resolve spontaneously, whereas persistent ones may lead to chronic deficits. In the original VAO report, attention was deliberately focused on persistent neurobehavioral dysfunction. Later reports, including this one, review all new data pertinent to clinical neurobehavioral dysfunction and peripheral neuropathy.
Case identification in neurology is often difficult. Despite advances in neuro-imaging, 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, are often reversible. Timing is important in assessing the effect of chemical exposure on neurologic function. Some symptoms of neurologic importance appear acutely but are short-lived, whereas others appear slowly and are detectable for extended periods. These caveats must be considered in the design and critique of epidemiologic studies aimed at evaluating an association between exposure to a 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 transient to severe and persistent. Those assessments have been conducted in three general settings: in relation to occupational, environmental, and Vietnam-veteran exposures. This chapter reviews reports of the following neurologic alterations associated with human exposure to the chemicals of interest (2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), 4-amino-3,5,6-trichloropicolinic acid (picloram), and cacodylic acid (dimenthylarsenic acid, DMA): cognitive and neuropsychiatric effects, motor or coordination dysfunction, chronic persistent peripheral neuropathy, and acute and subacute transient peripheral neuropathy. The potential neurotoxicity of those chemicals in recent animal studies is discussed in Chapter 3. The categories of association and the committee's approach to categorizing the health outcomes are discussed in Chapters 1 and 2.
On the basis of the data available at the time, it was concluded in Veterans and Agent Orange (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 chemicals of interest (2,4-D, 2,4,5-T or its contaminant TCDD, picloram, or cacodylic acid) and cognitive or neuropsychiatric disorders. The majority of the data that formed the basis for those conclusions