Download or read book Developmental Toxicity of Polycyclic Aromatic Hydrocarbons written by Britton C. Goodale and published by . This book was released on 2013 with total page 195 pages. Available in PDF, EPUB and Kindle. Book excerpt: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. Defining toxicity mechanisms for this large family of multi-ring structures and substituted derivatives is a substantial challenge. Several PAHs, such as benzo(a)pyrene (BaP), are mutagenic, toxic to wildlife, and classified as probable carcinogens to humans. PAHs are present in the environment both in the gaseous phase as well as associated with particulates, and exposures occur via complex mixtures; combustion emissions contain PAHs along with many other contaminants. Cardiac dysfunction and adverse birth outcomes associated with exposure to airborne PAHs suggest that this family of compounds may have non-mutagenic biological activities that affect human health. Some PAHs exert toxic effects via binding the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that mediates transcription of many downstream target genes, including cytochrome P450 metabolizing enzymes. Unlike planar halogenated hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), PAHs are readily metabolized by CYP1A, CYP1B1 and other enzymes, which create reactive intermediates and/or facilitate excretion. Mechanisms of PAH toxicity therefore include canonical AHR signaling, induction of oxidative stress, and other lesser-understood activities that do not require the AHR. We employed zebrafish as a model to rapidly assess developmental toxicity, global transcriptional responses and AHR activation in embryos exposed to parent and oxygenated PAHs (OPAHs). Using comparative analysis of mRNA expression profiles from microarrays with embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR), we identified expression biomarkers and disrupted biological processes that precede developmental abnormalities. These transcriptional responses were associated with PAH body burdens in the embryos detected by GC-MS. We found that uptake data were essential for discerning molecular pathways from dose-related differences, and identified two primary toxicity profiles. While BAA disrupted transcripts involved in vasculogenesis, DBT and PYR misregulated ion homeostasis and muscle-related genes. NfKB signaling was predicted to be involved in both responses, but canonical AHR signaling was only activated by BAA. In order to study the role of the AHR in mediating toxicity of PAHs, we developed an AHR2 mutant zebrafish line, which has a mutation in the transactivation domain of AHR2. We used AHR agonists TCDD and leflunomide as toxicological probes to characterize AHR activity in the mutant line, and determined that the mutants were functionally null. Finally, we used AHR2 deficient zebrafish embryos to investigate mechanisms by which two four-ring OPAHs induced developmental effects. 1,9 benz-10-anthrone (BEZO) and benz(a)anthracene-7,12-dione (7,12-B[a]AQ) both caused malformations in developing embryos, but they differentially induced CYP1A expression. Despite this difference, the toxicity produced from both compounds was AHR2-dependent. We used mRNA-seq to compare the transcriptional profiles of BEZO and 7,12-B[a]AQ, and identified transcriptional networks that will be investigated further to determine how ligands differentially modulate AHR activity. We also discovered novel transcripts that are potentially important mediators of AHR toxic effects. Comparison across all five parent and OPAHs highlighted clusters of genes that, surprisingly, were similarly expressed in response to the OPAHs, DBT and PYR. These commonly-regulated transcripts may be important to consider when investigating toxicity of PAH mixtures. Together, these studies show that PAHs act via different transcriptional mechanisms, but can be categorized based on transcriptional profiles and differential AHR activation. The clusters of transcripts identified may be involved in common pathways; further investigation of transcription factors and coactivators that interact with mixexpressed genes is a promising area of research for elucidating diverse functions of the AHR.
Download or read book Toxicological Profile for Polycyclic Aromatic Hydrocarbons written by and published by . This book was released on 1995 with total page 500 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Use of New Approach Methodologies to Study the Developmental Toxicity of Polycyclic Aromatic Hydrocarbons written by and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book WHO Guidelines for Indoor Air Quality written by and published by World Health Organization. This book was released on 2010 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents WHO guidelines for the protection of public health from risks due to a number of chemicals commonly present in indoor air. The substances considered in this review, i.e. benzene, carbon monoxide, formaldehyde, naphthalene, nitrogen dioxide, polycyclic aromatic hydrocarbons (especially benzo[a]pyrene), radon, trichloroethylene and tetrachloroethylene, have indoor sources, are known in respect of their hazardousness to health and are often found indoors in concentrations of health concern. The guidelines are targeted at public health professionals involved in preventing health risks of environmental exposures, as well as specialists and authorities involved in the design and use of buildings, indoor materials and products. They provide a scientific basis for legally enforceable standards.
Download or read book Mechanisms Underlying Synergistic Developmental Toxicity of Polycyclic Aromatic Hydrocarbons in Zebrafish written by Alicia Renee Vanston Timme-Laragy and published by . This book was released on 2007 with total page 442 pages. Available in PDF, EPUB and Kindle. Book excerpt: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants derived from the incomplete combustion of organics such as the burning of fossil fuels. Early life stages of fish are sensitive to the toxic effects of PAHs, which cause pericardial edema, craniofacial malformations, and other developmental abnormalities. PAHs in the environment exist as complex mixtures, and several PAHs can interact with a primary xenobiotic detoxification system, the aryl hydrocarbon receptor (AHR) pathway. Previous studies have shown that certain combinations of model PAHs result in synergistic rather than additive developmental toxicity in fish embryos. For example, co-exposure to the AHR agonist beta-naphthoflavone (BNF) and cytochrome P4501A (CYP1A) inhibitor alpha-naphthoflavone (ANF) demonstrate a very marked synergistic toxicity. Experiments conducted for this dissertation tested the hypotheses that this synergistic toxicity is mediated by the AHR pathway, and involves oxidative stress. Using zebrafish (Danio rerio) as a model organism, antisense morpholinos were used to knock down protein translation to investigate the roles of AHR2, CYP1A, and CYP1B1 in embryos exposed to combinations of BNF+ANF. Knock down of AHR2 rescued deformities in BNF+ANF co-exposures, indicating that toxicity is mediated by this receptor. Knock down of CYP1A enhanced toxicity of BNF alone and BNF+ANF co-exposures, thereby indicating a protective function for CYP1A. Studies including CYP1B1 knockdown alone and in combination with CYP1A knock down suggested that CYP1B1 does not have an important role in this synergistic toxicity. Analysis of gene expression of the AHR pathway using quantitative real-time PCR (QRT-PCR) showed that expression of AHR2 fit an additive model of induction by BNF and ANF. Several genes regulated by this receptor (cyp1a, cyp1b1, cyp1c1, ahrr2) were induced in a dose dependent manner by single compound exposures to BNF and to ANF, although BNF was substantially more potent than ANF as an AHR agonist. Interestingly, in the BNF+ANF co-exposures, these genes were synergistically induced to levels consistent with those observed with highest doses of BNF alone, suggesting the inhibitory action of ANF on CYP1A enzymatic activity (measured by ethoxyresorufin-O-deethylase activity), is altering metabolism and perhaps extending the half-life of the AHR agonist(s). To address the role of oxidative stress in this toxicity, QRT-PCR was used to examine changes in expression of the antioxidant genes Mnsod, CuZnsod, glutathione peroxidase 1, and glutathione cysteine-ligase, and the Phase II gene glutathione-s-transferase pi. These genes were significantly upregulated in the BNF+ANF co-exposures, indicative of redox fluctuations. Levels of gene induction were consistent with those observed in response to the model pro-oxidant tert-butyl hydroperoxide, which also upregulated expression of the DNA damage detector ataxia telangiectasia mutated. However, BNF+ANF co-exposure did not result in significant changes in total glutathione content, total oxyradical scavenging capacity, or DNA damage. Modulating redox status with antioxidants Vitamins C and E, and N-acetyl cysteine did not reduce deformities, nor did glutathione depletion with buthionine sulfoxamine worsen deformities. Knock down of the antioxidant response element transcription factor NRF2 showed a potential protective role against this toxicity, although further experiments and controls are needed. While these experiments have shown that the synergistic toxicity of BNF+ANF is mediated by AHR2, other potential mechanisms exist. For example, oxidative stress is a possible mediator; however, its role remains unclear. As current models of PAH risk assessment utilize additive models of risk, understanding the mechanisms of synergistic toxicity of PAH mixtures will assist risk assessors in developing more robust, mechanistic-based tools.
Download or read book The Role of Polycyclic Aromatic Hydrocarbons in Developmental Toxicity of Petroleum Substances written by and published by . This book was released on 2019 with total page 287 pages. Available in PDF, EPUB and Kindle. Book excerpt: cum laude graduation
Download or read book Provisional Guidance for Quantitative Risk Assessment of Polycyclic Aromatic Hydrocarbons written by and published by . This book was released on 1993 with total page 28 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book PAHs written by Peter E. T. Douben and published by John Wiley & Sons. This book was released on 2003-07-25 with total page 404 pages. Available in PDF, EPUB and Kindle. Book excerpt: Polycyclic aromatic hydrocarbons (PAHs), or polyarenes, are one of the largest and most structurally diverse class of organic molecules known. High percentages of polyarenes, representing a wide range of molecular sizes and structural types, are present in coal tars and petroleum residues. The major sources of PAHs are crude oil, coal and oil shale. The fuels produced from these fossil sources constitute the primary source of energy for the industrial nations of the world, and the petrochemicals from these raw materials are the basis of the synthetic fibre and plastics industries. PAHs are however, widespread pollutants and their impact on the environment and human health must be monitored and controlled. This book will review and assess our scientific understanding of the ecological exposure and effects PAHs have in different environments and habitats. It will accomplish this by taking the recipients of the pollution in the environment as starting points and working its way back through pathways to access what is required for our understanding of effects and rationale for control. Although this book will concentrate on ecological exposure of PAHs, the general impacts of PAHs on human populations will be touched upon. It is thought to be the first book to focus on the ecological aspects of PAHs.
Download or read book Utilization of the Zebrafish Model for Investigating Nitrated Polycyclic Aromatic Hydrocarbon Developmental Toxicity written by Anna C. Chlebowski and published by . This book was released on 2017 with total page 205 pages. Available in PDF, EPUB and Kindle. Book excerpt: Polycyclic aromatic hydrocarbons (PAHs) are among the most widely known and studied environmental contaminants, originating from a range of natural and anthropogenic sources. PAHs are known to occur in the environment as complex mixtures, containing both unsubstituted PAHs, as well as a range of PAH derivatives. Among the less-studied of these derivative PAH classes are nitrated PAHs (NPAHs). NPAHs are known to form from atmospheric reactions with PAHs and can be found in the environment in a variety of matrices. Many NPAHs are known to be mutagenic, in some cases more so than the corresponding unsubstituted PAH. Less is known about the toxicity of NPAHs in whole-animal systems and for non-cancer endpoints, in particular with regard to the developmental toxicity and metabolism across a wide number of NPAH compounds, in a consistent model system. One of the major challenges in studying PAHs, and related compounds, is the high hydrophobicity and low water solubility of these compounds, which can result in losses due to partitioning of the analytes out of the aqueous phase and on to the walls of the container or exposure vessel. Numerous in vitro and in vivo models utilize plastic plates as exposure vessels, including the use of polystyrene 96-well plates for developmental toxicity testing in the developing zebrafish (Danio rerio) model. We directly measured the losses which occur due to sorption to the polystyrene plates during zebrafish testing for a set of PAHs and NPAHs. Sorptive losses in some instances were greater than fifty percent, in particular for the lower of the two exposure concentrations tested. These sorptive losses decrease the concentration of chemical available to the zebrafish embryos, and therefore impact the interpretation of dose-response toxicity data. In an attempt to create a predictive model for sorptive losses, the measured sorption was modeled against the log K[subscript ow], molecular weight, and subcooled liquid solubilities of the corresponding compounds. The correlations between subcooled liquid solubility and PAH sorption was statistically significant (p
Download or read book Polycyclic Aromatic Hydrocarbons written by and published by National Academies. This book was released on 1983-01-01 with total page 486 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Mixture Toxicity written by Cornelis A. M. van Gestel and published by CRC Press. This book was released on 2016-04-19 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the last decade and a half, great progress has been made in the development of concepts and models for mixture toxicity, both in human and environmental toxicology. However, due to their different protection goals, developments have often progressed in parallel but with little integration. Arguably the first book to clearly link ecotoxicology an
Download or read book Polycyclic aromatic compounds PACs in oily wastewater from shipping with a focus on scrubber water written by Magnusson, Kerstin and published by Nordic Council of Ministers. This book was released on with total page 62 pages. Available in PDF, EPUB and Kindle. Book excerpt: Available online: https://pub.norden.org/temanord2023-550/ To reduce emissions of hazardous combustion gases to air, ship owners can switch to cleaner fuels or install so called “scrubbers”, onboard the ship. In a scrubber, combustions gases are sprayed with water and the dirty wash water, the scrubber water, is discharged to the sea. The number of ships with scrubbers and the volumes of discharged scrubber water have increased dramatically the past decade. When allowing the use of scrubbers, the focus was on improving the air quality, while the impact on the marine environment was not considered. We have here analysed polycyclic aromatic compounds (PACs), the most toxic fraction of oil, in scrubber water from ships, and reviewed recent ecotoxicological scientific literature on PAC toxicity to marine organisms. Our conclusion is that in areas with intense shipping there is a serious risk for negative effects on marine organisms.
Download or read book The Carcinogenic Effects Of Polycyclic Aromatic Hydrocarbons written by Andreas Luch and published by World Scientific. This book was released on 2005-08-22 with total page 514 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides an overview on the molecular mode of action of carcinogenic polycyclic aromatic hydrocarbons (PAHs). PAHs are by-products arising from incomplete combustion of organic matter that are frequently released into our environment, and thus are ubiquitously detectable. Many PAHs are strong carcinogens in rodent bioassays and have been linked to increased incidences of various types of cancer in humans. The present book covers all aspects of PAH-induced carcinogenesis; it is a collection of articles written by some of the most recognizable PAH researchers, reviewing the present knowledge in this field. The topics include: exposure to and biomonitoring of PAHs in the human population; metabolic activation of PAHs; genotoxicity and repair of PAH-induced DNA damage; and factors modulating individual susceptibility to the deleterious effects of PAHs.
Download or read book Functional Aspects of Developmental Toxicity of Polyhalogenated Aromatic Hydrocarbons in Experimental Animals and Human Infants written by A. Brouwer and published by . This book was released on 1995 with total page 40 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Toxicological Profile for Polycyclic Aromatic Hydrocarbons written by and published by . This book was released on 1993 with total page 308 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Bioavailability of Contaminants in Soils and Sediments written by National Research Council and published by National Academies Press. This book was released on 2003-05-03 with total page 433 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bioavailability refers to the extent to which humans and ecological receptors are exposed to contaminants in soil or sediment. The concept of bioavailability has recently piqued the interest of the hazardous waste industry as an important consideration in deciding how much waste to clean up. The rationale is that if contaminants in soil and sediment are not bioavailable, then more contaminant mass can be left in place without creating additional risk. A new NRC report notes that the potential for the consideration of bioavailability to influence decision-making is greatest where certain chemical, environmental, and regulatory factors align. The current use of bioavailability in risk assessment and hazardous waste cleanup regulations is demystified, and acceptable tools and models for bioavailability assessment are discussed and ranked according to seven criteria. Finally, the intimate link between bioavailability and bioremediation is explored. The report concludes with suggestions for moving bioavailability forward in the regulatory arena for both soil and sediment cleanup.
Download or read book Polycyclic Aromatic Hydrocarbons written by Kazuichi Hayakawa and published by Springer. This book was released on 2018-02-05 with total page 267 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book reviews Polycyclic Aromatic Hydrocarbons (PAHs) and Nitropolycyclic Aromatic Hydrocarbons (NPAHs) contamination in the context of environmental pollution in Asia. It is comprised of the following sections: 1. Fundamental Chemistry and General Characteristics; 2. Analytical Methods; 3. Emission Source and Atmospheric Behavior; 4. Atmospheric Polycyclic Aromatic Hydrocarbons and PM2.5; 5. Polycyclic Aromatic Hydrocarbons in Marine Environments; 6. Metabolic Activation/Toxicities; and 7. Environmental Standards and Guidelines. This volume concentrates on the Far East due to the massive consumption of coal and petroleum in China, which has led to considerable levels of air pollution. High concentration of atmospheric PM2.5 in Beijing have been reported since January 2013 and exposure to such high concentrations may cause respiratory, cardiac and lung diseases. Gathering contributions from international experts, this volume provides a valuable reference guide for global researchers and students interested in learning from the East Asian experience.
