subacute onset occurs over days or weeks and chronic onset over months or years. Finally, transient peripheral neuropathies resolve spontaneously, whereas persistent ones may lead to chronic deficits. In the original report, VAO, attention was deliberately focused on persistent neurobehavioral dysfunction. In later reports including the present one, all new data pertinent to clinical neurobehavioral dysfunction as well as transient acute and subacute peripheral neuropathy are reviewed.

Case identification in neurology is often difficult. Despite advances in neuroimaging, many types of neurologic alterations are biochemical and show no abnormalities on scanning tests. The nervous system is not usually accessible for biopsy, so pathologic confirmation is not feasible for many neurologic disorders. Behavioral and neurophysiologic changes can be partly or largely subjective and, even when objectively documented, may often be reversible. Timing is important in assessing the effect of chemical exposures on neurologic function. Some symptoms of neurologic importance will appear acutely but be short-lived, whereas others will appear slowly and be detectable for extended periods. These caveats must be considered in the design and critique of epidemiologic studies evaluating an association between exposure to any chemical agent and neurologic or neurobehavioral dysfunction.

Many reports have addressed the possible contribution of herbicides and pesticides to nervous system dysfunction, and reported abnormalities have ranged from mild and reversible to severe and long-standing. These assessments have been conducted in three general settings, related to occupational, environmental, and Vietnam veteran exposures. This chapter reviews reports of neurologic alterations associated with exposure to herbicides, TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), or other compounds used in herbicides in Vietnam. The potential neurotoxicity of TCDD and herbicides in animal studies is discussed in Chapter 3.

COGNITIVE AND NEUROPSYCHIATRIC EFFECTS

Update of the Scientific Literature

On the basis of the data available at the time, it was concluded in Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (hereafter referred to as VAO; IOM, 1994), Veterans and Agent Orange: Update 1996 (hereafter, Update 1996; IOM, 1996), and Veterans and Agent Orange: Update 1998 (hereafter, Update 1998; IOM, 1999) that there was inadequate or insufficient evidence to determine whether an association exists between exposure to the herbicides 2, 4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxy-acetic acid (2,4,5-T) and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); cacodylic acid, and picloram and cognitive or neuropsychiatric disorders. The majority of the data that formed the basis for these conclusions came from the Air Force Health Studies (AFHS, 1991, 1995). AFHS (1991), originally



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