Markers for chemical mixtures in Fundulus heteroclitus

接触从超级基金场址迁移的化学品通常包括接触复杂的混合物。这对人类和野生动物的接触都是如此。该项目的主旨是对选定的超级基金化学品对常见河口鱼（鳉鱼）的繁殖和生长的单一和综合影响进行深入的定量分析。这些化学品将代表与生殖和发育影响潜在相关的三种作用机制：芳香烃受体介导、性类固醇激素受体介导和氧化应激。该项目的主要目标是制定一项基于生物标志物的战略，以评估超级基金化学品对水生哨兵物种的影响及其对生殖/发育的影响，该战略在多重接触的情况下将是稳健的。本项目的具体目标是：1）量化选定的超级基金化学品，单独和组合，对底的生殖和发育的影响。2)确定所选化合物经母体转移至卵母细胞的能力。3)建立发育毒性和基于机制的生物标志物之间的相关性。4)确定基于机制的生物标志物和更广泛的细胞效应指数的效用，以预测多种化学品暴露的相关生殖/发育影响。5)制定基于生物标志物的战略，用于评估超级基金污染物的暴露及其对生殖/发育的影响，该战略在多种暴露情景中具有稳健性。6)将这一策略应用于从四个超级基金站点收集的沉积物。

Exposures to chemical migrating from Superfund sites are oftentimes comprised of exposures to complex mixtures. This is true for both human and wildlife exposures. The thrust of this project is to perform in-depth, quantitative analyses of the single and combined effects of selected Superfund chemicals on reproduction and growth in the common estuarine fish, the killifish (Fundulus heteroclitus). These chemicals will represent three mechanisms of action potentially related to reproductive and development effects: aryl hydrocarbon receptor-mediated, sex steroid hormone receptor-mediated, and oxidative stress. The principle goal of this project is to develop a biomarker-based strategy for assessing exposures to and reproductive/developmental effects of Superfund effects of Superfund chemicals in aquatic sentinel species that will be robust in the context of multiple exposures. The specific aims of this project are: 1) To quantify the effects of selected Superfund chemicals, singly and in combination, on reproduction and development in Fundulus heteroclitus (Fundulus). 2) To determine the ability of selected compounds to undergo maternal transfer to oocytes. 3) To establish correlations among developmental toxicities and mechanism-based biomarkers. 4) To determine the utility of mechanism-based biomarkers and broader indices of cellular effect to predict associated reproductive/developmental effects of multiple chemical exposure. 5) To develop a biomarker-based strategy for assessing exposures to and reproductive/developmental effects of Superfund contaminants that is robust in multiple exposure scenarios. 6) To apply this strategy to sediments collected from four Superfund sites.