Classification and toxicity mechanisms of novel flame retardants (NFRs) based on whole genome expression profiling.

Recently some novel alternative flame retardants (NFRs), which have been widely applied to meet demands for mandated flame retardation of products, have been detected in various matrices of the environment. However, knowledge on toxic effects and associated molecular mechanisms of these chemicals was limited. Here, toxic mechanisms of action of six NFRs, bis (2-ethylhexyl) phosphate (BEHP), chlorendic acid (Het acid), 2,2-bis (bromomethyl)-1,3-propanediol (BMP), tris (2-butoxyethyl) phosphate (TBEP), triethyl phosphate (TEP), tributyl phosphate (TBP) were investigated by use of a library containing ∼1820 modified green fluorescent protein (GFP) expressing promoter reporter vectors constructed from Escherichia coli K12(E.

Activation of AhR-mediated toxicity pathway by emerging pollutants polychlorinated diphenyl sulfides.

Polychlorinated diphenyl sulfides (PCDPSs) are a group of environmental pollutants for which limited toxicological information is available. This study tested the hypothesis that PCDPSs could activate the mammalian aryl hydrocarbon receptor (AhR) mediated toxicity pathways. Eighteen PCDPSs were tested in the H4IIE-luc transactivation assay, with 13/18 causing concentration-dependent AhR activation.

Causes of endocrine disrupting potencies in surface water in East China.

Surface water is essential for human health and ecological diversity, but some endocrine disrupting chemicals are detectable. Both thyroid receptor (TR) and androgen receptor (AR) agonistic/antagonistic potencies in grade II surface water in East China were investigated using reporter gene assays. While none of the water exhibited agonistic potency, significant AR and TR antagonistic potencies were detectable.

High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin)-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses.

Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.

The case for establishing a board of review for resolving environmental issues: The science court in Canada.

Technology and scientific advancements are accelerating changes in society at a pace that is challenging the abilities of government regulatory agencies and legal courts to understand the benefits and costs of these changes to humans, wildlife, and their environments. The social, economic, and political facets of concern, such as the potential effects of chemicals, complicate the preparation of regulatory standards and practices intended to safeguard the public. Court judges and attorneys and, in some cases, lay juries are tasked with interpreting the data and implications underlying these new advancements, often without the technical background necessary to understand complex subjects and subsequently make informed decisions.

Relative sensitivities among avian species to individual and mixtures of aryl hydrocarbon receptor-active compounds.

Dioxins and dioxin-like compounds (DLCs) are potent toxicants to most vertebrates. Sensitivities to DLCs vary among species. In the present study, the sensitivities of avian species (chicken [Gallus gallus], ring-necked pheasant [Phasianus colchicus], and Japanese quail [Coturnix japonica]) to some polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) were determined by using species-specific, in vitro, transactivation assays based on a luciferase reporter gene under control of species-specific aryl hydrocarbon receptors.

Loss of Hif-2α Rescues the Hif-1α Deletion Phenotype of Neonatal Respiratory Distress In Mice.

Hypoxia is a state of decreased oxygen reaching the tissues of the body. During prenatal development, the fetus experiences localized occurrences of hypoxia that are essential for proper organogenesis and survival. The response to decreased oxygen availability is primarily regulated by hypoxia-inducible factors (HIFs), a family of transcription factors that modulate the expression of key genes involved in glycolysis, angiogenesis, and erythropoiesis.

Bioaccessibility of AhR-active PAHs in sediments contaminated by the Hebei Spirit oil spill: Application of Tenax extraction in effect-directed analysis.

Bioaccessibility of toxic substances in sedimentary residual oil is a crucial factor that needs to be considered for accurate risk assessments posed by oil spills. However, information on oil weathering processes and bioaccessibility of residual oil is often not sufficient and clear. In the present study, bioaccessibility of aryl hydrocarbon receptor (AhR)-active polycyclic aromatic hydrocarbons (PAHs) in coastal sediments near the site of the Hebei Spirit oil spill (Korea, 2007) was assessed by Tenax extraction in effect-directed analysis (EDA).

Effects of environmentally-relevant mixtures of four common organophosphorus insecticides on the honey bee (Apis mellifera L.).

We assessed whether exposure to environmentally-relevant mixtures of four organophosphorus insecticides (OPs) exerted adverse effects on honey bees. Adult and worker bees were orally exposed for five days under laboratory conditions to mixtures of four insecticides, diazinon, malathion, profenofos and chlorpyrifos at two concentrations. Concentration in the mixtures tested were equivalent to the median and 95th centile concentrations of the OPs in honey, as reported in the literature.

Effects-Directed Analysis of Dissolved Organic Compounds in Oil Sands Process-Affected Water.

Acute toxicity of oil sands process-affected water (OSPW) is caused by its complex mixture of bitumen-derived organics, but the specific chemical classes that are most toxic have not been demonstrated. Here, effects-directed analysis was used to determine the most acutely toxic chemical classes in OSPW collected from the world's first oil sands end-pit lake. Three sequential rounds of fractionation, chemical analysis (ultrahigh resolution mass spectrometry), and acute toxicity testing (96 h fathead minnow embryo lethality and 15 min Microtox bioassay) were conducted.

Untargeted Identification of Organo-Bromine Compounds in Lake Sediments by Ultrahigh-Resolution Mass Spectrometry with the Data-Independent Precursor Isolation and Characteristic Fragment Method.

While previous studies have found that unknown natural and synthetic organo-bromine compounds (NSOBCs) contributed more than 99% of the total organic bromine (Br) in the environment, there was no efficient method for untargeted screening to identify NSOBCs in environmental matrixes. A novel untargeted method for identifying NSOBCs, based on ultrahigh-resolution mass spectrometry (UHRMS) with the Q Exactive instrument was developed. This method included a data-independent precursor isolation and characteristic fragment (DIPIC-Frag) procedure to identify NSOBCs.

Atrazine-Mediated Disruption of Steroidogenesis in BLTK1 Murine Leydig Cells.

Atrazine (ATR) is a broad-spectrum triazine herbicide that disrupts steroidogenesis resulting in reproductive and developmental toxicity at high doses. Mouse BLTK1 Leydig cells were used as a steroidogenic model to investigate the effects of ATR on testosterone (T) biosynthesis. Induction of steroidogenesis by 3 ng/ml recombinant human chorionic gonadotropin (rhCG) induced intracellular 3',5' cyclic adenosine monophosphate (cAMP) approximately 20-fold and T approximately 3-fold at 4 h.

Comparison of arsenic and antimony biogeochemical behavior in water, soil and tailings from Xikuangshan, China.

Although similar geochemical behaviors of arsenic (As) and antimony (Sb) in the environment has been assumed and widely reported, growing evidence suggests the two elements cannot, under some conditions, be assumed to behave similarly. In this four-year study (samples collected in each year), comparative investigation of the biogeochemistry of As and Sb in water/fish, soil/vegetable, tailings/plant samples were carried out at the world's largest active Sb mine area (Xikuangshan, China). Depending on duration the tailings had been stacked, significant differences in spatial distributions between As and Sb were found, and these were associated with change in pH over time.

Bioaccumulation and molecular effects of sediment-bound metals in zebrafish embryos.

Predicting the bioavailability and effects of metals in sediments is of major concern in context with sediment risk assessment. This study aimed to investigate the bioavailability and molecular effects of metals spiked into riverine sediments to zebrafish (Danio rerio) embryos. Embryos were exposed to a natural and an artificial sediment spiked with cadmium (Cd), copper (Cu), nickel (Ni) and zinc (Zn) individually or as a mixture at concentrations ranging from 150 to 3000 mg/kg dry weight (dw) over 48 h, and uptake of metals was determined.

Macrophage depletion lowers blood pressure and restores sympathetic nerve α2-adrenergic receptor function in mesenteric arteries of DOCA-salt hypertensive rats.

We tested the hypothesis that vascular macrophage infiltration and O2 (-) release impairs sympathetic nerve α2-adrenergic autoreceptor (α2AR) function in mesenteric arteries (MAs) of DOCA-salt hypertensive rats. Male rats were uninephrectomized or sham operated (sham). DOCA pellets were implanted subcutaneously in uninephrectomized rats who were provided high-salt drinking water or high-salt water with apocynin.

Murine Anorectic Response to Deoxynivalenol (Vomitoxin) Is Sex-Dependent.

Deoxynivalenol (DON, vomitoxin), a common trichothecene mycotoxin found in cereal foods, dysregulates immune function and maintenance of energy balance. The purpose of this study was to determine if sex differences are similarly evident in DON's anorectic responses in mice. A bioassay for feed refusal, previously developed by our lab, was used to compare acute i.

Measured and predicted affinities of binding and relative potencies to activate the AhR of PAHs and their alkylated analogues.

Polycyclic aromatic hydrocarbons (PAHs) and their alkylated forms are important components of crude oil. Both groups of PAHs have been reported to cause dioxin-like responses, mediated by aryl hydrocarbon receptor (AhR). Thus, characterization of binding affinity to the AhR of unsubstituted or alkylated PAHs is important to understand the toxicological consequences of oil contamination on ecosystems.

Hypoxia Inducible Factors Modulate Mitochondrial Oxygen Consumption and Transcriptional Regulation of Nuclear-Encoded Electron Transport Chain Genes.

Hypoxia inducible factor-1 (HIF1) is a stress-responsive nuclear transcription factor that is activated with a decrease in oxygen availability. HIF1 regulates the expression of genes involved in a cell's adaptation to hypoxic stress, including those with mitochondrial specific function. To gain a more comprehensive understanding of the role of HIF1 in mitochondrial homeostasis, we studied the link between hypoxia, HIF1 transactivation, and electron transport chain (ETC) function.

Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model.

Unlabelled: Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms.

Contributions of nonhematopoietic cells and mediators to immune responses: implications for immunotoxicology.

Immunotoxicology assessments have historically focused on the effects that xenobiotics exhibit directly on immune cells. These studies are invaluable as they identify immune cell targets and help characterize mechanisms and/or adverse outcome pathways of xenobiotics within the immune system. However, leukocytes can receive environmental cues by cell-cell contact or via released mediators from cells of organs outside of the immune system.

Silica Triggers Inflammation and Ectopic Lymphoid Neogenesis in the Lungs in Parallel with Accelerated Onset of Systemic Autoimmunity and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse.

Genetic predisposition and environmental factors influence the development of human autoimmune disease. Occupational exposure to crystalline silica (cSiO2) has been etiologically linked to increased incidence of autoimmunity, including systemic lupus erythematosus (SLE), but the underlying mechanisms are poorly understood. The purpose of this study was to test the hypothesis that early repeated short-term cSiO2 exposure will modulate both latency and severity of autoimmunity in the lupus-prone female NZBWF1 mouse.

RNA-Seq versus oligonucleotide array assessment of dose-dependent TCDD-elicited hepatic gene expression in mice.

Background: Dose-dependent differential gene expression provides critical information required for regulatory decision-making. The lower costs associated with RNA-Seq have made it the preferred technology for transcriptomic analysis. However, concordance between RNA-Seq and microarray analyses in dose response studies has not been adequately vetted.

Cytotoxic Synergy Between Cytokines and NSAIDs Associated With Idiosyncratic Hepatotoxicity Is Driven by Mitogen-Activated Protein Kinases.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequent causes of idiosyncratic, drug-induced liver injury (IDILI). Mechanisms of IDILI are unknown, but immune responses are suspected to underlie them. In animal models of IDILI, the cytokines tumor necrosis factor-alpha (TNFα) and interferon-gamma (IFNγ) are essential to the pathogenesis.

Organobromine compound profiling in human adipose: Assessment of sources of bromophenol.

Bromophenols (BRPs) have been widely detected in human tissues, however, relative proportions from natural products and/or anthropogenic flame retardants are not clear. 21 polybrominated diphenyl ethers (PBDEs), 15 MeO/OH-PBDEs, and 10 BRPs were simultaneously quantified in adipose collected from people from New York City, USA. An in vitro assay utilizing human liver microsomes was performed for detected predominant organobromine.

Comparison of Anorectic Potencies of the Trichothecenes T-2 Toxin, HT-2 Toxin and Satratoxin G to the Ipecac Alkaloid Emetine.

Trichothecene mycotoxins, potent translational inhibitors that are associated with human food poisonings and damp-building illnesses, are of considerable concern to animal and human health. Food refusal is a hallmark of exposure of experimental animals to deoxynivalenol (DON) and other Type B trichothecenes but less is known about the anorectic effects of foodborne Type A trichothecenes (e.g.