tant because, as noted earlier, inhaled insoluble uranium oxides lodge in the lung and the hilar lymph nodes, where they may remain for an estimated several hundred days. Cancer of the lymphoid system is another focus of attention for the same reason. Bone is one of the principal sites for the deposition of soluble forms of uranium, either after ingestion or after clearance from the lung and its lymph nodes, and uranium remains in bone for a long time. The kidney is the major site at which uranium acts as a toxic heavy metal. Effects on the nervous system are discussed, despite the dearth of evidence, because of their possible interest in relation to illnesses in Gulf War veterans. The committee discusses other organ systems only briefly due to the paucity of research in these areas.

Assessing the Evidence: Factors Influencing the Quality of Studies

The following discussion highlights several issues that the committee considered in its evaluation of the epidemiologic studies on uranium processing workers. The committee followed the principle of giving more weight to high quality studies and considered a number of factors including methodological issues (as discussed in Chapter 3), measures of exposure, comparison groups, and duration of follow-up.

Measurement of Exposure

The most convincing way to demonstrate an association between an agent and disease is to show that the incidence of the disease increases as the level of the exposure increases. This approach requires an internal unexposed comparison group, which increases the likelihood that the comparison group is otherwise similar to the exposed group. Studies of occupational exposure on which the committee relied to evaluate the effect of uranium on disease used several methods for measuring exposure. Some of the methods discussed below have serious flaws that the committee considered in the evaluation of the study. Table 4.5 categorizes the occupational studies according to the method used to measure exposure to radiation.

Direct measurement in individual workers. The preferred method for an occupational study is to measure the level of exposure directly in each worker. Radiation film badges give a measure of cumulative exposure but measure only external radiation, which is a greater concern for exposure to enriched uranium than for exposure to natural or depleted uranium. Measuring the internal dose of radiation is more difficult. The best method is mathematical modeling to infer the lung dose of uranium from measurements of uranium in the urine and/or ambient dust.



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