Bronze level automatically awarded US beta
This data has achieved Bronze level on 24 October 2015 which means this data makes a great start at the basics of publishing open data.
The purpose of this project is to adapt cellular in vitro assay systems of the rainbow trout pituitary, liver and ovary for high-throughput screening (HTS) of environmental contaminants, particularly those that disrupt the reproductive endocrine system of fish and potentially impair reproductive health. Each assay will measure essential reproductive endocrine functions of the corresponding organ, for example follicle stimulating hormone (FSH) synthesis and secretion by pituitary cells, and permit derivation of the lowest observed effect and activation concentrations for a test contaminant. Results from the in vitro assays will be used to parameterize a computational model of the trout brain-pituitary-ovary-liver (BPOL) axis to assess the impact of a contaminant on oocyte maturation and spawning. Along with the BPOL modeling is determination of the hypothetical water concentration necessary to achieve a target organ level comparable to the various in vitro dose metrics. This is also sometimes referred to as reverse toxicokinetics. Thus, our ultimate goal is to demonstrate the feasibility of integrating in vitro assays with computational modeling as a surrogate for fish life-cycle testing for assessing the reproductive toxicity of environmental contaminants. This project will address key challenges identified with implementing the toxicity pathway concept (NRC 2007) and its ecological counterpart, the adverse outcome pathway, by establishing linkages between sub-cellular/cellular responses and whole-animal effects and in vitro/in vivo extrapolation of chemical dosimetry. Our experimental approach consists of three teams of investigators (Dr. Penny Swanson, NWFSC; Professor Graham Young, University of Washington, and Professor James Nagler, University of Idaho) pursuing the in vitro studies combined with a fourth team (Dr. Irvin R. Schultz, Battelle Pacific Northwest Division) that will perform computational and toxicokinetic modeling and provide centralized support for test chemical analysis. Endocrine-disrupting activity of 8 chemicals
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