Integrating Liver, Kidney and Testis Nanomaterial Toxicity using the Adverse Outcome Pathway Approach

EPA Grant Number: R835738C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R835738
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Predictive Toxicology Center for Organotypic Cultures and Assessment of AOPs for Engineered Nanomaterials
Center Director: Faustman, Elaine
Title: Integrating Liver, Kidney and Testis Nanomaterial Toxicity using the Adverse Outcome Pathway Approach
Investigators: Griffith, William C. , Faustman, Elaine , Gao, Xiaohu
Current Investigators: Griffith, William C. , Gao, Xiaohu
Institution: University of Washington
EPA Project Officer: Klieforth, Barbara I
Project Period: December 1, 2014 through November 30, 2018
RFA: Organotypic Culture Models for Predictive Toxicology Center (2013) RFA Text |  Recipients Lists
Research Category: Safer Chemicals , Health , Human Health

Objective:

The goal of this project is to develop models for integrating organotypic culture responses to Engineered Nanomaterials (ENMs) across the lung, liver, kidney and testis and to predict whole organism response. We will use a systems-based Adverse Outcomes Pathway (AOP) approach linked with toxicokinetic and dynamic models to identify key molecular initiating events and cellular, tissue and organ responses from each organotypic model. These AOPs will then be integrated with lifestage and genetic susceptibility factors to model ENM toxicity response across organ systems, organisms and populations. This project will also identify critical data gaps and make recommendations for further testing of ENMs. 

Approach:

Design of custom applications for extraction of microphysiometer output data into PBTK models. 

Publications and Presentations:

Publications have been submitted on this subproject: View all 10 publications for this subprojectView all 74 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 2 journal articles for this subprojectView all 13 journal articles for this center

Relevant Websites:

The Predictive Toxicology Center (PTC) Exit

Progress and Final Reports:

2015 Progress Report
2016 Progress Report


Main Center Abstract and Reports:

R835738    Predictive Toxicology Center for Organotypic Cultures and Assessment of AOPs for Engineered Nanomaterials

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R835738C001 Airway Epithelium Organotypic Culture as a Platform for Adverse Outcomes Pathway Assessment of Engineered Nanomaterials
R835738C002 Organotypic Model of Human Kidney as a Platform for Adverse Outcomes Pathway Assessment of Engineered Nanomaterials
R835738C003 Organotypic Models of Mammalian Liver as a Platform for Adverse Outcomes Pathway Assessment of Engineered Nanomaterials
R835738C004 Organotypic Model of Testis as a Platform for Adverse Outcomes Pathway Assessment of Engineered Nanomaterials
R835738C005 Integrating Liver, Kidney and Testis Nanomaterial Toxicity using the Adverse Outcome Pathway Approach