Plutonium pharmacokinetics and blood biochemistry

Woodhouse, Jennifer Ann (1997) Plutonium pharmacokinetics and blood biochemistry. Doctoral thesis, University of Central Lancashire.

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Since its discovery in the early 1940s the element plutonium has been seen by mankind as both an opportunity and a threat. As a radioactive nuclide plutonium presents health hazards in its handling and if mankind is to make the most of this element's potential benefits it is essential that these hazards be understood. Both overestimation and underestimation of these hazards are damaging to its proper utilisation. Many studies have been carried out to determine the effects of plutonium exposure and a broad picture of the biological behaviour of plutonium has been built up. Radiological protection standards are based on such broad understanding and a "Central Dogma" has arisen viz, plutonium is bound avidly in liver and bone; clearance half-lives from these organs differ (by a factor of 2.5) but are very long - a minimum of 50 years for bone; this is why plutonium urinary excretion levels are very low.
Despite all the research work that has been carried out there are many important areas of plutonium behaviour which are not well understood or in which the central ideas adopted for radiological protection purposes are questionable. One such questionable area is extended half-life in the body. Two rather different areas relate to the molecular binding interactions which plutonium enters into in body tissues and transfer mechanisms from blood into cellular organelles. Very little is known about these processes and the speciation that plutonium demonstrates within the body.
This thesis explores understanding of plutonium behaviour by application of pharmacokinetic theory to observed human behaviour, both following occupational exposure and experimental injection. Occupational exposure data demonstrated
behaviour consistent with pharmacokinetic expectations over periods of 25 years or more. Long-term half-lives were 10 to 30 years rather than 50 to 100 years or more.
There was no evidence of differing half-lives between liver and bone. Very low renal clearance was seen in intravenous injection studies suggesting either very extensive plutonium binding to the protein transferrin in blood or pointing to reabsorption in the kidney tubule after glomerular filtration. This latter possibility might lead to a "Plutonium blood pressure" which effectively forces activity into tissues irrespective of the strength of binding forces. Experimental work indicated species differences in transferrin binding which may have relevance for extrapolation from animals to humans.

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