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Chemicals assessment and management frameworks rely on regulatory toxicity values, which are based on points of departure (POD) identified following rigorous dose–response assessments. Yet, regulatory PODs and toxicity values for inhalation exposure (i.e., reference concent...

Background: Mechanistic understanding of transient exposures that lead to adverse health outcomes will enhance our ability to recognize biological signatures of disease. Here, we measured the transcriptomic and epigenomic alterations due to exposure to the metabolic reprogramming...

When “The Principles of Humane Experimental Technique” was published in 1959, authors William Russell and Rex Burch had a modest goal: to make researchers think about what they were doing in the laboratory—and to do it more humanely. Sixty years later, their gro...

Per- and polyfluoroalkyl substances (PFAS) are widely used, and their fluorinated state contributes to unique uses and stability but also long half-lives in the environment and humans. PFAS have been shown to be toxic, leading to immunosuppression, cancer, and other adverse healt...

Mass-spectrometry-based non-targeted analysis (NTA), in which mass spectrometric signals are assigned chemical identities based on a systematic collation of evidence, is a growing area of interest for toxicological risk assessment. Successful NTA results in better identification ...

Indigenous nations and communities in the United States have rights as sovereign governments to exercise control and ownership over all data and information generated by or from the tribes, tribal members, or tribal resources. Indigenous nations exercise these rights through data...

Metals are used in 3-dimensional (3D) printer filaments in the manufacture of 3D printed objects. Exposure to the filaments, printed objects and emissions from printing may pose health risks from release of toxic metals. This study investigated the cytotoxicity of extruded 3D pri...

Recent advances in high-resolution mass spectrometry (HRMS) have enabled the detection of thousands of chemicals from a single sample, while computational methods have improved the identification and quantification of these chemicals in the absence of reference standards typicall...

Chemical safety assessment begins with defining the lowest level of chemical that alters one or more measured endpoints. This critical effect level, along with factors to account for uncertainty, is used to derive limits for human exposure. In the absence of data regarding the sp...

Animals and animal models have been invaluable for our current understanding of human and animal biology, including physiology, pharmacology, biochemistry, and disease pathology. However, there are increasing concerns with continued use of animals in basic biomedical, pharmacolog...

There are insufficient toxicity data to assess the ecological risks of many pharmaceuticals and personal care products (PPCPs). While data limitations are not uncommon for contaminants of environmental concern, PPCPs are somewhat unique in that an a priori understanding of their ...

The extent to which chemicals bioaccumulate in aquatic and terrestrial organisms represents a fundamental consideration for chemicals management efforts intended to protect public health and the environment from pollution and waste. Many chemicals, including most pharmaceuticals ...

The Laurentian Great Lakes have been experiencing dramatic change during the past half-century, highlighting the need for holistic, ecosystem-based approaches to management. To encourage ecosystem-based management (EBM) in the basin, we sought to assess the value of developing a ...

The rapid increase of publicly available chemical structures and associated experimental data presents a valuable opportunity to build robust QSAR models for applications in different fields. However, the common concern is the quality of both the chemical structure information an...

Animal toxicity testing is time and resource intensive, making it difficult to keep pace with the number of substances requiring assessment. Machine learning (ML) models that use chemical structure information and high-throughput experimental data can be helpful in predicting pot...

The Health and Environmental Sciences Institute Developmental and Reproductive Toxicology (HESI-DART) group held a hybrid in-person and virtual workshop in Washington, DC, in 2022. The workshop was entitled, "Interpretation of DART in Regulatory Contexts and Frameworks.&quot...

Systematic evidence mapping for PFAS structures to characterize human health literature for 430 prioritized PFAS. Systematic evidence maps are pre-decisional analyses that use systematic review methods to compile and summarize evidence, but do not include hazard assessment or tox...

Multi-walled carbon nanotubes (MWCNTs) lack sufficient quality cytotoxicity, toxicity, genotoxicity and genomic data on which to make environmental and regulatory decisions. Therefore, we did a multidisciplinary in vitro study of 3 MWCNTs in human lung cells (BEAS-2B) w...

Non-targeted analysis (NTA) is an increasingly popular technique for characterizing undefined chemical analytes. Generating quantitative NTA (qNTA) concentration estimates requires the use of training data from calibration “surrogates,” which can yield diminished pred...

Propranolol is a heavily prescribed, nonspecific beta-adrenoceptor (bAR) antagonist frequently found in wastewater effluents, prompting concern over its potential to adversely affect exposed organisms. In the present study, the transcriptional responses of 4, 5, and 6 days postfe...

Background:  Xenobiotic metabolites are widely present in human urine and can indicate recent exposure to environmental chemicals. Proper inference of which chemicals contribute to these metabolites can inform human exposure and risk. Furthermore, longitudinal biomonitoring...

The presence of numerous chemical contaminants from industrial, agricultural, and pharmaceutical sources in water supplies poses a potential risk to human and ecological health. Current chemical analyses suffer from limitations, including chemical coverage and high cost, and broa...

Humans interact with thousands of chemicals. This study aims to identify substances of emerging concern and in need of human health risk evaluations. Sixteen pooled human serum samples were constructed from 25 individual samples each from the National Institute of Environmental H...

Seven-day sublethal toxicity tests were performed with the freshwater invertebrates Ceriodaphnia dubia, Hyalella azteca, and Chironomus dilutus to determine the effects of per- or polyfluorinated alkyl substances (PFAS) of varying chain length within four clas...

This sub-product is a journal article that compares a variety of computational approaches for calculating transcriptomic points of departure (tPODs) from in vitro high-throughput transcriptomics (HTTr) screening data.  The manuscript uses a data set of 44 chemicals tested in...