Treatment of accidental intakes of plutonium and americium: guidance notes.

The scientific basis for the treatment of the contamination of the human body by plutonium, americium and other actinides is reviewed. Guidance Notes are presented for the assistance of physicians and others who may be called upon to treat workers or members of the public who may become contaminated internally with inhaled plutonium nitrate, plutonium tributyl phosphate, americium nitrate or americium oxide.

A review of measurements of radionuclides in members of the public in the UK.

This paper summarises a comprehensive review of radio-analytical data from autopsy, whole or partial body monitoring and the assay of teeth, foetuses and urine for non-occupationally exposed members of the public in the UK between 1957 and 2003. Most attention has been given to measurements of artificial radionuclides formed in the nuclear fuel cycle, uranium and thorium. The review concentrates on measurements on people in the UK who live or have lived in the vicinity of nuclear power sites. When UK data are unavailable, or for the purposes of comparison, information has been included from studies in other countries. Highlights of key findings of the document are listed: The concentrations of strontium-90 in bone and teeth have reflected changes in the amounts present in the environment due to fallout from nuclear testing. There are higher concentration levels of 239+240Pu in samples from West Cumbria compared with the rest of the UK. However, the levels are so low that any increase in risk of induced skeletal tumours (including leukaemia) would be very small compared with those arising from the intake of natural radionuclides. As expected there have been only a few published autopsy studies. Both tissue sample mass and radionuclide concentrations were low, leading to relatively large measurement uncertainties. Whole body measurements of 137Cs in residents in Berkshire and Oxfordshire clearly show the effect of atmospheric testing of nuclear weapons and of the Chernobyl accident. A survey of whole body 137Cs and 134Cs content following the Chernobyl accident showed that residents of Central Scotland, North-West England and North Wales had twice the radiocaesium content of residents in the rest of England and Wales. Measurements of 131I in the thyroid have been reported following the accidents at Windscale and Chernobyl for most regions of the UK. Few excretion studies have been reported although this does not diminish their importance. One study on the urinary excretion rate of 90Sr in adults and children living in the Dounreay area suggested that the results did not support this radionuclide as being the cause of increased childhood leukaemia. Similar conclusions were drawn from another study involving the assay of 239Pu. It is suggested that a national database of measurements made on members of the public should be initiated. The database would provide a means for identifying future trends.

Comparison of predicted with observed biokinetics of inhaled plutonium nitrate and gadolinium oxide in humans.

The absorption kinetics to blood of plutonium and gadolinium after inhalation as nitrate and oxide in humans and animals has been studied. For each material, values describing the time dependence of absorption were derived from the studies in animals and used with the ICRP human respiratory tract model to predict lung retention and cumulative amounts to blood for the volunteers inhaling the same materials. Comparison with the observed behaviour in the volunteers suggests that absorption of plutonium and gadolinium is reasonably species independent, and that data obtained from animal studies can be used to assess their biokinetic behaviour in humans.

Comparison of absorption after inhalation and instillation of uranium octoxide.

Values for the absorption parameters were compared after inhalation or intratracheal instillation of 1.5 microm mass median aerodynamic diameter (MMAD) 233U3O8 particles into the lungs of HMT strain rats. The two sets of parameter values were similar, as were the calculated dose coefficients and predicted biokinetics for workers. Hence the inhalation and instillation techniques can probably both be used to generate values of the absorption parameters for U3O8.

Biokinetics and assessment of intake of thorium dioxide.

The aim of this work was to investigate the biokinetics of thorium dioxide in animals for the purpose of assessing intakes of the compound by workers and the resulting doses. The results imply that measurements of the decay products in the chest or extrapolations from urine analysis data are unlikely to be of value for doses below 20 mSv. Even higher doses should be interpreted with caution as a consequence of uncertainties in particle size distribution and variations in dietary excretion.

Anomalously high excretion of Pu in urine following inhalation of plutonium nitrate?

A study of the biokinetics of inhaled plutonium nitrate in two volunteers has been carried out. Low doses (approximately 80 microSv) were achievable because tracers of high isotopic purity were used: 237Pu (measurable by X ray spectrometry) and 244Pu (measurable by accelerator mass spectrometry). Lung retention, amount in blood, uptake to the liver and skeleton, and urinary and faecal excretion were measured. The measured urinary excretion rates are about a factor of three higher than those predicted from urine excretion data measured following intravenous injection of plutonium to the same volunteers. If similar biokinetic behaviour occurs in workers exposed to plutonium nitrate, intakes by inhalation and corresponding committed doses assessed by urine bioassay could be consistently overestimated by a similar factor.

Biokinetics of radionuclides and treatment of accidental intakes.

This paper describes the objectives and reviews the progress of EULEP Working Party 5, convened under the auspices of the European Union's Fifth Framework Programme, to 'cluster' two EU-supported contracts, Biokinetics and Dosimetry of Internal Contamination (BIODOS (EU Contract FIS5-1999-00214)) and Radionuclide Biokinetics Database (EULEP) (RBDATA-EULEP (Concerted Action Contract FIS5-1999-00218), and two non-EU funded projects, Biokinetics of Radionuclides in Human Volunteers (RNHV (non-EU funded project)) and Treatment of Accidental Intakes of Radionuclides (TAIR (part funded by EULEP)).

Design and implementation of monitoring programmes for internal exposure (project OMINEX).

The costs of monitoring for internal exposure in the workplace are usually significantly greater than the equivalent costs for external exposure. Therefore, there is a need to ensure that resources are employed with maximum effectiveness. The EC-funded OMINEX (optimisation of monitoring for internal exposure) project is developing methods for optimising the design and implementation of internal exposure monitoring programmes. Current monitoring programmes are being critically reviewed, the major sources of uncertainty in assessed internal dose investigated, and guidance formulated on factors such as programme design, choice of method/techniques, monitoring intervals, and monitoring frequency. OMINEX will promote a common, harmonised approach to the design and implementation of internal dose monitoring programmes throughout the EU.

Optimising the removal of inhaled plutonium and americium from the rat by administration of ZnDTPA in drinking water.

1. The efficacy of ZnDTPA administered in drinking water has been investigated for removing 238Pu and 241Am from the rat after their simultaneous inhalation as nitrates. 2. The continual administration of ZnDTPA 95 mumol kg-1 d-1 over a 21 d interval commencing 1 h after exposure reduced the 238Pu content of the lungs and total body to 2% and 8% of those in untreated animals; the corresponding values for 241Am were 3% and 5%. 3. The continual intakes of 950 mumol kg-1 d-1, intermittent intakes of 3600 mumol kg-1 d-1 and the repeated injection of 30 mumol kg-1 body weight were considered no more effective. 4. All orally administered concentrations of ZnDTPA, commencing 7 d after exposure, reduced the total body contents of 238Pu and 241Am to 17% and 20% of controls by 28 d. 5. Histopathological examination of the kidneys, liver and gastrointestinal tract showed no apparent effects of these treatment protocols. 6. It is concluded that the oral administration of ZnDTPA could be an effective treatment for the removal of inhaled transportable forms of Pu and Am after human exposure.

Decorporation of thorium-228 from the rat by 3,4,3-LIHOPO and DTPA after simulated wound contamination.

1. With DTPA as a comparison, the siderophore analogue 3,4,3-LIHOPO has been examined for its ability to remove 228Th nitrate from the rat after subcutaneous (sc) and intramuscular (im) injection to simulate wound contamination. The commencement of treatment was delayed 30 min, 6 h or 1 d and the animals killed at 7 d. 2. In all cases 3,4,3-LIHOPO was appreciably more effective than DTPA although the efficacy of treatment and the relative effectiveness of the ligands decreased rapidly with their delay in administration. 3. Optimum removal with both ligands occurred when initial local administration at 30 min after exposure was followed by repeated intraperitoneal injection at 6 h, 1, 2 and 3 d. Under these conditions the body content of 228Th was reduced to 20% of controls after sc injection and 15% after im injection. The corresponding values using repeated DTPA administration were 80% and 54%. 4. It is concluded that 3,4,3-LIHOPO represents, potentially, a considerable advance on DTPA, the current agent of choice for the treatment of wounds contaminated by 228Th.

Comparative efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat after simulated wound contamination as nitrates.

With DTPA as a comparison, the siderophore analogue 3,4,3-LIHOPO has been examined for its ability to remove 238Pu and 241Am from the rat after subcutaneous (s.c.) and intramuscular (i.m.) injection of about 200 Bq of each actinide (0.3 ng Pu, 1.6 ng Am). After the s.c. deposition of 238Pu and 241Am, both ligands were more effective after local administration than (in decreasing order) their repeated interperitoneal (i.p.) injection, single i.p. injection and continuous infusion. Dosages of 3 mumol kg-1 of 3,4,3-LIHOPO were at least as effective as 30 mumol kg-1 DTPA after each mode of administration. The most effective regimen of those investigated for s.c. 238Pu and 241Am involved local administration of 30 mumol kg-1 of 3,4,3-LIHOPO at 30 min followed by i.p. injections at 6 h, 1, 2 and 3 day. By day 7 after exposure, the amounts of 238Pu and 241Am retained in the body were 2 and 7% of those in controls, respectively and 10 and four times less than when DTPA was administered using the same regimen. The ligand 3,4,3-LIHOPO was more effective for 238Pu and 241Am after their i.m. injection. This was attributed to the greater retention of these actinides at the wound site (97 versus 67%) when treatment commenced. After a single local injection of 30 mumol kg-1 at 30 min, the amounts of 238Pu and 241Am retained in the body at 7 day were 0.9 and 0.8% of controls. These values were 34 and 27 times less than after local and repeated i.p. injections of DTPA at dosages of 30 mumol kg-1. It is concluded that the administration of 3,4,3-LIHOPO represents potentially a most significant advance in the treatment of wound contamination by 238Pu and 241Am by chelating agents.

Removal of inhaled plutonium and americium from the rat by administration of ZnDTPA in drinking water.

This study has examined the efficacy of ZnDTPA administered in drinking water for removing 238Pu and 241Am from the rat after their simultaneous inhalation as nitrates; the dosage used was 95 mumol kg-1d-1. The continuous administration of ZnDTPA over a 14 d interval, commencing 1 h after exposure, reduced the lung and total body contents of 238Pu to, respectively, 11% and 18% of those in untreated rats; the corresponding values for 241Am were 11% and 14%. After the continuous administration of 95 mumol kg-1 from 4 d to 28 d post exposure, the lung and total body contents of 238Pu were, respectively, 5% and 16% of those in controls; the corresponding values for 241Am were 7% and 19%. Further reductions in the actinide contents of body tissues were found when treatment was extended to 52 d or 76 d. These regimens were as effective as twice weekly injections of 30 mumol kg-1 ZnDTPA commencing at 4 d. After the continuous administration of 95 mumol kg-1 d-1 for 72 d, some pathological changes to the gastrointestinal tract were observed but these were considered to be reparable. It was concluded that further work is required to evaluate the toxicity of the ligand and to establish the optimal treatment regimen.

Radiological implications of inhaled 239Pu and 241Am in dusts at the former nuclear test site in Maralinga.

The biokinetics of 239Pu and 241Am present in three dust samples obtained from Maralinga were investigated after their deposition in the rat lung. Results were used as an experimental basis for assessing the radiological implications for human exposure. The transfer rates of these actinides to blood in the various dusts differed by 50-fold. The most transportable forms were compatible with a material that had 25% class W and 75% class Y characteristics. The doses per unit intake for adults, children, and infants exposed to an aerosol of 5 microns AMAD were calculated to be, respectively, 0.059, 0.076, and 0.140 mSv Bq-1. The corresponding doses for the least transportable forms were the same as those calculated for a class Y compound, namely 0.036, 0.049, and 0.096 mSv Bq-1. The behavior of the actinides in humans was predicted by combining the transfer rates to blood with mechanical clearance data obtained after volunteers had inhaled 85Sr or 88Y labeled fused aluminosilicate particles. The results suggested that monitoring of 241Am in the chest could be used to advantage for assessing intakes incurred by workers involved with any further decontamination procedures but would be of little practical value for assessing inadvertent public exposure. The paper includes comments on the relevance of the 1990 ICRP recommendations and the proposed new dosimetric model for the respiratory tract.

The efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat: comparison with other siderophore analogues.

With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has been tested for its ability to remove 238Pu and 241Am from rats after their inhalation or intravenous injection as nitrate. The most effective treatment regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3-LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body were reduced respectively to 2 and 4% of those in untreated animals. These values were six and three times less than when DTPA was administered using the same protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally effective, the lung and total body contents being reduced respectively to 13 and 10% of those in controls. Some animals showed slight degenerative changes in the liver and proximal tubules of the kidneys after the repeated administration of 30 mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after DTPA treatment. After the intravenous injection of Pu, the most effective regimen was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7 days was reduced to 7% controls compared with 19% after the repeated administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO was less effective owing to the higher retention of Pu in the liver. With repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for the decorporation of Am; the body contents were 16 and 31% of those in controls respectively. Importantly, the body content was still reduced to 28% of control after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is also superior to other siderophore analogues, could represent a most significant development in the decorporation of Pu and Am.

The efficacy of DFO-HOPO, DTPA-DX and DTPA for enhancing the excretion of plutonium and ameriicum from the rat.

A hydroxypridinone derivative of desferrioxamine (Na-DFO-HOPO), a dihydroxamic derivative of diethylenetriaminepenta-acetic acid (ZnNa-DTPA-DX), and DTPA (CaNa3- and ZnNa3-DTPA) were tested at dosages of 30 mumol kg-1 for their ability to remove 238Pu or 241Am from rats after their intravenous injection as citrate or inhalation as nitrate. The most effective treatment regimen for injected Pu was the repeated administration of DFO-HOPO; by 7 days the body content was reduced to 8% of that in untreated animals. Repeated dosages of 3 mumol kg-1 DFO-HOPO were as effective as those of 30 mumol kg-1 DTPA. After inhalation of Pu nitrate, repeated treatment with DTPA, DTPA-DX or DFO-HOPO reduced the body content by 7 days to, respectively, 10, 15 and 31% of those in untreated animals. After inhalation of Am, DTPA-DX and DTPA were equally effective, the body contents being reduced to 7% of control values with repeated treatment. Injection of DFO-HOPO was ineffective for enhancing the elimination of inhaled or injected Am. The results confirm the strategy of examining the use of siderophore analogues for the decorporation of Pu or Am. However, at present DTPA should remain the agent of choice, particularly after inhalation.

Efficacy of tiron for enhancing the excretion of uranium from the rat.

Tiron (sodium 4,5-dihydroxybenzene-1,3-disulphonate) has been suggested as a possible antidote for acute uranium poisoning. In this study, the compound has been administered intraperitoneally to rats in dosages of 30, 300 or 1000 mumols kg-1 at 20, 60 and 180 min after the intratracheal instillation of uranyl nitrate. The amounts of uranium deposited in the lungs of rats were equivalent to intakes by workers of about 12 times the permitted daily limit of 2.5 mg. The average body content of uranium at 5 d after exposure were, respectively, about 100%, 78% and 65% of those in untreated animals. It is concluded that the administration of Tiron is of limited practical value for treatment of uranium exposures not greatly in excess of the permitted intake.

The efficacy of DTPA treatment after deposition of thorium nitrate in the rat lung.

The efficacy of CaDTPA and ZnDTPA, the chelating agents of choice for several actinide elements, have been evaluated after the deposition of thorium in the rat lung in widely different amounts. The results showed that: 1. When the initial mass concentration of thorium simulated human exposure to four times the annual limits on intake for 232Th, the prompt (300 or 1000 mumol kg-1 body weight at 0.02 d) or repeated (30 or 300 mumol kg-1 body weight at 0.02, 0.25, 1,2,3 d) administration of CaDTPA were at best only moderately successful for enhancing the elimination of thorium. By 7 d after exposure, the body contents of thorium were, respectively, about 74%, 65%, 90% and 74% of those present in untreated animals. 2. When the mass concentration simulated 1.7 x 10(-3) times the annual limits on intake for 232Th, the efficacy of treatment was not increased appreciably despite the substantial reduction in mass. After the repeated administration of CaDTPA at doses of 30 and 300 mumol kg-1 using the protocol above, the body contents of thorium by 7 d were, respectively, 69% and 51% of those in untreated animals. 3. Under comparable conditions, the efficacy of ZnDTPA was less than CaDTPA. The results suggest that more effective chelating agents are needed for the treatment of workers exposed to water soluble thorium compounds.

The efficacies of pure LICAM(C) and DTPA on the retention of plutonium-238 and americium-241 in rats after their inhalation as nitrate and intravenous injection as citrate.

The pure carboxylated catechoyl amide LICAM(C) and the calcium and zinc salts of diethylenetriaminepenta-acetic acid (DTPA), were tested for efficacy for removing 238Pu and 241Am from rats after inhalation of the nitrate or intravenous injection of the citrate. The results were compared with the efficacy of methylated LICAM(C) used in previous experiments. It was shown that: (1) after inhalation of 238Pu nitrate, DTPA was far superior to pure LICAM(C); (2) after intravenous injection of 238Pu citrate, the infusion of DTPA plus LICAM(C) was only marginally more effective than DTPA alone; and (3) after inhalation or intravenous injection of 238Pu plus 241Am, the efficacy of pure LICAM(C) was only marginally more effective than the methylated form and neither form was effective for the decorporation of 241Am. It was concluded that DTPA, at present, remains the chelating agent of choice for treating persons accidentally contaminated with transportable forms of Pu and Am.

The use of animal experiments for assessing annual limits on intake and interpreting chest-monitoring data for workers exposed to industrial actinide-bearing dusts.

The metabolic behavior of 239Pu and 241Am present in three industrial dusts has been studied after their inhalation by the rat. A comparative experiment has also been carried out with a mixture of these actinides, inhaled as their nitrates. The aim of this work was to provide an experimental basis for assessing limits on intake and to establish whether the 239Pu content in the lungs could be interpolated from measurements of 241Am. The results (1) demonstrate the wide differences in the lung retention kinetics of the actinides and in the absolute and relative amounts which translocate to the blood that can occur for industrially produced materials; (2) show that the annual limits on intake (ALI) for the different materials vary between those postulated for class W and Y compounds by the International Commission on Radiological Protection; (3) indicate that, depending on the nature of the dust, acute intakes of 239Pu equivalent to the ALI can be estimated from 241Am chest-monitoring data at times from a few days up to about 3 y after exposure.

A new small animal inhalation facility: design and performance.

A new inhalation facility is described which allows any combination of up to 72 rodents ranging in size from the mouse to the guinea pig to be exposed simultaneously. Typically for aerosols of MMD 1.5 microns the initial lung deposit in the rat is 0.05 to 0.07% of the total amount of material used and the coefficient of variation between animals is 15 to 20%.