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| INNOVATIVE RESEARCH FOR A SUSTAINABLE FUTURE
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Virtual Tissue Modeling Research Area
chemical safety To understand the effects of chemical exposures, risk assessors must understand how chemicals impact human systems,
for susTAiNABiLn jnciuljing tissues and organs. EPA's Chemical Safety for Sustainability Research Program research focuses on developing
tools that can bridge the gap between observations in lab-based experiments and more complex biological interactions.



EPA's Chemical Safety for Sustainability Research Program
The goal of EPA's Chemical Safety for Sustainability (CSS) National
Research Program is to provide information and methods to make better-
informed, more timely decisions about the safety of chemicals, many of
which have not been thoroughly evaluated for potential risks to human
health and the environment.
About Virtual Tissue Modeling Research
The Virtual Tissue Modeling Research Area examines complex chemical-
biological interactions using cutting-edge technologies such as organ-on-
chip (3-D cell cultures designed to mimic the architecture and physiology
of organs), in vitro (cell-based), and alternative in vivo (animal) models.
Ultimately, these data are used to computationally simulate and predict
how chemicals impact key biological processes such as human
development.
Research in this area will focus on:
•	Developing models of increasing levels of biological complexity to
capture cell-based impacts of chemical exposures to the developing
embryo
•	Developing data and methods to link high-throughput toxicity data
with outcomes at the organ or individual level
Why Is Virtual Tissue Modeling Research Important?
To bridge the gap from molecular changes to endpoints relevant for
hazard assessment, models of biological systems are needed that can be
experimentally probed and computationally simulated. Virtual tissue
models provide this flexibility while providing data needed for faster
chemical risk assessments and minimizing dependence on animal study
data.
Interested In Learning More?
EPA's Chemical Safety Research Program: epa.gov/chemical-research
Contact Us:
Jeffrey Frithsen, National Program Director: frithsen.ieff(Sepa.gov
JoeTietge, Deputy Program Director: tietge.ioe(a>epa.gov
The Question
How can we use innovative approaches
to simulate biological interactions that
occur after exposure to a chemical?
New Approach Methods
EPA is developing and incorporating new approach methods to
assess the safety of chemicals at a lower cost and in less time
High-Throughput Screening: era scientists
are growing neural cells that mimic important
processes of brain development, which can be
used to screen and prioritize thousands of
chemicals not yet evaluated.
Virtual Tissue Models: era scientists are
using computational methods to create virtual
tissue models to simulate how chemicals may
affect human development.
Alternative Animal Models: era scientists
are investigating the potential of chemicals to
affect human development bytesting chemicals in
developing zebrafish.
Adverse Outcome Pathways: era scientists
are using aop frameworks to organize data to
predict changes in biological pathways and the
potential effects of chemicals on the developing
nervous system.
Learn more about EPA's New Approach Methods on our webpage:
h ttps://www. epa.go v/ch em ical-research/e val uating-effects-ch em icals-nervo us
-system-development
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U.S. Environmental Protection Agency
Office of Research and Development
Last Updated March 2019

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science in ACTION
INNOVATIVE RESEARCH FOR A SUSTAINABLE FUTURE
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Virtual Tissue Modeling Research Area Up Close
Examples of Research and Products
Visualizing the CSS Program
How Virtual Tissue Modeling Fits In
CSS is organized around three research topics
that address specific science challenges in
assessing the safety of chemicals: Chemical
Evaluation, Complex Systems Science, and
Knowledge Translation & Delivery.
Included in our Complex Systems Science
research topic, our Virtual Tissue Modeling
research is focused on developing tools that
can be used to bridge the gap between
observations in lab-based experiments and
more complex biological interactions. These
methods can provide data needed for
chemical risk assessments while minimizing
dependence on animal study data.
Science To Achieve Results (STAR) Organotypic Culture Model
Development
=> What is it?: Through our Science to Achieve Results (STAR) grant
program, the EPA has funded four Research Centers to develop in
vitro systems of cell cultures that replicate human biological
interactions within complex tissues or organs, called Organotypic
Culture Models (OCMs). When developed and evaluated, these OCMs
will provide information needed to help predict toxicity due to
chemical exposures.
=> Impact: The OCMs will provide the biological understanding and data
to help evaluate, improve and extend computational models
currently being developed by EPA scientists.
=> Who Can Use It?: Once completed, researchers and risk assessors
looking for new ways to predict chemical toxicity
=> Learn More: epa.gov/sites/production/files/2016-02/documents/
ocm factsheet.pdf
Blood-brain barrier development: systems modeling and
predictive toxicology
=> What is it?: A journal article published in Toxicological Sciences
providing useful research into understanding the relationship
between in vitro bioactivity dose and external exposure
concentration.
=> Impact: This research will inform adverse outcome pathways to
reduce uncertainty in translating in vitro data and in silico (computer-
based) models for use in risk assessments that aim to protect
neurodevelopmental health.
=> Who Can Use It?: Researchers and risk assessors interested in
modeling neurodevelopment
=> Learn More: doi.org/10.1002/bdr2.1180
I
Learn more
EPA's Chemical Safety Research Program: epa.gov/chemical-research
U.S. Environmental Protection Agency
Office of Research and Development
Last Updated March 2019

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