Posted: October 16, 2019

Letter of Intent due December 3, 2019; Application due January 3, 2020

The National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), within the Division of the National Toxicology Program at NIEHS, supports the development and evaluation of method for replacement or reduction of animal use in toxicity testing, including the development and evaluation of new, revised, and alternative methods to identify potential hazards to human health and the environment https://ntp.niehs.nih.gov/pubhealth/evalatm/index.html. The development of alternative in vitro organotypic models for drug development and toxicity screening through programs such as the NIH/NCATS Tissue Chip program, https://ncats.nih.gov/tissuechip, has the potential for meeting NICEATM goals of reducing animal use as well as reducing the cost and effort of drug and toxicant screening through the development of validated organ-on-a-chip systems for safety testing. However, these systems are currently developed primarily using human cells. A critical enabler for building confidence in human-relevant test systems is an understanding of how to mechanistically, phenotypically, and quantitatively extrapolate in vitro biology to in vivo biology. Our inability to ethically model toxicity in human subjects prevents us from building that confidence experimentally. Therefore, animal-based in vitro systems that complement our current animal-based in vivo testing are our best opportunity to develop that understanding and move toward a less animal-dependent future. Development of experimental animal OCMs that recapitulate key features of in vivohuman biology and outcomes will enable initial screening efforts that reduce the need for extensive in vivo animal studies. In addition, finding concordance between in vitro OCMs and in vivo toxicology results in animals can help to strengthen the confidence in testing results from human OCMs.

Therefore, there is a need for development of OCM or 3D culture in vitro systems. The proposed technology and/or product development must use animal cells in the context of OCMs or in vitro 3D cultures. This FOA is not intended to support research using human cells, but the platforms developed may be applicable to human cells for comparison.

Objectives

Areas of interest and examples of applications that are responsive to this FOA include, but are not limited to development of:

  • 3D tissue, OCM, or microphysiological systems for toxicology testing derived from experimental animal tissues including but not limited to: liver, lung, heart, brain, and kidney.
  • OCM models derived from embryonic stem (ES) cells or pluripotent stem cells, or from single or multiple cell types, that replicate the biological function and responses of the target organ of interest.
  • OCM models that assess critical biological targets and or biomarkers that are comparable to in vivo toxicology endpoints.
  • in vitro models that capture complex cell-cell and cell-extracellular matrix interactions to help link molecular initiating events to chemical risks at the tissue or organ level in an Adverse Outcome Pathway framework.
  • in vitro models that incorporate metabolism and other critical features of biological responses to toxicants in the target tissue.

Read full solicitation here

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