Hylton Smith

The Behaviour of Uranium-233 Oxide and Uranyl-233 Nitrate in Rats

233UO2 and 233UO2(NO3)2 in aqueous suspension have been administered to rats by pulmonary intubation. The 233U associated with the fraction of the 233UO2 less than 4 nm in diameter translocates from lungs to blood at the same rapid rate as 233U from 233UO2(NO3)2. Identical reactions with blood plasma and lung fluid were observed whether the 233U was administered as less than 4 nm 233UO2 particles or 233UO2(NO3)2. It is suggested that oxidation of UO2 to UO3 occurs followed by the formation of uranyl ion. In blood plasma, approximately 50 per cent of the 233U is bound to transferrin, 25 per cent to citrate and 25 per cent on bicarbonate.

Factors affecting the mobility of plutonium-238 dioxide in the rat.

A major factor influencing the movement of plutonium-238 from the lungs to blood after the intubation of oxide suspensions is the presense of 0.001 micrometer diameter particles. In a polydisperse suspension of particles this fraction increases with time, due it is thought, to fragmentation of larger particles induced by alpha decay. The rate of this process could account for the greater transportability in vivo of plutonium-238 relative to plutonium-239 when the oxides are inhaled. In blood, 0.001 micrometer diameter plutonium-238 oxide particles undergo a rapid reaction to form a low molecular weight species before plutonium is complexed with transferrin and citrate ions. The filtration of this species through the kidneys may explain the observed enhanced urinary excretion of plutonium relative to administered plutonium citrate. The mechanism of urinary excretion and relationship between cumulative urinary excretion and body content for plutonium-238 is similar to that previously observed for plutonium-239, even though different methods of preparation of the oxides were used.

The reactions of 1.0 nanometre diameter plutonium-238 dioxide particles with rat lung fluid.

The reactions of 1.0 nm particles of plutonium-238 dioxide with rat lung fluid have been studied both in vivo and in vitro. In both cases two products have been identified, (i) plutonium-labelled pulmonary surfactant and (ii) a heterogeneous plutonium-labelled material isolated by column chromatography. The formation of plutonium-labelled pulmonary surfactant results in the rapid translocation of plutonium from lungs to blood and in a high urinary excretion relative to administered plutonium citrate.

The Mobility of Curium-244 Dioxide in the Bronchially Intubated Rat

The mobility of curium dioxide in the rat after pulmonary intubation has been investigated by administering suspensions containing different particle size ranges of the oxide. A major factor influencing the movement of curium from lungs to blood is the formation of hydroxide or hydrous oxide particles about 0.001 micrometer in diameter. This process is sufficiently rapid for the lung clearance kinetics of the dioxide to resemble those of a soluble compound more closely than those of an insoluble one. Filtration of 0.001 micrometer particles through the kidneys results in considerably enhanced excretion of curium relative to administered curium citrate. It is concluded that current metabolic models, which assume that solubility in the lung is a prerequisite for transport in body fluids, do not adequately describe the behaviour of curium fromthe standpoint of radiological protection.

The environmental safety and health implications of plutonium

The physical and chemical properties of plutonium are related to its environmental transfer and uptake by man. Once incorporated, plutonium is avidly retained in the lungs, liver and skeleton, the relevant amounts being determined by its solubility in body fluids. A knowledge of the toxicity of plutonium is largely dependent upon animal studies where exposure to relatively large amounts, compared with those associated with known human exposure, can cause tumours in those tissues where it is retained. With one exception, epidemiological studies have not been able to demonstrate adverse health effects in humans. Precautions taken in the processing of plutonium have ensured that average intakes by workers have been consistently low. When it has been released to the environment, it has been of little ecological importance and has caused only small doses to man with no observable adverse effects. The long half-life of plutonium causes anxiety about its storage and disposal, but plutonium is not unique. It is often forgotten that very much larger amounts of permanently toxic elements such as arsenic, cadmium and lead are stored and disposed of with much less concern. Plutonium is a valuable resource and for that reason should not be treated as a waste for disposal into the environment.

Histological changes in kidney, liver and duodenum of the mouse following the acute and subacute administration of diethylenetriaminepentaacetic acid

Abstract CaNa 3 diethylenetriaminepentaacetic acid (DTPA) was found to produce transient histological changes in liver and kidney but not intestine in mice after the acute and subacute administration of doses between 6 and 30 time above the maximum recommended therapeutic dose.

The Reactions of 1 nm Particles of Plutonium-238 Dioxide and Curium-244 Dioxide with Lung Fluid

The reactions of 1 nm particles of plutonium-238 dioxide and curium-244 dioxide with rat lung fluid have been studied both in vitro and in vivo. The plutonium-238 particles are positively charged and combine by electrostatic attraction with the negative pulmonary surfactant which mediates the transfer of radioactivity to the blood. In contrast the curium-244 particles are negative and are assumed to diffuse passively through the alveolar walls. The results emphasise that electrostatic charge is an important factor governing the reaction of 1 nm actinide oxide particles with macromolecules.

The effect of acute and sub-acute treatment with diethylenetriaminepentaacetic acid on the hepatic function of mice

Abstract The effect of the calcium chelate of diethylenetriaminepentaacetic acid (CaNa 3 DTPA) on the functional status of liver cells of mice has been investigated following the observation of fatty vacuoles in hepatocytes after the administration of large doses of the chelate. Two sensitive tests of hepatic cell function have been employed; namely sulphobromophthalein (BSP) retention and plasma aminotransferase concentration. Chelate administration at doses up to 1000 mg/kg body weight, administered either acutely or sub-acutely, produced no detectable changes in the ability of the liver to clear BSP from the blood or in the concentration of glutamic-pyruvic aminotransferase in the blood plasma.

The use of DTPA for removing extrapulmonary curium-244 from the rat

Abstract Following the uptake of curium-244 dioxide, a major factor influencing the movement of 244 Cm from lungs to blood and urine is the formation and transport of 0.001 μm particles, believed to be the hydroxide. These particles are neither dissolved nor is 244 Cm chelated by the trisodium calcium and zinc salts of diethylenetriaminepentaacetic acid (DTPA) when the compounds are administered at therapeutic levels. By inhibiting the reaction between the particles and serum proteins in the blood, however, DTPA permits the rapid dialysis of the particles into the urine. This process is so efficient that the deposition of 244 Cm in extrapulmonary tissue can be reduced to trivial amounts by administering Na 3 ZnDTPA at concentrations appreciably below the currently recommended level.