Disposition and Metabolomic Effects of 2,2',5,5'-Tetrachlorobiphenyl in Female Rats Following Intraperitoneal Exposure.

Unlabelled: The disposition and toxicity of lower chlorinated PCBs (LC-PCBs) with less than five chlorine substituents have received little attention. This study characterizes the distribution and metabolomic effects of PCB 52, an LC-PCB found in indoor and outdoor air, three weeks after intraperitoneal exposure of female Sprague Dawley rats to 0, 1, 10, or 100 mg/kg BW. PCB 52 exposure did not affect overall body weight.

Disposition and metabolomic effects of 2,2',5,5'-tetrachlorobiphenyl in female rats following intraperitoneal exposure.

The disposition and toxicity of lower chlorinated PCBs (LC-PCBs) with less than five chlorine substituents have received little attention. This study characterizes the distribution and metabolomic effects of PCB 52, an LC-PCB found in indoor and outdoor air, three weeks after intraperitoneal exposure of female Sprague Dawley rats to 0, 1, 10, or 100 mg/kg BW. PCB 52 exposure did not affect overall body weight.

A systematic evidence map for the evaluation of noncancer health effects and exposures to polychlorinated biphenyl mixtures.

Assessing health outcomes associated with exposure to polychlorinated biphenyls (PCBs) is important given their persistent and ubiquitous nature. PCBs are classified as a Group 1 carcinogen, but the full range of potential noncancer health effects from exposure to PCBs has not been systematically summarized and evaluated. We used systematic review methods to identify and screen the literature using combined manual review and machine learning approaches.

Dataset of transcriptomic changes that occur in human preadipocytes over a 3-day course of exposure to 3,3',4,4',5-Pentachlorobiphenyl (PCB126).

Exposure to polychlorinated biphenyls (PCBs) has been associated with the development of metabolic syndrome, a cluster of diseases that includes obesity, diabetes, liver steatosis, and cardiovascular problems. PCBs accumulate and fat and are known to act on adipocytes and their precursors, termed preadipocytes. The PCB congener, PCB126, has been shown to activate the aryl hydrocarbon receptor (AhR) as well as proinflammatory genes.

Transcriptome sequencing of 3,3',4,4',5-Pentachlorobiphenyl (PCB126)-treated human preadipocytes demonstrates progressive changes in pathways associated with inflammation and diabetes.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that accumulate in adipose tissue and have been associated with cardiometabolic disease. We have previously demonstrated that exposure of human preadipocytes to the dioxin-like PCB126 disrupts adipogenesis via the aryl hydrocarbon receptor (AhR). To further understand how PCB126 disrupts adipose tissue cells, we performed RNAseq analysis of PCB126-treated human preadipocytes over a 3-day time course.

PCB126 induced toxic actions on liver energy metabolism is mediated by AhR in rats.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in the regulation of biological responses to more planar aromatic hydrocarbons, like TCDD. We previously described the sequence of events following exposure of male rats to a dioxin-like polychlorinated biphenyl (PCB) congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), that binds avidly to the AhR and causes various types of toxicity including metabolic syndrome, fatty liver, and disruption of energy homeostasis. The purpose of this study was, to investigate the role of AhR to mediate those toxic manifestations following sub-acute exposure to PCB126 and to examine possible sex differences in effects.

Human hepatic microsomal sulfatase catalyzes the hydrolysis of polychlorinated biphenyl sulfates: A potential mechanism for retention of hydroxylated PCBs.

Polychlorinated biphenyls (PCBs) are persistent environmental contaminants that continue to be of concern due to their varied toxicities. Upon human exposure, many PCBs with lower numbers of chlorine atoms are metabolized to hydroxylated derivatives (OH-PCBs), and cytosolic sulfotransferases can subsequently catalyze the formation of PCB sulfates. Recent studies have indicated that PCB sulfates bind reversibly with a high affinity to human serum proteins, and that they are also taken up by cells and tissues.

The Aryl hydrocarbon receptor mediates reproductive toxicity of polychlorinated biphenyl congener 126 in rats.

Polychlorinated biphenyls (PCBs) are endocrine disrupting chemicals with documented, though mechanistically ill-defined, reproductive toxicity. The toxicity of dioxin-like PCBs, such as PCB126, is mediated via the aryl hydrocarbon receptor (AHR) in non-ovarian tissues. The goal of this study was to examine the uterine and ovarian effects of PCB126 and test the hypothesis that the AHR is required for PCB126-induced reproductive toxicity.

Comprehensive Subchronic Inhalation Toxicity Assessment of an Indoor School Air Mixture of PCBs.

Few inhalation studies have explored the toxicity of environmentally relevant mixtures of polychlorinated biphenyls (PCBs). The manufacture of industrial PCBs was banned in 1978, but PCBs continue to be formed in industrial and consumer products. Schools represent a significant source of airborne exposures to legacy and nonlegacy PCBs, placing children at risk.

Cardiovascular Effects of Polychlorinated Biphenyls and Their Major Metabolites.

Background: Xenobiotic metabolism is complex, and accounting for bioactivation and detoxification processes of chemicals remains among the most challenging aspects for decision making with new approach methods data.

Objectives: Considering the physiological relevance of human organotypic culture models and their utility for high-throughput screening, we hypothesized that multidimensional chemical-biological profiling of chemicals and their major metabolites is a sensible alternative for the toxicological characterization of parent molecules vs. metabolites .

Skeletal Toxicity of Coplanar Polychlorinated Biphenyl Congener 126 in the Rat Is Aryl Hydrocarbon Receptor Dependent.

Epidemiological evidence links polychlorinated biphenyls (PCBs) to skeletal toxicity, however mechanisms whereby PCBs affect bone are poorly studied. In this study, coplanar PCB 126 (5 μmol/kg) or corn oil vehicle was administered to N = 5 and 6 male and female, wild type (WT) or AhR -/- rats via intraperitoneal injection. Animals were sacrificed after 4 weeks.

Skeletal toxicity resulting from exposure of growing male rats to coplanar PCB 126 is associated with disruption of calcium homeostasis and the GH-IGF-1 axis and direct effects on bone formation.

Skeletal toxicity has been reported following exposure to polychlorinated biphenyl (PCB) mixtures. However, molecular mechanisms remain poorly understood. We exposed groups of male 4-5-week-old Sprague-Dawley rats to 3,3', 4, 4', 5-pentachlorobiphenyl (PCB 126), a dioxin-like coplanar PCB congener by a single i.

PCB126 blocks the thermogenic beiging response of adipocytes.

Subcutaneous white adipose tissue is capable of becoming thermogenic in a process that is referred to as "beiging." Beiging is associated with activation of the uncoupling protein, UCP1, and is known to be important for preventing adipose hypertrophy and development of insulin resistance. Polychlorinated biphenyls (PCBs) accumulate in fat, and it is hypothesized that disruption of adipogenesis and adipocyte function by PCBs may be causative in the development of obesity and diabetes.

Hydroxylated and sulfated metabolites of commonly observed airborne polychlorinated biphenyls display selective uptake and toxicity in N27, SH-SY5Y, and HepG2 cells.

Although neurotoxicity and hepatotoxicity have long been associated with exposure to polychlorinated biphenyls (PCBs), less is known about the selective toxicity of those hydroxylated PCBs (OH-PCBs) and PCB sulfates that are metabolites derived from exposure to PCBs found in indoor air. We have examined the toxicity of OH-PCBs and PCB sulfates derived from PCBs 3, 8, 11, and 52 in two neural cell lines (N27 and SH-SY5Y) and an hepatic cell line (HepG2). With the exception of a similar toxicity seen for N27 cells exposed to either OH-PCB 52 or PCB 52 sulfate, these OH-PCBs were more toxic to all three cell-types than their corresponding PCB or PCB sulfate congeners.

PCB126 Inhibits the Activation of AMPK-CREB Signal Transduction Required for Energy Sensing in Liver.

3,3',4,4',5-pentachlorobiphenyl (PCB126), a dioxin-like PCB, elicits toxicity through a wide array of noncarcinogenic effects, including metabolic syndrome, wasting, and nonalcoholic fatty-liver disease. Previously, we reported decreases in the transcription of several enzymes involved in gluconeogenesis, before the early onset of lipid accumulation. Hence, this study was aimed at understanding the impact of resultant decreases gluconeogenic enzymes on growth, weight, and metabolism in the liver, upon extended exposure.

Hydroxylated and sulfated metabolites of commonly occurring airborne polychlorinated biphenyls inhibit human steroid sulfotransferases SULT1E1 and SULT2A1.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that are associated with varied adverse health effects. Lower chlorinated PCBs are prevalent in indoor and outdoor air and can be metabolized to their hydroxylated derivatives (OH-PCBs) followed by sulfation to form PCB sulfates. Sulfation is also a means of signal termination for steroid hormones.

Authentication of synthetic environmental contaminants and their (bio)transformation products in toxicology: polychlorinated biphenyls as an example.

Toxicological studies use "specialty chemicals" and, thus, should assess and report both identity and degree of purity (homogeneity) of the chemicals (or toxicants) under investigation to ensure that other scientists can replicate experimental results. Although detailed reporting criteria for the synthesis and characterization of organic compounds have been established by organic chemistry journals, such criteria are inconsistently applied to the chemicals used in toxicological studies. Biologically active trace impurities may lead to incorrect conclusions about the chemical entity responsible for a biological response, which in turn may confound risk assessment.

Spatial distribution of metals within the liver acinus and their perturbation by PCB126.

Animal studies show that exposure to the environmental pollutant 3,3',4,4',5-pentachlorobiphenyl (PCB126) causes alterations in hepatic metals as measured in acid-digested volume-adjusted tissue. These studies lack the detail of the spatial distribution within the liver. Here we use X-ray fluorescence microscopy (XFM) to assess the spatial distribution of trace elements within liver tissue.

Sources and toxicities of phenolic polychlorinated biphenyls (OH-PCBs).

Polychlorinated biphenyls (PCBs), a group of 209 congeners that differ in the number and position of chlorines on the biphenyl ring, are anthropogenic chemicals that belong to the persistent organic pollutants (POPs). For many years, PCBs have been a topic of interest because of their biomagnification in the food chain and their environmental persistence. PCBs with fewer chlorine atoms, however, are less persistent and more susceptible to metabolic attack, giving rise to chemicals characterized by the addition of one or more hydroxyl groups to the chlorinated biphenyl skeleton, collectively known as hydroxylated PCBs (OH-PCBs).

A delayed proinflammatory response of human preadipocytes to PCB126 is dependent on the aryl hydrocarbon receptor.

Inflammation in adipose tissue is recognized as a causative factor in the development of type II diabetes. Adipocyte hypertrophy as well as bacterial and environmental factors have been implicated in causing inflammation in mature adipocytes. Exposure to persistent organic pollutants such as polychlorinated biphenyls (PCBs) has been associated with the development of type II diabetes.

Population Structure and Phylogenetic Relationships in a Diverse Panel of L.

The crop species L. has significant economic importance around the world. However, the global distribution and complex evolutionary history of the species has made investigating its genetic population structure difficult.

Polychlorinated biphenyls target Notch/Dll and VEGF R2 in the mouse placenta and human trophoblast cell lines for their anti-angiogenic effects.

The intrauterine environment is particularly vulnerable to environmental exposures. We previously established a mouse model that provided evidence for pregnancy complications and placental anti-angiogenesis in response to Aroclor 1254 (A-1254), a mixture of polychlorinated biphenyls (PCBs). Importantly, these effects were observed in IL-10, but not wild type, mice, suggesting that IL-10 deficiency predisposes to pregnancy disruptive effects of environmental toxicants.

Identification of a sulfate metabolite of PCB 11 in human serum.

Despite increasing evidence for a major role for sulfation in the metabolism of lower-chlorinated polychlorinated biphenyls in vitro and in vivo, and initial evidence for potential bioactivities of the resulting sulfate ester metabolites, the formation of PCB sulfates in PCB exposed human populations had not been explored. The primary goal of this study was to determine if PCB sulfates, and potentially other conjugated PCB derivatives, are relevant classes of PCB metabolites in the serum of humans with known exposures to PCBs. In order to detect and quantify dichlorinated PCB sulfates in serum samples of 46 PCB-exposed individuals from either rural or urban communities, we developed a high-resolution mass spectrometry-based protocol using 4-PCB 11 sulfate as a model compound.