Ethyltoluenes Regulate Inflammatory and Cell Fibrosis Signaling in the Liver Cell Model.

Crude oil naphtha fraction C9 alkylbenzenes consist of trimethylbenzenes, ethyltoluenes, cumene, and n-propylbenzene. The major fraction of C9 alkylbenzenes is ethyltoluenes (ETs) consisting of three isomers: 2-ethyltoluene (2-ET), 3-ethyltoluene (3-ET), and 4-ethyltoluene (4-ET). Occupational and environmental exposure to ETs can occur via inhalation and ingestion and cause several health problems.

Review of per- and poly-fluoroalkyl treatment in combustion-based thermal waste systems in the United States.

Per- and poly-fluoroalkyl substances (PFAS) are a class of synthetic chemicals known for their widespread presence and environmental persistence. Carbon-fluorine (C-F) bonds are major components among PFAS and among the strongest organic bonds, thus destroying PFAS may present significant challenge. Thermal treatment such as incineration is an effective and approved method for destroying many halogenated organic chemicals.

Cadmium modulates steatosis, fibrosis, and oncogenic signaling in liver cancer cells by activating notch and AKT/mTOR pathways.

Cadmium (Cd) is an environmental pollutant that increases hepatotoxicity and the risk of liver diseases. In the current study, we investigated the effect of a physiologically relevant, low concentration of Cd on the regulation of liver cancer cell proliferation, steatosis, and fibrogenic/oncogenic signaling. Exposure to low concentrations of Cd increased endogenous reactive oxygen species (ROS) production and enhanced cell proliferation in a human bipotent progenitor cell line HepaRG and hepatocellular carcinoma (HCC) cell lines.

Per- and Polyfluoroalkyl Substances (PFASs) in Airborne Particulate Matter (PM) Emitted During Floor Waxing: A Pilot Study.

Per- and polyfluoroalkyl substances (PFASs), with their water- and heat-resistant properties, have been widely used in industrial and consumer products, including floor waxes. Adverse health effects are associated with PFAS exposures (e.g.

Double-Blind, Randomized Clinical Trial Comparing One Percent Buffered Versus Two Percent Unbuffered Lidocaine Injections in Children.

Buffered local anesthetics offer an alternative to conventional, unbuffered anesthetic formulations; however, evidence about their use in children is scant. The purpose of this study was to determine the anesthetic and physiologic differences associated with the use of buffered one percent and unbuffered two percent lidocaine (both with 1:100,000 epinephrine) in children. In this randomized, double-blinded, crossover study, 25 children ages 10 to 12 years old received two inferior alveolar never blocks, at least one week apart, randomized to alternating sequences of two drug formulations: (1) formula A-three mL buffered one percent lidocaine (i.

Gut Microbiome Toxicity: Connecting the Environment and Gut Microbiome-Associated Diseases.

The human gut microbiome can be easily disturbed upon exposure to a range of toxic environmental agents. Environmentally induced perturbation in the gut microbiome is strongly associated with human disease risk. Functional gut microbiome alterations that may adversely influence human health is an increasingly appreciated mechanism by which environmental chemicals exert their toxic effects.

Isomer-selective biodegradation of high-molecular-weight azaarenes in PAH-contaminated environmental samples.

Polycyclic aromatic nitrogen heterocycles, or azaarenes, normally co-occur with polycyclic aromatic hydrocarbons (PAHs) in contaminated soils. We recently reported that nontarget analysis using high resolution mass spectrometry of samples from four PAH-contaminated sites revealed a previously unrecognized diversity and abundance of azaarene isomers and their methylated derivatives. Here we evaluated their biodegradability by natural microbial communities from each site in aerobic microcosm incubations under biostimulated conditions.

Population-Based Analysis of DNA Damage and Epigenetic Effects of 1,3-Butadiene in the Mouse.

Metabolism of 1,3-butadiene, a known human and rodent carcinogen, results in formation of reactive epoxides, a key event in its carcinogenicity. Although mice exposed to 1,3-butadiene present DNA adducts in all tested tissues, carcinogenicity is limited to liver, lung, and lymphoid tissues. Previous studies demonstrated that strain- and tissue-specific epigenetic effects in response to 1,3-butadiene exposure may influence susceptibly to DNA damage and serve as a potential mechanism of tissue-specific carcinogenicity.

Evaluation of inhaled low-dose formaldehyde-induced DNA adducts and DNA-protein cross-links by liquid chromatography-tandem mass spectrometry.

As a widespread industrial chemical, formaldehyde carcinogenicity has been highly controversial. Meanwhile, formaldehyde is an essential metabolite in all living cells. Previously, we have demonstrated exogenous formaldehyde causes DNA adducts in a nonlinear manner between 0.

Sex-specific differences in genotoxic and epigenetic effects of 1,3-butadiene among mouse tissues.

Exposure to environmental chemicals has been shown to have an impact on the epigenome. One example is a known human carcinogen 1,3-butadiene which acts primarily by a genotoxic mechanism, but also disrupts the chromatin structure by altering patterns of cytosine DNA methylation and histone modifications. Sex-specific differences in 1,3-butadiene-induced genotoxicity and carcinogenicity are well established; however, it remains unknown whether 1,3-butadiene-associated epigenetic alterations are also sex dependent.

Development of a hydrophilic interaction liquid chromatography (HILIC) method for the chemical characterization of water-soluble isoprene epoxydiol (IEPOX)-derived secondary organic aerosol.

Acid-catalyzed multiphase chemistry of isoprene epoxydiols (IEPOX) on sulfate aerosol produces substantial amounts of water-soluble secondary organic aerosol (SOA) constituents, including 2-methyltetrols, methyltetrol sulfates, and oligomers thereof in atmospheric fine particulate matter (PM2.5). These constituents have commonly been measured by gas chromatography interfaced to electron ionization mass spectrometry (GC/EI-MS) with prior derivatization or by reverse-phase liquid chromatography interfaced to electrospray ionization high-resolution mass spectrometry (RPLC/ESI-HR-MS).

Tracing the Biotransformation of Polycyclic Aromatic Hydrocarbons in Contaminated Soil Using Stable Isotope-Assisted Metabolomics.

Biotransformation of organic pollutants may result in the formation of oxidation products more toxic than the parent contaminants. However, to trace and identify those products, and the metabolic pathways involved in their formation, is still challenging within complex environmental samples. We applied stable isotope-assisted metabolomics (SIAM) to PAH-contaminated soil collected from a wood treatment facility.

Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription.

Epigenetic effects of environmental chemicals are under intense investigation to fill existing knowledge gaps between environmental/occupational exposures and adverse health outcomes. Chromatin accessibility is one prominent mechanism of epigenetic control of transcription, and understanding of the chemical effects on both could inform the causal role of epigenetic alterations in disease mechanisms. In this study, we hypothesized that baseline variability in chromatin organization and transcription profiles among various tissues and mouse strains influence the outcome of exposure to the DNA damaging chemical 1,3-butadiene.

Trisaminohexyl isocyanurate, a urinary biomarker of HDI isocyanurate exposure.

Biological monitoring of occupational exposure to 1,6-hexamethylene diisocyanate (HDI)-containing spray-paints is limited to analysis of metabolites of HDI monomer although polymeric HDI isocyanurate constitutes the predominant inhalation and skin exposure for workers in the automotive paint industry. A novel method using nanoflow ultra-performance liquid chromatography coupled to nano-electrospray ionization tandem mass spectrometry (nano-UPLC-ESI-MS/MS) was developed to quantify trisaminohexyl isocyanurate (TAHI), a hydrolysis product of HDI isocyanurate, in the urine of spray-painters. Analytical and internal standards were synthesized in-house and weighted linear regression calibration curves were generated using spiked control urine from non-exposed persons (0.

Diversity and Abundance of High-Molecular-Weight Azaarenes in PAH-Contaminated Environmental Samples.

Azaarenes are N-heterocyclic polyaromatic pollutants that co-occur with polycyclic aromatic hydrocarbons (PAHs) in contaminated soils. Despite the known toxicity of some high-molecular-weight azaarenes, their diversity, abundance, and fate in contaminated soils remain to be elucidated. We applied high-resolution mass spectrometry and mass-defect filtering to four PAH-contaminated samples from geographically distant sites and detected 232 azaarene congeners distributed in eight homologous series, including alkylated derivatives and two hitherto unknown series.

Toxic metals in amniotic fluid and altered gene expression in cell-free fetal RNA.

Both exposures to toxic metals, as well as deficiencies in essential metals, during pregnancy has been linked to a variety of negative reproductive outcomes. The exact etiologies of such outcomes and the effects of fetal exposure to these metals are largely unknown. Therefore, the ability to assess levels of these elements is critical to determining the underlying causes of such conditions and the effects that both essential and nonessential metals have on fetal development.

Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene) in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene Transcription Profiles in C57BL/6J and CAST/EiJ Mice.

Background: The damaging effects of exposure to environmental toxicants differentially affect genetically distinct individuals, but the mechanisms contributing to these differences are poorly understood. Genetic variation affects the establishment of the gene regulatory landscape and thus gene expression, and we hypothesized that this contributes to the observed heterogeneity in individual responses to exogenous cellular insults.

Objectives: We performed an study of how genetic variation and chromatin organization may dictate susceptibility to DNA damage, and influence the cellular response to such damage, caused by an environmental toxicant.

Response of Posidonia oceanica seagrass and its epibiont communities to ocean acidification.

The unprecedented rate of CO2 increase in our atmosphere and subsequent ocean acidification (OA) threatens coastal ecosystems. To forecast the functioning of coastal seagrass ecosystems in acidified oceans, more knowledge on the long-term adaptive capacities of seagrass species and their epibionts is needed. Therefore we studied morphological characteristics of Posidonia oceanica and the structure of its epibiont communities at a Mediterranean volcanic CO2 vent off Panarea Island (Italy) and performed a laboratory experiment to test the effect of OA on P.

Editor's Highlight: Collaborative Cross Mouse Population Enables Refinements to Characterization of the Variability in Toxicokinetics of Trichloroethylene and Provides Genetic Evidence for the Role of PPAR Pathway in Its Oxidative Metabolism.

Background: Trichloroethylene (TCE) is a known carcinogen in humans and rodents. Previous studies of inter-strain variability in TCE metabolism were conducted in multi-strain panels of classical inbred mice with limited genetic diversity to identify gene-environment interactions associated with chemical exposure.

Objectives: To evaluate inter-strain variability in TCE metabolism and identify genetic determinants that are associated with TCE metabolism and effects using Collaborative Cross (CC), a large panel of genetically diverse strains of mice.

Measurement of Endogenous versus Exogenous Formaldehyde-Induced DNA-Protein Crosslinks in Animal Tissues by Stable Isotope Labeling and Ultrasensitive Mass Spectrometry.

DNA-protein crosslinks (DPC) arise from a wide range of endogenous and exogenous chemicals, such as chemotherapeutic drugs and formaldehyde. Importantly, recent identification of aldehydes as endogenous genotoxins in Fanconi anemia has provided new insight into disease causation. Because of their bulky nature, DPCs pose severe threats to genome stability, but previous methods to measure formaldehyde-induced DPCs were incapable of discriminating between endogenous and exogenous sources of chemical.

Placental Cadmium Levels Are Associated with Increased Preeclampsia Risk.

Environmental exposure to heavy metals is a potentially modifiable risk factor for preeclampsia (PE). Toxicologically, there are known interactions between the toxic metal cadmium (Cd) and essential metals such as selenium (Se) and zinc (Zn), as these metals can protect against the toxicity of Cd. As they relate to preeclampsia, the interaction between Cd and these essential metals is unknown.

Xenobiotic Metabolism in Mice Lacking the UDP-Glucuronosyltransferase 2 Family.

UDP-Glucuronosyltransferases (UGTs) conjugate a glucuronyl group from glucuronic acid to a wide range of lipophilic substrates to form a hydrophilic glucuronide conjugate. The glucuronide generally has decreased bioactivity and increased water solubility to facilitate excretion. Glucuronidation represents an important detoxification pathway for both endogenous waste products and xenobiotics, including drugs and harmful industrial chemicals.

Pharmaceutical occurrence in groundwater and surface waters in forests land-applied with municipal wastewater.

The occurrence and fate of pharmaceutical and personal care products in the environment are of increasing public importance because of their ubiquitous nature and documented effects on wildlife, ecosystems, and potentially humans. One potential, yet undefined, source of entry of pharmaceuticals into the environment is via the land application of municipal wastewater onto permitted lands. The objective of the present study is to determine the extent to which pharmaceuticals are mitigated by or exported from managed tree plantations irrigated with municipal wastewater.

The Contribution of Peroxisome Proliferator-Activated Receptor Alpha to the Relationship Between Toxicokinetics and Toxicodynamics of Trichloroethylene.

Exposure to the ubiquitous environmental contaminant trichloroethylene (TCE) is associated with cancer and non-cancer toxicity in both humans and rodents. Peroxisome proliferator-activated receptor-alpha (PPARα) is thought to be playing a role in liver toxicity in rodents through activation of the receptor by the TCE metabolite trichloroacetic acid (TCA). However, most studies using genetically altered mice have not assessed the potential for PPARα to alter TCE toxicokinetics, which may lead to differences in TCA internal doses and hence confound inferences as to the role of PPARα in TCE toxicity.