Thesis (M.Sc.)--Memorial University of Newfoundland, 2005. / Restricted until October 2006. Bibliography: leaves 99-106.

Alkyl-polycyclic aromatic hydrocarbons (alkyl-PAHs) constitute more than 90% of the total PAHs in crude oil and are the main constituents toxic to fish. Little characterization of alkyl-PAHs has been reported and is needed to predict the effects of crude oil following spills. The objectives of this thesis were: (1) to evaluate the toxicity of alkyl-phenanthrenes and alkyl-anthracenes to the early life-stages of medaka (Oryzias latipes) using the partition controlled delivery of toxicants (PCD); (2) to investigate the effect of light on alkyl-anthracene toxicity; (3) to further characterize the PCD method; (4) to better understand alkyl-PAH mechanisms of toxicity; and (5) to identify the major phase I and phase II alkyl-PAH metabolites in rainbow trout (Oncorhynchus mykiss) and in medaka by both in vitro and in vivo methods. It was determined that the toxicity of both series of alkyl-PAHs increased with the number of carbon substituents on the rings. Some alkyl-PAHs had EC50 values lower than the value from conventional semi-static exposure methods. These values were below the water solubility limit, consistent with the ability of PCD to correct for values from nominal concentrations above solubility. PCD provided stable concentrations for up to 17 days but could not always compensate for losses of alkyl-anthracenes by photodegradation. Both series of alkyl-PAHs were toxic through different mechanisms that resulted from their physical and chemical properties. Alkyl-phenanthrenes such as 7-isopropyl-1-methylphenanthrene (retene) were more toxic to medaka embryos than phenanthrene. The appearance of blue sac disease suggested toxicity enhancement through the aryl hydrocarbon receptor pathway. Alkyl-anthracenes were toxic by narcosis in the absence of light and by phototoxicity in the presence of light. The photoproducts of alkyl-anthracenes were not toxic to fish. The in vitro phase I metabolism by rainbow trout CYP1a enzymes and in vivo phase II metabolism in rainbow trout produced alkyl-anthracenes metabolites substituted mainly on the ring system. The phase II in vivo metabolites of alkyl-phenanthrenes in medaka larvae were substituted mainly on their alkyl chains. For all alkyl-PAHs, a predominance of glucuronide conjugates was identified in the phase II metabolites. This characterization of the toxicity of alkyl-PAHs may contribute to predicting the toxicity of crude oil based on its composition. / Thesis (Ph.D, Chemistry) -- Queen's University, 2008-08-29 14:18:10.308

Thesis (Ph.D.)--McMaster University (Canada), 1996. / Source: Dissertation Abstracts International, Volume: 58-06, Section: B, page: 3006. Adviser: B. E. McCarry.

Thesis (Ph.D.) - Simon Fraser University, 2004. / Theses (Dept. of Biological Sciences) / Simon Fraser University.

Thesis (M.S.)--Oregon State University, 2008. / Printout. Includes bibliographical references (leaves 40-46). Also available on the World Wide Web.

The structures of Diels-Alder cycloaddition of cyclopentadiene to 2,6-dimethyl-p-benzoquinone and methylcyclopentadiene to 2,6-dimethyl-p-benzoquinone were assigned by analysis of 1-D and 2-D proton and carbon-13 NMR spectra. The structures of the cycloadduct of methylcyclopentadiene to 2,6-dimethyl-p-benzoquinone and that of the corresponding intramolecular [2+2] photocyclization product were also obtained by single crystal X-ray structural analysis. As the second part of the study, a new polycyclic "cage" molecule, a substituted trishomocubane isomer, was synthesized. In this synthesis, reductive bond cleavage followed by Dieckmann condensation was employed. Wolff-Kishner reduction then was used to convert a β-keto ester "cage" molecule to the corresponding carboxylic acid. A compound that possesses twofold symmetry was isolated from reaction product mixture. The structure of this compound has been established by single crystal X-ray crystallography.

The purpose of this dissertation is to investigate the behavior of polycyclic aromatic hydrocarbons (PAHs) in binary solvent systems and determine and/or develop predictive mathematical expressions for describing solutions in which hydrogen-bonding occurs.

The contamination of soils, with polycyclic aromatic hydrocarbons (PAHs), remains a widespread environmental concern. In the past two decades, many physical, chemical and biological methods have been developed and evaluated for the degradation of PAHs. However, due to their low aqueous solubility, high sorption affinity, hydrophobicity and recalcitrance, the environmental remediation of PAHs in soil continues to be economically challenging. In addition to PAH contamination, the presence of oxygenated derivatives of PAHs (OPAHs), in soils, has increasingly become a concern due to their greater toxic properties compared to parent PAH compounds. To date, no investigations on OPAH-remediation methods have been presented in the literature. The use of zero-valent metals (ZVMs) has been reported for several halogenated contaminants in solution systems, but the effectiveness of ZVM to degrade sorbed PAHs and OPAHs has been rarely addressed. This present research focuses on the development of a combined technique for the feasible desorption and degradation of PAHs and OPAHs in soils. PAH and OPAH degradation efficiency, using activated magnesium (Mg) metal combined with an ethanol-ethyl lactate cosolvent (1:1 ratio), was initially examined in soil-free systems. This metal/cosolvent system demonstrated adequate degradation (above 80%) for high-molecularweight (HMW) PAHs, which were subsequently converted into hydroaromatic compounds; while OPAHs were degraded and converted into hydroxylated or hydrogenated derivatives. Further soil-free studies revealed that the degradation rate was affected by the surface or reactive iv sites of the metal and that optimum degradation efficiency were obtained with Mg ball milled with graphite (Mg/C). In a bench-scale feasibility test, the efficacy of this system was assessed on a soil spiked with a mixture of three HMW PAHs compounds and three OPAHs compounds with amounts ranging from 0.033 mmol to 0.060 mmol. The experimental results show that 2 mL of an ethanol-ethyl lactate solvent mixture resulted in 58% to 85% extraction efficiency for the selected contaminants in 1 g of spiked soil, followed by 64 - 87% degradation efficiency of the extracted contaminants with 4.11 mmol of the activated metal. This activated-Mg/cosolvent system can be considered as a promising alternative method for ex situ remediation of PAH and OPAH-contaminated soils.

Humans are continuously exposed to mixtures of environmental pollutants. Polycyclic aromatic hydrocarbons (PAHs), such as 2-naphthol, and heavy metals, such as lead, are some of these pollutants. Results from epidemiological studies show associations between exposure to 2-naphthol, exposure to lead, and obesity. However, the individual and combined effects of 2-naphthol and lead on fat cell development (adipogenesis) have not been directly characterized in a biological system. In this study, we evaluated the effects of 2-naphthol and/or lead on adipogenesis using mouse 3T3-L1 cells. Cells were exposed to different doses of 2-naphthol and/or lead. Induced terminal differentiation was evaluated by cell morphology, lipid production, and mRNA expression of marker genes characteristic of either early adipocyte differentiation: CCAAT-enhancer-binding protein β (C/EBPβ), insulin receptor substrate 2 (IRS2), and sterol responsive element binding protein 1 c (SREBP1c); or terminal differentiation: C/EBPα, peroxisome proliferator-activated receptor-γ (PPARγ), and fatty acid binding protein 4 (aP2). Production of antimicrobial peptide cathelicidin (Camp), which is produced by differentiating adipocytes and modulates inflammation and immunity, was also evaluated. Cell morphology changes and increased lipid accumulation indicated that, individually, 2-naphthol and lead induced 3T3-L1 differentiation; however, the highest dose of lead (10 μM) showed the lowest induction level. During terminal differentiation, 2-naphthol and low doses of lead increased C/EBPα, PPARγ, and aP2 expression, whereas 10 μM lead suppressed PPARγ and aP2. During early differentiation, 2-naphthol stimulated C/EBPβ, IRS2, and SREBP1c expression, while lead upregulated C/EBPα and aP2. The 2-naphthol/10 μM lead mixture induced a counterbalancing effect on 3T3-L1 adipogenesis, where 10 μM lead suppressed 2-naphthol-induced adipogenesis. Moreover, 2-naphthol elevated Camp expression in a dose-dependent manner, whereas lead slightly increased Camp at lower doses but suppressed it at 10 μM. The 2-naphthol/10 μM lead mixture showed no effect on Camp expression. In conclusion, 2-naphthol and low lead doses accelerate adipocyte differentiation and Camp production in 3T3-L1 cells; however, high doses of lead attenuate the induction. This effect of lead at high dose counterbalances the upregulation of adipocyte differentiation and Camp production by 2-naphthol. Together, these findings indicate that 2-naphthol and lead play potential roles in the development of inflammation and obesity.

Polycyclic aromatic hydrocarbons (PAHs) are common soil contaminants due to their lipophilic nature which limits partitioning to water or air. Soil properties such as organic carbon can affect PAH release from soil, and thus affect PAH bioavailability of ingested soil. Risk assessment of PAHs in soil generally assumes equal bioavailability of PAHs ingested in soil compared to PAHs ingested in reference dose media, leading to environmental cleanup guidelines that are potentially too conservative. This research intended to use the juvenile swine model to assess PAH bioavailability from impacted soil to better inform bioavailability estimates for risk assessment. This was done by assessing PAH bioavailability from single and repeated exposure to PAHs in different spiked exposure media, assessing PAH bioavailability from soil collected from PAH impacted sites, and assessing biomarkers of exposure and effect following PAH exposure. The effect of exposure duration on bioavailability was assessed because people are usually chronically exposed to PAHs, rather than acutely exposed, as most bioavailability studies are performed, and chronic exposure may lead to increases in xenobiotic metabolizing enzymes and transporters which may affect bioavailability. This research found that exposure duration did not significantly affect anthracene and benzo[a]pyrene bioavailability (p>0.075), but exposure media did (p<0.004). These results suggest that exposure medium has a more important effect on bioavailability than exposure duration, and also bioavailability calculated from a single exposure is appropriate for use in risk assessment. Bioavailability from 24 naturally impacted soils was assessed to determine which soil characteristics had the greatest effect on PAH bioavailability. Area under the curve (AUC) measurements for benzo[a]pyrene (BaP) and anthracene in swine blood after oral exposure from a soil matrix for benzo[a]pyrene and anthracene in soils had s very poor relationship with soil concentrations in soils collected from impacted sites (r2<0.15), but a very strong relationship with soil concentrations from spiked artificial soils (r2<0.95). As spiked soils had much higher concentrations of PAH, these results suggest there is a point of departure in soil concentrations where internal exposure becomes linearly related to soil concentration. Point of departure modeling indicates that this point occurs at soil PAH concentrations greater than 1,900 mg kg-1. Thus, risk assessment can assume a constant exposure to PAHs at soil concentrations lower than the point of departure. Comparison of terminal rate constants from intravenous (IV) exposure to PAHs and oral exposure to PAHs in a soilmatrix suggest that flip-flop kinetics occur in swine, where absorption occurs at a slower rate than elimination. Flip-flop kinetics likely explains the lack of relationship between real world soil concentrations and area under the curve measurements as absorption is the rate limiting step of elimination. Biomarkers of exposure and effect were assessed in swine liver and ileum tissue, as well as blood following single and subchronic exposure to PAHs to determine if relationships could be drawn between exposure magnitude and duration and biomarker formation. Biomarkers included cytochrome P450 (P450) 1A1, 1A2, and 1B1 expression and activity as biomarkers of exposure and DNA adducts, carbonylated proteins, and micronucleated reticulocytes as biomarkers of effect. Biomarkers of exposure were not affected by exposure magnitude or duration, indicating that they would serve best as exposure markers rather than indicators of bioavailability or other effects. However, DNA adduct and protein carbonyl formation was significantly affected by exposure duration (p<0.045), but micronuclei formation was not. The micronuclei results suggest the liver was effective at clearing PAHs to non-toxic metabolites at the study doses, while tissue biomarkers of effect may correlate more effectively with exposure iv length and magnitude of dose. This work indicates that PAH bioavailability from soil is lower than 100%, but additional work needs to be done to determine soil characteristics that affect bioavailability and to determine a bioavailability value relative to reference material.