toxicological, chemical, historical, and regulatory information were examined. The majority of these data bases were bibliographic, providing citations to scientific literature. Committee staff examined the reference lists of major review articles, books, and reports for relevant citations. Reference lists of individual articles were also scanned for pertinent citations. Internet search engines were used to scan for information posted on the Internet. Literature identification continued through September 30, 1997. The input received both in written and oral form from veterans and other interested persons at public hearings and in written submissions served as a valuable source of additional information. Appendix A gives additional detail on the search strategies used to generate reference sources. Information submitted to the committee by interested persons is also listed in Appendix A.

This second biennial update concentrates on evaluating the evidence published following the completion of work on Veterans and Agent Orange: Update 1996 (hereafter Update 1996) (IOM, 1996) and VAO. For each health outcome, the new evidence is reviewed in detail. Conclusions are based on the totality of the accumulated evidence, not just on recently published studies. In other words, new evidence is not interpreted alone but is put into the context of evidence addressed in the two previous reports.

In addition to bringing earlier work up to date, the committee has addressed other areas of concern identified by the Department of Veterans Affairs (DVA). Specifically, the committee was asked to do the following:

  1. Pay particular attention to the relationship between exposure to herbicides and the subsequent development of diabetes. Chapter 11 contains an extended discussion of this topic. Special attention has also been given to adverse reproductive outcomes, which are addressed in Chapter 9. This area attracted heightened interest after a finding, reported in Update 1996, of limited/suggestive evidence of an association between herbicide exposure and spina bifida in the children of veterans.

  2. Examine the issue of the latency between exposure to herbicides and development of adverse health outcomes. In response to DVA's request, Chapter 8 (1) proposes a methodology to address issues concerning the timing of herbicide exposure and the risk of cancer; (2) reviews the literature on herbicide exposure and cancers classified in the sufficient and limited/suggestive evidence of an association categories for results that describe how the timing of exposure affects relative risk; and (3) describes timing-of-exposure characteristics of the Vietnam veterans and summarizes the implications of these factors for their risk of cancer.

  3. Discuss the classification of chondrosarcomas of the skull. This subject is addressed in Chapter 7 as part of the discussion of bone cancer.

  4. Offer advice on herbicide exposure assessment for Vietnam veterans. Chapter 5 of the report contains an extended discussion of this issue. In addition, a separate effort by another Institute of Medicine (IOM) committee is facilitating



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