herbicides sprayed in Vietnam. At the time of the spraying, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, one form of dioxin) was an unintended contaminant from the production of 2,4,5-T and was present in Agent Orange and some other herbicide formulations sprayed in Vietnam. Databases, therefore, were searched for the names of those compounds, their synonyms and abbreviations, and their Chemical Abstract Service (CAS) numbers. The evidence indicates that a tissue protein, the aryl hydrocarbon receptor (AhR), mediates the toxicity of TCDD. As such, the AhR also was used as a key word, as were “dioxin,” “Agent Orange,” and “Vietnam veteran.”

As discussed in Chapter 3, one of the herbicides used in Vietnam, cacodylic acid, is an organic form of arsenic, dimethylarsinic acid (DMA). In addition to being synthesized as an herbicide, DMA is a metabolite of inorganic arsenic in humans. DMA was long thought to be a biologically inactive metabolite of inorganic arsenic, but recent evidence suggests that one form—DMAIII—might be responsible for some of the adverse effects of inorganic arsenic. That evidence, however, is not sufficient to support a conclusion that exposure to cacodylic acid results in the same adverse health effects as does exposure to toxic concentrations of inorganic arsenic. Therefore, the literature on the health effects of inorganic arsenic was not considered in this report. Further details on the effects of inorganic arsenic can be found in Arsenic in Drinking Water (NRC, 1999) and Arsenic in Drinking Water: 2001 Update (NRC, 2001). For cacodylic acid and picloram, the search terms were the synonyms for the herbicides’ chemical names and their CAS numbers.

This report concentrates on the evidence published after the completion of work on Veterans and Agent Orange: Update 2002 (IOM, 2003a). For each health outcome, new evidence was reviewed in detail. The conclusions, however, are based on the accumulated evidence, and not just on recently published studies. When statistics have been generated on the same study population over time (as noted in Chapter 4), there will be multiple entries corresponding to successive updates in the summary tables of Chapters 69, but only the most comprehensive version of the information on a given population is factored into the committee’s conclusion on any health outcome. A detailed description of the committee’s general approach to the evaluation of scientific evidence is delineated in Chapter 5 of VAO. Later committees have adopted the original committee’s approach.

The information the committee used was compiled from a comprehensive electronic search by keyword of public and commercial databases—biologic, medical, toxicologic, chemical, historical, and regulatory—that provide citations from the scientific literature. In addition, the reference lists of some review and research articles, books, and reports were examined for potentially relevant articles. Literature identification continued through June 1, 2004. That search strategy helped ensure that all potentially relevant articles were identified, however, it also resulted in a large number of non-relevant studies being identified. More than 3,000 citations were identified in those searches, including some



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