Biokinetic Method on Simultaneous Intake of Radionuclides from Multiple Intake Scenarios for Application in Internal Exposures.

Biokinetics underlies the basis for assessment of internal exposures. This paper develops a biokinetic method on simultaneous intake of radionuclides from multiple intake scenarios in internal exposures. With numerical techniques that transform the whole biokinetics between the coupled and decoupled representations of the same problem, this method applies to coupled biokinetics with complex structures and has no restrictions of practical importance on the number of intake scenarios, the number of intake parent radionuclides and decay products, and the complexity of decay relationships between parent and progeny nuclides. For illustration, this method is applied to an assumed case of mixed inhalation and ingestion of weapon-grade plutonium material for reference workers that is focused on Pu and Am. Due to coupled biokinetics between the direct intake and ingrowth parts in different intake pathways, the multiple intake results (the contents of lungs, daily excretions, and cumulative contents) display richer behaviors as compared to single intake cases. This method benefits both the prospective and retrospective assessment of internal exposures for complex intake cases in actual applications.

COMPARING LUNGS, LIVER AND KNEE MEASUREMENT GEOMETRIES AT VARIOUS TIMES POST INHALATION OF 239Pu AND 241Am.

In-vivo measurement of Pu/241Am in workers is carried out by placing suitable detector above lungs, liver and skeleton, as major fraction of Pu/Am is transferred to liver and skeleton, after its retention in entry organ. In this work, committed effective dose (CED) corresponding to minimum detectable activity for Type M and Type S 239Pu/241Am deposited in these organs are presented and a monitoring protocol of organ measurement giving lowest CED at different time intervals post inhalation is described. We have observed, for Type M compounds, lung measurement is most sensitive method during initial days after exposure. Liver measurement yields lowest CED between 100 and 5000 d and beyond that bone measurement gives lowest CED. For Type S compounds lung measurement remains most sensitive method even up to 10 000 d post inhalation. This study will be useful for the assessment of CED due to internally deposited 239Pu/241Am in the workers.

Comparison of ICRP 67 and Other Plutonium Systemic Model Predictions with the Biokinetic Data from Nonhuman Primates.

Despite the presence of a relatively large amount of human data available on the metabolism of plutonium, the experimental animal data is still important in constructing and parameterizing the biokinetic models. Recognizing this importance, the biokinetic data obtained from studies done by P.W. Durbin in nonhuman primates (NHP) were evaluated against the ICRP 67 systemic model and the two human models developed thereafter. The default transfer rates recommended for adult humans in these models predict the urinary excretion in NHP to a certain extent. However, they were unable to describe the fecal excretion rates several days post intake and the activities in skeleton and liver at the time of the death. These inconsistencies between the human reference models and the NHP biokinetic data are the result of metabolic and physiological differences between the species, as demonstrated by early biokinetic studies.

Ischemic heart disease in workers at Mayak PA: latency of incidence risk after radiation exposure.

We present an updated analysis of incidence and mortality from atherosclerotic induced ischemic heart diseases in the cohort of workers at the Mayak Production Association (PA). This cohort constitutes one of the most important sources for the assessment of radiation risk. It is exceptional because it comprises information on several other risk factors. While most of the workers have been exposed to external gamma radiation, a large proportion has additionally been exposed to internal radiation from inhaled plutonium. Compared to a previous study by Azizova et al. 2012, the updated dosimetry system MWDS-2008 has been applied and methods of analysis have been revised. We extend the analysis of the significant incidence risk and observe that main detrimental effects of external radiation exposure occur after more than about 30 years. For mortality, significant risk was found in males with an excess relative risk per dose of 0.09 (95% CI: 0.02; 0.16) [Formula: see text] while risk was insignificant for females. With respect to internal radiation exposure no association to risk could be established.

Application of Bayesian inference to the bioassay data from long-term follow-up of two refractory PuO2 inhalation cases.

The dominant contribution to the uncertainty in internal dose assessment can often be explained by the uncertainty in the biokinetic model structure and parameters. The International Commission on Radiological Protection (ICRP) is currently updating its biokinetic models, including the Human Respiratory Tract Model (HRTM). Gregoratto et al. (2010) proposed a physiologically-based particle transport model that simplifies significantly the representation of particle clearance from the alveolar interstitial region. Bayesian inference using the Weighted Likelihood Monte-Carlo Sampling (WeLMoS) method is applied to the bioassay and autopsy data from the U.S. Transuranium and Uranium Registries' (USTUR) tissue donors 0202 and 0407 exposed to "high fired," refractory PuO2 aerosols in order to examine the applicability of the revised model and to estimate the uncertainties in model parameters and the lung doses as expressed by the posterior probability distributions. It is demonstrated that, with appropriate adjustments, the Gregoratto et al. particle transport model can describe situations involving exposure to highly insoluble particles. Significant differences are observed in particle clearance pattern characteristics to these two individuals' respiratory systems. The respiratory tract of registrant 0202 was most likely compromised by his prior occupational exposure to coal dust, smoking habit, and chronic obstructive pulmonary disease, while donor 0407 was a non-smoker and had no prior history of lung disorder. However, the central values of the particle transport parameter posterior distributions for both cases are found to be still within the 68% probability range for the inter-subject variability derived by Gregoratto et al. PuO2 particles produced by the plutonium fire were extremely insoluble, with about 99% absorbed into blood at a rate of approximately 4.8 × 10 d (Case 0202) and 5.1 × 10 d (Case 0202). When considering this type of plutonium material, doses to other body organs are small in comparison to those to tissues of the respiratory tract. More than 95% of the total committed weighted equivalent dose is contributed by the lungs.

Plutonium behavior after pulmonary administration according to solubility properties, and consequences on alveolar macrophage activation.

The physico-chemical form in which plutonium enters the body influences the lung distribution and the transfer rate from lungs to blood. In the present study, we evaluated the early lung damage and macrophage activation after pulmonary contamination of plutonium of various preparation modes which produce different solubility and distribution patterns. Whatever the solubility properties of the contaminant, macrophages represent a major retention compartment in lungs, with 42 to 67% of the activity from broncho-alveolar lavages being associated with macrophages 14 days post-contamination. Lung changes were observed 2 and 6 weeks post-contamination, showing inflammatory lesions and accumulation of activated macrophages (CD68 positive) in plutonium-contaminated rats, although no increased proliferation of pneumocytes II (TTF-1 positive cells) was found. In addition, acid phosphatase activity in macrophages from contaminated rats was enhanced 2 weeks post-contamination as compared to sham groups, as well as inflammatory mediator levels (TNF-α, MCP-1, MIP-2 and CINC-1) in macrophage culture supernatants. Correlating with the decrease in activity remaining in macrophages after plutonium contamination, inflammatory mediator production returned to basal levels 6 weeks post-exposure. The production of chemokines by macrophages was evaluated after contamination with Pu of increasing solubility. No correlation was found between the solubility properties of Pu and the activation level of macrophages. In summary, our data indicate that, despite the higher solubility of plutonium citrate or nitrate as compared to preformed colloids or oxides, macrophages remain the main lung target after plutonium contamination and may participate in the early pulmonary damage.

238Pu: accumulation, tissue distribution, and excretion in Mayak workers after exposure to plutonium aerosols.

The alpha spectrometry measurements of specific activity of 238Pu and 239Pu in urine from bioassay examinations of 1,013 workers employed at the radiochemical and plutonium production facilities of the Mayak Production Association and in autopsy specimens of lung, liver, and skeleton from 85 former nuclear workers who died between 1974-2009, are summarized.The accumulation fraction of 238Pu in the body and excreta has not changed with time in workers involved in production of weapons-grade plutonium production (e.g., the plutonium production facility and the former radiochemical facility). The accumulation fraction of 238Pu in individuals exposed to plutonium isotopes at the newer Spent Nuclear Fuel Reprocessing Plant ranged from 0.13% up to 27.5% based on the autopsy data. No statistically significant differences between 238Pu and 239Pu in distribution by the main organs of plutonium deposition were found in the Mayak workers. Based on the bioassay data,the fraction of 238Pu activity in urine is on average 38-69% of the total activity of 238Pu and 239Pu, which correlates with the isotopic composition in workplace air sampled at the Spent Nuclear Fuel Reprocessing Plant. In view of the higher specific activity of 238Pu, the contribution of 238Pu to the total internal dose, particularly in the skeleton and liver, might be expected to continue to increase, and continued surveillance is recommended.

238Pu: a review of the biokinetics, dosimetry, and implications for human exposures.

Plutonium-238 (238Pu) has a half-life of about 87.7 y and thus a higher specific activity than 239Pu. It is used in radioisotope thermoelectric generators and is a substantial source of plutonium alpha-radiation in spent nuclear fuels. Early animal studies demonstrated differences in the biokinetics of inhaled oxides of 238Pu and 239Pu with 238Pu having a substantially more rapid translocation from the lungs to the systemic organs, particularly the skeleton. This resulted in the predominant occurrence of skeletal cancers in animals exposed to 238Pu oxides but lung cancers in those with exposures to 239Pu oxides. The anatomical distribution of osteogenic sarcomas seen in animal studies was similar to that observed with 239Pu and also in plutonium workers but differed from naturally occurring tumors. The in vivo "solubility" of 238Pu has been associated with the relative amounts of 238Pu/239Pu in the particles and calcination temperatures during the preparation of the dioxides. There is experimental evidence of in vivo 238Pu particle fragmentation attributed to nuclear recoil during radioactive decay. The resulting conversion of microparticles to nanoparticles may alter their interactions with macrophages and transport across epithelial barriers. There are few documented cases of human exposures, but the biokinetics appeared to depend on the chemical and physical nature of the aerosols. Robust human biokinetic and dosimetric models have not been developed, due in part to the lack of data. With the acceleration of nuclear technologies and the greater demand for reprocessing and/or disposal of spent nuclear fuels, the potential for human exposure to 238Pu will likely increase in the future.

A method for calculating Bayesian uncertainties on internal doses resulting from complex occupational exposures.

Estimating uncertainties on doses from bioassay data is of interest in epidemiology studies that estimate cancer risk from occupational exposures to radionuclides. Bayesian methods provide a logical framework to calculate these uncertainties. However, occupational exposures often consist of many intakes, and this can make the Bayesian calculation computationally intractable. This paper describes a novel strategy for increasing the computational speed of the calculation by simplifying the intake pattern to a single composite intake, termed as complex intake regime (CIR). In order to assess whether this approximation is accurate and fast enough for practical purposes, the method is implemented by the Weighted Likelihood Monte Carlo Sampling (WeLMoS) method and evaluated by comparing its performance with a Markov Chain Monte Carlo (MCMC) method. The MCMC method gives the full solution (all intakes are independent), but is very computationally intensive to apply routinely. Posterior distributions of model parameter values, intakes and doses are calculated for a representative sample of plutonium workers from the United Kingdom Atomic Energy cohort using the WeLMoS method with the CIR and the MCMC method. The distributions are in good agreement: posterior means and Q(0.025) and Q(0.975) quantiles are typically within 20 %. Furthermore, the WeLMoS method using the CIR converges quickly: a typical case history takes around 10-20 min on a fast workstation, whereas the MCMC method took around 12-72 hr. The advantages and disadvantages of the method are discussed.

Late-occurring pulmonary pathologies following inhalation of mixed oxide (uranium + plutonium oxide) aerosol in the rat.

Accidental exposure by inhalation to alpha-emitting particles from mixed oxide (MOX: uranium and plutonium oxide) fuels is a potential long-term health risk to workers in nuclear fuel fabrication plants. For MOX fuels, the risk of lung cancer development may be different from that assigned to individual components (plutonium, uranium) given different physico-chemical characteristics. The objective of this study was to investigate late effects in rat lungs following inhalation of MOX aerosols of similar particle size containing 2.5 or 7.1% plutonium. Conscious rats were exposed to MOX aerosols and kept for their entire lifespan. Different initial lung burdens (ILBs) were obtained using different amounts of MOX. Lung total alpha activity was determined by external counting and at autopsy for total lung dose calculation. Fixed lung tissue was used for anatomopathological, autoradiographical, and immunohistochemical analyses. Inhalation of MOX at ILBs ranging from 1-20 kBq resulted in lung pathologies (90% of rats) including fibrosis (70%) and malignant lung tumors (45%). High ILBs (4-20 kBq) resulted in reduced survival time (N = 102; p < 0.05) frequently associated with lung fibrosis. Malignant tumor incidence increased linearly with dose (up to 60 Gy) with a risk of 1-1.6% Gy for MOX, similar to results for industrial plutonium oxide alone (1.9% Gy). Staining with antibodies against Surfactant Protein-C, Thyroid Transcription Factor-1, or Oct-4 showed differential labeling of tumor types. In conclusion, late effects following MOX inhalation result in similar risk for development of lung tumors as compared with industrial plutonium oxide.

Carcinogenesis from inhaled (239)PuO(2) in beagles: Evidence for radiation homeostasis at low doses?

From the early 1970's to the late 1980's, Pacific Northwest National Laboratory conducted life-span studies in beagle dogs on the biological effects of inhaled plutonium ((238)PuO(2), (239)PuO(2), and Pu[NO(3)](4)) to help predict risks associated with accidental intakes in workers. Years later, the purpose of the present follow-up study was to reassess the dose-response relationship for lung cancer in the PuO(2) dogs compared to controls-with particular focus on the dose-response at relatively low lung doses. A PuO(2) aerosol (2.3 mum activity-median aerodynamic diameter, 1.9 mum geometric standard deviation) was administered to six groups of 20 young (18-mo-old) beagle dogs (10 males and 10 females) by inhalation at six different activity levels, as previously described in Laboratory reports. Control dogs were sham-exposed. In dose level 1, initial pulmonary lung depositions were 130 + or - 48 Bq (3.5 + or - 1.3 nCi), corresponding to 1 Bq g lung tissue (0.029 + or - 0.001 nCi g(-1)). Groups 2 through 6 received initial lung depositions (mean values) of 760, 2,724, 10,345, 37,900, and 200,000 Bq (22, 79, 300, 1,100, and 5,800 nCi) PuO(2), respectively. For each dog, the absorbed dose to lungs was calculated from the initial lung burden and the final lung burden at time of death and lung mass, assuming a single, long-term retention function. Insoluble plutonium oxide exhibited long retention times in the lungs. Increased dose-dependent mortality due to lung cancer (bronchiolar-alveolar carcinoma, adenocarcinoma, and epidermoid carcinoma) and radiation pneumonitis (in the highest exposure group) were observed in dogs exposed to PuO(2). Calculated lung doses ranged from a few cGy (lowest exposure level) to 7,764 cGy in dogs that experienced early deaths from radiation pneumonitis. Data were regrouped by lifetime lung dose and plotted as a function of lung tumor incidence. The lung tumor incidence in controls and zero-dose exposed dogs was 18% (5/28). However, no lung tumors were observed in 16 dogs with the lowest lung doses (8 to 22 cGy, mean 14.4 + or - 7.6 cGy), and only one lung tumor was observed in the next 10 dogs with lung doses ranging from 27 to 48 cGy (mean 37.5 + or - 10.9 cGy). By least-squares analysis, a pure-quadratic function represented the overall dose-response (n = 137, r = 0.96) with no apparent dose-related threshold. Reducing this function to three linear dose-response components, we calculated risk coefficients for each. However, the incidence of lung tumors at zero dose was significantly greater than the incidence at low dose (at the p < or = 0.053 confidence level), suggesting a protective effect (radiation homeostasis) of alpha-particle radiation from PuO(2). If a threshold for lung cancer incidence exists, it will be observed in the range 15 to 40 cGy.

Isotopic and elemental composition of plutonium/americium oxides influence pulmonary and extra-pulmonary distribution after inhalation in rats.

The biodistribution of plutonium and americium has been studied in a rat model after inhalation of two PuO(2) powders in lungs and extra-pulmonary organs from 3 d to 3 mo. The main difference between the two powders was the content of americium (approximately 46% and 4.5% of total alpha activity). The PuO(2) with a higher proportion of americium shows an accelerated transfer of activity from lungs to blood as compared to PuO(2) with the lower americium content, illustrated by increased urinary excretion and higher bone and liver actinide retention. The total alpha activity measured reflects mostly the americium biological behavior. The activity contained in epithelial lining fluid, recovered in the acellular phase of broncho-alveolar lavages, mainly contains americium, whereas plutonium remains trapped in macrophages. Epithelial lining fluid could represent a transitional pulmonary compartment prior to translocation of actinides to the blood and subsequent deposition in extra-pulmonary retention organs. In addition, differential behaviors of plutonium and americium are also observed between the PuO(2) powders with a higher dissolution rate for both plutonium and americium being obtained for the PuO(2) with the highest americium content. Our results indicate that the biological behavior of plutonium and americium after translocation into blood differ two-fold: (1) for the two actinides for the same PuO(2) aerosol, and (2) for the same actinide from the two different aerosols. These results highlight the importance of considering the specific behavior of each contaminant after accidental pulmonary intake when assessing extra-pulmonary deposits from the level of activity excreted in urine or for therapeutic strategy decisions.

Lung fibrosis and lung cancer incidence in beagle dogs that inhaled 238PuO2 or 239PuO2.

Determination of radiation protection guidelines for persons working with plutonium has been complicated by limited human data on the biological behavior and subsequent health effects from internally deposited plutonium. One solution has been the use of animal models to predict likely health effects in humans. To compare the relationships between plutonium inhalation and lung fibrosis and lung cancer, data from life-span studies of beagle dogs given a single exposure to either plutonium-238 dioxide (238PuO2) or plutonium-239 dioxide(239PuO2) were analyzed. Estimates of the cumulative hazard of lung fibrosis and lung cancer after exposure to either were generated. The hazard of lung fibrosis was not consistent with a linear no-threshold model, although the magnitude of the threshold differed by radionuclide. In dogs given 239PuO2,the best model of lung fibrosis incorporated a linear dose response function; a linear-quadratic dose-response function fit the data better in dogs given 238PuO2. At any given cumulative dose, the lung fibrosis hazard was greater for dogs given 238PuO2. In dogs given 238PuO2, with or without covariates, aquadratic dose-response function for lung cancer hazard fit better than a linear no-threshold model. In dogs given 239PuO2, models of lung cancer with the dose-response function as the sole predictor variable were consistent with a linear no-threshold model; however, a quadratic dose-response function with a cell-killing term fit better. These findings have implications for radiation protection because, while lung cancer hazard was dependent on cumulative dose, regardless of isotope, the lung fibrosis hazard depended on both cumulative dose and isotope.

Lauriston S. Taylor Lecture: the quest for therapeutic actinide chelators.

All of the actinides are radioactive. Taken into the body, they damage and induce cancer in bone and liver, and in the lungs if inhaled, and U(VI) is a chemical kidney poison. Containment of radionuclides is fundamental to radiation protection, but if it is breached accidentally or deliberately, decontamination of exposed persons is needed to reduce the consequences of radionuclide intake. The only known way to reduce the health risks of internally deposited actinides is to accelerate their excretion with chelating agents. Ethylendiaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were introduced in the 1950's. DTPA is now clinically accepted, but its oral activity is low, it must be injected as a Ca(II) or Zn(II) chelate to avoid toxicity, and it is structurally unsuitable for chelating U(VI) or Np(V). Actinide penetration into the mammalian iron transport and storage systems suggested that actinide ions would form stable complexes with the Fe(III)-binding units found in potent selective natural iron chelators (siderophores). Testing of that biomimetic approach began in the late 1970's with the design, production, and assessment for in vivo Pu(IV) chelation of synthetic multidentate ligands based on the backbone structures and Fe(III)-binding groups of siderophores. New efficacious actinide chelators have emerged from that program, in particular, octadentate 3,4,3-LI(1,2-HOPO) and tetradentate 5-LIO(Me-3,2-HOPO) have potential for clinical acceptance. Both are much more effective than CaNa3-DTPA for decorporation of Pu(IV), Am(III), U(VI), and Np(IV,V), they are orally active, and toxicity is acceptably low at effective dosage.

A Monte Carlo method for calculating Bayesian uncertainties in internal dosimetry.

This paper presents a novel Monte Carlo method (WeLMoS, Weighted Likelihood Monte-Carlo sampling method) that has been developed to perform Bayesian analyses of monitoring data. The WeLMoS method randomly samples parameters from continuous prior probability distributions and then weights each vector by its likelihood (i.e. its goodness of fit to the measurement data). Furthermore, in order to quality assure the method, and assess its strengths and weaknesses, a second method (MCMC, Markov chain Monte Carlo) has also been developed. The MCMC method uses the Metropolis algorithm to sample directly from the posterior distribution of parameters. The methods are evaluated and compared using an artificially generated case involving an exposure to a plutonium nitrate aerosol. In addition to calculating the uncertainty on internal dose, the methods can also calculate the probability distribution of model parameter values given the observed data. In other words, the techniques provide a powerful tool to obtain the estimates of parameter values that best fit the data and the associated uncertainty on these estimates. Current applications of the methodology, including the determination of lung solubility parameters, from volunteer and cohort data, are also discussed.

Uncertainties in internal doses calculated for Mayak workers--a study of 63 cases.

This study makes use of 63 cases of Mayak workers exposed to Pu-239 with autopsy data and some late-time urine bioassay data. In addition, air-concentration data--used to construct monthly average values--are available for each case, which provide the time dependence and potential magnitudes of normal inhalation intakes for each case. The purpose of the study is to develop and test Bayesian methods of dose calculation for the Mayak workers. The first part of the study was to quantitatively characterise the uncertainties of the bioassay data. Then, starting with three different published biokinetic models, the data are fit by varying intake and model perturbation parameters, e.g., parameters influencing the lung, thoracic lymph nodes, liver and bone retention. Statistical self-consistency arguments are used to check the measurement uncertainty parameters within the Poisson-lognormal model. The second part of the study is to set up and test Bayesian dose calculations, which use the point determinations of biokinetic parameters from the study cases within a discrete, empirical Bayes approximation. The main conclusion of the study is that these methods are now ready to be applied to the entire Mayak worker population.

Radiotoxicity of inhaled (239)PuO(2) in dogs.

Beagle dogs inhaled graded exposure levels of insoluble plutonium dioxide ((239)PuO(2)) aerosols in one of three monodisperse particle sizes at the Lovelace Respiratory Research Institute (LRRI) to study the life-span health effects of different degrees of alpha-particle dose non-uniformity in the lung. The primary noncarcinogenic effects seen were lymphopenia, atrophy and fibrosis of the thoracic lymph nodes, and radiation pneumonitis and pulmonary fibrosis. Radiation pneumonitis/ pulmonary fibrosis occurred from 105 days to more than 11 years after exposure, with the lowest associated alpha-particle dose being 5.9 Gy. The primary carcinogenic effects also occurred almost exclusively in the lung because of the short range of the alpha-particle emissions. The earliest lung cancer was observed at 1086 days after the inhalation exposure. The most common type seen was papillary adenocarcinoma followed by bronchioloalveolar carcinoma. These lung cancer results indicate that a more uniform distribution of alpha-particle dose within the lung has an equal or possibly greater risk of neoplasia than less uniform distributions of alpha-particle dose. The results are consistent with a linear relationship between dose and response, but these data do not directly address the response expected at low dose levels. No primary tumors were found in the tracheobronchial and mediastinal lymph nodes despite the high alpha-particle radiation doses to these lymph nodes, and no cases of leukemia were observed.

Comparisons of 239Pu inhalation doses calculated with ICRP 67 and proposed systemic models.

The International Commission on Radiological Protection (ICRP) has issued an age-specific systemic biokinetic model for plutonium (Pu), which was later modified to give better agreement with measured urinary excretion data. Recently, the current ICRP systemic Pu model was improved by Leggett et al. based on recently developed data. Incorporation of 239Pu in the human body may result in significant internal radiation exposure. In the present work, the retentions in organs and tissues, the equivalent dose and effective dose from 239Pu for workers and members of the public were estimated and compared under the current ICRP and the proposed models. 239Pu contents in liver and in other soft tissue calculated with the proposed model are higher than predicted by the ICRP model, whereas bone content is lower than predicted by the ICRP model. Based on the proposed model, the inhalation equivalent dose coefficient in some organs, e.g. liver and kidneys, is increased, but there is no significant change in the effective inhalation dose coefficients of 239Pu for workers and members of the public.

Practical action levels for chelation therapy in plutonium inhalation using nose swab.

The aim of this study is to propose action levels for chelation therapy in the case of inhalation of plutonium compounds using nose swabs. The relationship between the activity found in the nose swabs and early faecal excretion was investigated using actual cases at JAEA-NFCEL. The ratio was found to be in log-normal distribution. The action levels based on the activity of nose swab corresponding to 10 ALI (=200 mSv) are determined for the facilities at JAEA-NFCEL by using the relationship and specific information such as isotopic ratio and physicochemical characteristics of plutonium compounds.

Decorporation of plutonium by pulmonary administration of Ca-DTPA dry powder: a study in rat after lung contamination with different plutonium forms.

This study evaluates the decorporation efficacy of a pulmonary administration of a new Ca-DTPA (diethylenetriaminepentaacetic acid) dry powder (18 micromol kg(-1) of body mass) after pulmonary contamination of rats with different Pu compounds. After inhalation of PuO2, a delayed intratracheal administration of DTPA cannot reduce significantly the retention of Pu in the lungs but limits its transfer in liver and skeleton. After pulmonary contamination by Pu nitrate, early insufflation of the DTPA powder appears twice as more efficient than an i.v injection of DTPA (30 micromol kg(-1)) to reduce Pu retention in the lungs and is as effective as i.v. injection to limit the extrapulmonary deposit. In contrast, a delayed administration of DTPA cannot reduce the lung or extrapulmonary retention. In conclusion, the improvement of aerodynamic properties of DTPA powder leads to an increase of DTPA amount deposited in the lungs and enhances the body decorporation.