EPA Science Inventory

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Records with

  • Keyword = adverse outcome pathway.
  (Sorted by Fiscal Year)
Records 1 to 25 of 374

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...
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...
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...
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...
Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity (JOURNAL)
To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecula...
Differentiating pathway-based toxicity from non-specific effects in high throughput data: A foundation for prioritizing targets for AOP development. (PRESENTATION)
The Environmental Protection Agency has implemented a high throughput screening program, ToxCast, to quickly evaluate large numbers of chemicals for their effects on hundreds of different biological targets. To understand how these measurements relate to adverse effects in an or...
Disruption of epithelial cell migration as a potential mechanism of cleft palate induction (PRESENTATION)
Cleft palate occurs in about one in seven hundred births per year, making it the most prevalent craniofacial birth defect in the world. During embryonic development, tissue fusion is a critical step in the formation of the palate, cornea, urethra, and neural tube. Epithelial cell...
Dose addition models based on biologically-relevant reductions in fetal testosterone accurately predict postnatal reproductive tract alterations by a phthalate mixture in rats (JOURNAL)
Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the curren...