Science Inventory

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The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human health risk assessment and ethics of this system, demanding a change of paradigm...

Traditional methods for cancer risk assessment are retrospective, resource-intensive, and not feasible for the vast majority of environmental chemicals. In earlier studies, we used a set of six biomarkers to accurately identify liver tumorigens in transcript profiles derived from...

Thyroid hormones (TH) are essential for normal brain development. There is a significant public health need to protect the developing brain of the fetus, newborn, and young child from thyroid system-disrupting chemicals. Environmental chemicals can interfere with the thyroid syst...

In a joint effort involving scientists from academia, industry and regulatory agencies, ECETOC's activities in Omics have led to conceptual proposals for: (1) A framework that assures data quality for reporting and inclusion of Omics data in regulatory assessments; and (2) an app...

This AOP describes the sequence of events leading from thyroperoxidase inhibition to increased mortality&nbsp;via reduced anterior swim bladder inflation. The enzyme thyroperoxidase (TPO) is essential for the synthesis&nbsp;of thyroxine (T4) and triiodothyronine (T3) in the thyro...

This AOP describes the sequence of events leading from deiodinase inhibition to increased mortality via&nbsp;reduced anterior swim bladder inflation. Thyroid hormones (THs) are critical during development and&nbsp;disruption of the TH system can interfere with normal development....

New approach methodologies (NAMs) in biological and computational sciences can generate mechanistic information which can be used to support safety assessments of chemicals. The Adverse outcome pathway (AOP) is a conceptual construct that portrays existing knowledge concerning th...

This AOP describes the sequence of events leading from deiodinase inhibition to increased mortality via reduced&nbsp;posterior swim bladder inflation. Thyroid hormones (THs) are critical during embryonic development and&nbsp;disruption of the TH system can interfere with normal d...

This AOP describes the sequence of events leading from deiodinase inhibition to increased mortality via&nbsp;reduced anterior swim bladder inflation. Disruption of the thyroid hormone system is increasingly being&nbsp;recognized as an important toxicity pathway that can cause man...

This AOP describes the sequence of events leading from deiodinase inhibition to increased mortality&nbsp;via reduced posterior swim bladder inflation. Disruption of the thyroid hormone system is increasingly&nbsp;being recognized as an important toxicity pathway that can cause ma...

Recent technological advances have moved the field of toxicogenomics from reliance on microarray platforms to high-throughput transcriptomic technologies that measure global gene expression. Gene expression biomarkers are emerging as useful tools for interpreting gene expression ...

The guest lecture / presentation focused on how various data streams used in evidence integration for risk assessment can be better integrated through use of mechanistic constructs, including source to outcome modeling with dosimetry providing the critical link between aggregate ...

All-trans retinoic acid (ATRA) gradients determine skeletal patterning morphogenesis and can be disrupted by diverse genetic or environmental factors, leading to fetal skeleton malformations. Here, a data-driven model was constructed to identify chemicals associated with both ATR...

Homeotic transformations and malformations of the fetal skeleton can occur as locally-regulated all-trans retinoic acid (ATRA) gradients. Such gradients determine skeletal patterning morphogenesis and can be disrupted by diverse genetic or environmental factors. Adverse Outcome P...

I Some phthalate esters alter male rat reproductive development during sexual differentiation by interfering with fetal testis maturation resulting in reduced Leydig Cell synthesis of testosterone and insulin-like 3 (Insl3) hormones. Gene transcripts associated with steroid hormo...

There are 92 thyroid-relevant assay endpoints from the ToxCast/Tox21 project that can be mapped to molecular initiating events (MIEs) within the thyroid adverse outcome pathway (AOP) network. However, a synthesis and interpretation of the data across MIEs and at the tissue level ...

There is significant regulatory need to identify and evaluate chemicals that may disrupt the thyroid endocrine system. Thyroid new approach methods (NAMs) are being developed and applied to increase data coverage across the ToxCast/Tox21 chemical inventories using a tiered testin...

Early neurodevelopmental periods are vulnerable to environmental compounds. Unfortunately, there are few adverse outcome pathways (AOP) that explore these critical periods. AOPs detail a series of biological responses linked by key events following a molecular initiating event an...

Multiple in vivo test guidelines focusing on the estrogen, androgen, thyroid, and steroidogenesis pathways have been developed and validated for mammals, amphibians, or fish. However, these tests are resource-intensive and often use a large number of laboratory animals. Developin...

Despite high regulatory need, there remains a lack of internationally harmonized approaches to identify chemical respiratory allergens. Depending on the regulatory context, approaches are needed for determining the potential of a low molecular weight (LMW) compound to sensitize t...

Epigenetics, the interface between the environment and genome, can change quickly in response to environmental stressors. Epigenetic modifications may cause changes in gene expression leading to potential adverse biological outcomes. Here, we present differential DNA methylation ...

Per- and polyfluoroalkyl substances (PFAS) are a large group of chemicals of concern due to their widespread use, accumulation in humans and wildlife, and potential for toxicity. Based on bioactivity screening, over 25% of PFAS evaluated showed some degree of estrogenic activity....

Several AOPs have been developed to coalesce literature-derived information on separate adverse outcomes of COVID-19, including acute respiratory distress, hyperinflammation, thrombosis, and gut dysbiosis, to name a few. All start with the molecular initiating event of the viral ...

The adverse outcome pathway (AOP) framework provides a systematic approach for organizing biological knowledge and evidence causally linking molecular and biochemical effects of stressors to adverse effects on human health and/or ecosystems. Molecular screening assays are being a...

Quantitative adverse outcome pathways (qAOPs) have been broadly defined as AOPs for which the quantitative understanding of the key event relationships is sufficient to allow for estimation of the probability or severity of the adverse outcome occurring based on measured or model...