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disease under study. These factors, referred to as confounders, usually include exposures to

other workplace hazards. In studies of workers, it is the exposure information that allows causal

associations to be derived. The quantity and quality of available exposure information largely

determine the strength of the associations drawn from the research. For this reason,it is
imperative that full advantage be taken ofall existing information.

To reconstruct past occupational exposures the following activities are typically performed:
1. Site visits - to obtain a general overview ofsite activities and records available.
2. Historical study
+ Records review andretrieval - to identify population demographics and
exposure potential.
+ Coding, QA/QC to transform data into a usable format and assureintegrity
of data.
+ Institutional memory - to obtain unrecorded knowledge from current and
former worker or others knowledgeable about past operations.
+ Exposure assessment- to assign gradation of exposures to individuals/groups.
3. Mathematical modeling and simulations - to evaluate the utility if the exposure data
and to compensate for missing data.

4, Measure present exposures - to augmenthistorical exposure data and fill information
5. Multiple site comparisons - to examine consistency of exposures acrosssites.

Once past exposures have been estimated, epidemiologic analytic techniques are used to describe
the disease experience of a population and to comparethis with referent populations. Such
analyses seek to document the presence or absence of a causal association between the disease(s)
and exposures understudy.
Multiple myelomais a progressive, usually fatal, cancer of the blood-forming organs. There are
over 12,000 new cases of multiple myeloma each year in the U.S.; therefore, the identification of
a causal factor for this deadly cancer is of substantial public health interest. Previous
epidemiologic evaluations at DOEfacilities have suggested that multiple myeloma may be a

consequence of exposure to ionizing radiation and/or chemicals present at thosefacilities.

In excess of 65 cases of multiple myeloma have occurred among workers at the K-25 facility since

the plant began operation. On the surface, this appears to be a relatively large numberofcases,
compared with what one would expect in a population the size of the K-25 workforce. The K-25
workforce presents a unique research opportunity, both because of the apparently high number
of multiple myeloma cases and becausethe facility has maintained exposure data of unusually
high quality extending back to the plant’s inception. In order to examine the possible workrelated exposures that may have contributed to the occurrence of multiple myeloma to K-25
workers, an in-depth exploration ofall records pertaining to radiologic and chemical hazards
experienced by K-25 workers is essential.

NIOSHresearchers have identified from the generalliterature a number of exposures that have
been previously implicated as potentially causative agents in the development of multiple
myeloma. Described in more detail in the study protocol, they are: internal and external ionizing
radiation, metals (U, Ni, Cd, Pb, As, Cu, Cr), and solvents (benzene, carbon tetrachloride).

Although the biological mechanisms in the development of multiple myeloma has not as yet been
established,it is clear that several of the above chemicals, as well as fluoride, accumulate in the

bone andtherefore are suspect in causing hematopoietic diseases.

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