sures are often to mixtures of chemicals. Some studies of herbicides are conducted using herbicide mixtures and are noted as such in the text.

This chapter begins with a brief summary of major conclusions derived from the literature reviews in VAO, Update 1996, and Update 1998. This is followed by a summary of toxicological research findings as they relate to human health, and then an overview of the scientific literature published since release of Update 1998, reviewed in detail in this chapter. Note that these more general summaries do not include references to the scientific literature because they are intended to provide background for the nonspecialist.

The “Toxicity Profile Updates” section then provides details of the relevant scientific studies, with references, that have been conducted on 2,4-D,2,4,5-T, picloram, cacodylic acid, and TCDD since Update 1998. The toxicity profile update for TCDD includes a section that discusses the issues involved in estimating potential health risk and factors influencing toxicity. That subsection includes a discussion of the toxic equivalency factor approach to estimating the toxicity of TCDD. It is important, when evaluating the experimental data for all of the compounds, to keep in mind the advantages, disadvantages, and limitations of various types of studies. These considerations are discussed in the final section of the chapter, “Issues in Evaluating the Evidence.”


Highlights of Previous Reports

Chapter 4 of VAO and Chapter 3 of both Update 1996 and Update 1998 review the results of animal and in vitro studies published through 1997 that investigate the toxicokinetics, mechanism of action, and disease outcomes of TCDD and herbicides. According to these earlier reviews, TCDD elicits a diverse spectrum of biological sex-, strain-, age-, and species-specific effects, including carcinogenicity, immunotoxicity, reproductive and developmental toxicity, hepatotoxicity, neurotoxicity, chloracne, and loss of body weight. The scientific consensus is that TCDD is not directly genotoxic and that its ability to influence the carcinogenic process is mediated via epigenetic events such as effects on enzyme induction, cell proliferation, apoptosis, and intracellular communication. The toxicity of the herbicides used in Vietnam has been poorly studied. In general, the herbicides 2,4-D,2,4,5-T, cacodylic acid, and picloram have not been identified as particularly toxic substances since high concentrations are often required to modulate cellular and biochemical processes. A comprehensive description of the toxicological literature published through 1997 can be found in VAO, Update 1996, and Update 1998.

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