Science Inventory

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The last two decades have seen a marked increase in concern over the effects of PFAS on humans and wildlife.&nbsp; PFAS, or polyfluoralkyl substances, often called &ldquo;the forever chemicals,&rdquo; are persistent contaminants that enter the environment from a variety of source...

There is significant regulatory need in the Endocrine Disruptor Screening Program (EDSP) to identify and evaluate chemicals that may disrupt the thyroid endocrine system. The New Approach Methods (NAMs) Work Plan seeks to support refinement and replacement of animal testing by ad...

This talk will give an overview of the US EPA's efforts in using new approach methods (NAMs) to accelerate chemical hazard assessment, data acquisition and translate effects to protect human health and the environment. It will also describe the organotypic and microphysiological ...

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...

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 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. Thyroid hormones (THs) are critical during development and&nbsp;disruption of the TH system can interfere with normal development....

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...

Inhaled chemical exposures are a ubiquitous aspect of daily life around the world.&nbsp; While there are thousands of inhalable chemicals and materials in use, there are few, or often no, data available to evaluate potential hazards posed by most of these agents.&nbsp; Traditiona...

Gastrulation is a critical period of embryonic development, featuring the formation of the primitive streak and differentiation of epiblast cells into primary germ layers. The developmental potential of human pluripotent stem cells (hPSCs) in culture most closely resembles the pl...

It is well known that the adult brain is protected from some infections and toxic molecules by the blood-brain and the blood-cerebrospinal fluid barriers. Contrary to the immense data collected in other fields, it is deeply entrenched in environmental toxicology that xenobiotics ...

Complex multi-cellular in vitro models of the human respiratory tract have provided novel opportunities to advance our understanding of the effects of inhaled particulate exposures on human health.&nbsp; These &ldquo;organotypic&rdquo; cell culture models also provide new opportu...

Biologically inspired multicellular systems models that are fully computable (eg, virtual embryo) can be used to titrate critical phenomena during tissue development, homeostasis, and disease; however, in silico reconstitution of a complex, self-organizing morphogenetic system fr...

Cleft palate is one of the most common birth defects in the United States, effecting an estimated 1 in 1700 births. Palatogenesis is a multistage process that includes fusion, the dissolution of the palatal shelves&rsquo; medial edge epithelium (MEE) allowing the mesenchymal core...

Per- and Polyfluoroalkyl substances (PFAS) are long lasting chemicals found in the environment that have been linked to adverse impacts in fish and other species, including humans. PFAS contamination may adversely impact fish on the organismal level through a variety of pathways ...

The global regulatory landscape surrounding chemical safety is shifting away from animal testing and moving toward greater reliance on New Approach Methodologies (NAMs) including a rapid growth in molecular data and computational methods to achieve human and environmental protect...

Zebrafish are a popular model organism because they share many developmental pathways with humans. Zebrafish developmental toxicity assays can indicate whether a chemical causes malformations (e.g., heart defects) or lethality; however, they do not indicate the specific mechanism...

An estimated 3.5-million people die annually from air pollution-induced cardiovascular disease (API-CVD); however, the molecular mechanisms driving API-CVD remain unclear. To identify these mechanisms, we developed a novel in vitro model of the lung that mimics the in vivo exposu...

The use of primary human bronchial epithelial cells (pHBECs) has increased in recent years because they can be differentiated under air-liquid interface (ALI) culture conditions and offer greater in vivo physiological relevance than their cell line counterparts. pHBEC ALI models ...

Cleft palate (CP) is a birth defect that occurs in nearly 1 in 1000 human births worldwide. The mammalian palate is formed by fusion of two palatal shelves consisting of mesenchymal tissue surrounded by an epithelial layer. Disruption of this fusion process can lead to CP. This p...

This presentation is on methylene blue, the first fully synthetic drug used in medicine. It has been used on humans, mice and for aquaculture/research by tropical fish hobbyists. Including our previous work, methylene blue appears safe for use with zebrafish embryos up to 10 &mic...

Regulatory decisions surrounding chemical safety are based on human and environmental (ecological) protection goals. Historically, such decisions have relied on data from animal toxicity testing to inform hazard and risk assessment and determine whether chemicals pose a threat to...

High throughput screening (HTS) assays with pluripotent stem cells (PSCs) offer a promising alternative to pregnant animals for assessing developmental toxicity. Their unique properties help them to be excellent models of the developing embryo during stages when the basic body pl...

The &ldquo;Toxicology in the 21st Century&rdquo; program goal is to increase the throughput and human relevance of chemical testing by integrating new approach methodologies (NAMs). The use of primary human cell-based in vitro NAMs for the evaluation of inhaled chemicals on the r...

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. Adverse Outcome Pathway (AOP) frameworks for ATRA metabolism, signaling, and homeostasis...