The physiological and biochemical basis of potency thresholds modeled using human estrogen receptor alpha: implications for identifying endocrine disruptors.

The endocrine system functions by interactions between ligands and receptors. Ligands exhibit potency for binding to and interacting with receptors. Potency is the product of affinity and efficacy.

A mechanistic evaluation of the potential for octamethylcyclotetrasiloxane to produce effects via endocrine modes of action.

This review is a hypothesis driven, mechanistic evaluation of the potential for octamethylcyclotetrasiloxane (D4) to produce any effects via endocrine modes of action. D4 is a volatile, lipophilic liquid used in the production of high molecular weight dimethylsiloxane polymers. These are used in a variety of industrial, medical, cleaning, and personal care products, and they may contain low levels of residual D4.

Synergistic utilization of diverse industrial wastes for reutilization in steel production and their geopolymerization potential.

Recycling wastes back into a manufacturing process, or into a separate product, is an important challenge. The primary aim of this work was to combine wastes from the steel industry, the galvanizing industry and the pulp and paper industry to form two new useful products. The steel industry generates the wastes red dust, mill scale, blast oxygen furnace slag and iron ore fines.

Human-relevant potency threshold (HRPT) for ERα agonism.

The European Commission has recently proposed draft criteria for the identification of endocrine disrupting chemicals (EDCs) that pose a significant hazard to humans or the environment. Identifying and characterizing toxic hazards based on the manner by which adverse effects are produced rather than on the nature of those adverse effects departs from traditional practice and requires a proper interpretation of the evidence regarding the chemical's ability to produce physiological effect(s) via a specific mode of action (MoA). The ability of any chemical to produce a physiological effect depends on its pharmacokinetics and the potency by which it acts via the various MoAs that can lead to the particular effect.

Demonstration and Evaluation of Innovative Rehabilitation Technologies for Water Infrastructure Systems.

The needs associated with the deteriorating water infrastructure are immense and have been estimated at more than $1 trillion over the next 20 years for water and wastewater utilities. To meet this growing need, utilities require the use of innovative technologies and procedures for managing their systems. The U.

Potency matters: thresholds govern endocrine activity.

Whether thresholds exist for endocrine active substances and for endocrine disrupting effects of exogenous chemicals has been posed as a question for regulatory policy by the European Union. This question arises from a concern that the endocrine system is too complex to allow estimations of safe levels of exposure to any chemical with potential endocrine activity, and a belief that any such chemical can augment, retard, or disrupt the normal background activity of endogenous hormones. However, vital signaling functions of the endocrine system require it to continuously discriminate the biological information conveyed by potent endogenous hormones from a more concentrated background of structurally similar, endogenous molecules with low hormonal potential.

Characterization of the role of glutathione in repin-induced mitochondrial dysfunction, oxidative stress and dopaminergic neurotoxicity in rat pheochromocytoma (PC12) cells.

Repin, a major constituent in extracts of the plant Centaurea repens is thought to be the active principal responsible for the development of equine nigropallidal encephalomalacia (ENE), a fatal Parkinson-like neurodegenerative disorder in horses. Although the exact mechanism by which ingestion of this weed causes ENE is uncertain, a limited body of experimental evidence suggests a critical role for the glutathione redox system. In the present study, the mechanism of repin neurotoxicity was examined in PC12 cells with a focus on determining the role of glutathione (GSH) in repin-induced mitochondrial dysfunction, oxidative stress and dopaminergic toxicity.

Inactivation of the cytotoxic activity of repin, a sesquiterpene lactone from Centaurea repens.

Prolonged ingestion of Yellow Starthistle (Centaurea solstitialis) and Russian Knapweed (Centaurea repens) by horses has been shown to result in a fatal neurodegenerative disorder called equine nigropallidal encephalomalacia (ENE). Bioassay-guided fractionation of extracts from Centaurea species using the PC12 cell line have led to the identification of one of several putative agents, which may contribute to ENE, namely, the sesquiterpene lactone (SQL) repin (1), previously linked to ENE due to its abundance in C. repens.