Biological Consequences of Exposure to Soluble Forms of Natural Uranium

Depending on dose, route of administration and chemical form of the administered uranium, exposure to uranium compounds can produce effects in a variety of organs. Of these, the kidney is most sensitive, and is considered to be a critical target organ for hazard assessment. Literature concerning nephrotoxic properties of uranium in experimental animals is extensive and provides a detailed description of the pathophysiology of uranium nephrotoxicity in experimental animals. Although dose-effect relationships differ among species, injury and necrosis of the terminal segments of the renal proximal tubule is characteristic in all mammalian species that have been studied. Glomerular injury has also been reported. The critical occupational health issue is thus, "To what extent can laboratory animal models be useful for predicting human health hazards to uranium?". While direct quantitative extrapolations of dose-effect relationships in laboratory animals to humans is not a reality at present, it is possible, nevertheless, to explore in laboratory animal models certain specific questions regarding the biological effects of uranium in kidney that are relevant to hazard assessment. Indeed, a complete understanding of the laboratory animal model is critical for establishing valid extrapolations to humans. Issues relating to mechanisms of renal injury, dose-effect relationships and biological monitoring for uranium-induced nephrotoxicity are considered in this review.