Grantee Research Project Results
2016 Progress Report: Cell-Free Neurochemical Screening Assays to Predict Adverse Effects in Mammals, Fish, and Birds
EPA Grant Number: R835170Title: Cell-Free Neurochemical Screening Assays to Predict Adverse Effects in Mammals, Fish, and Birds
Investigators: Basu, Niladri , Murphy, Cheryl A. , Head, Jessica Anne , Neitzel, Richard L.
Current Investigators: Basu, Niladri , Head, Jessica A , Murphy, Cheryl A. , Neitzel, Richard L.
Institution: University of Michigan
Current Institution: University of Michigan , McGill University , Michigan State University
EPA Project Officer: Aja, Hayley
Project Period: September 1, 2012 through August 31, 2015 (Extended to August 31, 2017)
Project Period Covered by this Report: September 1, 2015 through August 31,2016
Project Amount: $1,199,222
RFA: Developing High-Throughput Assays for Predictive Modeling of Reproductive and Developmental Toxicity Modulated Through the Endocrine System or Pertinent Pathways in Humans and Species Relevant to Ecological Risk Assessment (2011) RFA Text | Recipients Lists
Research Category: Chemical Safety for Sustainability
Objective:
The overall objective of this proposal is to advance an existing in vitro, cell-free neurochemical screening assay platform, and model data outputs to predict adverse, individual-level reproductive effects associated with toxicant exposure in mammalian, fish, and avian wildlife. The overall hypothesis is that several environmental toxicants will emerge to interact with and disrupt the function of neurotransmitter receptors, enzymes and transporters that have critical roles in vertebrate reproduction.
Progress Summary:
In Year 4, we conducted a series of in vitro screening assays contained within Phase #2 of our proposed work. The selected neurochemical receptors and enzymes were isolated from different organisms (n=8) of multiple taxa, including freshwater and marine fish, birds, terrestrial and marine mammals, and biomedical species including human. The isolated neurochemical receptors and enzymes were dosed in vitro with a diverse set of 10 potentially neurotoxic chemicals that were identified in Phase #1 of our project. Here, we expanded to work to characterize exposure-response profiles. The results enabled us to better understand the utility of cell-free assay results. We also initiated Phase #3 of our project which involves screening the U.S. EPA E1K library of chemicals against our assays. Thus far, the work has resulted in the establishment of a mid-throughput screening assay (up to 10,000 data points per week) that can be used to predict neurochemical effects across multiple ecologically relevant species (birds, fish and mammals).
Future Activities:
Finalize Phase 3 assays on selected chemicals, complete validation study, and develop and test computational models by linking in vitro with molecular, biochemical, and whole animal results.
Journal Articles on this Report : 1 Displayed | Download in RIS Format
| Other project views: | All 19 publications | 4 publications in selected types | All 2 journal articles |
|---|
| Type | Citation | ||
|---|---|---|---|
|
|
Arini A, Cavallin JE, Berninger JP, Marfil-Vega R, Mills M, Villeneuve DL, Basu N. In vivo and In vitro neurochemical-based assessments of wastewater effluents from the Maumee River area of concern. Environmental Pollution 2016;211:9-19. |
R835170 (2016) R835170 (Final) |
Exit Exit Exit |
Supplemental Keywords:
alternative testing, screening, in vitro, chemical testing, chemical prioritization, wildlife, cell-free assays, high-throughput, computational modelsRelevant Websites:
http://basulab.weebly.com/ Exit Exit
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.