By the late 1950s, the views had evolved that 1) U does not enter cells but damages the kidneys by binding to the luminal membranes of renal tubular cells, interfering with reabsorption of glucose, sodium, amino acids, protein, water, and other substances, and causing slow cell death by suppression of respiration; and 2) U does not cause significant damage to the kidneys at concentrations below 3 micrograms U g-1 kidney. Although there has not been a major unified effort in the past three decades to update the toxicology of U as a nephrotoxin, there have been numerous isolated studies that may be useful in reevaluating these longstanding views on the behavior and action of U in the kidneys and the renal U concentration at which toxic effects may become evident. This paper is a brief review and synthesis of current information on U nephrotoxicity. Much more experimental research and reevaluation of existing data are needed concerning U nephrotoxicity, particularly for the case of chronic exposure.

The lack of a reliable quantitative description of blood flow in man has hampered the development of accurate biokinetic models of essential elements, drugs, imaging agents, and carcinogens. In this paper we review and analyse data on blood flow and identify representative percentages of cardiac output and absolute blood flow rates to organs and tissues of man for use as reference values for biokinetic models. To keep the review and analysis to a manageable size we have limited attention to the resting state and have suggested reference values for absolute and relative flow rates only for adult males and females.

under contract DE-AC05-84OR21400 with Martin Marietta Energy Systems, Inc. Completion of the model was funded by the Office of Radiation and Indoor Air, U.S. Environmental Protection Agency, under Interagency Agreement DOE no.

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The death of Alexander Litvinenko on 23 November 2006 has brought into focus scientific judgements concerning the radiotoxicity of polonium-210 ((210)Po). This paper does not consider the specific radiological circumstances surrounding the tragic death of Mr Litvinenko; rather, it provides an evaluation of published human and animal data and models developed for the estimation of alpha radiation doses from (210)Po and the induction of potentially fatal damage to different organs and tissues. Although uncertainties have not been addressed comprehensively, the reliability of key assumptions is considered. Concentrating on the possibility of intake by ingestion, the use of biokinetic and dosimetric models to estimate organ and tissue doses from (210)Po is examined and model predictions of the time-course of dose delivery are illustrated. Estimates are made of doses required to cause fatal damage, taking account of the possible effects of dose protraction and the relative biological effectiveness (RBE) of alpha particles compared to gamma and x-rays. Comparison of LD(50) values (dose to cause death for 50% of people) for different tissues with the possible accumulation of dose to these tissues suggests that bone marrow failure is likely to be an important component of multiple contributory causes of death occurring within a few weeks of an intake by ingestion. Animal data on the effects of (210)Po provide good confirmatory evidence of intakes and doses required to cause death within about 3 weeks. The conclusion is reached that 0.1-0.3 GBq or more absorbed to blood of an adult male is likely to be fatal within 1 month. This corresponds to ingestion of 1-3 GBq or more, assuming 10% absorption to blood. Well-characterised reductions in white cell counts would be observed. Bone marrow failure is likely to be compounded by damage caused by higher doses to other organs, including kidneys and liver. Even if the bone marrow could be rescued, damage to other organs can be expected to prove fatal.