toxicologic, chemical, historical, and regulatory information. The majority of those databases were bibliographic, providing citations to scientific literature. The reference lists of major review and research articles, books, and reports were examined. Literature identification continued through July 1, 2002. More than 9,000 potentially relevant studies were identified in those searches, and more than 1,000 were reviewed. Suggestions received from veterans and other interested persons at public hearings and in written submissions were a valuable source of additional information.
This report concentrates on the evidence published after the completion of work on Veterans and Agent Orange: Update 2000 (IOM, 2001) and Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans (IOM, 2002). For each health outcome, the new evidence is reviewed in detail. Conclusions, however, are based on the totality of accumulated evidence, not just on recently published studies. That is, new evidence is interpreted not alone but in the context of evidence addressed in previous reports.
The committee's judgments have both quantitative and qualitative aspects; they reflect both the evidence examined and the approach taken to evaluate it. In VAO, the committee delineated how it approached its task so that readers would be able to assess and interpret its findings. In offering that information, the committee wished to make the report useful to those seeking to update its conclusions as new information was obtained. The committees responsible for later reports have adopted the original committee's approach.
As discussed in Chapter 3, cacodylic acid, or dimethylarsinic acid (DMA), in addition to being synthesized as a herbicide, is a metabolite of inorganic arsenic in humans. It is important, therefore, to consider the relationship between inorganic arsenic and DMA and the potential for similar adverse health effects after exposure to inorganic arsenic and to DMA. DMA was long thought to be a biologically inactive metabolite of inorganic arsenic, but evidence has been accumulating in recent years that one form of DMA (DMAV) is an active metabolite of inorganic arsenic and might be responsible for some of the adverse effects observed after exposure to inorganic arsenic. It has yet to be determined, however, whether human exposure to DMA results in the same effects as exposure to toxic concentrations of inorganic arsenic (skin, bladder, and lung cancer and cardiovascular effects). Although some experimental evidence indicates that DMA induces effects similar to those of inorganic arsenic (see Chapter 3), it is insufficient to support a conclusion that exposure to inorganic arsenic is directly relevant to exposure to cacodylic acid. Therefore, the literature on the effects of inorganic arsenic is not considered in this report. Further details on the effects of inorganic arsenic are in Arsenic in Drinking Water (NRC, 1999) and Arsenic in Drinking Water: 2001 Update (NRC, 2001).