Developmental Neurotoxicity Health Effects | National Institute of Environmental Health Sciences
Source: https://www.niehs.nih.gov/research/atniehs/dtt/strategic-plan/health/developmental
Archived: 2026-04-23 17:25
Developmental Neurotoxicity Health Effects | National Institute of Environmental Health Sciences
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Developmental Neurotoxicity Health Effects
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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
Public Health Significance
Neurodevelopmental disorders such as autism and attention-deficit hyperactivity disorder (ADHD) are on the rise worldwide, and environmental exposures are likely contributing factors. Currently, almost no chemicals have been formally screened for developmental neurotoxicity (DNT) potential.
Current methods to evaluate the thousands of chemical compounds with unknown DNT potential remain inadequate and are rarely used. The complexity of neurodevelopment, which involves multiple key processes, one or more of which may be perturbed by a given environmental agent, requires a more modern and comprehensive approach.
It can take more than a decade for regulations to be put into effect from the time a compound is identified as potentially developmentally neurotoxic, due to the lack of emphasis on this health outcome and the insensitivity of traditional studies. In the interim, people continue to be exposed to environmental chemicals that may result in neurodevelopmental disorders.
An integrated testing strategy that incorporates novel, innovative methods and provides quicker results could better inform public health decisions and boost understanding of how to mitigate environmental contributions to neurodevelopmental disorders.
Research Objectives
Developmental Neurotoxicity Health Effects (DNT HE) research within the Division of Translational Toxicology (DTT) is structured around the following four objectives:
Generate screening level information using new approach methodologies in compounds with unknown DNT potential as an interim means to evaluate hazard and prioritize further in-depth evaluation.
Refine
in vivo
DNT testing by incorporating human-relevant mechanistic, behavioral, and brain network assessments to address complex neurodevelopmental issues.
Contextualize
in vitro
and
in vivo
findings with human exposure using
in vitro
to
in vivo
extrapolation and
in silico
approaches to provide more relevant and translatable information that can be used to protect children’s health, working towards the additional goal of developing predictive DNT tools.
Establish communication pipelines with stakeholders to spur progress in DNT research, enable knowledge generated by DTT to be used in further evaluations (e.g., for decision-making), and inform the public about the latest advancements through a range of diverse media.
An important aspect of this research is that it will complement global DNT research efforts and help move the field forward. Ultimately, this strategy is designed to provide more rapid identification of DNTs as well as mechanistic understanding of environmental contributions to neurodevelopmental disorders such as autism.
Background
DNT HE research is a high priority and aims to effectively develop a comprehensive method to evaluate environmental compounds with unknown DNT potential. There are concerns about the current framework of DNT assessment, which is largely based on rodent guideline studies that have been deemed inadequate. These studies are time- and resource-intensive and are performed only when there is an a priori trigger — for example, clinical observations or histopathological changes in the brain noted from acute or subchronic studies, and structural and/or use patterns of concern to known DNTs (such as extensive exposure to pesticides with an organophosphate backbone in children).
As a result, environmental compounds with unknown potential to cause DNT remain largely untested. Even in cases with guideline
in vivo
data, uncertainties remain in the current DNT test strategies due to limitations with respect to sensitivity, reproducibility, and relevance when extrapolating data from rodents to humans for complex diseases such as autism and ADHD.
To address some of these concerns, the DNT HE research will use novel, relevant tools and technologies that incorporate a tiered strategy in line with the DTT pipeline. This research will use new approach methodologies in conjuction with refined
in vivo
studies. The initiative also will use exposure information to provide reliable data to stakeholders for timely protection of children’s health.
The DNT-HE aligns with the NIEHS strategic plan and supports the goal of advancing predictive toxicology and the cross-divisional focus area of neuroscience. The development of innovative, human-relevant tools to predict potential hazards for regulators and the public in a timely manner aligns with the DTT mission.
Select Studies
Study
Description
Findings/Supporting Files
DNT screening assay battery
Cover key neurodevelopmental events to prioritize compounds with DNT potential
Developmental Neurotoxicity Screening Data (Pilot)
Developmental Neurotoxicity Screening Assay Chemical List - Phase 1
Developmental Neurotoxicity Screening Assay Chemical List - Phase 2
Testing Status of Developmental Neurotoxicity Screening 21005
Developmental NeuroToxicity Data Integration and Visualization Enabling Resource (DNT-DIVER)
Neuroimmune cells as targets for neurotoxicity assessments
Assess microglia and astrocyte functional changes contributing to chemical-induced neurotoxicity
Childers GM, Perry CA, Blachut B, Martin N, Bortner CD, Sieber S, Li JL, Fessler MB, Harry GJ. 2021. Assessing the association of mitochondrial function and inflammasome activation in murine macrophages exposed to select mitotoxic tri-organotin compounds.
Environ Health Perspect
129(4):47015. [
Abstract
Childers GM, Perry CA, Blachut B, Martin N, Bortner CD, Sieber S, Li JL, Fessler MB, Harry GJ. 2021. Assessing the association of mitochondrial function and inflammasome activation in murine macrophages exposed to select mitotoxic tri-organotin compounds. Environ Health Perspect 129(4):47015.
]
Harry GJ, Childers G, Giridharan S, Hernandes IL. 2020. An association between mitochondria and microglia effector function. What do we think we know?
Neuroimmunol Neuroinflamm
7:150–165. [
Abstract
Harry GJ, Childers G, Giridharan S, Hernandes IL. 2020. An association between mitochondria and microglia effector function. What do we think we know? Neuroimmunol Neuroinflamm 7:150–165.
]
Bowen C, Childers G, Perry C, Martin N, McPherson CA, Lauten T, Santos J, Harry GJ. 2020. Mitochondrial-related effects of pentabromophenol, tetrabromobisphenol A, and triphenyl phosphate on murine BV-2 microglia cells.
Chemosphere
255:126919. [
Abstract
Bowen C, Childers G, Perry C, Martin N, McPherson CA, Lauten T, Santos J, Harry GJ. 2020. Mitochondrial-related effects of pentabromophenol, tetrabromobisphenol A, and triphenyl phosphate on murine BV-2 microglia cells. Chemosphere 255:126919.
]
Kraft AD, McPherson CA, Harry GJ. 2016. Association between microglia, inflammatory factors, and complement with loss of hippocampal mossy fiber synapses induced by trimethyltin.
Neurotox Res
30(1):53–66. [
Abstract
Kraft AD, McPherson CA, Harry GJ. 2016. Association between microglia, inflammatory factors, and complement with loss of hippocampal mossy fiber synapses induced by trimethyltin. Neurotox Res 30(1):53–66.
]
Orihuela R, McPherson CA, Harry GJ. 2016. Microglial M1/M2 polarization and metabolic states.
Br J Pharmacol
173(4):649–65. [
Abstract
Orihuela R, McPherson CA, Harry GJ. 2016. Microglial M1/M2 polarization and metabolic states. Br J Pharmacol 173(4):649–65.
]
Assessing outcomes from prophylactic use of HIV therapeutics
Study neurovascular, neuroinflammation processes in rats exposed during development, aging
Modified One-Generation 18 months Neurotoxic Assessment study number
MOG18001D
Incorporating genetic susceptibility into DNT screening
Evaluate role of genetic diversity in susceptibility to neurotoxicity
Tox21 Cross Partner Project
Population-wide toxicodynamic variability, mode of action of methyl mercury for protecting sensitive subpopulations
Investigate variability of genetically diverse mouse cells in response to methyl mercury, using transcriptomics
Parkinson’s disease; associations with environmental exposures
Scoping review to systematically map evidence between exposures to environmental chemicals and Parkinson’s disease
Health Assessment and Translation Project on Parkinson’s Disease
Fluoride developmental neurotoxicity
Systematic review to evaluate potential neurobehavioral effects from exposure to fluoride
Back
to Top
Last Reviewed: February 03, 2026
Skip Navigation
Developmental Neurotoxicity Health Effects
Close the left navigation
Add
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
Public Health Significance
Neurodevelopmental disorders such as autism and attention-deficit hyperactivity disorder (ADHD) are on the rise worldwide, and environmental exposures are likely contributing factors. Currently, almost no chemicals have been formally screened for developmental neurotoxicity (DNT) potential.
Current methods to evaluate the thousands of chemical compounds with unknown DNT potential remain inadequate and are rarely used. The complexity of neurodevelopment, which involves multiple key processes, one or more of which may be perturbed by a given environmental agent, requires a more modern and comprehensive approach.
It can take more than a decade for regulations to be put into effect from the time a compound is identified as potentially developmentally neurotoxic, due to the lack of emphasis on this health outcome and the insensitivity of traditional studies. In the interim, people continue to be exposed to environmental chemicals that may result in neurodevelopmental disorders.
An integrated testing strategy that incorporates novel, innovative methods and provides quicker results could better inform public health decisions and boost understanding of how to mitigate environmental contributions to neurodevelopmental disorders.
Research Objectives
Developmental Neurotoxicity Health Effects (DNT HE) research within the Division of Translational Toxicology (DTT) is structured around the following four objectives:
Generate screening level information using new approach methodologies in compounds with unknown DNT potential as an interim means to evaluate hazard and prioritize further in-depth evaluation.
Refine
in vivo
DNT testing by incorporating human-relevant mechanistic, behavioral, and brain network assessments to address complex neurodevelopmental issues.
Contextualize
in vitro
and
in vivo
findings with human exposure using
in vitro
to
in vivo
extrapolation and
in silico
approaches to provide more relevant and translatable information that can be used to protect children’s health, working towards the additional goal of developing predictive DNT tools.
Establish communication pipelines with stakeholders to spur progress in DNT research, enable knowledge generated by DTT to be used in further evaluations (e.g., for decision-making), and inform the public about the latest advancements through a range of diverse media.
An important aspect of this research is that it will complement global DNT research efforts and help move the field forward. Ultimately, this strategy is designed to provide more rapid identification of DNTs as well as mechanistic understanding of environmental contributions to neurodevelopmental disorders such as autism.
Background
DNT HE research is a high priority and aims to effectively develop a comprehensive method to evaluate environmental compounds with unknown DNT potential. There are concerns about the current framework of DNT assessment, which is largely based on rodent guideline studies that have been deemed inadequate. These studies are time- and resource-intensive and are performed only when there is an a priori trigger — for example, clinical observations or histopathological changes in the brain noted from acute or subchronic studies, and structural and/or use patterns of concern to known DNTs (such as extensive exposure to pesticides with an organophosphate backbone in children).
As a result, environmental compounds with unknown potential to cause DNT remain largely untested. Even in cases with guideline
in vivo
data, uncertainties remain in the current DNT test strategies due to limitations with respect to sensitivity, reproducibility, and relevance when extrapolating data from rodents to humans for complex diseases such as autism and ADHD.
To address some of these concerns, the DNT HE research will use novel, relevant tools and technologies that incorporate a tiered strategy in line with the DTT pipeline. This research will use new approach methodologies in conjuction with refined
in vivo
studies. The initiative also will use exposure information to provide reliable data to stakeholders for timely protection of children’s health.
The DNT-HE aligns with the NIEHS strategic plan and supports the goal of advancing predictive toxicology and the cross-divisional focus area of neuroscience. The development of innovative, human-relevant tools to predict potential hazards for regulators and the public in a timely manner aligns with the DTT mission.
Select Studies
Study
Description
Findings/Supporting Files
DNT screening assay battery
Cover key neurodevelopmental events to prioritize compounds with DNT potential
Developmental Neurotoxicity Screening Data (Pilot)
Developmental Neurotoxicity Screening Assay Chemical List - Phase 1
Developmental Neurotoxicity Screening Assay Chemical List - Phase 2
Testing Status of Developmental Neurotoxicity Screening 21005
Developmental NeuroToxicity Data Integration and Visualization Enabling Resource (DNT-DIVER)
Neuroimmune cells as targets for neurotoxicity assessments
Assess microglia and astrocyte functional changes contributing to chemical-induced neurotoxicity
Childers GM, Perry CA, Blachut B, Martin N, Bortner CD, Sieber S, Li JL, Fessler MB, Harry GJ. 2021. Assessing the association of mitochondrial function and inflammasome activation in murine macrophages exposed to select mitotoxic tri-organotin compounds.
Environ Health Perspect
129(4):47015. [
Abstract
Childers GM, Perry CA, Blachut B, Martin N, Bortner CD, Sieber S, Li JL, Fessler MB, Harry GJ. 2021. Assessing the association of mitochondrial function and inflammasome activation in murine macrophages exposed to select mitotoxic tri-organotin compounds. Environ Health Perspect 129(4):47015.
]
Harry GJ, Childers G, Giridharan S, Hernandes IL. 2020. An association between mitochondria and microglia effector function. What do we think we know?
Neuroimmunol Neuroinflamm
7:150–165. [
Abstract
Harry GJ, Childers G, Giridharan S, Hernandes IL. 2020. An association between mitochondria and microglia effector function. What do we think we know? Neuroimmunol Neuroinflamm 7:150–165.
]
Bowen C, Childers G, Perry C, Martin N, McPherson CA, Lauten T, Santos J, Harry GJ. 2020. Mitochondrial-related effects of pentabromophenol, tetrabromobisphenol A, and triphenyl phosphate on murine BV-2 microglia cells.
Chemosphere
255:126919. [
Abstract
Bowen C, Childers G, Perry C, Martin N, McPherson CA, Lauten T, Santos J, Harry GJ. 2020. Mitochondrial-related effects of pentabromophenol, tetrabromobisphenol A, and triphenyl phosphate on murine BV-2 microglia cells. Chemosphere 255:126919.
]
Kraft AD, McPherson CA, Harry GJ. 2016. Association between microglia, inflammatory factors, and complement with loss of hippocampal mossy fiber synapses induced by trimethyltin.
Neurotox Res
30(1):53–66. [
Abstract
Kraft AD, McPherson CA, Harry GJ. 2016. Association between microglia, inflammatory factors, and complement with loss of hippocampal mossy fiber synapses induced by trimethyltin. Neurotox Res 30(1):53–66.
]
Orihuela R, McPherson CA, Harry GJ. 2016. Microglial M1/M2 polarization and metabolic states.
Br J Pharmacol
173(4):649–65. [
Abstract
Orihuela R, McPherson CA, Harry GJ. 2016. Microglial M1/M2 polarization and metabolic states. Br J Pharmacol 173(4):649–65.
]
Assessing outcomes from prophylactic use of HIV therapeutics
Study neurovascular, neuroinflammation processes in rats exposed during development, aging
Modified One-Generation 18 months Neurotoxic Assessment study number
MOG18001D
Incorporating genetic susceptibility into DNT screening
Evaluate role of genetic diversity in susceptibility to neurotoxicity
Tox21 Cross Partner Project
Population-wide toxicodynamic variability, mode of action of methyl mercury for protecting sensitive subpopulations
Investigate variability of genetically diverse mouse cells in response to methyl mercury, using transcriptomics
Parkinson’s disease; associations with environmental exposures
Scoping review to systematically map evidence between exposures to environmental chemicals and Parkinson’s disease
Health Assessment and Translation Project on Parkinson’s Disease
Fluoride developmental neurotoxicity
Systematic review to evaluate potential neurobehavioral effects from exposure to fluoride
Back
to Top
Last Reviewed: February 03, 2026