives. This paper reviews and critically analyzes in vitro dissolution techniques that have been described historically and recommends methods shown to be useful in estimating the in vivo solubility of radioactive particles.

The effects of the initial lung deposit on uranium biokinetics after administration as UF4 and UO4.

This study was designed to assess the effect of the initial lung deposit (ILD) on uranium biokinetics in rats after intracheal instillation of biologically soluble uranium compounds. Rats received various doses of either UO4 or UF4 dust. The uranium content was determined in the kidneys, lungs, remaining carcass, urine and faeces at intervals of up to 30 days. The percentages of uranium absorbed into blood, transferred to tissues, and excreted in urine were independent of the uranium lung deposit for the two compounds. The K/K + U ratio 24 h after installation (K is the per cent of uranium retained in the kidneys and U the per cent excreted in urine) which can be used to evaluate kidney function, was essentially constant in the range from 0.02 to 12.5 microg U g(-1) kidneys.

Assessment of physico-chemical and biokinetic properties of uranium peroxide hydrate UO4.

Comprehensive studies on the radiotoxicological risk of an intermediate compound UO4, which is not specified in ICRP Recommendations, were motivated by its increased use in the nuclear fuel cycle and the lack of information such as physico-chemical and biokinetic properties. The aim of this work was to give an experimental basis for assessing the appropriate limits on intake for workers exposed to UO4 and to provide guidance for the interpretation of personal monitoring data. Particle size measurement of the UO4 dust indicated a geometric diameter D of 0.5 microm, which corresponds to an activity median aerodynamic diameter (AMAD) of 1.1 microm. In vitro experiments conducted in culture medium showed that UO4 is a soluble compound with 66.2% dissolved in 1.9 d and 33.8% in 78 d. Results of dissolution obtained with macrophages showed a significant decrease of 50% at 1 d in terms of solubility. Biokinetic data in the rat obtained from two in vivo studies involving intratracheal instillation in rats indicated half-times in the lung of 0.5 d (96.6%) and 27 d (3.4%) for an initial lung deposit (ILD) of 195 microg, and 1.2 d (90.3%) and 38 d (9.7%) for an ILD of 7.6 microg. Absorption parameters to blood as defined in the ICRP Publication 66 human respiratory tract model were calculated with the specific software GIGAFIT and led to the rapid fraction fr (0.800 to 0.873), the rapid rate sr (0.525 to 0.928 d(-1)), and the slow rate ss (1.57 x 10(-2) to 2.42 x 10(-3) d(-1)). Effective dose coefficients by inhalation for this UO4 compound using the in vivo experimental results were calculated to be between 0.52 and 0.70 x 10(-6) Sv Bq(-1). Comparison of these values with effective dose coefficients defined in ICRP Publication 68 for workers showed that UO4 could be considered as a fast soluble compound of Type F.