Novel Tools and Approaches | National Institute of Environmental Health Sciences
Source: https://www.niehs.nih.gov/research/atniehs/dtt/strategic-plan/strength/novel
Archived: 2026-04-23 17:09
Novel Tools and Approaches | National Institute of Environmental Health Sciences
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Novel Tools and Approaches
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Much of the work carried out by DTT is in support of the National Toxicology Program (NTP), an interagency partnership of the Food and Drug Administration, National Institute for Occupational Safety and Health, and NIEHS.
Visit the NTP Website
Table of Contents
Public Health Significance
Research Objectives
Background
Select Studies
Additional Resources
Public Health Significance
The field of toxicology is moving toward more efficient and reduced use of animals, with a greater reliance on
in vitro
models as well as analytical methods and innovative technologies that rapidly provide human-relevant data to better inform public health decision-making. The NIEHS Division of Translational Toxicology (DTT) has historically sought innovative methods for addressing toxicological problems in hazard and risk assessment. There is a critical need for a portfolio of fit-for-purpose tools and approaches that can be easily and rapidly deployed to provide information on potential human hazards and risks from exposure.
Research Objectives
The three main objectives of Novel Tools and Approaches (NTA) research are to:
Identify and adapt promising new tools, technologies, and approaches that could enhance the efficiency and translational relevance of DTT hazard assessments.
Ensure that novel capability development is aligned with contemporary problems that DTT is attempting to solve.
Increase confidence in — and adoption of — novel methods within and outside DTT, and foster the development of novel, non-standard methods where none currently exist, focusing on high-interest
in vitro
systems and short-term
in vivo
assays.
The NTA will focus on three research areas to advance these objectives. These three broad areas, along with examples of each, are:
Spheroids and Organoids
HepaRG 3D liver cell, metabolically competent spheroids
Neural stem cell spheroids for developmental neurotoxicology
Embryoid bodies driven to specific cell types to form organoids
Microphysiological Systems
Organs-on-a-chip
Microfluidic chip
Novel Technologies with high dimensional data streams
Innovative imaging systems and analysis
Tox21 high-throughput screening program and cross-partner projects
High-throughput transcriptomics (e.g., S1500+ platform)
Air-liquid interface exposure system
Ultimately, the NTA will identify, evaluate, and implement new research tools and approaches that advance translatable, predictive, and timely toxicology in areas critical to the DTT mission and to DTT stakeholders.
Background
DTT has a long history of using innovative tools to better solve toxicology problems in hazard and risk assessment. For example, DTT has been involved in the
Tox21 Program
, which began as an interagency collaboration to predict (with improved accuracy) the toxicological effects of substances within large chemical libraries more rapidly than standard approaches by integrating computational biology and robotic high-throughput screening for biological activity.
Initial efforts of the Tox21 Program resulted in the development of a chemical library of about 10,000 compounds covering a sizeable range of chemical space. The chemical library was screened for activity in nuclear receptor and cellular stress response signaling pathways. By the beginning of 2021, just under one million data points generated through Tox21 Program activities have been deposited into PubChem, and the program has generated more than 200 publications in more than 50 journals to date.
Now, the Tox21 Program is in its third phase, investigating in greater detail toxicologic features such as metabolic competence and genome-wide transcriptional responses that are relevant to chemical exposures of environmental and pharmaceutical interest.
The S1500+ high-throughput transcriptomic platform is another example of the successful development by DTT of a new technology platform that has now gained widespread acceptance and use. This platform helps to measure chemical exposure-induced gene expression changes in more than 3,000 genes, covering 96% of all known human cell signaling pathways.
At the time of its establishment, the NTA was assigned a broad portfolio of research and development projects and capabilities that represent increasing complexity, spanning from in vitro methods to short-term in vivo tests. Going forward, in addition to managing current projects in that portfolio, the NTA will perform regular reviews of the entire landscape of emerging technologies and applications to identify new bioassays or biological systems as well as novel technologies and unconventional approaches that could be useful to ongoing DTT research projects and the wider toxicology community.
Select Studies
Study
Description
Findings/Supporting Files
5-day
in Vivo
Rat Studies
To examine 10 aromatic phosphate and per- and polyfluoroalkyl substances in short-term,
in vivo
studies with multiple endpoints to define their transcriptomic signatures.
The goal is to determine whether these short-term studies can yield data useful for public health decision-making.
Complete
CASRN 1241-94-7
(3MB)
CASRN 56803-37-3
(3MB)
CASRN 29761-21-5
(3MB)
CASRN 68937-41-7
(3MB)
CASRN 1330-78-5
(3MB)
CASRN 375-82-6
(2MB)
ASRN 865-86-1
(2MB)
CASRN 243-17-4
(1MB)
CASRN 41997-13-1
(2MB)
In Vitro
to
in Vivo
Extrapolation (IVIVE)
Projects to evaluate hepatic clearance of PFAS (per- and polyfluoroalkyl substances) and estimate internal dose to compare with results from studies in cells.
Ongoing
Retrofitting Existing Tox21 High-throughput Screening (HTS) Assays With Metabolic Capability
To screen the Tox21 10K library in the p53RE assay in the presence of human or rat liver microsomes to evaluate this method for providing xenobiotic metabolism capability to Tox21 HTS assays.
Ongoing
Identification of Environmental Chemicals That Activate P53 Signaling After in Vitro Metabolic Activation
Toxicity Studies in the HepaRG 2D and 3D Models
To investigate liver toxicity, metabolism, and genotoxicity of substances in HepaRG cells using both 2D and 3D model systems.
Optimization and validation of the 3D spheroid model systems is ongoing.
Pluripotent Stem Cell-Based Models
To develop several 2D/3D model systems to be used for directed differentiation to specific cell types and development of multiple organoid models. These model systems will be used for screening and mechanistic investigations into the effects of chemicals on embryonic and early-life development.
Ongoing
Pluripotent Stem Cells for Target Organ Developmental Toxicity Testing
Pluripotent Stem Cell-Derived Dopaminergic Neurons for Studying Developmental Neurotoxicity
Additional Resources
Back
to Top
Last Reviewed: December 23, 2025
Skip Navigation
Novel Tools and Approaches
Close the left navigation
Much of the work carried out by DTT is in support of the National Toxicology Program (NTP), an interagency partnership of the Food and Drug Administration, National Institute for Occupational Safety and Health, and NIEHS.
Visit the NTP Website
Table of Contents
Public Health Significance
Research Objectives
Background
Select Studies
Additional Resources
Public Health Significance
The field of toxicology is moving toward more efficient and reduced use of animals, with a greater reliance on
in vitro
models as well as analytical methods and innovative technologies that rapidly provide human-relevant data to better inform public health decision-making. The NIEHS Division of Translational Toxicology (DTT) has historically sought innovative methods for addressing toxicological problems in hazard and risk assessment. There is a critical need for a portfolio of fit-for-purpose tools and approaches that can be easily and rapidly deployed to provide information on potential human hazards and risks from exposure.
Research Objectives
The three main objectives of Novel Tools and Approaches (NTA) research are to:
Identify and adapt promising new tools, technologies, and approaches that could enhance the efficiency and translational relevance of DTT hazard assessments.
Ensure that novel capability development is aligned with contemporary problems that DTT is attempting to solve.
Increase confidence in — and adoption of — novel methods within and outside DTT, and foster the development of novel, non-standard methods where none currently exist, focusing on high-interest
in vitro
systems and short-term
in vivo
assays.
The NTA will focus on three research areas to advance these objectives. These three broad areas, along with examples of each, are:
Spheroids and Organoids
HepaRG 3D liver cell, metabolically competent spheroids
Neural stem cell spheroids for developmental neurotoxicology
Embryoid bodies driven to specific cell types to form organoids
Microphysiological Systems
Organs-on-a-chip
Microfluidic chip
Novel Technologies with high dimensional data streams
Innovative imaging systems and analysis
Tox21 high-throughput screening program and cross-partner projects
High-throughput transcriptomics (e.g., S1500+ platform)
Air-liquid interface exposure system
Ultimately, the NTA will identify, evaluate, and implement new research tools and approaches that advance translatable, predictive, and timely toxicology in areas critical to the DTT mission and to DTT stakeholders.
Background
DTT has a long history of using innovative tools to better solve toxicology problems in hazard and risk assessment. For example, DTT has been involved in the
Tox21 Program
, which began as an interagency collaboration to predict (with improved accuracy) the toxicological effects of substances within large chemical libraries more rapidly than standard approaches by integrating computational biology and robotic high-throughput screening for biological activity.
Initial efforts of the Tox21 Program resulted in the development of a chemical library of about 10,000 compounds covering a sizeable range of chemical space. The chemical library was screened for activity in nuclear receptor and cellular stress response signaling pathways. By the beginning of 2021, just under one million data points generated through Tox21 Program activities have been deposited into PubChem, and the program has generated more than 200 publications in more than 50 journals to date.
Now, the Tox21 Program is in its third phase, investigating in greater detail toxicologic features such as metabolic competence and genome-wide transcriptional responses that are relevant to chemical exposures of environmental and pharmaceutical interest.
The S1500+ high-throughput transcriptomic platform is another example of the successful development by DTT of a new technology platform that has now gained widespread acceptance and use. This platform helps to measure chemical exposure-induced gene expression changes in more than 3,000 genes, covering 96% of all known human cell signaling pathways.
At the time of its establishment, the NTA was assigned a broad portfolio of research and development projects and capabilities that represent increasing complexity, spanning from in vitro methods to short-term in vivo tests. Going forward, in addition to managing current projects in that portfolio, the NTA will perform regular reviews of the entire landscape of emerging technologies and applications to identify new bioassays or biological systems as well as novel technologies and unconventional approaches that could be useful to ongoing DTT research projects and the wider toxicology community.
Select Studies
Study
Description
Findings/Supporting Files
5-day
in Vivo
Rat Studies
To examine 10 aromatic phosphate and per- and polyfluoroalkyl substances in short-term,
in vivo
studies with multiple endpoints to define their transcriptomic signatures.
The goal is to determine whether these short-term studies can yield data useful for public health decision-making.
Complete
CASRN 1241-94-7
(3MB)
CASRN 56803-37-3
(3MB)
CASRN 29761-21-5
(3MB)
CASRN 68937-41-7
(3MB)
CASRN 1330-78-5
(3MB)
CASRN 375-82-6
(2MB)
ASRN 865-86-1
(2MB)
CASRN 243-17-4
(1MB)
CASRN 41997-13-1
(2MB)
In Vitro
to
in Vivo
Extrapolation (IVIVE)
Projects to evaluate hepatic clearance of PFAS (per- and polyfluoroalkyl substances) and estimate internal dose to compare with results from studies in cells.
Ongoing
Retrofitting Existing Tox21 High-throughput Screening (HTS) Assays With Metabolic Capability
To screen the Tox21 10K library in the p53RE assay in the presence of human or rat liver microsomes to evaluate this method for providing xenobiotic metabolism capability to Tox21 HTS assays.
Ongoing
Identification of Environmental Chemicals That Activate P53 Signaling After in Vitro Metabolic Activation
Toxicity Studies in the HepaRG 2D and 3D Models
To investigate liver toxicity, metabolism, and genotoxicity of substances in HepaRG cells using both 2D and 3D model systems.
Optimization and validation of the 3D spheroid model systems is ongoing.
Pluripotent Stem Cell-Based Models
To develop several 2D/3D model systems to be used for directed differentiation to specific cell types and development of multiple organoid models. These model systems will be used for screening and mechanistic investigations into the effects of chemicals on embryonic and early-life development.
Ongoing
Pluripotent Stem Cells for Target Organ Developmental Toxicity Testing
Pluripotent Stem Cell-Derived Dopaminergic Neurons for Studying Developmental Neurotoxicity
Additional Resources
Back
to Top
Last Reviewed: December 23, 2025