of humans and for assessing the risk of effects of a chemical. The principles involved in toxicokinetics are similar among chemicals, although the degree to which different processes influence the distribution depends on the structure and other inherent properties of the chemicals. Thus, the lipophilicity or hydrophobicity of a chemical and its structure influence the pathways by which it is metabolized and whether it persists in the body or is excreted. The degree to which different toxicokinetic processes influence the toxic potential of a chemical depends on metabolic pathways, which often differ among species. For that reason, attempts at extrapolation from experimental animal studies to human exposures must be extremely careful.

Many chemicals were used by the US armed forces in Vietnam. The nature of the substances themselves was discussed in more detail in Chapter 6 of the original Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (VAO) report (IOM, 1994). Four herbicides documented in military records were of particular concern and are examined here: 2,4-D, 2,4,5-T, picloram, and cacodylic acid. This chapter also examines TCDD, the most toxic congener of the tetrachlorodibenzo-p-dioxins (tetraCDDs), also commonly referred to as dioxin, a contaminant of 2,4,5-T, because its potential toxicity is of concern. Considerably more information is available on TCDD than on the herbicides themselves. Other contaminants present in 2,4-D and 2,4,5-T are of less concern. Except as noted, the laboratory studies of the chemicals of concern used pure compounds or formulations; the epidemiologic studies discussed in later chapters often tracked exposures to mixtures.



Picloram (Chemical Abstracts Service Number [CAS No.] 1918-02-1; see chemical structure in Figure 4-1) was used with 2,4-D in the herbicide formulation Agent White, which was sprayed in Vietnam. It is also used commonly in Australia in a formulation with the trade name Tordon 75D®. Tordon 75D


FIGURE 4-1 Structure of picloram.

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