EPA Science Inventory

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Records with

  • Keyword = endocrine disruption.
  (Sorted by Fiscal Year)
Records 1 to 25 of 267

2017
(Chemical Research in Toxicology) Development and Validation of a Computational Model for Androgen Receptor Activity (JOURNAL)
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 mo...
A High-Throughput Screening Assay to Detect Thyroperoxidase Inhibitors (Teratology Society) (PRESENTATION)
In support of the Endocrine Disruption Screening Program (EDSP21), the US EPA ToxCast program is developing assays to enable screening for chemicals that may disrupt thyroid hormone synthesis. Thyroperoxidase (TPO) is critical for TH synthesis and is a known target of thyroid-dis...
A QSAR Model for Thyroperoxidase Inhibition and Screening of a Large Set of Environmental Chemicals (SOT) (PRESENTATION)
Thyroid hormones (THs) are critical modulators of a wide range of biological processes from neurodevelopment to metabolism. Well regulated levels of THs are critical during development and even moderate changes in maternal or fetal TH levels produce irreversible neurological defi...
A tiered approach to evaluate an iodine recycling inhibition adverse outcome pathway (AOP) in amphibians (PRESENTATION)
The enzyme iodotyrosine deiodinase (dehalogenase, IYD) catalyzes iodide recycling and promotes iodide retention in thyroid follicular cells. Loss of function or chemical inhibition of IYD reduces thyroid hormone synthesis, which leads to insufficiency in tissues and subsequent ne...
Adverse outcome pathways (AOPs) to enhance EDC screening and testing: Overview of recent activities and future efforts (PRESENTATION)
Screening and testing for endocrine active chemicals was mandated under 1996 amendments to the Safe Drinking Water Act and Food Quality Protection Act. Efficiencies can be gained in the endocrine disruptor screening program by using available biological and toxicological knowledg...
An integrated approach for identifying priority contaminant in the Great Lakes Basin -Investigations in the Lower Green Bay/Fox River and Milwaukee Estuary areas of concern (JOURNAL)
Environmental assessment of complex mixtures typically requires integration of chemical and biological measurements. This study demonstrates the use of a combination of instrumental chemical analyses, effects-based monitoring, and bio-effects prediction approaches to help identi...
Application of computational and high-throughput in vitro screening for prioritization (ECHA workshop) (PRESENTATION)
Abstract: There are tens of thousands of man-made chemicals to which humans are exposed, but only a fraction of these have the extensive in vivo toxicity data used in most traditional risk assessments. This lack of data, coupled with concerns about testing costs and animal use, a...
Avoiding false positives and optimizing identification of true negatives in estrogen receptor binding and agonist/antagonist assays (JOURNAL)
The potential for chemicals to affect endocrine signaling is commonly evaluated via in vitro receptor binding and gene activation, but these assays, especially antagonism assays, have potential artifacts that must be addressed for accurate interpretation. Results are presented fr...
Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis: Incorporating Protein Synthesis in Improving Predictability of Responses to Endocrine Active Chemicals (JOURNAL)
There is international concern about chemicals that alter endocrine system function in humans and/or wildlife and subsequently cause adverse effects. We previously developed a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minno...
Computational modeling of the amphibian thyroid axis supported by targeted in vivo testing to advance quantitative adverse outcome pathway development (PRESENTATION)
In vitro screening of chemicals for bioactivity together with computational modeling are beginning to replace animal toxicity testing in support of chemical risk assessment. To facilitate this transition, an amphibian thyroid axis model has been developed to describe thyroid home...
Consensus models to predict endocrine disruption for all human-exposure chemicals (AAAS Annual Meeting) (PRESENTATION)
Humans are potentially exposed to tens of thousands of man-made chemicals in the environment. It is well known that some environmental chemicals mimic natural hormones and thus have the potential to be endocrine disruptors. Most of these environmental chemicals have never been te...
Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances (JOURNAL)
In this paper existing regulatory frameworks and test systems for assessing potential endocrine-active chemicals are described, and associated challenges discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across organizatio...
Developing confidence in adverse outcome pathway-based toxicity predictions effects of the fungicide imazalil on fathead minnow reproduction (PRESENTATION)
An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD (https://aopwiki.org/wiki/index.php/Aop:25). An intended application of t...
Developing confidence in adverse outcome pathway-based toxicity predictions effects of the fungicide imazalil on fathead minnow reproduction (Poster) (PRESENTATION)
An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD. An intended application of the AOP framework is to support the use of me...
Ecdysone receptor agonism leading to lethal molting disruption in arthropods: Review and adverse outcome pathway development (JOURNAL)
Molting is a key biological process in growth, development, reproduction and survival in arthropods. Complex neuroendocrine pathways are involved in the regulation of molting and may potentially become targets of environmental endocrine disrupting compounds (EDCs). For example, s...
Effects of the anti-microbial contaminant triclocarban and co-exposure with the androgen 17â-trenbolone, on reproductive function and ovarian transcriptome of the fathead minnow (Pimephales promelas) (JOURNAL)
Triclocarban (TCC) is a widely used antimicrobial agent that is routinely detected in surface waters. The present study was designed to examine TCC’s efficacy and mode of action as a reproductive toxicant in fish. Reproductively mature Pimephales promelas were continuously ...
Effects of the fungicide imazalil on the fathead minnow (Pimephales promelas) reproductive axis a case study in 21st century toxicity testing (PRESENTATION)
Since its introduction in 1983 imazalil has been used primarily as a fungicide on crops post-harvest, such as tubers and citrus fruits. Its effectiveness lies in the ability to inhibit the fungal enzyme, lanosterol 14 á-demethylase. However, like other azole fungicides, im...
Effects of the fungicide imazalil on the fathead minnow (Pimephales promelas) reproductive axis a case study in 21st century toxicity testing (PRESENTATION)
Since its introduction in 1983, imazalil has been used primarily as a fungicide on crops post-harvest. Its effectiveness lies in the ability to inhibit the fungal cytochrome P450 (cyp), lanosterol 14 á-demethylase. However, like other azole fungicides, imazalil can inhibit...
Higher Throughput Toxicokinetics to Allow Extrapolation (EPA-Japan Bilateral EDSP meeting) (PRESENTATION)
As part of "Ongoing EDSP Directions & Activities" I will present CSS research on high throughput toxicokinetics, including in vitro data and models to allow rapid determination of the real world doses that may cause endocrine disruption.
How adverse outcome pathways can aid the development and use of computational prediction models for regulatory toxicology (JOURNAL)
Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumu...
Identification of Chemical Features Linked to Thyroperoxidase Inhibition (SOT) (PRESENTATION)
Disruption of maternal serum thyroid hormone (TH) adversely affects fetal neurodevelopment. Therefore, assay development within the US EPA ToxCast program is ongoing to enable screening for chemicals that may disrupt TH, in support of the Endocrine Disruption Screening Program (E...
Impaired swim bladder inflation in early-life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid (presentation) (PRESENTATION)
The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4) to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior chamber of the swim bladder, processes previously ...
Literature Mining Methods for Toxicology and Construction of Adverse Outcome Pathways (OECD Retinoid Project workshop) (PRESENTATION)
Webinar Presentation on text-mining methodologies in use at NCCT and how they can be used to assist with the OECD Retinoid project.
Modeling Steroidogenesis Disruption Using High-Throughput In Vitro Screening Data (SOT) (PRESENTATION)
Environmental chemicals can elicit endocrine disruption by altering steroid hormone biosynthesis and metabolism (steroidogenesis) causing adverse reproductive and developmental effects. Historically, a lack of assays resulted in few chemicals having been evaluated for effects on ...
Prioritization of contaminants of emerging concern in wastewater treatment plant discharges using chemical: Gene interactions in caged fish (JOURNAL)
We examined whether contaminants present in surface waters could be prioritized for further assessment by linking the presence of specific chemicals to gene expression changes in exposed fish. Fathead minnows were deployed in cages for 2, 4, or 8 days at three locations near two ...