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  • Keyword = endocrine disruption.
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2020
A Case study on the utility of predictive toxicology tools in alternatives assessments for hazardous chemicals in children’s consumer products (JOURNAL)
Children’s consumer products represent an important exposure source for many toxicants. Chemicals of high concern, as designated by the Washington State Child Safe Product Act include phthalates, Bisphenol A (BPA) and parabens, among others. As regulation and reporting requ...
Aromatase inhibition in fishes with group-synchronous oocyte development: The importance of reproductive traits (PRESENTATION)
Quantitative adverse outcome pathways (qAOPs) include descriptions of quantitative response-response relationships between key biological processes to allow prediction of the probability or severity of an apical-level toxicity for a given magnitude of chemical interaction with a ...
2019
A cross-species model for predicting reproductive dysfunction in fishes exposed to aromatase inhibiting chemicals (PRESENTATION)
Chemicals in the environment can prevent proper reproduction in fish. However, it was unknown whether models developed using data collected from the commonly studied fathead minnow could accurately predict adverse effects to other fish species. Results of our study suggest that t...
A transient window of hypothyroidism alters neural progenitor cells and results in abnormal brain development (JOURNAL)
Cortical heterotopias are characterized as clusters of ectopic neurons in the brain, and are associated with neurodevelopmental disorders like epilepsy and learning disabilities in patients. We have previously characterized the robust penetrance of a heterotopia in a rat model, i...
An International Perspective on the Tools and Concepts for Effluent Toxicity Assessments in the Context of Animal Alternatives: Reduction in vertebrate use (JOURNAL)
Since the 1940s, effluent toxicity testing has been used to assess potential ecological impacts of effluents and help determine necessary treatment options for environmental protection prior to release. Strategic combinations of toxicity tests, analytical tools, and biological mo...
Antiandrogen mixology: Cumulative effects of environmental chemicals on male rat reproductive tract development (PRESENTATION)
Male reproductive impairments, such as hypospadias, cryptorchidism and reduced sperm counts, are relatively common and have reportedly been increasing in prevalence over the last several decades. These effects can be induced in laboratory animals by a wide range of environmental...
Application of Chemical Informatics to Alternatives Assessment (PRESENTATION)
The evaluation of potential alternatives for chemicals of concern (CoC) requires an understanding of their potential human health and environmental impacts during the manufacture, use, recycle and disposal life stages. During the manufacturing phase, the processes used to produce...
Bridging the Data Gap from in vitro Toxicity Testing to Chemical Safety Assessment through Computational Modeling (JOURNAL)
Chemical toxicity testing is moving steadily toward a human cell and organoid-based in vitro approach for reasons including scientific relevancy, efficiency, cost, and ethical rightfulness. Inferring human health risk from chemical exposure based on in vitro testing data is a cha...
Chemical Prioritization Methods for Nuclear Receptor Modulators at the U.S. EPA (PRESENTATION)
In vitro/alternative and computational approaches are valuable for chemical prioritization, especially where we understand the targets and toxicity pathways. Nuclear receptors are an inherently important target of environmental chemicals. Endocrine disruption is one important mod...
Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, Focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways (ASSESSMENT DOCUMENT)
The focus of this meeting is the SAP's review and comment on the Agency's proposed high-throughput computational model of androgen receptor pathway activity as an alternative to the current Tier 1 androgen receptor assay (OCSPP 890.1150: Androgen Receptor Binding Rat Prostate Cyt...
Cross-species Applicability of a quantitative AOP describing inhibition of aromatase activity leading to reproductive dysfunction in fishes (PRESENTATION)
Quantitative adverse outcome pathways (qAOPs) describe quantitative response-response relationships linking the molecular initiating event (MIE) and adverse outcome (AO) to enable quantitative prediction of the probability of occurrence or severity of an AO for a given magnitude ...
Cross-species applicability of a quantitative AOP describing inhibition of aromatase activity leading to reproductive dysfunction in fathead minnow (PRESENTATION)
Chemicals in the environment can prevent proper reproduction in fish. However, it was unknown whether models developed using data collected from the commonly studied fathead minnow could accurately predict adverse effects to other fish species. Results of our study suggest that t...
Development of a Curated Hershberger Database (JOURNAL)
• A systematic literature review was conducted to identify Hershberger assays testing in vivo (anti)androgens effects of chemicals. • Details on study designs and experimental results for 134 chemicals that met pre-defined criteria were entered in a database. • Results for ...
Developmental Exposure to Perfluorohexane Sulfonate (PFHxS) induces hypothyroxinemia in Rat Dams and Offspring: Examination of the Thyroid Gland and Behavior (PRESENTATION)
Introduction Thyroid hormones (TH) are critical for mammalian brain development. In humans, low maternal serum thyroxine (T4) levels are associated with neurological deficiencies and cognitive impairment. Perfluorohexane sulfonate (PFHxS) is a widespread environmental contaminant...
Differential sensitivity to in vitro inhibition of cytochrome P450 aromatase (CYP19) activity among 18 freshwater fishes (JOURNAL)
There is significant concern regarding potential impairment of fish reproduction associated with endocrine disrupting chemicals. Aromatase (CYP19) is a steroidogenic enzyme involved in the conversion of androgens to estrogens. Inhibition of aromatase by chemicals can result in re...
Endocrine disruption in crustaceans - a “new” environmental challenge? (PRESENTATION)
A number of exogenous compounds have the potential to interfere with the endocrine system of animals. This may perturb vital endocrine processes to a degree causing an adverse effect (outcome) on ecologically relevant endpoints such as growth, development, and reproduction. These...
Gene transcription ontogeny of thyroid-axis development in early-life stage fathead minnow and zebrafish (JOURNAL)
Disruption of thyroid hormone signaling is a form of endocrine disruption that is of concern to both human health and ecosystems. Research is being conducted to define the biological targets chemicals may interact with to disrupt thyroid hormone signaling and the stages in develo...
Generalized concentration addition mixtures model predicts glucocorticoid receptor activation by environmental full and partial agonists (PRESENTATION)
Abstract describing study design, results and conclusions will be presented in poster or platform format to attendees of the 2018 Society of Environmental Toxicology and Chemistry annual meeting pending acquisition of travel funds. Abstract: Endocrine disrupting compounds are pe...
Identification of potential chemical carcinogens in compendia of gene expression profiles. (PRESENTATION)
Chemicals induce cancer through partially characterized adverse outcome pathways (AOPs) that include molecular initiating events (MIEs) and downstream key events (KEs). We developed computational strategies to identify chemicals in large microarray compendia that activate cancer ...
In vitro water quality screening tools for quantifying human and ecological-related endocrine activity (PRESENTATION)
Abstract describing value of specific water quality monitoring approach and overall conclusions after multiple years of application of tools to several case studies. Summary will be presented in platform format to attendees of the 2018 National Water Quality Monitoring Council Me...
LINKAGE OF EXPOSURE AND EFFECTS USING GENOMICS, PROTEOMICS, AND METABONOMICS IN SMALL FISH MODELS ()
Over the past decade there has been a focused international effort to identify possible adverse effects of EDCs on humans and wildlife. Effects on reproduction and development mediated through alterations in the HPG axis have been of particular concern (USEPA 1998). There is co...
Linking Molecular Structure to Functional Group and Chemical Literature Using a Chemical Reaction Database (PRESENTATION)
The evaluation of potential alternatives for chemicals of concern requires understanding the implications of the chemical of concern during the manufacture, use, and disposal phases of its life cycle. Identifying potential reaction pathways and synthesis routes is an important co...
Linking Molecular Structure via Functional Group to Chemical Literature for Establishing a Reaction Lineage for Application to Alternatives Assessment (JOURNAL)
The evaluation of potential alternatives for chemicals of concern (CoC) requires an understanding of their potential human health and environmental impacts during the manufacture, use, recycle and disposal life stages. During the manufacturing phase, the processes used to produce...
MODELING MOLECULAR TARGETS FOR TOXICITY, A COMPUTATIONAL APPROACH TO UNDERSTANDING KEY STEPS IN THE MECHANISMS FOR TOXICITY AND A TOOL FOR PRIORITIZING BIOASSAY REQUIREMENTS ()
The Agency frequently encounters situations where it must make decisions about the potential health and environmental effects of chemicals when all of the relevant data is not available. One rational approach to this problem is to estimate the relevant missing information by ext...
Mapping of chemical identifiers to DSSTox to enable data integration in the US-EPA CompTox Chemicals Dashboard (PRESENTATION)
The Computational Toxicology Program within the U.S. Environmental Protection Agency (EPA) integrates advances in biology, chemistry, and computer science to help prioritize chemicals for further research based on potential human and environmental health risks. A key component o...
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