Science Inventory

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Neurotoxicology is the study of adverse effects on the structure or function of the developing or mature adult nervous system following exposure to chemical, biological, or physical agents. The development of more informative alternative methods to assess developmental (DNT) and ...

Current developmental neurotoxicity (DNT) tests that are used for environmental agents call for cognitive testing around the age of weaning as well as adulthood. There are challenges associated with testing weanling rodents that are not present with testing older subjects, inclu...

Soni and colleagues recently reported that perinatal maternal exposure to cyfluthrin, a pyrethroid insecticide, caused fetal malformations and behavioral changes in offspring, including skeletal malformations and alterations in righting reflexes and locomotion (Soni et al., 2011)...

There is considerable public concern that the majority of commercial chemicals have not been evaluated for their potential to cause developmental neurotoxicity. Although several chemicals are assessed annually under the current developmental neurotoxicity guidelines, time, resour...

Given the minimal developmental neurotoxicity data available for the large number of new and existing chemicals, there is a critical need for alternative methods to identify and prioritize chemicals for further testing. We outline a developmental neurotoxicity screening approach ...

Thousands of compounds in the environment have not been characterized for developmental neurotoxicity (DNT) hazard. To address this issue, methods to screen compounds rapidly for DNT hazard evaluation are necessary and are being developed for key neurodevelopmental processes. In...

New approaches in developmental neurotoxicity (DNT) screening are needed due to the tens of thousands of chemicals requiring hazard assessments. Zebrafish (Danio rerio) are an alternative vertebrate model for DNT testing, but without a standardized protocol for larval behavioral ...

Changes in resident microbiota may have wide-ranging effects on human health. We investigated whether early life microbial disruption alters neurodevelopment and behavior in larval zebrafish. Conventionally colonized, axenic, and axenic larvae colonized at 1&thinsp;day post ferti...

ABSTRACT: Tris(1,3-dichloro-2-propyl)phosphate (TDICPP) and tris(2-chloro-2-ethyl)phosphate (TCEP) are organophosphorous flame retardants with widespread usage and human exposures through food, inhalation, and dust ingestion. They have been detected in human tissues including ur...

The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and l...

High-throughput test methods including molecular, cellular, and alternative species-based assays that examine critical events of normal brain development are being developed for detection of developmental neurotoxcants. As new assays are developed, a "training set' of chemicals i...

Susceptibility to xenobiotic exposures is variable. One factor that might account for this is the microbiome, which encompasses all microorganisms, their encoded genes, and associated functions that colonize a host organism. Microbiota harbor the capacity to affect the toxicokine...

The use of larval zebrafish developmental testing and assessment, specifically larval zebrafish locomotor activity, has been recognized as a higher throughput testing strategy to identify developmentally toxic and neurotoxic chemicals. There are, however, no standardized protocol...

A manuscript summarizes a workshop aimed at developing a framework to determine the relevancy of animal modes-of-action for extrapolation to humans. This specific report used animal data on the neurodevelopmental effects of hypothyroidism to test the framework. Propylthiouracil,...

AbstractHigh-throughput methods are useful for rapidly screening large numbers of chemicals for biological activity, including the perturbation of pathways that may lead to adverse cellular effects. In vitro assays for the key events of neurodevelopment, including apoptosis, may ...

Many xenobiotics are identified as potential thyroid disruptors due to their action to reduce circulating levels of thyroid hormone, most notably thyroxine (T4). Developmental neurotoxicity is a primary concern for thyroid disrupting chemicals yet correlating the impact of chemic...

Traditional developmental neurotoxicity tests performed in vivo are costly, time-consuming and utilize a large number of animals. In order to address these inefficiencies, in vitro models of neuronal development have been used in a first tier screening approach for developmenta...

Thyroid hormones (TH) are essential for brain development and iodine is required for TH synthesis. Environmental chemicals that perturb the thyroid axis result in modest reductions in TH, yet there is a paucity of data on the extent of neurological impairments associated with low...

High-throughput assays that can quantify chemical-induced changes at the cellular and molecular level have been recommended for use in chemical safety assessment. High-throughput, high content imaging assays for the key cellular events of neurodevelopment have been proposed to ra...

To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecula...

Thyroid hormones are critical for mammalian brain development. Thus, chemicals that can affect thyroid hormone signaling during pregnancy are of great concern. Perfluorohexane sulfonate (PFHxS) is a widespread environmental contaminant found in human serum, breastmilk, and other ...

Severe thyroid hormone (TH) deficiency during critical phases of brain development results in irreversible neurological and cognitive impairments. The mechanisms accounting for this are likely multifactorial, and are not fully understood. Here we pursue the possibility that one i...

Anatoxin-a acts as a neuro-muscular blocking agent. Acute toxicity is characterized by rapid onset of paralysis, tremors, convulsions, and death. Human exposures may occur from recreational water activities and dietary supplements, but are primarily through drinking water. The...

Abstract: Environmental contaminants are often flagged as thyroid system disruptors due to their actions to reduce serum thyroxine (T4) in rodent models. The presence of a periventricular heterotopia (PVH), a brain malformation resulting from T4 insufficiency, has been described ...

The blood-brain barrier (BBB) serves as a gateway for passage of drugs, chemicals, nutrients, metabolites and hormones between vascular and neural compartments. Here, we review the current understanding of BBB development with regard to microphysiology of the neurovascular unit (...