S.A. Gray

Use of DTPA for Increasing the Rate of Elimination of Plutonium-238 and Americium-241 from Rodents after their Inhalation as the Nitrates

This study has shown that: 1 both inhaled (2 μmol/kg) and injected (30 μmol/kg) diethylenetriaminepentaacetic acid (DTPA) can reduce the lung deposit of 238Pu and 241 Am inhaled as nitrate to about 1% of that in untreated controls; 2 injection of DTPA is more effective than aerosolized DTPA for reducing deposits of 238 Pu and 241Am in the liver and skelton; 3 combined treatment involving early inhalation of DTPA followed by repeated intravenous injections is likely to be the most effective treatment for workers who have accidentally inhaled plutonium and americium nitrates.

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 μmol 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.

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.

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.

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 μmol 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 238 Pu 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 μmol 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 μmol kg-1 ZnDTPA commencing at 4 d. After the continuous administration of 95 μmol 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.

The metabolism of ceramic and non-ceramic forms of uranium dioxide after deposition in the rat lung

Ceramic and non-ceramic forms of uranium dixoide, produced industrially, were administered to rats either by inhalation or as an aqueous suspension which was injected directly into the pulmonary region of the lungs. The results showed that: 1 both materials should be assigned to inhalation class Y as defined by the International Commission on Radiological Protection; 2 whilst the translocation of uranium to the blood for the non-ceramic UO2 was about twice that obtained for the ceramic form, the two dioxides were unlikely to be differentiated on the basis of their lung retention kinetics; 3 the distribution of uranium amongst body tissues and the relationship between systemic content and cumulative urinary excretion indicated that it was transported in the hexavalent form; 4 in addition to air sampling procedures, lung radioactivity counting measurements could be used to advantage for assessing occupational exposures; 5 the exposure limits should be based on radiation dose rather than chemical toxicity.

Studies on the Metabolic Behaviour of Industrial Actinide-bearing Aerosols after Deposition in the Rat Lung: An Experimental Basis for Interpreting Chest Monitoring Data and Assessing Limits on Intake for Workers

The metabolism of 239Pu and 241Am in 3 site-specific industrial dusts has been studied after their deposition in the rat lung. A comparative experiment has also been carried out with a mixture of these actinides inhaled as their nitrates. The aim of this study 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 translocated to the blood that can occur for industrially produced materials; 2 show that the annual limits on intake (ALIs) for the different materials vary between those postulated for class W and Y compounds by the International Commission on Radiological Protection; 3 indicate that acute intakes of 239Pu equivalent to the ALI can, depending on the nature of the dust, be estimated from 241Am chest monitoring data at times from a few days up to about 3 years after 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 treat ment 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 effec tive 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 con tent of 228Th was reduced to 20% of controls after sc injection and 15% after im injection. The correspond ing values using repeated DTPA administration were 80% and 54%. 4 It is concluded that 3,4,3-LIHOPO represents, poten tially, a considerable advance on DTPA, the current agent of choice for the treatment of wounds contami nated by 228Th.

Efficacies of LICAM (C) and DTPA for the decorporation of inhaled transportable forms of plutonium and americium from the rat

Fhe efficacies of N 1, N 5 , N 10 , N 14-tetrakis (2,3-dihydroxy-4-carboxybenzoyl)-tetra-azatetradecane LICAM(C)] and diethylenetriaminepenta-acetic acid (DTPA) (30 μmol/kg body wt.) have been nvestigated for plutonium (Pu) decorporation after inhalation as the nitrate or tributyl phosphate TBP) complexes and the data compared with those obtained after its intravenous injection as the :itrate. The efficacy of removal of americium (Am) inhaled as the nitrate has also been examined. The results show that: . whereas LICAM(C) and DTPA were similarly effective for removing Pu from the blood, -ICAM(C) was considerably inferior to DTPA when transportable forms of Pu were inhaled; LICAM(C) is ineffective for the decorporation of Am; the optimum treatment regimen for both Pu and Am involved the prompt and repeated administration of DTPA.

Metabolism of uranium in the rat after inhalation of two industrial forms of ore concentrate: the implications for occupational exposure.

Aerosols produced from two commercially available ore concentrates in which the uranium was present essentially in the one as ammonium diuranate (ADU) and in the other as uranium octoxide (U3O8) were administered to rats. The results show that: 1 uranium in the ADU bearing material was cleared rapidly from the lungs, mainly to the blood, such that the retention kinetics were similar to those for a class D (highly transportable) compound as defined by ICRP; 2 uranium in the U 3O8 bearing material was removed from the lungs principally by mechanical processes, the retention kinetics in this case being similar to those defined for a class Y (poorly transportable) compound; 3 for both materials the distribution of uranium amongst body tissues and the fraction of the systemic content excreted in urine were similar to those obtained after the injection of soluble hexavalent compounds; 4 for workers potentially exposed to both these materials, urine monitoring and lung radioactivity counting measurements should be used in addition to air sampling procedures for assessing the intake of uranium. 5 intakes of the ADU bearing material should be restricted to those permitted for short-term exposures on the basis of chemical toxicity, whereas those for the U3O 8 bearing material should be governed by radiation dose.