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Records with

  • Keyword = adverse outcome pathway.
  (Sorted by Fiscal Year)
Records 26 to 50 of 754

2023
Gestational Exposure to Perchlorate in the rat: Thyroid Hormones in Fetal Thyroid Gland, Serum, and Brain
(JOURNAL) [Published : Jul 01, 2022]
Iodine is essential for the production of thyroid hormones. Perchlorate is an environmental contaminant that interferes with iodine uptake into the thyroid gland to reduce thyroid hormone synthesis. As thyroid hormones are critical for brain development, exposure to perchlorate d...
Regulation of Thyroid Disrupting Chemicals to Protect the Developing Brain
(JOURNAL) [Published : Oct 01, 2020]
Synthetic chemicals with endocrine disrupting properties are pervasive in the environment and are present in the bodies of humans and wildlife. As thyroid hormones (THs) control normal brain development, and maternal hypothyroxinemia is associated with neurological impairments in...
Thyroid Hormone Action Controls Multiple Components of Cell Junctions at the Ventricular Zone in the Newborn Rat Brain
(JOURNAL) [Published : Feb 10, 2023]
Thyroid hormone (TH) action controls brain development in a spatiotemporal manner. Previously, we demonstrated that perinatal hypothyroidism led to formation of a periventricular heterotopia in developing rats. This heterotopia occurs in the posterior telencephalon, and its forma...
New Approach Methodologies in human regulatory toxicology – not if, but how and when!
(JOURNAL) [Published : Aug 01, 2023]
The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human health risk assessment and ethics of this system, demanding a change of paradigm...
A set of six Gene expression biomarkers and their thresholds identify rat liver tumorigens in short-term assays
(JOURNAL) [Published : Oct 01, 2020]
Traditional methods for cancer risk assessment are retrospective, resource-intensive, and not feasible for the vast majority of environmental chemicals. In earlier studies, we used a set of six biomarkers to accurately identify liver tumorigens in transcript profiles derived from...
Thyroid Disrupting Chemicals Protecting the Developing Rat Brain
(PRESENTATION) [Presented : Jun 28, 2023]
Thyroid hormones (TH) are essential for normal brain development. There is a significant public health need to protect the developing brain of the fetus, newborn, and young child from thyroid system-disrupting chemicals. Environmental chemicals can interfere with the thyroid syst...
Applying Genomics in Regulatory Toxicology: a report of the ECETOC workshop on Omics threshold on non-adversity
(JOURNAL) [Published : Aug 01, 2023]
In a joint effort involving scientists from academia, industry and regulatory agencies, ECETOC's activities in Omics have led to conceptual proposals for: (1) A framework that assures data quality for reporting and inclusion of Omics data in regulatory assessments; and (2) an app...
OECD Series on Adverse Outcome Pathways No. 26: Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
(PUBLISHED REPORT) [Published : Dec 15, 2022]
This AOP describes the sequence of events leading from thyroperoxidase inhibition to increased mortality via reduced anterior swim bladder inflation. The enzyme thyroperoxidase (TPO) is essential for the synthesis of thyroxine (T4) and triiodothyronine (T3) in the thyro...
OECD Series on Adverse Outcome Pathways No. 25: Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
(PUBLISHED REPORT) [Published : Dec 15, 2022]
This AOP describes the sequence of events leading from deiodinase inhibition to increased mortality via reduced anterior swim bladder inflation. Thyroid hormones (THs) are critical during development and disruption of the TH system can interfere with normal development....
Methods2AOP: An International Collaboration to Integrate Assay Annotations into the AOP Key Event Descriptions
(PRESENTATION) [Presented : Mar 23, 2023]
New approach methodologies (NAMs) in biological and computational sciences can generate mechanistic information which can be used to support safety assessments of chemicals. The Adverse outcome pathway (AOP) is a conceptual construct that portrays existing knowledge concerning th...
OECD Series on Adverse Outcome Pathways No. 24: Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
(PUBLISHED REPORT) [Published : Dec 15, 2022]
This AOP describes the sequence of events leading from deiodinase inhibition to increased mortality via reduced posterior swim bladder inflation. Thyroid hormones (THs) are critical during embryonic development and disruption of the TH system can interfere with normal d...
OECD Series on Adverse Outcome Pathways No. 23: Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
(PUBLISHED REPORT) [Published : Dec 15, 2022]
This AOP describes the sequence of events leading from deiodinase inhibition to increased mortality via reduced anterior swim bladder inflation. Disruption of the thyroid hormone system is increasingly being recognized as an important toxicity pathway that can cause man...
OECD Series on Adverse Outcome Pathways No. 22: Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
(PUBLISHED REPORT) [Published : Dec 15, 2022]
This AOP describes the sequence of events leading from deiodinase inhibition to increased mortality via reduced posterior swim bladder inflation. Disruption of the thyroid hormone system is increasingly being recognized as an important toxicity pathway that can cause ma...
Systematic Analysis of High-Throughput Transcriptomics to Identify Potential Carcinogens
(PRESENTATION) [Presented : Mar 23, 2023]
Recent technological advances have moved the field of toxicogenomics from reliance on microarray platforms to high-throughput transcriptomic technologies that measure global gene expression. Gene expression biomarkers are emerging as useful tools for interpreting gene expression ...
New Approach Methods (NAMs) and lntegrated Approaches to Testing and Assessment (IATA)
(PRESENTATION) [Presented : Apr 13, 2023]
The guest lecture / presentation focused on how various data streams used in evidence integration for risk assessment can be better integrated through use of mechanistic constructs, including source to outcome modeling with dosimetry providing the critical link between aggregate ...
Identification of Chemicals Associated with Retinoid Signaling Pathway Disturbance and Skeletal Dysmorphogenesis for the Development of Computational Toxicology Models for New Approach Methods’ (NAMs) Hazard Predictions
(PRESENTATION) [Presented : Jun 29, 2022]
All-trans retinoic acid (ATRA) gradients determine skeletal patterning morphogenesis and can be disrupted by diverse genetic or environmental factors, leading to fetal skeleton malformations. Here, a data-driven model was constructed to identify chemicals associated with both ATR...
NAMs Use in the Development of AOPs and the Application of Systematic Review Practices for Hazard Evaluation and Predictive Toxicology
(PRESENTATION) [Presented : Nov 09, 2021]
Homeotic transformations and malformations of the fetal skeleton can occur as locally-regulated all-trans retinoic acid (ATRA) gradients. Such gradients determine skeletal patterning morphogenesis and can be disrupted by diverse genetic or environmental factors. Adverse Outcome P...
Biologically relevant reductions in fetal testosterone and Insl3 induced by in utero exposure to high levels of di-isononyl phthalate (DINP) in male rats
(JOURNAL) [Published : Apr 15, 2023]
I Some phthalate esters alter male rat reproductive development during sexual differentiation by interfering with fetal testis maturation resulting in reduced Leydig Cell synthesis of testosterone and insulin-like 3 (Insl3) hormones. Gene transcripts associated with steroid hormo...
Interpretation of thyroid-relevant bioactivity for comparison to in vivo exposures
(PRESENTATION) [Presented : Mar 23, 2023]
There are 92 thyroid-relevant assay endpoints from the ToxCast/Tox21 project that can be mapped to molecular initiating events (MIEs) within the thyroid adverse outcome pathway (AOP) network. However, a synthesis and interpretation of the data across MIEs and at the tissue level ...
Evaluating the Human Relevance of Potential Thyroid-Disrupting Chemicals Using In vitro New Approach Methods.
(PRESENTATION) [Presented : Mar 23, 2023]
There is significant regulatory need to identify and evaluate chemicals that may disrupt the thyroid endocrine system. Thyroid new approach methods (NAMs) are being developed and applied to increase data coverage across the ToxCast/Tox21 chemical inventories using a tiered testin...
Developmental emamectin benzoate exposure alters behavior and proteomics in Long Evans rats
(PRESENTATION) [Presented : Apr 21, 2023]
Early neurodevelopmental periods are vulnerable to environmental compounds. Unfortunately, there are few adverse outcome pathways (AOP) that explore these critical periods. AOPs detail a series of biological responses linked by key events following a molecular initiating event an...
New Approach Methodologies for the Endocrine Activity Toolbox: Environmental Assessment for Fish and Amphibians
(JOURNAL) [Published : Mar 29, 2023]
Multiple in vivo test guidelines focusing on the estrogen, androgen, thyroid, and steroidogenesis pathways have been developed and validated for mammals, amphibians, or fish. However, these tests are resource-intensive and often use a large number of laboratory animals. Developin...
Weight-of-Evidence Analysis for the Development of a Reference List of Chemical Respiratory Sensitizers
(PRESENTATION) [Presented : Mar 23, 2023]
Despite high regulatory need, there remains a lack of internationally harmonized approaches to identify chemical respiratory allergens. Depending on the regulatory context, approaches are needed for determining the potential of a low molecular weight (LMW) compound to sensitize t...
Epigenetic and transcriptomic changes resulting from long-term exposure to contaminant mixture associated with agricultural land use
(PRESENTATION) [Presented : Nov 22, 2022]
Epigenetics, the interface between the environment and genome, can change quickly in response to environmental stressors. Epigenetic modifications may cause changes in gene expression leading to potential adverse biological outcomes. Here, we present differential DNA methylation ...