Markers for chemical mixtures in Fundulus heteroclitus

暴露于从超级基金站点迁移的化学物质通常包括暴露于复杂的混合物。对人类和野生动物都是如此。该项目的重点是对选定的超级基金化学物质对河口常见鱼类鳉鱼（Fundulus heteroclitus）繁殖和生长的单一和联合影响进行深入的定量分析。这些化学物质将代表三种可能与生殖和发育影响相关的作用机制：芳烃受体介导、性类固醇激素受体介导和氧化应激。该项目的主要目标是开发一种基于生物标志物的策略，用于评估超级基金化学品对水生哨兵物种的暴露和生殖/发育影响，这些影响在多次暴露的情况下将是稳健的。该项目的具体目标是：1)量化选定的超级基金化学物质，单独和组合，对异交底（眼底）的繁殖和发育的影响。2)测定所选化合物经母体转移到卵母细胞的能力。3)建立发育毒性与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标在预测多种化学物质暴露相关的生殖/发育影响方面的效用。5)开发一种基于生物标志物的策略，用于评估在多种暴露情景下对超级基金污染物的暴露和生殖/发育影响。6)将此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.