EPA Science Inventory

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Records with

  • Keyword = adverse outcome pathway.
  (Sorted by Fiscal Year)
Records 1 to 25 of 382

2018
Identification of vascular disruptor compounds by a tiered analysis in zebrafish embryos and mouse embryonic endothelial cells (JOURNAL)
The large number of diverse chemicals in production or in the environment has motivated medium to high throughput in vitro or small animal approaches to efficiently profile chemical-biological interactions and to utilize this information to assess risks of chemical exposures on h...
3D-QSAR Study of Steroidal and Azaheterocyclic Human Aromatase Inhibitors using Quantitative Profile of Protein-Ligand Interactions (JOURNAL)
Aromatase is a member of the cytochrome P450 superfamily responsible for a key step in the biosynthesis of estrogens. As estrogens are involved in the control of important reproduction-related processes, including sexual differentiation and maturation, aromatase is a potential ta...
A Network of AOPs for reduced thyroid hormone synthesis derived from inhibition of Thyroperoxidase - A common Molecular Initiating Event Leading to Species-Specific Indices of Adversity. (EXTRAMURAL DOCUMENT)
This collection of 3 AOPs describe varying outcomes of adversity dependent upon species in response to inhibition of thyroperoxidase (TPO) during development. Chemical inhibition of TPO, the molecular-initiating event (MIE), results in decreased thyroid hormone (TH) synthesis, a...
A method for CRISPR/Cas9 mutation of genes in fathead minnow (PRESENTATION)
Product Description: CRISPR/Cas9 is a system that can be used to disrupt a gene of interest in any animal. It allows us to study each gene’s role by observing changes in the animal when the gene isn’t functional. We worked out a method to use this technology in the f...
A reduced transcriptome approach to assess environmental toxicants using zebrafish embryo tests (JOURNAL)
This paper reports on the pilot testing of a new bioassay platform that monitors expression of 1600 genes in zebrafish embryos exposed to either single chemicals or complex water samples. The method provides a more cost effective, high throughput means to broadly evaluate the pot...
AOP-DB Frontend: A user interface for the Adverse Outcome Pathways Database (PRESENTATION)
The EPA Adverse Outcome Pathway Database (AOP-DB) is a database resource that aggregates association relationships between AOPs, genes, chemicals, diseases, pathways, species orthology information, ontologies. The AOP-DB frontend is a simple yet powerful user interface in the for...
Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources (JOURNAL)
The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledg...
Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain (JOURNAL)
The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute an...
Addressing species diversity in biotransformation: Variability in expressed transcripts of Phase I and II hepatic enzymes among fishes (PRESENTATION)
The ability of an organism to metabolize a pollutant is critical to understanding the risk the chemical poses to the organism. In the environment, fish are uniquely exposed to pollutants found in agricultural runoff and discharges from industry and wastewater treatment plants. M...
Advancing the adverse outcome pathway framework - An international horizon scanning approach (presentation) (PRESENTATION)
In preparation for a Society of Environmental Toxicology and Chemistry Pellston Workshop titled “Advancing the Adverse Outcome Pathway (AOP) Concept: An International Horizon Scanning Approach,” a horizon scanning effort was undertaken to gather input from the global ...
Adverse Outcome Database (AOPdb) (DATA)
The AOPwiki serves to make expert knowledge of biological mechanism of adverse effects publically available, but also organizes the information for further consumption and processing. What is not yet possible with existing tools is to look across individual AOPs for potential bio...
Adverse Outcome Pathway Network Analyses: Techniques and benchmarking the AOPwiki (PRESENTATION)
Abstract: As the community of toxicological researchers, risk assessors, and risk managers adopt the adverse outcome pathway (AOP) paradigm for organizing toxicological knowledge, the number and diversity of adverse outcome pathways and AOP networks are continuing to grow. This ...
Adverse Outcome Pathways – Organizing Toxicological Information to Improve Decision Making (JOURNAL)
The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High throughput screening (HTS) commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP)...
Adverse outcome pathway networks: Development, analytics, and applications (PRESENTATION)
Product Description:The US EPA is developing more cost effective and efficient ways to evaluate chemical safety using high throughput and computationally based testing strategies. An important component of this approach is the ability to translate chemical effects on fundamental ...
Aggregate Exposure Pathway Workshop (EPA PUBLISHED PROCEEDINGS)
Recognizing the growing demands for conducting rapid, cost-effective, and reliable exposure assessment on the thousands of chemicals in commerce, a committee convened by the National Research Council (NRC) developed its vision for exposure science in the 21st century. A necessary...
An Integrative data mining approach to identifying Adverse Outcome Pathway (AOP) Signatures (JOURNAL)
The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or populatio...
Assessment of differences in sensitivity to aromatase inhibitors among freshwater fish species (PRESENTATION)
There is significant concern regarding potential impairment of fish reproduction associated with exposure to endocrine disrupting chemicals (EDCs). Aromatase is a steroidogenic enzyme involved in the conversion of androgens to estrogens. Inhibition of aromatase can reduce levels ...
Characterizing "Adversity" of Pathology Findings in Nonclinical Toxicity Studies: Results from the 4th ESTP International Expert Workshop. (JOURNAL)
The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment in the toxicologic pathology community regarding how nonclinical adversity is det...
Chemical-gene interaction networks and causal reasoning for biological effects prediction and prioritization of contaminants for environmental monitoring and surveillance (poster) (PRESENTATION)
Product Description:Evaluation of the potential effects of complex mixtures of chemicals in the environment is challenged by the lack of extensive toxicity data for many chemicals. However, there are growing sources of online information that curate and compile literature reports...
Comprehensive target-chemical assessment reveals extensive mixed-organic-contaminant exposure in USA streams (JOURNAL)
Surface-water from 38 streams nation-wide was assessed using 14 target-organic methods (719 compounds). Designedbioactive anthropogenic contaminants (biocides, pharmaceuticals) comprised 57% of 406 organics detected at least once. The 10 most-frequently detected anthropogenic-org...
Computational Integration of Human Genetic Data to Evaluate AOP-Specific Susceptibility (PRESENTATION)
There is a need for approaches to efficiently evaluate human genetic variability and susceptibility related to environmental chemical exposure. Direct estimation of the genetic contribution to variability in susceptibility to environmental chemicals is only possible in special ca...
Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis: Incorporating Protein Synthesis in Improving Predictability of Responses to Endocrine Active Chemicals (JOURNAL)
There is international concern about chemicals that alter endocrine system function in humans and/or wildlife and subsequently cause adverse effects. We previously developed a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minno...
Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, Focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways (ASSESSMENT DOCUMENT)
The focus of this meeting is the SAP's review and comment on the Agency's proposed high-throughput computational model of androgen receptor pathway activity as an alternative to the current Tier 1 androgen receptor assay (OCSPP 890.1150: Androgen Receptor Binding Rat Prostate Cyt...
Creating a Structured Adverse Outcome Pathway Knowledgebase via Ontology-Based Annotations (JOURNAL)
The Adverse Outcome Pathway (AOP) framework is increasingly used to integrate data based on traditional and emerging toxicity testing paradigms. As the number of AOP descriptions has increased, so has the need to define the AOP in computable terms. Herein, we present a comprehens...
Cross-species extrapolation of an adverse outcome pathway for ecdysone receptor activation (PRESENTATION)
Different invertebrate nuclear receptors serve as targets for a variety of environmental contaminants. One of these is the ecdysteroid receptor (EcR). Due to the important role of this nuclear receptor in regulating development and reproduction in invertebrates, particularly duri...