High-throughput toxicity testing technologies along with the World Wide Web are revolutionizing both generation of and access to data regarding the biological activities that chemicals can elicit when they interact with specific proteins, genes, or other targets in the body of an organism. To date, however, most of the focus has been on the application of such data to assessment of individual chemicals. The authors suggest that environmental surveillance and monitoring represent the next frontiers for high-throughput toxicity testing. Resources already exist in curated databases of chemical-biological interactions, including highly standardized quantitative dose-response data generated from nascent high-throughput toxicity testing programs such as ToxCast and Tox21, to link chemicals detected through environmental analytical chemistry to known biological activities. The emergence of the adverse outcome pathway framework and the associated knowledge base for linking molecular-level or pathway-level perturbations of biological systems to adverse outcomes traditionally considered in risk assessment and regulatory decision-making through a series of measurable biological changes provides a critical link between activity and hazard. Furthermore, environmental samples can be directly analyzed via high-throughput toxicity testing platforms to provide an unprecedented breadth of biological activity characterization that integrates the effects of all compounds present in a mixture, whether known or not. Novel application of these chemical-biological interaction data provides an opportunity to transform scientific characterization of potential hazards associated with exposure to complex mixtures of environmental contaminants.
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SLAS Discov
January 2025
Center for Discovery and Innovation, Hackensack Meridian Health, 111 Ideation Way. Nutley, New Jersey 07110, United States. Electronic address:
The COVID-19 pandemic has emphasized the necessity for rapid and adaptable drug screening platforms against live pathogenic viruses that require high levels of biosafety containment. Conventional antiviral testing is time-consuming and labor-intensive. Here, we outline the design and validation of a semi-automated drug-screening platform for SARS-CoV-2 that utilizes multiple liquid handlers, a stable A549 cell line expressing ACE2 and TMPRSS2 receptors, and a recombinant SARS-CoV-2 strain harboring the nano-luciferase gene.
View Article and Find Full Text PDFEnviron Int
January 2025
State Key Laboratory of Marine Pollution and Department of Chemistry, City University of Hong Kong, Hong Kong 999077, China; Department of Applied Science, School of Science and Technology, Hong Kong Metropolitan University, Hong Kong 999077, China.
Despite the ubiquity and complexity of atmospheric polycyclic aromatic compounds (PACs), many of these compounds are largely unknown and lack sufficient toxicity data for comprehensive risk assessments. In this study, nontarget screening assisted by in-house and self-developed spectra databases was, therefore, employed to identify PACs in atmospheric particulate matter collected from multiple outdoor settings. Additionally, absorption, distribution, metabolism, excretion, and toxicity properties were evaluated to indicate PAC's overall abilities to cause adverse outcomes and incorporated into a novel health risk assessment model to assess their inhalation risks.
View Article and Find Full Text PDFToxicol Sci
January 2025
Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, MD, 21702, USA.
Because the liver plays a vital role in the clearance of exogenous chemical compounds, it is susceptible to chemical-induced toxicity. Animal-based testing is routinely used to assess the hepatotoxic potential of chemicals. While large-scale high-throughput sequencing data can indicate the genes affected by chemical exposures, we need system-level approaches to interpret these changes.
View Article and Find Full Text PDFAnnu Rev Food Sci Technol
January 2025
1Shanghai Institute of Doping Analyses, Shanghai University of Sport, Shanghai, China;
The emergence of several chemical substances continues to enrich and facilitate the development of food science, but their irrational use also poses a threat to food safety and human health. Nontargeted screening (NTS) has become an important tool for rapid traceability and efficient identification of chemical hazards in food matrices. NTS in food analysis is highly integrated with sample pretreatment, instrumental analysis platforms, data acquisition and analysis, and toxicology.
View Article and Find Full Text PDFJ Cheminform
January 2025
National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, 9800 Medical Center Drive, Rockville, MD, 20850, USA.
Traditional best practices for quantitative structure activity relationship (QSAR) modeling recommend dataset balancing and balanced accuracy (BA) as the key desired objective of model development. This study explores the value of the conventional norms in the context of using QSAR models for virtual screening of modern large and ultra-large chemical libraries. For this increasingly common task, we now recommend the use of models with the highest positive predictive value (PPV) built on imbalanced training sets as preferred virtual screening tools.
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