quantify the concentration of Ah receptors in the central or peripheral nervous systems.

In VAO, the committee concluded that the literature was insufficient to determine whether an association existed between exposure to herbicides and related compounds and chronic cognitive or neuropsychiatric disorders. As suggested by Sharp et al. (1986), the delayed effects of such exposures on human health are difficult to detect, and the health risks may be sufficiently small that they are below the power of present epidemiologic studies to detect.

Although there was no shortage of studies concerning this topic, methodologic problems made it difficult to reach definitive conclusions. Shortcomings in defining exposure included absent or poor exposure assessments; inconsistencies in identifying exposed individuals for study (i.e., some studies relied upon the presence of chloracne for inclusion, while others assumed that all subjects were exposed); and concomitant exposure to different chemicals, mixtures of chemicals, or concentrations of chemicals. Studies of cognitive or neuropsychiatric disorders are also weakened by the small numbers of subjects; poor selection or absence of comparison groups; confounding of the possible effects of herbicides with the effects of stress; and inadequate statistical analyses. Self-reports of exposure and symptoms may not be verified independently.

The committee noted that in order to maximally define the direct effects of dioxin on cognitive and neuropsychiatric function, future studies should focus primarily on occupationally exposed groups for whom levels of exposure were better known and should include neurobehavioral testing in relative proximity to the time of exposure.

VAO also concluded that significantly exposed subjects should be followed for the development of neuropsychological dysfunction in middle and later life. It is possible that minor CNS changes acquired in early adulthood were too subtle to be detected by current neuropsychological testing methods, but they could manifest themselves later when compounded by ''normal age-related changes" of the CNS. Theoretically, exposure to neurotoxins could produce "accelerated aging" of the brain due to premature neuronal loss, which could then result in neurobehavioral deficits.

Several papers on this topic have appeared since VAO. In the study by Peper et al. (1993) of chronic exposure to environmental polychlorinated dibenzodioxins and dibenzofurans (PCDD/PCDF) at high and low exposures, the group with