NEUROBEHAVIORAL CONSEQUENCES OF PRENATAL TCDD EXPOSURE

描述：(改编自《调查者摘要》)内分泌 干扰物是一类在环境中普遍存在的化合物，包括 二恶英，如2，3，7，8-四氯二苯并对二恶英(TCDD)， 多氯联苯和一些异黄酮类植物雌激素。他们的 直到最近，潜在的健康危害一直是人们对 成人暴露在高剂量下后的致癌性。发展中 毒性现在似乎正在发挥主导作用，甚至可能取代 癌症作为评估这些化合物构成的人类风险的基础。 这种转移关注的一个来源是描述性行为受损的数据 出生前暴露于低剂量TCDD的大鼠的发育。 TCDD和相关的内分泌干扰物似乎改变了围产期的性腺 荷尔蒙环境。这种活动会引发大脑一连串的紊乱。 发育和神经内分泌功能。尽管这样的骚乱可能 在生殖研究中最容易被看到，一个多得多的星座 微妙的后果是可以想象的。这些结果可能包括改变 特定性别的认知。例如，雌性老鼠倾向于释放不同的 比雄性大鼠在时序控制操作中的反应模式 行为分析。目前的提议是以以下假设为指导的 产前TCDD改变了男性和女性之间通常的差异模式 雌性老鼠。对该假设的检验将基于以下三种情况 评估哪些性别特定的学习、记忆和空间认知。 一种评估情况将检查 暴露的雌性，第二种情况将检验性动机 暴露的男性，第三种情况将检查非性认知 在男性和女性身上都有作用。为了确定敏感度 产前发育的关键时期，行为终点将是 对暴露在以下环境中的一组后代进行了检查 三种不同的产前计划。所有这些措施都将得到审查 在暴露于新的低剂量TCDD的受试者中， 环境中的背景水平。多个泛函的耦合 作为风险评估的一种模型，本文引用了测量方法。

DESCRIPTION: (Adapted from the Investigator's Abstract) 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.