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Uranium Toxicity
What Are the Physiological Effects of Uranium Exposure?

Course: WB 1524
CE Original Date: May 6, 2009
CE Renewal Date: May 6, 2012
CE Expiration Date: May 6, 2014
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Learning Objectives

Upon completion of this section, you will be able to

  • describe the medical conditions associated with uranium exposure.

Introduction

The majority of adverse health outcomes related to uranium exposure have been observed in uranium mine, mill, and fabrication workers. Outcomes that may occur with uranium exposure based on both observed human effects and animal studies include

  • non-malignant respiratory disease (fibrosis, emphysema) and
  • nephrotoxicity
    • elevated β2 microglobulin, BUN, Non-protein nitrogen (NPN),
    • glucosuria,
    • proteinuria,
    • tubule degeneration, lesions and
    • cell necrosis.

Extremely high acute exposures have also been lethal due to renal failure (from oral or inhaled exposure) or pulmonary failure (from inhalation exposure).

In addition, uranium overexposure by either inhalation or ingestion is associated with renal abnormalities, regardless of solubility. However, there is some question as to whether the same cytotoxic effects to the kidney from exposure to uranium in experimental settings occurs in humans [Kurttio et al. 2002, 2006].

Additional health effects involving the reproductive/developmental systems and indicating potential neurologic effects from uranium exposure have been reported at higher doses in the literature and more studies have been indicated for some of them [ATSDR 1999].

Nephrotoxicity in Experimental vs. Non-experimental Settings

Recent studies have raised questions concerning the cytotoxic effects on the kidney from exposure to uranium in experimental animal settings vs. in humans. In one study of people drinking well water with high natural uranium concentrations, the median urinary concentration was 0.078 microgram/Liter (µg/L) (ranging up to 5.65 µg/L). Here, a subtle effect of uranium on calcium and phosphate fractional clearance was indicated (within the normal range of these measures), but without effect on other biochemical or traditional markers of renal function [Kurttio et al. 2002]. In another study, uranium was measured in 193 people who used drinking water from drilled wells for an average of 16 years. Possible toxic effects of uranium on kidney cells and renal function were evaluated by measuring

  • urinary N-acetyl-gamma-D-glucosaminidase,
  • alkaline phosphatase,
  • lactate dehydrogenase,
  • gamma-glutamyltransferase and glutathione-S-transferase,
  • serum cystatin C,
  • urinary and serum calcium phosphate,
  • glucose, and
  • creatinine.

The study concluded that continuous uranium intake from drinking water, even at relatively high exposures, was not found to have cytotoxic effects on kidneys in humans [Kurttio et al. 2006].

Health Effect Differences between Children and Adults

It is not known whether exposure to uranium affects children differently. No cases have been reported where exposure to uranium is known to have caused health effects in children. Very young animals absorb more uranium than adults do when fed uranium, but we do not know if this happens in children.

It is also not known whether exposure to naturally occurring uranium can affect the developing human fetus. In laboratory animals, extremely high doses of uranium in drinking water resulted in birth defects and an increase in fetal deaths. We do not think that uranium can cause these problems in pregnant women who are exposed to background levels of uranium in food, water, and air.

There is not a significant amount of information to suggest that children are affected differently than adults when exposed to uranium.

Key Points

  • The majority of adverse health outcomes related to uranium exposure have been observed in uranium mine, mill, and fabrication workers.
  • Outcomes that may occur with uranium exposure based on both observed human effects and animal studies include non-malignant respiratory disease (fibrosis, emphysema) and nephrotoxicity.
  • Abnormalities consistent with nephrotoxicity include elevated β2 microglobulin, BUN, Non-protein nitrogen (NPN), glucosuria, proteinuria, tubule degeneration, lesions and cell necrosis.
  • Nephrotoxicity should reverse as overexposure ceases.
   

Progress Check

10. Uranium may cause which of the following nephrotoxic effects?

A. Cell necrosis.
B. Tubule degeneration.
C. Elevated β2 microglobulin.
D. All of the above.

Answer:

To review relevant content, see Introduction in this section.

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Agency for Toxic Substances and Disease Registry, 4770 Buford Hwy NE, Atlanta, GA 30341
Contact CDC: 800-232-4636 / TTY: 888-232-6348

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