Read by QxMD icon Read


Sloane K Tilley, David M Reif, Rebecca C Fry
BACKGROUND: The Superfund program of the Environmental Protection Agency (EPA) was established in 1980 to address public health concerns posed by toxic substances released into the environment in the United States. Forty-two of the 1328 hazardous waste sites that remain on the Superfund National Priority List are located in the state of North Carolina. METHODS: We set out to develop a database that contained information on both the prevalence and biological activity of chemicals present at Superfund sites in North Carolina...
January 30, 2017: Environment International
Qingda Zang, Kamel Mansouri, Antony J Williams, Richard S Judson, David G Allen, Warren M Casey, Nicole C Kleinstreuer
There are little available toxicity data on the vast majority of chemicals in commerce. High-throughput screening (HTS) studies, such as those being carried out by the U.S. Environmental Protection Agency (EPA) ToxCast program in partnership with the federal Tox21 research program, can generate biological data to inform models for predicting potential toxicity. However, physicochemical properties are also needed to model environmental fate and transport, as well as exposure potential. The purpose of the present study was to generate an open-source quantitative structure-property relationship (QSPR) workflow to predict a variety of physicochemical properties that would have cross-platform compatibility to integrate into existing cheminformatics workflows...
January 9, 2017: Journal of Chemical Information and Modeling
Nicole C Kleinstreuer, Patricia Ceger, Eric D Watt, Matthew Martin, Keith Houck, Patience Browne, Russell S Thomas, Warren M Casey, David J Dix, David Allen, Srilatha Sakamuru, Menghang Xia, Ruili Huang, Richard Judson
Testing thousands of chemicals to identify potential androgen receptor (AR) agonists or antagonists would cost millions of dollars and take decades to complete using current validated methods. High-throughput in vitro screening (HTS) and computational toxicology approaches can more rapidly and inexpensively identify potential androgen-active chemicals. We integrated 11 HTS ToxCast/Tox21 in vitro assays into a computational network model to distinguish true AR pathway activity from technology-specific assay interference...
December 9, 2016: Chemical Research in Toxicology
Jenny McCann, Terry McCann
The Lush Prize supports animal-free testing by rewarding the most effective projects and individuals who have been working toward the goal of replacing animals in product or ingredient safety testing. Prizes are awarded for developments in five strategic areas: Science; Lobbying; Training; Public Awareness; and Young Researchers. Should there be a major breakthrough in 21st century toxicology, a Black Box Prize equivalent to the entire annual fund of £250,000 is awarded. A Background Paper is prepared each year, prior to the judging process, to provide the panel with a brief overview of current developments in the field of Replacement alternatives, particularly those relevant to the concept of toxicity pathways...
October 2016: Alternatives to Laboratory Animals: ATLA
Daland R Juberg, Thomas B Knudsen, Miriam Sander, Nancy B Beck, Elaine M Faustman, Donna L Mendrick, John R Fowle, Thomas Hartung, Raymond R Tice, Emmanuel Lemazurier, Richard A Becker, Suzanne Compton Fitzpatrick, George P Daston, Alison Harrill, Ronald N Hines, Douglas A Keller, John C Lipscomb, David Watson, Tina Bahadori, Kevin M Crofton
Future Tox III, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in November 2015. Building upon Future Tox I and II, Future Tox III was focused on developing the high throughput risk assessment paradigm and taking the science of in vitro data and in silico models forward to explore the question-what progress is being made to address challenges in implementing the emerging big-data toolbox for risk assessment and regulatory decision-making. This article reports on the outcome of the workshop including 2 examples of where advancements in predictive toxicology approaches are being applied within Federal agencies, where opportunities remain within the exposome and AOP domains, and how collectively the toxicology community across multiple sectors can continue to bridge the translation from historical approaches to Tox21 implementation relative to risk assessment and regulatory decision-making...
January 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
Chia-Wen Hsu, Jui-Hua Hsieh, Ruili Huang, Dirk Pijnenburg, Thai Khuc, Jon Hamm, Jinghua Zhao, Caitlin Lynch, Rinie van Beuningen, Xiaoqing Chang, René Houtman, Menghang Xia
Chemicals that alter normal function of farnesoid X receptor (FXR) have been shown to affect the homeostasis of bile acids, glucose, and lipids. Several structural classes of environmental chemicals and drugs that modulated FXR transactivation were previously identified by quantitative high-throughput screening (qHTS) of the Tox21 10K chemical collection. In the present study, we validated the FXR antagonist activity of selected structural classes, including avermectin anthelmintics, dihydropyridine calcium channel blockers, 1,3-indandione rodenticides, and pyrethroid pesticides, using in vitro assay and quantitative structural-activity relationship (QSAR) analysis approaches...
December 15, 2016: Toxicology and Applied Pharmacology
Jin Zhang, Afshan Begum, Kristoffer Brännström, Christin Grundström, Irina Iakovleva, Anders Olofsson, A Elisabeth Sauer-Eriksson, Patrik L Andersson
Thyroid disruption by xenobiotics is associated with a broad spectrum of severe adverse outcomes. One possible molecular target of thyroid hormone disrupting chemicals (THDCs) is transthyretin (TTR), a thyroid hormone transporter in vertebrates. To better understand the interactions between TTR and THDCs, we determined the crystallographic structures of human TTR in complex with perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2,2',4,4'-tetrahydroxybenzophenone (BP2). The molecular interactions between the ligands and TTR were further characterized using molecular dynamics simulations...
October 10, 2016: Environmental Science & Technology
Kathryn Ribay, Marlene T Kim, Wenyi Wang, Daniel Pinolini, Hao Zhu
Estrogen receptors (ERα) are a critical target for drug design as well as a potential source of toxicity when activated unintentionally. Thus, evaluating potential ERα binding agents is critical in both drug discovery and chemical toxicity areas. Using computational tools, e.g., Quantitative Structure-Activity Relationship (QSAR) models, can predict potential ERα binding agents before chemical synthesis. The purpose of this project was to develop enhanced predictive models of ERα binding agents by utilizing advanced cheminformatics tools that can integrate publicly available bioassay data...
March 2016: Frontiers in environmental science
Jui-Hua Hsieh
Compound activity identification is the primary goal in high-throughput screening (HTS) assays. However, assay artifacts including both systematic (e.g., compound auto-fluorescence) and nonsystematic (e.g., noise) complicate activity interpretation. In addition, other than the traditional potency parameter, half-maximal effect concentration (EC50), additional activity parameters (e.g., point-of-departure, POD) could be derived from HTS data for activity profiling. A data analysis pipeline has been developed to handle the artifacts and to provide compound activity characterization with either binary or continuous metrics...
2016: Methods in Molecular Biology
Ruili Huang
The US Tox21 program has developed in vitro assays to test large collections of environmental chemicals in a quantitative high-throughput screening (qHTS) format, using triplicate 15-dose titrations to generate over 50 million data points to date. Counter screens are also employed to minimize interferences from non-target-specific assay artifacts, such as compound auto fluorescence and cytotoxicity. New data analysis approaches are needed to integrate these data and characterize the activities observed from these assays...
2016: Methods in Molecular Biology
Chia-Wen Amy Hsu, Jinghua Zhao, Menghang Xia
The farnesoid X receptor (FXR) is a nuclear receptor responsible for homeostasis of bile acids, lipids, and glucose. Compounds that alter endogenous FXR signaling can be used as therapeutic candidates or identified as potentially hazardous compounds depending on exposure doses and health states. Therefore, there is an increasing need for high-throughput screening assays of FXR activity to profile large numbers of environmental chemicals and drugs. This chapter describes a workflow of FXR modulator identification and characterization...
2016: Methods in Molecular Biology
Caroline L Pinto, Kamel Mansouri, Richard Judson, Patience Browne
The US Environmental Protection Agency's (EPA) Endocrine Disruptor Screening Program (EDSP) is using in vitro data generated from ToxCast/Tox21 high-throughput screening assays to assess the endocrine activity of environmental chemicals. Considering that in vitro assays may have limited metabolic capacity, inactive chemicals that are biotransformed into metabolites with endocrine bioactivity may be missed for further screening and testing. Therefore, there is a value in developing novel approaches to account for metabolism and endocrine activity of both parent chemicals and their associated metabolites...
September 19, 2016: Chemical Research in Toxicology
Michelle M Miller, Rebecca A Alyea, Caroline LeSommer, Daniel L Doheny, Sean M Rowley, Kristin M Childs, Pergentino Balbuena, Susan M Ross, Jian Dong, Bin Sun, Melvin A Andersen, Rebecca A Clewell
A toxicity pathway approach was taken to develop an in vitro assay using human uterine epithelial adenocarcinoma (Ishikawa) cells as a replacement for measuring an in vivo uterotrophic response to estrogens. The Ishikawa cell was determined to be fit for the purpose of recapitulating in vivo uterine response by verifying fidelity of the biological pathway components and the dose-response predictions to women of child-bearing age. Expression of the suite of estrogen receptors that control uterine proliferation (ERα66, ERα46, ERα36, ERβ, G-protein coupled estrogen receptor (GPER)) were confirmed across passages and treatment conditions...
August 7, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Ming Hao, Stephen H Bryant, Yanli Wang
BACKGROUND: As one of the largest publicly accessible databases for hosting chemical structures and biological activities, PubChem has been processing bioassay submissions from the community since 2004. With the increase in volume for the deposited data in PubChem, the diversity and wealth of information content also grows. Recently, the Tox21 program, has deposited a series of pairwise data in PubChem regarding to different mechanism of actions (MOA), such as androgen receptor (AR) agonist and antagonist datasets, to study cell toxicity...
2016: Journal of Cheminformatics
Salomon Sand, Fred Parham, Christopher J Portier, Raymond R Tice, Daniel Krewski
BACKGROUND: The National Research Council's vision for toxicity testing in the 21(st) century anticipates that points of departure (PODs) for establishing human exposure guidelines in future risk assessments will increasingly be based on in vitro high-throughput screening (HTS) data. OBJECTIVES: The aim of this study was to compare different PODs for HTS data. Specifically, benchmarks doses (BMDs) were compared to the signal-to-noise crossover dose (SNCD) introduced by Sand et al...
July 6, 2016: Environmental Health Perspectives
Ann M Richard, Richard S Judson, Keith A Houck, Christopher M Grulke, Patra Volarath, Inthirany Thillainadarajah, Chihae Yang, James Rathman, Matthew T Martin, John F Wambaugh, Thomas B Knudsen, Jayaram Kancherla, Kamel Mansouri, Grace Patlewicz, Antony J Williams, Stephen B Little, Kevin M Crofton, Russell S Thomas
The U.S. Environmental Protection Agency's (EPA) ToxCast program is testing a large library of Agency-relevant chemicals using in vitro high-throughput screening (HTS) approaches to support the development of improved toxicity prediction models. Launched in 2007, Phase I of the program screened 310 chemicals, mostly pesticides, across hundreds of ToxCast assay end points. In Phase II, the ToxCast library was expanded to 1878 chemicals, culminating in the public release of screening data at the end of 2013. Subsequent expansion in Phase III has resulted in more than 3800 chemicals actively undergoing ToxCast screening, 96% of which are also being screened in the multi-Agency Tox21 project...
August 15, 2016: Chemical Research in Toxicology
Ulf Norinder, Scott Boyer
Quantitative structure-activity relationships (QSAR) are critical to exploitation of the chemical information in toxicology databases. Exploitation can be extraction of chemical knowledge from the data but also making predictions of new chemicals based on quantitative analysis of past findings. In this study, we analyzed the ToxCast and Tox21 estrogen receptor data sets using Conformal Prediction to enhance the full exploitation of the information in these data sets. We applied aggregated conformal prediction (ACP) to the ToxCast and Tox21 estrogen receptor data sets using support vector machine classifiers to compare overall performance of the models but, more importantly, to explore the performance of ACP on data sets that are significantly enriched in one class without employing sampling strategies of the training set...
June 20, 2016: Chemical Research in Toxicology
Warren M Casey
The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) provides validation support for US Federal agencies and the US Tox21 interagency consortium, an interagency collaboration that is using high throughput screening (HTS) and other advanced approaches to better understand and predict chemical hazards to humans and the environment. The use of HTS data from assays relevant to the estrogen receptor signaling data pathway is used as an example of how HTS data can be combined with computational modeling to meet the needs of US agencies...
January 2016: Toxicological Research
Anthony L Schroeder, Gerald T Ankley, Keith A Houck, Daniel L Villeneuve
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...
March 2016: Environmental Toxicology and Chemistry
Thomas Luechtefeld, Alexandra Maertens, Daniel P Russo, Costanza Rovida, Hao Zhu, Thomas Hartung
The European Chemicals Agency (ECHA) warehouses the largest public dataset of in vivo and in vitro toxicity tests. In December 2014 this data was converted into a structured, machine readable and searchable database using linguistic search engines. It contains data for 9,801 unique substances, 3,609 unique study descriptions and 816,048 study documents.This allows exploring toxicological data on a scale far larger than previously available. Substance similarity analysis was used to determine clustering of substances for hazards by mapping to PubChem...
2016: ALTEX
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"