Office of Research and Development Publications

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The goal of this project is to address the question, “Can existing toxicogenomics (TG) data improve Environmental Protection Agency (EPA) chemical health or risk assessments?” Although genomics data promises to impact multiple areas of science, medicine, law, and policy, there ar...

This text-mining/literature-mining tool was built to support the writing of a draft Review Paper on the Retinoid System for the OECD Test Guidelines Programme. The tool gathers and allows navigation through the concepts (biological and chemical) related to retinoid activity in ma...

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...

The US-EPA CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard) is a web-based application providing access to various types of data associated with ~880,000 chemical substances. These data include in vivo hazard and in vitro bioactivity data, experimental physicochemi...

The CompTox Chemicals Dashboard (available at https://comptox.epa.gov/dashboard) is the latest in a suite of dashboards that have been delivered to the community by EPA’s National Center for Computational Toxicology. The dashboard delivers access to data for >875,000 che...

New approach methodologies are being explored for their ability to quickly evaluate the human toxicity potential of chemicals with less reliance on animal testing using ToxCast/Tox21 generated in vitro data on thousands of chemicals utilizing high-throughput screening (HTS) assay...

One of the key challenges to using in vitro data for risk assessment is differentiating adaptive from adverse cellular responses. We studied the effects of hundreds of chemicals in primary rat hepatocytes using high-content imaging (HCI) to measure dose and time-dependent perturb...

Computational approaches have recently gained popularity in the field of read-across to automatically fill data-gaps for untested chemicals. To this end, we developed a generalized read-across (GenRA) approach, which utilizes chemical descriptor information and/or in vitro bioact...

Synthesis of 11 steroid hormones in human adrenocortical carcinoma cells (H295R) was measured in a high-throughput steroidogenesis assay (HT-H295R) for 656 chemicals in concentration-response as part of the US Environmental Protection Agency’s ToxCast program. This work ext...

There is a growing recognition that application of mechanistic approaches to understand cross-species shared molecular targets and pathway conservation in the context of hazard characterization, provide significant opportunities in risk assessment (RA) for both human health and e...

Computational approaches have recently gained popularity in the field of read-across to automatically fill data-gaps for untested chemicals. Previously, we developed the generalized read-across (GenRA) tool, which utilizes in vitro bioactivity data in conjunction with chemical de...

High(er) throughput toxicokinetics (HTTK) encompasses in vitro measures of key determinants of chemical toxicokinetics and reverse dosimetry approaches for in vitro-in vivo extrapolation (IVIVE). With HTTK, the bioactivity identified by any in vitro assay can be converted to huma...

The toxicokinetic (TK) parameters fraction of the chemical unbound to plasma proteins and metabolic clearance are critical for relating exposure and internal dose when building in vitro-based risk assessment models. However, experimental toxicokinetic studies have only been carri...

The present study adapted an existing high content imaging-based high-throughput phenotypic profiling (HTPP) assay known as “Cell Painting” for bioactivity screening of environmental chemicals. This assay uses a combination of fluorescent probes to label a variety of ...

Screening certain environmental chemicals for their ability to interact with endocrine targets, including the androgen receptor (AR), is an important global concern. We previously developed a model using a battery of eleven in vitro AR assays to predict in vivo AR activity. Here ...

Mitochondrial toxicity drives several adverse health outcomes. Current high-throughput screening assays for chemically induced mitochondrial toxicity typically measure changes to mitochondrial structure and may not detect known mitochondrial toxicants. We adapted a respirometric ...

Advances in the biological sciences have led to an ongoing paradigm shift in toxicity testing, based on expanded application of high-through put in vitro screening and in silico methods to assess potential health risks of environmental agents. This review examines progress on th...

The identification of volatile compounds detected through breath sampling is generally performed using mass spectrometry. The data, including extracted masses, formulae and retention indices, coupled with searching against reference databases, is essential for the identification ...

Embryonic development commences with the formation of three germ layers from the primitive streak during gastrulation. The endoderm layer gives rise to the gut tube, leading to development of several internal organs, including the thyroid, thymus, lungs, stomach, liver, pancreas,...

The Toxic Substances Control Act (TSCA) mandates the US EPA perform risk-based prioritisation of chemicals in commerce and then, for high-priority substances, develop risk evaluations that integrate toxicity data with exposure information. One approach being considered for chemic...

Time courses of compound concentrations in plasma are used in chemical safety analysis to evaluate the relationship between external administered doses and internal tissue exposures. This type of experimental data is rarely available for the thousands of non-pharmaceutical chemic...

The initiating steps for many mechanisms of toxicological action comprise the reactive, covalent binding between an exogenous electrophile and an endogenous nucleophile. The target sites for electrophiles are typically peptides, proteins, enzymes or DNA. Of these, the formation o...

Thyroid hormones (TH) are essential for regulating a number of diverse physiological processes required for normal growth, development, and metabolism. The US EPA Endocrine Disruptor Screening Program (EDSP) has identified several molecular thyroid targets relevant to hormone syn...

Objective read-across approaches continue to evolve as does their utility in the field of risk assessment. Previously we presented our generalized read-across (GenRA) approach (Shah et al., 2016), which utilizes chemical descriptor and/or in vitro bioactivity data to make read-ac...

Use of high-throughput, in vitro bioactivity data in setting a point-of-departure (POD) has the potential to accelerate the pace of human health safety evaluation by informing screening level assessments. The primary objective of this work was to compare PODs based on high-throug...