Science Inventory

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There are insufficient toxicity data to assess the ecological risks of many pharmaceuticals and personal care products (PPCPs). While data limitations are not uncommon for contaminants of environmental concern, PPCPs are somewhat unique in that an a priori understanding of their ...

An understanding of the combined effects of climate change (CC) and other anthropogenic stressors, such as chemical exposures, is essential for improving ecological risk assessments of vulnerable ecosystems. In the Great Barrier Reef, coral reefs are under increasingly severe dur...

This is a presentation abstract for proposed session, ID 141, Advances in New Approach Methods for Thyroid Toxicity Testing, for the SOT 2024 Annual Meeting.  Abstract: There is significant regulatory need to evaluate chemicals that may disrupt the thyroid endocrine system. ...

Background and purpose Dicyclohexyl phthalate (DCHP) is a high production volume phthalate ester with reproductive toxicity concerns. Previous research identified that DCHP reduced overall testosterone production and expression of 14 genes vital to reproductive development in a d...

High-throughput transcriptomics (HTTr) is increasingly being used to identify molecular targets of chemicals that can be linked to adverse outcomes. Cell proliferation is an important key event in chemical carcinogenesis. Here, we describe the construction and characterization of...

Investigators across the AOP research area are expected to contribute AOP content to the AOP-KB. This product will compile and summarize EPA contributions to the AOP-Wiki on an annual basis. Additionally, growth and connectivity of the AOP-KB as a whole, including both EPA and no...

Several adverse outcome pathways (AOPs) have linked molecular initiating events like aromatase inhibition, androgen receptor (AR) agonism, and estrogen receptor (ER) antagonism to reproductive impairment in adult fish. Estrogen receptor agonists can also cause adverse reproductiv...

AOP-Wiki release 2.6 is intended to implement the following feature upgrades/changes to the AOP-Wiki (aopwiki.org):  (6) removal of stressor fields from KE and KER pages; (7) introduction of prototypical stressor fields to AOP pages; (8) "searchable but hidden" fea...

AOP-Wiki release 2.5 is intended to implement the following feature upgrades/changes to the AOP-Wiki (aopwiki.org):  (1) automatic assignment of molecular initiating event (MIE) and adverse outcome (AO) designations in the AOP search table; (2) ability to filter displayed AO...

Thyroid hormone system disrupting compounds are considered potential threats for human and environmental health. Multiple adverse outcome pathways (AOPs) for thyroid hormone system disruption (THSD) are being developed in different taxa. Combining these AOPs results in a cross-sp...

New approach methodologies (NAMs) are being developed to reduce and replace vertebrate animal testing in support of ecotoxicology and risk assessment. The US Environmental Protection Agency's Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) bioinformatic too...

For the majority of developed adverse outcome pathways (AOPs), the taxonomic domain of applicability (tDOA) is typically narrowly defined with a single or a handful of species. Defining the tDOA of an AOP is critical for use in regulatory decision-making, particularly when consid...

Screening and testing of potential endocrine-disrupting chemicals for ecological effects are examples of risk assessment/regulatory activities that can employ adverse outcome pathways (AOPs) to establish linkages between readily measured alterations in endocrine function and whol...

The gut has been proposed as a potential alternative entry route for SARS-CoV-2. This was mainly based on the high levels of SARS-CoV-2 receptor expressed in the gastrointestinal (GI) tract, the observations of GI disorders (such as diarrhea) in some COVID-19 patients and the det...

To reduce the use of intact animals for chemical safety testing, while ensuring protection of ecosystems and human health, there is a demand for new approach methodologies (NAMs) that provide relevant scientific information at a quality equivalent to or better than traditional ap...

Thyroid-relevant bioassay data in the publicly available ToxCast database (and browseable in the CompTox Chemicals Dashboard) will be reviewed by molecular-initiating event. Example case studies of how to interpret the suite of bioactivity assay data will be shown. Work-in-progre...

Since 2014, the AOP-Wiki (aopwiki.org) has served as the internationally accessible and harmonized repository of scientific knowledge and evidence organized according to the adverse outcome pathway (AOP) framework. While the knowledgebase continues to grow steadily there remains ...

The AOP-Wiki provides a central repository for development of adverse outcome pathways (AOPs) and dissemination of AOP information without restrictions. Each AOP is described in narrative form with interconnected pages that house information on the key events (KEs) and key event ...

All-trans retinoic acid (ATRA) gradients determine skeletal patterning morphogenesis and can be disrupted by diverse genetic or environmental factors during pregnancy, leading to fetal skeleton defects. Adverse Outcome Pathway (AOP) frameworks for ATRA metabolism, signaling, and ...

The adverse outcome pathway (AOP) framework is intended to describe the causal linkages from a direct molecular interaction with a stressor to an adverse outcome of regulatory concern. Capturing such existing knowledge across biological levels of organization in this manner allow...

A number of xenobiotics interfere with thyroid hormone (TH) signaling. Although adequate supplies of TH are necessary for normal brain development, regulatory reliance on serum TH as proxies for brain TH insufficiency is fraught with significant uncertainties. A more direct causa...

Iodine is essential for the production of thyroid hormones. Perchlorate is an environmental contaminant that interferes with iodine uptake into the thyroid gland to reduce thyroid hormone synthesis. As thyroid hormones are critical for brain development, exposure to perchlorate d...

Synthetic chemicals with endocrine disrupting properties are pervasive in the environment and are present in the bodies of humans and wildlife. As thyroid hormones (THs) control normal brain development, and maternal hypothyroxinemia is associated with neurological impairments in...

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Thyroid hormone (TH) action controls brain development in a spatiotemporal manner. Previously, we demonstrated that perinatal hypothyroidism led to formation of a periventricular heterotopia in developing rats. This heterotopia occurs in the posterior telencephalon, and its forma...