with herbicide exposure exists, taking into account the strength of the scientific evidence and the appropriateness of the statistical and epidemiologic methods used to detect the association; (2) the increased risk of the disease among those exposed to herbicides during Vietnam service; and (3) whether there is a plausible biological mechanism or other evidence of a causal relationship between herbicide exposure and the disease.
In addition to bringing the earlier scientific evidence up to date, the committee has addressed five specific areas of interest identified by the Department of Veterans Affairs (DVA). These are: (1) the relationship between exposure to herbicides and the subsequent development of diabetes; (2) the issue of the latency between exposure to herbicides and development of adverse health outcomes; (3) the classification of chondrosarcomas of the skull; (4) herbicide exposure assessment for Vietnam veterans; and (5) the potential for using data combination methodologies to informatively reexamine existing data on the health effects of herbicide or dioxin exposure.
In conducting its study, the IOM committee operated independently of the DVA and other government agencies. The committee was not asked to and did not make judgments regarding specific cases in which individual Vietnam veterans have claimed injury from herbicide exposure. Rather, the study provides scientific information for the Secretary of Veterans Affairs to consider as the DVA exercises its responsibilities to Vietnam veterans.
The conclusions in this updated report are based on cumulative evidence from the scientific literature reviewed in VAO and Update 1996. This present update is intended to supplement rather than replace the two previous reports; therefore, much of the information on studies reviewed in those reports has not been repeated. Most chapters begin with brief summaries of the scientific data in VAO and Update 1996 , followed by a more thorough discussion of the newly published data and their interpretation. The reader is referred to relevant sections of the previous reports for additional detail and explanation.
Chapter 2 provides an overview of the methods and conclusions of VAO and Update 1996. In addition, it provides a summary of the recent activities of several federal government agencies that are relevant to the health effects of Agent Orange and other herbicides used in Vietnam. Chapter 3 provides an update of the recent experimental toxicology data on the effects of the herbicides and of 2,3,7,8-TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly referred to as TCDD or "dioxin"), a compound found as a contaminant in the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). These data serve as the basis for the biological plausibility of potential health effects in human populations. Chapter 4 describes the methodological considerations that guided the committee's review and its of evaluation. Chapter 5 addresses exposure assessment issues. Chapter 6