DEVELOPMENTAL NEUROTOXICITY OF METALLIC MERCURY

金属汞的发育神经毒性

• 批准号: 2462441
• 负责人: Bernard Weiss
• 金额: $ 36.02万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2462441
• 关键词: animal developmental psychology; behavioral /social science research tag; body physical activity; developmental neurobiology; embryo /fetus; embryo /fetus toxicology; environmental toxicology; histochemistry /cytochemistry; laboratory rat; mercury poisoning; neurotoxicology; neurotoxins; newborn animals; operant conditionings; startle reaction

DESCRIPTION: (Adapted from the Investigator's Abstract) Metallic mercury, a neurotoxicant usually viewed as an occupational hazard, is a more general environmental hazard as well. Although we know a great deal about its effects in adults, our knowledge of its impact on the developing brain is fragmentary. This information gap is disquieting. (1) Many women in the work force are exposed to mercury vapor. (2) Many, perhaps most, women have dental amalgam fillings. These emit mercury vapor. Maternal tissue and fetal levels are correlated with the number of fillings. (3) Mercury is a more common contaminant of indoor environments than is generally recognized. Because of its physical properties it can lurk undetected and continue to evaporate. (4) Young children are considerably more vulnerable to mercury toxicity than adults; the syndrome of Pink Disease is a childhood affliction. (5) Organic mercury compounds are potent disrupters of brain development; some authorities believe that its conversion to the inorganic form in brain cells is the toxic mechanism responsible. (6) The experimental literature devoted to neurobehavioral effects consists of a handful of studies. To enhance our ability to evaluate the risks of metallic mercury to the developing brain, we intend to expose both pregnant rats and neonates to mercury vapor. Pregnant rats will be exposed to air, 30 ug/cubic meter, 100 ug/cubic meter, the OSHA permissible level, and 300 ug/cubic meter. Neonatal rats will be exposed to air, 10, 30, and 100 ug/cubic meter. Exposure will last two hours. The different levels are based on reports indicating widely different sensitivities between prenatal and neonatal exposures. Dam and pup blood levels will be monitored, and tissue assays, especially of brain, will be conducted at selected times. To determine the functional consequences of developmental exposure, three behavioral endpoints will be assayed: (1) The acoustic startle response, which will provide measures of habituation, sensory dysfunction, and the total neuromuscular response pattern to sound. (2) Spontaneous locomotor activity in the rats, a common index of neurotoxicity. (3) Acquisition of schedule-controlled operant behavior. Histochemical techniques will be deployed to map localization of brain mercury deposits.

描述：（改编自研究者的摘要）金属汞，一种 神经毒物通常被视为职业危害，是一种更普遍的 还有环境危害。 尽管我们对其了解很多 对成年人的影响，我们对其对发育中大脑的影响的了解是 零碎的。 这种信息差距令人不安。 (1) 女性较多 劳动力暴露于汞蒸气。 (2) 许多（也许是大多数）女性 牙科汞合金填充物。 它们会释放出汞蒸气。 母体组织和 胎儿水平与填充物的数量相关。 (3) 汞是 室内环境中的污染物比人们普遍认识的更为常见。 由于其物理特性，它可以潜伏不被发现并持续存在 蒸发。 (4) 幼儿更容易受到汞的影响 毒性高于成人；粉红病综合症是童年时期 痛苦。 (5) 有机汞化合物是大脑的有效干扰物 发展;一些权威人士认为，它转化为无机物 脑细胞中的形式是负责的毒性机制。 (6) 的 致力于神经行为效应的实验文献包括 少数研究。 增强我们评估风险的能力 金属汞对发育中的大脑有影响，我们打算让怀孕的 大鼠和新生儿接触汞蒸气。 怀孕的老鼠会暴露在空气中， 30 微克/立方米、100 微克/立方米、OSHA 允许水平和 300 微克/立方米。 新生大鼠将暴露在空气中，10、30、100 微克/立方米。 曝光将持续两个小时。 不同的级别是 根据报告表明产前人群之间的敏感性存在很大差异 和新生儿暴露。 将监测母鼠和幼鼠的血液水平，并且 组织检测，特别是脑组织检测，将在选定的时间进行。 到 确定发育暴露的功能后果，三个 将分析行为终点：(1) 声音惊吓反应， 这将提供习惯、感觉功能障碍和 对声音的总神经肌肉反应模式。 (2) 自发运动 大鼠的活动，神经毒性的一个常见指标。 (3) 收购 时间表控制的操作行为。 组织化学技术将 用于绘制脑汞沉积物的定位图。