Endocrine disruptors are a class of environmentally prevalent compounds that include the dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the polychlorinated biphenyls, and some isoflavonoid phytoestrogens. Their potential health hazards, until recently, were dominated by concerns over carcinogenicity following exposure of adults to high doses. Developmental toxicity now seems to be achieving a leading role and may even displace cancer as the basis for assessing the human risks posed by these compounds. One source of this shifting concern is data describing impaired sexual development in rats exposed prenatally to surprisingly low doses of TCDD. TCDD and related endocrine disrupters appear to alter the perinatal gonadal hormone milieu. Such activity triggers a cascade of disturbances in brain development and neuroendocrine function. Although such disturbances might be seen most readily in reproductive studies, a constellation of much more subtle consequences is conceivable. These outcomes might include altered gender-specific cognition. For example, female rats tend to emit different patterns of responding than male rats on schedule-controlled operant behavior assays. The current proposal is guided by the hypothesis that prenatal TCDD modifies the usual pattern of differences between male and female rats. Tests of the hypothesis will be based on three situations in which gender-specific learning, memory, and spatial cognition are assessed. One assessment situation will examine a sexually-motivated behavior in exposed females, a second situation will examine sexual motivation in exposed males, and the third situation will examine nonsexual cognitive function in both males and females. In order to determine sensitive critical periods of prenatal development, the behavioral endpoints will be examined across groups of offspring that have been exposed under one of three different prenatal schedules. All of these measures will be examined in subjects exposed to a new, low dose range of TCDD that approaches background levels in the environment. The coupling of several functional measures is adduced as a model of risk assessment.
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