Science Inventory

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The retinoic acid (RA) pathway serves as a prototype for adverse outcome pathway (AOP) elucidation for developmental defects. The biology of the RA pathway was used for the construction of an ontology for neural tube closure defects. The ontology describes an AOP network incorpor...

Defining a predictive model of developmental toxicity from in vitro and high-throughput screening (HTS) assays can be limited by the availability of developmental defects data. ToxRefDB (www.epa.gov/ncct/todrefdb) was built from animal studies on data-rich environmental chemicals...

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...

The challenge of assessing the potential developmental health risks for the tens of thousands of environmental chemicals is beyond the capacity for resource-intensive animal protocols. Large data streams coming from high-throughput (HTS) and high-content (HCS) profiling of biolog...

Computer modeling and simulation of complex dynamical systems can provide a virtual framework for translating biomolecular lesions into critical phenomena underlying developmental processes and toxicities. In silico cell agent-based models (ABMs) may be executed to simulate how b...

Retinoid signaling plays an important role in vertebrate embryo-fetal development and its disruption is teratogenic. The retinoic acid (RA) pathway controls retinoid homeostasis and regulates embryonic cell fate via nuclear receptor (RAR, RXR) activation. The RA pathway thus serv...

Morphogenesis is mediated by coordinated action of cells interacting with one another and their micro-environment through systems of genetic signals and responses that are potentially vulnerable to chemical disruption. Computer models that integrate high-dimensional data on chemi...

Cells in developing tissues must integrate and respond to highly dynamic information in the form of metabolic intermediates, genetic signals, and molecular gradients. Understanding the cellular decision-making process, and how these decisions may be perturbed by genetic errors or...

Discusses the EPA/NCCT ToxRefDB database. The EPA is building capacity for multi-dimensional evaluation of toxicity using information aboout chemical properties, genome-wide responses, and cell-based assays.

Vascular development is a complex process regulated by dynamic biological networks that vary in topology and state across different tissues and developmental stages. Signals regulating de novo blood vessel formation (vasculogenesis) and remodeling (angiogenesis) come from a varie...

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...

Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new prod...

Development of the neurovascular unit (NVU) is a complex, multistage process that requires orchestrated cell signaling mechanisms across several cell types and ultimately results in formation of the blood-brain barrier. Typical high-throughput screening (HTS) assays investigate s...

Computational models of biological processes are expected to revolutionize chemical safety assessment in the not too far future. Such models provide the template for establishing quantitative adverse outcome pathway (AOP) networks that define critical key events that need monitor...

Blood vessel formation is crucial for normal embryo development and is sensitive to disruption by diverse teratogens. Recent studies have begun to reveal the cell signaling networks underlying vasculogenesis and angiogenesis and how these pathways might be perturbed by specific c...

Addressing the chemical evaluation bottleneck that currently exists can only be achieved through progressive changes to the current testing paradigm. The primary resources for addressing these issues lie in computational toxicology, a field enriched by recent advances in computer...

New approach methodologies (NAMs) based on high-throughput screening (HTS) assays can test large numbers of chemicals for bioactivity but interpretation of the data remains a challenge, especially for complex processes such as developmental toxicity. A pragmatic solution is to ma...

The biomedical literature contains an abundance of information about the activity of chemicals in biological systems. Literature informatics approaches applied to chemical toxicity research can help researchers make use of this vast literature in more effective ways, including th...

By the year 2035, the US EPA aims to eliminate animal testing in chemical safety assessment by adopting a set of new approach methods (NAMs). These methods will rely on rich data and an understanding of the mechanisms underpinning chemical toxicity. The biomedical literature is a...

The biomedical literature contains an abundance of information about the activity of chemicals in biological systems. The goal of literature informatics research at the EPA’s Center for Computational Toxicology and Exposure is to use the literature more effectively in compu...

The biomedical literature contains an abundance of information about the activity of chemicals in biological systems. The goal of literature informatics research at the EPA’s National Center for Computational Toxicology is to use the literature more effectively in computati...

Identifying environmental chemicals that adversely affect children’s health outcomes requires assembling information from a wide variety of sources, particularly from the millions of articles in the biomedical literature. Literature informatics approaches can help researchers ma...

Summary: The Abstract Sifter is a Microsoft Excel based application that enhances the user experience associated with literature searching of PubMed. The Sifter assists researchers to search effectively, triage results, and keep track of articles of interest. The tool implements ...

Understanding the potential health risks posed by environmental chemicals is a significant challenge elevated by the large number of diverse chemicals with generally uncharacterized exposures, mechanisms, and toxicities. The present study is a performance evaluation and critical ...

Understanding potential health risks posed by environmental chemicals is a significant challenge elevated by large numbers of diverse chemicals with generally uncharacterized exposures, mechanisms and toxicities. The present study is a performance evaluation and critical analysis...