Antony John Williams

Antony John Williams
United States Environmental Protection Agency | US EPA · Center for Computational Toxicology and Exposure

PhD

About

601
Publications
92,406
Reads
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10,956
Citations
Introduction
I am presently a Computational Chemist at the Center for Computational Toxicology and Exposure with the US Environmental Protection Agency in Research Triangle Park, North Carolina. I am one of the founders of the ChemSpider database (http://www.chemspider.com),one of the top chemistry databases in the world that was acquired by the Royal Society of Chemistry in 2009. Prolific author with almost 200 peer-reviewed scientific publication and book chapters, 3 patents and 100s of public presentations.
Additional affiliations
May 2015 - present
Environmental Protection Agency, Research Triangle Park, NC, United States
Position
  • Computational Chemist
Description
  • I am a computational chemist in the NCCT team. The National Center for Computational Toxicology (NCCT) is the largest component of EPA's Computational Toxicology Research Program.
May 2015 - present
United States Environmental Protection Agency
Position
  • Computational Chemist
Description
  • The National Center for Computational Toxicology (NCCT) is the largest component of EPA's Computational Toxicology Research Program. I am a computational chemist in the NCCT team.
March 2011 - March 2014
Multiple pharma companies and academia
Position
  • Open PHACTS
Description
  • Pharmaceutical
Education
September 1985 - December 1988
University of London
Field of study
  • Chemistry
September 1982 - June 1985
University of Liverpool
Field of study
  • Chemistry

Publications

Publications (601)
Article
Background Systematic evidence maps (SEMs) are gaining visibility in environmental health for their utility to serve as problem formulation tools and assist in decision-making, especially for priority setting. SEMs are now routinely prepared as part of the assessment development process for the US Environmental Protection Agency (EPA) Integrated Ri...
Preprint
Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals tha...
Article
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Direct monitoring of chemical concentrations in different environmental and biological media is critical to understanding the mechanisms by which human and ecological receptors are exposed to exogenous chemicals. Monitoring data provides evidence of chemical occurrence in different media and can be used to inform exposure assessments. Monitoring da...
Article
Non-targeted analysis (NTA) methods are widely used for chemical discovery but seldom employed for quantitation due to a lack of robust methods to estimate chemical concentrations with confidence limits. Herein, we present and evaluate new statistical methods for quantitative NTA (qNTA) using high-resolution mass spectrometry (HRMS) data from EPA’s...
Article
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There have been many attempts to compile comprehensive lists of flame retardants. However, this goal has proven challenging due to the heterogeneity of compounds that can be used as flame retardants coupled with changes in formulation chemistry over time. Flame retardants have been the focus of many recent existing hazard, exposure, and risk assess...
Article
Background Environmental health research has recently undergone a dramatic shift, with ongoing technological advancements allowing for broader coverage of exposure and molecular biology signatures. Approaches to integrate such measures are still needed to increase understanding between systems-level exposure and biology. Objectives We address this...
Article
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CAS Common Chemistry (https://commonchemistry.cas.org/) is an open web resource that provides access to reliable chemical substance information for the scientific community. Having served millions of visitors since its creation in 2009, the resource was extensively updated in 2021 with significant enhancements. The underlying dataset was expanded f...
Article
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Background: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram n...
Article
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Section 405(d) of the Clean Water Act requires the US Environmental Protection Agency to review sewage sludge regulations every two years to identify any additional pollutants that may occur in biosolids and to set regulations for pollutants identified in biosolids if sufficient scientific evidence shows they may harm human health or the environmen...
Article
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Per- and polyfluoroalkyl substances (PFAS) are a class of man-made chemicals of global concern for many health and regulatory agencies due to their widespread use and persistence in the environment (in soil, air, and water), bioaccumulation, and toxicity. This concern has catalyzed a need to aggregate data to support research efforts that can, in t...
Article
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Background The advent of high-throughput transcriptomic screening technologies has resulted in a wealth of publicly available gene expression data associated with chemical treatments. From a regulatory perspective, data sets that cover a large chemical space and contain reference chemicals offer utility for the prediction of molecular initiating ev...
Article
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Amphibian populations are undergoing a global decline worldwide. Such decline has been attributed to their unique physiology, ecology, and exposure to multiple stressors including chemicals, temperature, and biological hazards such as fungi of the Batrachochytrium genus, viruses such as Ranavirus, and habitat reduction. There are limited toxicity d...
Article
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Perfluorooctanoic acid (PFOA) and related compounds are per- and polyfluorinated alkyl substances (PFASs) of concern from toxicological, environmental, and regulatory perspectives. In 2019, the Conference of the Parties to the Stockholm Convention on Persistent Organic Pollutants listed PFOA, its salts, and PFOA-related compounds in Annex A to the...
Article
Children in low- and middle-income countries are often exposed to higher levels of chemicals and are more vulnerable to the health effects of air pollution. Little is known about the diversity, toxicity, and dynamics of airborne chemical exposures at the molecular level. We developed a workflow employing state-of-the-art wearable passive sampling t...
Chapter
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This chapter aims to introduce the reader to the basic principles of environmental risk assessment of chemicals and highlights the usefulness of tiered approaches within weight of evidence approaches in relation to problem formulation i.e., data availability, time and resource availability. In silico models are then introduced and include quantitat...
Article
Non-targeted analysis (NTA) encompasses a rapidly evolving set of mass spectrometry techniques aimed at characterizing the chemical composition of complex samples, identifying unknown compounds, and/or classifying samples, without prior knowledge regarding the chemical content of the samples. Recent advances in NTA are the result of improved and mo...
Article
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Toxicology has been an active research field for many decades, with academic, industrial and government involvement. Modern omics and computational approaches are changing the field, from merely disease-specific observational models into target-specific predictive models. Traditionally, toxicology has strong links with other fields such as biology,...
Article
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The first methods associated with the Computer-Assisted Structure Elucidation (CASE) of small molecules were published over fifty years ago when spectroscopy and computer science were both in their infancy. The incredible leaps in both areas of technology could not have been envisaged at that time, but both have enabled CASE expert systems to achie...
Article
With the increasing availability of high-resolution mass spectrometers, suspect screening and non-targeted analysis are becoming popular compound identification tools for environmental researchers. Samples of interest often contain a large (unknown) number of chemicals spanning the detectable mass range of the instrument. In an effort to separate t...
Article
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For the past six decades, human health risk assessment of chemicals has relied on in vivo data from human epidemiological and experimental animal toxicological studies to inform the derivation of cancer and non-toxicity values. The ongoing evolution of this risk assessment paradigm in an environmental landscape of data-poor chemicals has highlighte...
Article
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Unknown chemical releases constitute a large portion of the rapid response situations to which the U.S. Environmental Protection Agency (U.S. EPA) is called upon to respond. Workflows used to address unknown chemical releases currently involve screening for a large array of known compounds using many different targeted methods. When matches are not...
Preprint
Full-text available
Children in low- and middle-income countries are often exposed to higher levels of, and more vulnerable to, the health effects of air pollution. Little is known about the diversity, toxicity, and dynamics of airborne chemical exposures at the molecular level. We developed a workflow employing state-of-the-art wearable passive sampling technology co...
Article
There is an increasing need for comparable and harmonized retention times (tR) in liquid chromatography (LC) among different laboratories, to provide supplementary evidence for the identity of compounds in high-resolution mass spectrometry (HRMS)-based suspect and nontarget screening investigations. In this study, a rigorously tested, flexible, and...
Article
Recycled materials are found in many consumer products as part of a circular economy; however, the chemical content of recycled products is generally uncharacterized. A suspect screening analysis using two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOFMS) was applied to 210 products (154 recycled, 56 virgin) across sev...
Article
Omics methodologies are widely used in toxicological research to understand modes and mechanisms of toxicity. Increasingly, these methodologies are being applied to questions of regulatory interest such as molecular point-of-departure derivation and chemical grouping/read-across. Despite its value, widespread regulatory acceptance of omics data has...
Article
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The EPA developed the Adverse Outcome Pathway Database (AOP-DB) to better characterize adverse outcomes of toxicological interest that are relevant to human health and the environment. Here we present the most recent version of the EPA Adverse Outcome Pathway Database (AOP-DB), version 2. AOP-DB v.2 introduces several substantial updates, which inc...
Article
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Because of the pervasiveness, persistence, and toxicity of per- and polyfluoroalkyl substances (PFAS), there is growing concern over PFAS contamination, exposures, and health effects. The diversity of potential PFAS is astounding, with nearly 10,000 PFAS catalogued in databases to date (and growing). The ability to detect the thousands of known PFA...
Article
Per- and polyfluoroalkyl substances (PFAS) are a broad class of hundreds of fluorinated chemicals with environmental health concerns due to their widespread presence and persistence in the environment. Several of these chemicals have been comprehensively studied for experimental toxicity, environmental fate and exposure, and human epidemiology; how...
Article
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The core goal of cheminformatics is to efficiently store robust and accurate chemical information and make it accessible for drug discovery, environmental analysis, and the development of prediction models including quantitative structure-activity relationships (QSAR). The U.S. Environmental Protection Agency (EPA) has developed a web-based applica...
Article
The U.S. EPA CompTox Chemicals Dashboard is a freely available web-based application providing access to chemistry, toxicity, and exposure data for ~900,000 chemicals. Data, search functionality, and prediction models within the Dashboard can help identify chemicals found in environmental analyses and human biomonitoring. It was designed to deliver...
Article
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Since 2009, the Tox21 project has screened ∼8500 chemicals in more than 70 high-throughput assays, generating upward of 100 million data points, with all data publicly available through partner websites at the United States Environmental Protection Agency (EPA), National Center for Advancing Translational Sciences (NCATS), and National Toxicology P...
Article
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Software applications for high resolution mass spectrometry (HRMS)-based non-targeted analysis (NTA) continue to enhance chemical identification capabilities. Given the variety of available applications, determining the most fit-for-purpose tools and workflows can be difficult. The Critical Assessment of Small Molecule Identification (CASMI) contes...
Article
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The COVID-19 pandemic has highlighted an important role for drug repurposing. Quaternary ammonium compounds such as ammonium chloride, cetylpyridinium and miramistin represent widely accessible antiseptic molecules with well-known broad-spectrum antiviral activities and represent a repurposing opportunity as therapeutics against SARS-CoV-2.
Article
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Background: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need i...
Article
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High-resolution mass spectrometry (HRMS) enables rapid chemical annotation via accurate mass measurements and matching of experimentally derived spectra with reference spectra. Reference libraries are generated from chemical standards and are therefore limited in size relative to known chemical space. To address this limitation, in silico spectra (...
Chapter
The identification of volatile compounds detected through breath sampling is generally performed using mass spectrometry (MS). The data, including extracted masses, formulae, and retention indices, coupled with searching against reference databases, are essential for the identification of candidate chemicals detected in the breath. The application...
Article
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Background The logarithmic acid dissociation constant pKa reflects the ionization of a chemical, which affects lipophilicity, solubility, protein binding, and ability to pass through the plasma membrane. Thus, pKa affects chemical absorption, distribution, metabolism, excretion, and toxicity properties. Multiple proprietary software packages exist...
Article
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Confident identification of unknown chemicals in high resolution mass spectrometry (HRMS) screening studies requires cohesive workflows and complementary data, tools, and software. Chemistry databases, screening libraries, and chemical metadata have become fixtures in identification workflows. To increase confidence in compound identifications, the...
Article
This editorial presents a free-access internet tool for the breath research community to directly query accumulated knowledge for breath-borne chemicals including name, structure, and references. It is a subset of the U.S. Environmental Protection Agency (EPA) "Distributed Structure Searchable Toxicity" (DSSTox) database containing over 875,000 com...
Article
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Connecting chemical exposures over a lifetime to complex chronic diseases with multifactorial causes such as neurodegenerative diseases is an immense challenge requiring a long-term, interdisciplinary approach. Rapid developments in analytical and data technologies, such as non-target high resolution mass spectrometry (NT-HR-MS), have opened up new...
Article
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Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) is increasingly popular for the non-targeted exploration of complex samples, where tandem mass spectrometry (MS/MS) is used to characterize the structure of unknown compounds. However, mass spectra do not always contain sufficient information to unequivocally identify th...
Article
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The US Environmental Protection Agency’s (EPA) Distributed Structure-Searchable Toxicity (DSSTox) database, launched publicly in 2004, currently exceeds 875 K substances spanning hundreds of lists of interest to EPA and environmental researchers. From its inception, DSSTox has focused curation efforts on resolving chemical identifier errors and con...
Article
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The U.S. Environmental Protection Agency (EPA) is faced with the challenge of efficiently and credibly evaluating chemical safety often with limited or no available toxicity data. The expanding number of chemicals found in commerce and the environment, coupled with time and resource requirements for traditional toxicity testing and exposure charact...
Article
Non-targeted analysis (NTA) methods are increasingly used to discover contaminants of emerging concern (CECs), but the extent to which these methods can support exposure and health studies remains to be determined. EPA’s Non-Targeted Analysis Collaborative Trial (ENTACT) was launched in 2016 to address this need. As part of ENTACT, 1269 unique subs...
Article
Full-text available
Per- and polyfluoroalkyl substances (PFASs) are a group of fluorinated substances of interest to researchers, regulators, and the public due to their widespread presence in the environment. A few PFASs have comparatively extensive amounts of human epidemiological, exposure, and experimental animal toxicity data (e.g., perfluorooctanoic acid), where...
Article
Full-text available
The numbers of potential neurotoxicants in the environment are raising and pose a great risk for humans and the environment. Currently neurotoxicity assessment is mostly performed to predict and prevent harm to human populations. Despite all the efforts invested in the last years in developing novel in vitro or in silico test systems, in vivo tests...
Article
In August 2015, the US Environmental Protection Agency (EPA) convened a workshop entitled “Advancing non-targeted analyses of xenobiotic chemicals in environmental and biological media.” The purpose of the workshop was to bring together the foremost experts in non-targeted analysis (NTA) to discuss the state-of-the-science for generating, interpret...
Article
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High-throughput screening (HTS) and computational technologies have emerged as important tools for chemical hazard identification. The US Environmental Protection Agency (EPA) launched the Toxicity ForeCaster (ToxCastTM) Program, which has screened thousands of chemicals in hundreds of mammalian-based HTS assays for biological activity. The data ar...
Article
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Chemical database searching has become a fixture in many non-targeted identification workflows based on high-resolution mass spectrometry (HRMS). However, the form of a chemical structure observed in HRMS does not always match the form stored in a database (e.g., the neutral form versus a salt; one component of a mixture rather than the mixture for...