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; thus, it should be noted that TCDD and Agent Orange are not synonymous. Therefore, databases have been searched for the names of those compounds, their synonyms and abbreviations, and their Chemical Abstracts Service (CAS) numbers. The evidence indicates that a tissue protein, the aryl hydrocarbon receptor (AhR), mediates most of the toxicity of TCDD, so “AhR” also was used as a keyword, as were “dioxin,” “Agent Orange,” and “Vietnam veteran.”

As discussed in Chapter 3, one of the herbicides used in Vietnam, cacodylic acid, is dimethylarsinic acid (DMA), an organic form of arsenic. 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 would 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 chemical names, synonyms, and CAS numbers of the herbicides.

This report concentrates on the evidence published after the completion of work on Veterans and Agent Orange: Update 2004 (IOM, 2005). Relevant new contributions to the literature made during the period June 1, 2004, through September 30, 2006, were sought. The information the committee used was compiled from a comprehensive electronic search 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. As noted above, the terms used in the search strategy included the chemical names, synonyms, and CAS numbers of the specific chemicals of interest (2,4-D, 2,4,5-T, TCDD, cacocylic acid, and picloram—see Figure 2-1 for chemical structures and CAS numbers), and the more generic terms involved with this project (“Vietnam veteran,” “Agent Orange,” “AhR,” “dioxin,” “herbicide,” “phenoxy”). By analogy, results on other specific phenoxy herbicides are also of interest: 2-methyl, 4-chlorophenoxyacetic acid (MCPA) and 2-(2-methyl-4-chlorophenoxy) propionic acid (MCPP or Mecoprop) for 2,4-D; 2-(2,4,5-trichlorophenoxy) propionic acid (2,4,5-TP or Silvex) for 2,4,5-T (see Figure 2-1 for chemical structures and CAS numbers). Findings only related to exposure to the diverse chemical families of pesticides were considered too nonspecific for



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