DEVELOPMENTAL EFFECTS OF FISH BORNE TOXICANTS IN THE RAT

描述：(改编自《调查者摘要》)近期 流行病学研究表明，摄入 五大湖鱼类受孕妇污染及发育和 他们的婴儿和儿童存在认知缺陷。尽管多氯化 最近的数据显示，接触联苯(PCB)与这些功能障碍有关 我们从围产期暴露在含有以下物质的饮食中的大鼠身上收集到 冻干五大湖鲑鱼表明观察到的神经心理学 影响可能是由于鱼中的其他神经活性污染物或 多氯联苯与其他污染物之间的协同作用。为了 确定五大湖鱼类中存在的哪些毒物会导致神经行为 围产期暴露后的变化我们将：(1)测量 安大略湖有机和无机污染物的浓度 (LO)三文鱼和太平洋(PO)三文鱼，将作为管制 在所有实验中；(2)测定大鼠的神经行为效应 围产期暴露于冻干三文鱼(含所有污染物)或 罗鲑鱼的硫酸提取物(含有所有有机污染物)。 如果冻干三文鱼和溶剂对神经行为的影响 提取相等，我们将假设不可提取的组件 (包括甲基汞)没有参与调解影响，我们将继续 目的：(3)测定两种花柱的神经行为效应。 LO溶剂萃取物的级分--含有大部分 多氯联苯、DDE、六氯苯、灭蚁灵和氯丹，另一种含有共面 多氯联苯、二恶英、二苯并呋喃和极性农药；(4)测定 行为暴露动物的区域特异性神经化学变化 活性部位(S)。或者，如果在(2)中获得的结果表明 未分馏的溶剂萃取物不会产生与 对于冻干的罗鲑鱼，我们将进行研究以确定 内源(脂肪酸、硒)和外源(甲基汞、砷、铅) 必须将不可提取的成分添加到溶剂萃取物中，以产生 行为等价性。这些实验将使我们能够确定 污染物的种类是导致神经心理变化的原因 可见于围产期接触过的人类。这些发现将有助于降低风险 评估过程，也将成为以后研究的基础 确定导致行为改变的机制。

DESCRIPTION: (Adapted from the Investigator's Abstract) Recent epidemiological studies suggest a relationship between consumption of contaminated Great Lakes fish by pregnant women and developmental and cognitive deficits in their infants and children. Although polychlorinated biphenyl (PCB) exposure is correlated with these dysfunctions, recent data we have collected from rats perinatally exposed to diets containing lyophilized Great Lakes salmon suggest that the observed neuropsychological effects may be due to other neuroactive contaminants in the fish or to synergistic interactions between PCBs and other contaminants. In order to determine which toxicants present in Great Lakes fish induce neurobehavioral alterations following perinatal exposure we will: (1) measure concentrations of the organic and inorganic contaminants in Lake Ontario (LO) salmon and in Pacific Ocean (PO) salmon, which will serve as a control in all experiments; (2) determine neurobehavioral effects in rats perinatally exposed to lyophilized LO salmon (contains all contaminants) or a sulfuric acid extract of LO salmon (contains all organic contaminants). If the neurobehavioral effects of the lyophilized LO salmon and the solvent extract are equal we will assume that the non-extractable components (including MeHg) are not involved in mediating the effects and we will go on to; (3) determine the neurobehavioral effects of two florisil column fractions of the LO solvent extract -- one containing the majority of the PCBs, DDE, HCB, mirex and chlordanes, and the other containing the coplanar PCBs, dioxins, dibenzofurans and polar pesticides and; (4) determine regio-specific neurochemical changes in animals exposed to the behaviorally active fraction(s). Alternatively, if the results obtained in (2) indicate that the unfractionated solvent extract does not yield effects equivalent to those of the lyophilized LO salmon, we will conduct studies to determine which endogenous (fatty acids, selenium) and exogenous (MeHg, arsenic, lead) non-extractable components must be added to the solvent extract to result in behavioral equivalence. These experiments will allow us to determine which class(es) of contaminants are responsible for the neuropsychological changes seen in perinatally-exposed humans. The findings will aid in the risk assessment process and will also form the basis for later studies to determine the mechanisms responsible for the behavioral alterations.