Science Inventory

<< Previous

Next >>

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signal...

Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

Locally-regulated all-trans retinoic acid (ATRA) gradients are important determinants of skeletal morphogenesis and can be disrupted by diverse genetic or environmental factors, leading to homeotic transformations and malformations of skeletal structures. Adverse Outcome Pathway ...

Cell-based models utilizing high-content screening (HCS) data have applications for predictive toxicology. Evaluating concentration-dependent effects on cell fate and state response is a fundamental utilization of HCS data.Although HCS assays may capture quantitative readouts at ...

New approach methodologies (NAMs) that enable in vitro profiling of chemical-biological interactions come with the need for in silico models that translate vast amounts of data and information into toxicological prediction. We are building and testing a dynamic agent-based model ...

Retinoid signaling plays an important role in embryo- fetal development and its disruption is teratogenic. The biology of the RA pathway, leading to defects in neural tube closure was the basis for the construction of an ontology for developmental toxicity.

Retinoid signaling plays an important role in embryo-fetal development and its disruption is teratogenic. The retinoic acid (RA) pathway includes elements in retinoid metabolism and nuclear receptor (RAR, RXR) activation and thus serves as an excellent prototype for adverse outco...

Retinoid signaling plays an important role in embryo-fetal development and its disruption is teratogenic. The retinoic acid (RA) pathway includes elements in retinoid metabolism and nuclear receptor (RAR, RXR) activation and thus serves as an excellent prototype for adverse outco...

Angiogenesis is a critical developmental process and a potential target for chemical teratogenesis. Over one-tenth of the Tox21 library of 10,000 compounds have been shown to disrupt mitochondrial function [Attene-Ramos et al., 2015]. Previous studies utilizing ToxCast chemicals ...

The blood-brain barrier (BBB) limits passage of toxicants into brain tissue and may be an important tissue interface for developmental neurotoxicity, although the extent to which drugs and chemicals interact with BBB anatomical development is not well known. We utilized a computa...

In recent years, the development and implementation of animal-free approaches to chemical and pharmaceutical hazard and risk assessment has taken off. Alternative approaches are being developed starting from the perspective of human biology and physiology. Neural tube closure is ...

The Deepwater Horizon oil spill has led to the use of >1 M gallons of oil spill dispersants, which are mixtures of surfactants and solvents. Because of this large scale use there is a critical need to understand the potential for toxicity of the currently used dispersant and pote...

Recent studies have shown the importance of blood vessel formation during embryo development and the strong correlation to developmental toxicity. Several developmental toxicants, such as thalidomide, have been identified which specifically target the forming embryonic vasculatur...

Chemical toxicity can arise from disruption of specific biomolecular functions or through more generalized cell stress and cytotoxicity-mediated processes. Here, concentration-dependent responses of 1063 chemicals including pharmaceuticals, natural products, pesticidals, consumer...

AOP-based ontologies provide the necessary structure for quantitative prediction of cellular and tissue responses to molecular perturbation(s). For DevTox, this can be demonstrated by an AOP framework for embryonic vascular disruption represented in the OECD AOP-KB (Aop43). Becau...

Associating putative molecular initiating events (MIE) with downstream cell signaling pathways and modeling fetal exposure kinetics is an important challenge for integration in developmental systems toxicology. Here, we describe an integrative systems toxicology model for develop...

Chemical perturbation of vascular development is a putative toxicity pathway which may result in developmental toxicity. EPA’s high-throughput screening (HTS) ToxCast program contains assays which measure cellular signals and biological processes critical for blood vessel develop...

EPA’s ToxCast research program is profiling chemical bioactivity in order to generate predictive signatures of toxicity. The present study evaluated 320 chemicals across 239 biochemical assays. ToxCast phase I chemicals include 309 unique structures, most of which are pesticide ...

The Food Quality Protection Act of 1996 mandates that EPA implement a validated screening program for detecting estrogenic chemicals, as well as other endocrine targets deemed appropriate by the Administrator. EPA’s Endocrine Disruptor Screening Program (EDSP) has been developing...

The Food Quality Protection Act of 1996 mandates that EPA implement a validated screening program for detecting estrogenic chemicals, as well as other endocrine targets deemed appropriate by the Administrator. EPA’s Endocrine Disruptor Screening Program (EDSP) has been developing...

The U.S. EPA’s ToxCast research project was developed to address the need for high-throughput testing of chemicals and a pathway-based approach to hazard screening. Phase I of ToxCast tested over 300 unique compounds (mostly pesticides and antimicrobials). With the addition of Ph...

The blood-brain barrier (BBB) serves as a gateway for passage of drugs, chemicals, nutrients, metabolites and hormones between vascular and neural compartments. Here, we review the current understanding of BBB development with regard to microphysiology of the neurovascular unit (...

Morphogenesis of the blood-brain barrier (BBB) is a complex process linked to neovascularization of the neural tube. The process involves regulation of angiogenic sprouting and microvascular differentiation to create a selective transport interface between vascular-neural compart...

This report outlines an approach to construct a developmental toxicity ontology. Such an ontology will facilitate computer-based prediction of substances likely to induce human developmental toxicity.

Interpreting EPA’s ToxCast in vitro assay data in the context of Adverse Outcome Pathway (AOP) development is a significant challenge. While chemical activation in these assays may shed light on the molecular initiating event, the downstream effect of these activities at higher ...