In carrying out its charge, the committee used animal and other nonhuman studies in several ways, particularly to look for markers of health effects that might be important for humans. If animal studies showed absorption and deposition in specific tissues or organs, the committee looked especially closely for possible abnormalities at these sites in human studies, as it did for uranium deposition in bone and kidney. One of the problems with animal studies, however, is the difficulty of finding animal models to study symptoms that are related to uniquely human attributes, such as cognition, purposive behavior, and the perception of pain.

The toxic effects of uranium also have been reviewed in a recent National Research Council report, Review of Toxicologic and Radiologic Risks to Military Personnel from Exposure to Depleted Uranium During and After Combat (NRC, 2008), which assessed the US Army’s “Capstone report” (USACHPPM, 2004) on toxicologic and radiologic risks to soldiers posed by exposure to depleted uranium.

This chapter begins with a summary of the findings presented in Gulf War and Health, Volume 1: Depleted Uranium, Pyridostigmine Bromide, Sarin, Vaccines (IOM, 2000), hereafter referred to as Volume 1. It next addresses experimental data from toxicokinetic (also called pharmacokinetic), animal, and in vitro studies published since Volume 1. The chapter ends with a discussion of how the committee applied the experimental data. Tables 3-1 to 3-10 are included at the end of this chapter.

Chapter 4 of Volume 1 includes a review of studies of the toxicology of uranium. It covers toxicokinetics and animal and in vitro studies.

Uranium is both a heavy metal and a low-specific-activity radioactive element. Studies on the toxicity of uranium have examined both its chemical and its radiologic effects. The primary routes of human exposure to uranium are ingestion and inhalation; the effects of dermal exposure and embedded fragments have also been studied.

The amount of uranium that the body absorbs depends largely on the route of exposure and the solubility of the uranium compounds to which a person is exposed. Insoluble uranium compounds may remain in the pulmonary tissues, especially the pulmonary lymph nodes, for a long time and thus pose a localized radiologic hazard. As a general rule, uranium absorption from the intestinal tract is lower than that from the respiratory tract and results in lower doses per unit intake. Renal dysfunction and lung injury are the best-characterized consequences of exposure to uranium compounds. The chemical and radiologic properties of uranium could act cooperatively to cause tissue damage, so it cannot be assumed that excess cancers would be due solely to the radiologic effects of uranium or that organ damage is due exclusively to its heavy-metal properties.