EPA Scientists Share Their Advances in Toxicology Research at the Society of Toxicology’s Annual Meeting

Published March 12, 2019

Science is a collaborative process, often the result of researchers from many different fields engaging in dialogue and building off each other’s research. It’s in this spirit that EPA scientists from across the country will be attending the Society of Toxicology’s (SOT) annual conference this week in Baltimore, Maryland to present their work and hear from other scientists who are also at the cutting edge of toxicological research. To learn more about some of EPA’s toxicology work, read on for a summary of the research EPA scientists will be presenting at SOT including models that look at chemical exposures, research findings on the health effects of smoke exposure, and more.

Computational Toxicology Chemicals Dashboard

EPA creates many different types of tools to help decision makers and stakeholders quickly and efficiently evaluate chemicals. As part of its ongoing computational toxicology work, EPA continues to add functionality and chemical information to the Computational Toxicology Chemicals Dashboard (CompTox Chemicals Dashboard). The online resource provides one-stop access to chemistry, toxicity, and exposure information to help EPA, states, industry, international groups, and other stakeholders make decisions about the safety of chemicals. 

EPA scientists will present new online tools such as the Chemical and Products Database (CPDat), available in the CompTox Chemicals Dashboard. CPDat is a database containing information mapping more than 49,000 chemicals to a set of terms categorizing their usage or function in 16,000 consumer products types (e.g. shampoo, soap).

Exposure from Consumer Products

To help further understand chemical exposure, EPA researchers developed the Stochastic Human Exposure and Dose Simulation (SHEDS) model to estimate people’s exposures to chemicals encountered in everyday activities. EPA scientists will be presenting on new high-throughput SHEDS models that can produce exposure estimates for thousands of chemicals in a rapid and cost-effective manner. This approach can be used to quickly provide data that can then be used to prioritize chemicals for future study based on risk. 

Agent-Based Models

Another important element of characterizing exposure to chemicals in consumer products and indoor environments is understanding where and how an individual spends their time. EPA scientists won SOT’s best paper of the year for their work creating an Agent-Based Model that simulates long-term patterns in human behavior. The model is based on an artificial intelligence system that mimics human decisions on behaviors relevant for determining exposure to chemicals and other stressors with the goal of generating longitudinal human behavior data for use in exposure assessments.

Evaluating In Vitro-In Vivo Extrapolation

Sometimes chemicals don’t behave the same way in the real world as they do in models. To help evaluate whether EPA models are adequately predicting how a given chemical will behave, EPA scientists will compare their results to animal studies. This is especially important for understanding toxicokinetics, or how quickly a chemical enters and leaves the body. Since most of the available data from toxicokinetic tests performed on live animals is for pharmaceuticals, a benchmark must be set to compare models for environmental chemicals of interest. In a paper to be presented at SOT, EPA scientists found that their high-throughput toxicokinetics models, when compared to tests performed on rats, were adequately robust for prioritizing relevant environmental chemicals based on human health risks. These models are publicly available as an R package.

ECOTOXicology Knowledgebase

The ECOTOXicology Knowledgebase is a publicly available, comprehensive application that is used to develop and validate models to extrapolate data from in vitro (cell-based) to in vivo (whole organism) effects, and across species to evaluate the safety of chemicals. ECOTOX provides known chemical environmental toxicity data on aquatic life, terrestrial plants, and wildlife from data which are curated from scientific literature. ECOTOX data are used by researchers as well as by local, state, and tribal governments to develop site-specific criteria, or to interpret findings from monitoring data for chemicals which do not have established criteria.

Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS)

Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) is a fast, online screening tool which predicts chemical susceptibility for hundreds of species without data, by using available protein sequence and structural information.  SeqAPASS uses existing data from model organisms to predict likely or unlikely chemical interactions for untested species, minimizing the need for additional resource-intensive toxicity testing and making the process more rapid for scientist and regulator users. 

High-Throughput Transcriptomics

While the EPA’s current assays cover many genes and pathways, they do not provide a complete coverage of biological space. To supplement current research, researchers are using an approach called high-throughput Transcriptomics (HTTr) to monitor gene expression and provide a more comprehensive evaluation of chemically-induced changes in biological processes. Using the high-throughput approach is possible in part because of the declining costs associated with generating whole transcriptome profiles, which have made HTTr a more practical option for determining bioactivity thresholds.

Zebrafish Microbiome Research

Another important element of toxicology research is understanding how environmental chemicals can affect the microbiome, a complex network of bacteria, viruses, fungi, archaea, and protozoa that colonize the skin and gut of a host animal (including humans) and play important roles in health and disease. Research has found that these microbial communities help regulate many diverse and complex biological processes, including brain development and behavior, lipid metabolism, and immune responses. As part of their research on Bisphenol A (BPA) exposure to zebrafish, EPA scientists found that many of the less toxic analogues of BPA significantly disrupt microbial community structure. This study is the first to show that BPA and its commonly used alternatives have a disruptive effect on microbial community structure. 

Wildfire Smoke Exposure

SOT will hold a first-of-its-kind session chaired by EPA staff titled “Science at the Nexus of Wildfire Smoke and Public Health” that will share research findings by EPA, US Forest Service, and other organizations on the health effects of smoke exposure.

Exposure to wildland fire smoke can be sudden and unexpected, can last hours to weeks, and can affect communities that may or may not have a public health response plan to reduce the adverse impacts of smoke exposure. EPA is continuing to advance the science and technology required to understand the impacts of smoke on air quality and public health, as well as improve delivery and timing of information about the potential health risks of smoke to those who are impacted by wildland fires. As part of this effort, EPA developed a mobile app called Smoke Sense to give citizen scientists a tool to both learn about the potential health effects of wildfire smoke and contribute to a study about these effects.