The allylic bromide functionality in brominated poly(isoprene-co-isobutylene) rubber (BIIR) reacted readily to nucleophilic substitution by imidazole-derivatives. When reacted with the rubber, alkylimidazoles formed a stable non-thermoset ionomeric elastomer that has dynamic mechanical properties similar to those of vulcanizates; however, the strength is in its ion-pair aggregation. Structural characterization of the polymeric products was accomplished by spectroscopy with comparisons to the model compound prepared from brominated 2,2,4,8,8-pentamethyl-4-nonene (BPMN). Physical properties tests on the elastomers of varying ionic content (0-1 mol%) were done using solution viscosity and rheology, and demonstrated that small amounts of ionic functionality noticeably improved properties with a plateau of properties being attained as full conversion to ionic content was reached. The reaction of imidazole with BIIR created a thermoset elastomer that formed an ionomer and thermoset after its second alkylation. These materials provided excellent scorch protection and delayed curing at high temperatures, while still reaching good storage modulus. Formation of an elastomer with a pendant imidazole group was also achieved; however, it did not perform as well as the free imidazole. / Thesis (Master, Chemical Engineering) -- Queen's University, 2010-10-27 11:52:54.442

An investigation of the dichioromethane extract of the sponge, Xestospongia testudinaria indicated that the extract was composed of approximately 40% sterols, 30% saturated fatty acids, 10% mono-unsaturated fatty acids and 20% poly-unsaturated acids. The sterol profile was found to vary between two collections of the sponge. In the first collection the major sterol was the C30 compound, xestosterol (4), which had not previously been reported to occur in this species. In the second collection there was a wider distribution of components with cholesterol (2a) being a major constituent and xestosterol being present in a much lower percentage than in the first collection. The poly-unsaturated acid fraction contained an extremely complex mixture. The novel brominated bisacetylenic C18 (47) and brominated C28 (65) acids were found to be the major components. Another six novel brominated acetylenic acids, which were very unstable, were also identified as well as an ester of 4 with 47. The method developed for the separation of the poly-unsaturated acids from the other classes of metabolites and for the isolation of the pure compounds is discussed and their structural elucidation, largely on the basis of NIMR spectroscopy is described. From the hexane extract of Carteriospongia foliascens, two novel bisalkylated norscalarane derivatives (114 and 116) and a bisalkylated scalarane derivative (130) have been isolated. By use of high field NMR and multipulse NMR techniques a complete assignment of the 111 and 13C NMR spectra of 130 has been achieved on 1.5mg of material. This represents the first report of a complete assignment of the 1J4 NMR spectrum of a scalarane derivative. The C-4 stereochemistry of 130 was determined by use of 1H NMR spectroscopic techniques, which gave results in agreement with the previously used 13C NMR method.

Antimony trioxide (Sb2O3) is a common additive in flame retardant formulations and a study has been made to determine the effects of adding it alone, or with four commercial brominated materials (OBDPO, BTBPE, TBBA and PDBS80) to ABS polymer. The results focus upon mechanical, rheological, microscopical and flame retardant properties, and the effects of different Sb2O3 grades with average particle sizes ranging from 0.1 to 11.8 μm. The Sb2O3 was mainly studied up to 12 wt% loading in ABS, since this is considered to be the maximum level used in commercial flame retardant formulations.

Due to the increasing use of electronic components and the accelerated rate in which these components become obsolete, there has been a dramatic increase of discarded electronic waste (E-waste). E-waste includes obsolete electronic products such as computers, scanners, cellular phones, etc. These electronic components are manufactured using a variety of hazardous materials. As these components are discarded, the toxic and hazardous substances may become mobile and could impact human health and the environment. The toxic substances of concern contained in E-waste include heavy metals and brominated flame retardants (BFRs). This study attempts to identify the leaching potential of BFRs and metals.

The studies in this dissertation research were conducted to investigate the possible mode of action by which a brominated flame retardant, 2, 2-Bis (bromomethyl)-1, 3-propanediol (BMP) causes genotoxicity. Binding of BMP to DNA and BMP induced DNA strand breaks were investigated in SV-40 immortalized human uroepithelial cells (UROtsa) as an in vitro model for the bladder (a tissue that developed cancer after two year exposure to BMP in rodents). Results showed binding of [¹⁴C]-BMP equivalents to DNA increased with increased exposure time and concentration of [¹⁴C]-BMP. Comet analysis indicated BMP significantly increased the extent of DNA strand breaks at 1 and 3 h of incubation. However, strand breaks were repaired by 6 h of incubation. The DNA damaging effects of BMP at 1 h was concentration dependent. Compared with the parent compound, BMP-glucuronide (the predominant metabolite of BMP) bound less to DNA and produced less DNA strand breaks in UROtsa cells. Evidences that the BMP induced strand breaks were the result of an oxidative stress include: a concentration and time dependent increase in ROS generation; increased expression of Nrf2 and HSP70; complete attenuation of BMP induced DNA strand breaks by the antioxidant, NAC; and the presence of the oxidized base 8-OHguanine. UROtsa cells appear to be target cells for BMP because, as compared to rat hepatocytes (non-target cells), these cells lack the ability to detoxify BMP via glucuronidation and also because they are deficient in glutathione, a major intracellular antioxidant molecule. Both of these genotoxic events, DNA binding and oxidative DNA damage may, in part, contribute to BMP carcinogenicity observed in rodents. The relevance of current results to humans is remained to be established.

Brominated flame retardants (BFR) such as hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO), bis(2-ethylhexyl)tetrabromophthalate (BEHTBP), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and decabromodiphenylethane (DBDPE) are contaminants of environmental concern. These BFRs are replacement alternatives for some of the major production BFRs, which have been restricted from the marketplace due to their adverse health effects. Their presence in environmental matrices, including wild birds, suggests they should be tested for possible toxic effects. BFR alternatives have been detected in the eggs of colonial fish-eating birds, suggesting maternal transfer during ovogenesis and the potential for these chemicals to bioaccumulate through the food chain. However, information regarding the toxicity of HCDBCO, BEHTBP, BTBPE and DBDPE exposure in birds is lacking. This thesis consisted of a combined in vitro/in ovo approach to determine: 1) the concentration-dependent effects of these four BFR alternatives in chicken embryonic hepatocytes (CEH), and 2) the dose-dependent effects of HCDBCO and BTBPE in chicken embryos following injection into the air cell of eggs prior to incubation. Changes in the mRNA expression levels of genes previously found to be responsive to other BFRs were assessed in CEH and liver tissue, in addition to examining overt toxicity (i.e. cytotoxicity, pipping success). None of the BFRs tested were cytotoxic up to 60 µM HCDBCO, 60 µM BEHTBP, 1.4 µM BTBPE or 0.2 µM DBDPE in CEH. Injection doses up to 50 µg/g egg HCDBCO and 10 µg/g egg BTBPE had no effect on embryonic pipping success. The accumulation of HCDBCO and BTBPE was variable in liver and did not follow a linear uptake pattern with respect to injection dose, due in part to difficulties with the solubility of these chemicals in the dimethyl sulfoxide (DMSO) vehicle. In, CEH, HCDBCO caused a decrease in CYP1A4/5 mRNA at all concentrations tested, while CYP2H1 and CYP3A37 were induced only at 10 µM. In contrast, only TTR mRNA was down-regulated in hepatic tissue at all injection concentrations of HCDBCO. The highest concentration of BTBPE induced CYP1A4/5 mRNA to 115- and 18-fold in CEH, and 6.5- and 1.8-fold in liver tissue. In vitro and in ovo exposure to BTBPE caused a concentration-dependent decrease in DIO3 mRNA, while CYP3A37 was down-regulated 2-fold at 10 µg/g in liver tissue. In CEH, DBDPE induced CYP1A4/5 mRNA to a maximum of 29- and 59-fold at 0.2 µM, and increases in DIO1 mRNA and decreases in CYP3A37 mRNA were also observed. None of the gene targets were responsive to BEHTBP exposure in CEH. This is the first study to report on the toxicological and molecular effects of HCDBCO, BEHTBP, BTBPE and DBDPE in an avian species. Using this combined in vitro/in ovo approach has permitted the characterization of these four BFR alternatives by defining possible mechanisms of biological action in a model avian species, the chicken.

Brominated flame retardants (BFR) such as hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO), bis(2-ethylhexyl)tetrabromophthalate (BEHTBP), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and decabromodiphenylethane (DBDPE) are contaminants of environmental concern. These BFRs are replacement alternatives for some of the major production BFRs, which have been restricted from the marketplace due to their adverse health effects. Their presence in environmental matrices, including wild birds, suggests they should be tested for possible toxic effects. BFR alternatives have been detected in the eggs of colonial fish-eating birds, suggesting maternal transfer during ovogenesis and the potential for these chemicals to bioaccumulate through the food chain. However, information regarding the toxicity of HCDBCO, BEHTBP, BTBPE and DBDPE exposure in birds is lacking. This thesis consisted of a combined in vitro/in ovo approach to determine: 1) the concentration-dependent effects of these four BFR alternatives in chicken embryonic hepatocytes (CEH), and 2) the dose-dependent effects of HCDBCO and BTBPE in chicken embryos following injection into the air cell of eggs prior to incubation. Changes in the mRNA expression levels of genes previously found to be responsive to other BFRs were assessed in CEH and liver tissue, in addition to examining overt toxicity (i.e. cytotoxicity, pipping success). None of the BFRs tested were cytotoxic up to 60 µM HCDBCO, 60 µM BEHTBP, 1.4 µM BTBPE or 0.2 µM DBDPE in CEH. Injection doses up to 50 µg/g egg HCDBCO and 10 µg/g egg BTBPE had no effect on embryonic pipping success. The accumulation of HCDBCO and BTBPE was variable in liver and did not follow a linear uptake pattern with respect to injection dose, due in part to difficulties with the solubility of these chemicals in the dimethyl sulfoxide (DMSO) vehicle. In, CEH, HCDBCO caused a decrease in CYP1A4/5 mRNA at all concentrations tested, while CYP2H1 and CYP3A37 were induced only at 10 µM. In contrast, only TTR mRNA was down-regulated in hepatic tissue at all injection concentrations of HCDBCO. The highest concentration of BTBPE induced CYP1A4/5 mRNA to 115- and 18-fold in CEH, and 6.5- and 1.8-fold in liver tissue. In vitro and in ovo exposure to BTBPE caused a concentration-dependent decrease in DIO3 mRNA, while CYP3A37 was down-regulated 2-fold at 10 µg/g in liver tissue. In CEH, DBDPE induced CYP1A4/5 mRNA to a maximum of 29- and 59-fold at 0.2 µM, and increases in DIO1 mRNA and decreases in CYP3A37 mRNA were also observed. None of the gene targets were responsive to BEHTBP exposure in CEH. This is the first study to report on the toxicological and molecular effects of HCDBCO, BEHTBP, BTBPE and DBDPE in an avian species. Using this combined in vitro/in ovo approach has permitted the characterization of these four BFR alternatives by defining possible mechanisms of biological action in a model avian species, the chicken.

Tradtional brominated flame retardants (BFRs), namely the polybrominated diphenyl ethers (PBDEs), have persistent, bioaccumulative, and toxic properties that have resulted in the phase out of their production and their be banned in certain jurisdictions. To meet regulatory flame retardancy requirements, non-PBDE BFRs have entered the marketplace. Much remains unknown regarding the environmental fate and toxicity of these emerging BFRs. The objective of this thesis was to use outdoor mesocosms to examine the fate and toxicity of three emerging BFRs; bis(tribromophenoxy)ethane (BTBPE), tetrabromobisphenol A bis(dibromopropyl ether) (TBBPA-DBPE), and BZ-54, which consists of two BFRs, ethylhexyl-tetrabromobenzoate (EHTeBB) and bis(ethylhexyl)tetrabromophthalate (BEHTBP). While it was difficult to accurately determine degradation rates because of fluctuating concentrations, the estimated half-lives indicated these compounds are persistent (> 60 days in sediments). The partitioning of the compounds between the particulates and the sediment resulted in differential degradation rates (greater in the particulates), and products formed; those formed on the particulates were consistent with photodegradation products. The effects of these emerging BFRs on Hyalella azteca and the benthic macroinvertebrate community were assessed through the use of in situ exposure and sampling techniques. The in situ Hyalella cages showed a high degree of variability for most endpoints, regardless of their placement (e.g., water column vs. sediment) in the mesocosm. BTBPE accumulated in the H. azteca (0.03 – 1.4 ng/g ww), however this was not associated with any changes in growth or reproduction. There was high variability in abundance and diversity between the mesocosms, which limited the ability to detect statistically significant differences. Interestingly, the BZ-54 treated mesocosms had the greatest abundance, and the least amount of community diversity. This thesis examined the bioaccumulation potential of these compounds in fathead minnow (Pimephales promelas), as well as the associated effects on growth and development as measured through physical and biochemical endpoints. There was considerable uptake and persistence of BTBPE and TBBPA-DBPE, as well as indication of metabolism of these compounds, but limited physical effects observed. There were indications of increased oxidative stress in the BZ-54 treatment, and increased induction of vitellogenin in fathead minnow from the BTBPE treatment. / Environment Canada's Chemicals Management Plan

Tetrabromobisphenol A, (TBBPA or Br4BPA), is a widely used brominated flame retardant (BFR). Although TBBPA and its breakdown products been found in river sediments, the environmental impact of their contamination is largely unknown. One breakdown product of TBBPA is bisphenol A (BPA), which has been studied intensively for its toxicology because it is used in the manufacturing of plastics and leaches from food containers, water bottles and pipes. Other breakdown products of TBBPA include tribromobisphenol A (Br3BPA), dibromobisphenol A (Br2BPA), and monobromobisphenol A (BrBPA) but little is known about their toxicology. Since TBBPA is toxic, there is a need to search for an alternative BFR, with one being tetrabromobisphenol A bis(2,3-dibromopropylether) or TBBPA-DBPE. However, almost nothing is known about the toxicology of this compound. Hence, two rainbow trout cell lines, RTL-W1 from liver and RTgill-W1 from gill, were used to evaluate the cellular toxicity of TBBPA, BPA, BrBPA, Br2BPA, Br3BPA and TBBPA-DBPE. The cells were exposed to these compounds for 24 h in the basal medium, L-15, to study their cytotoxicity and in L-15 with fetal bovine serum (FBS) to evaluate their capacity to induce 7-ethoxyresorufin o-deethylase (EROD) activity. Viability was measured with three fluorometric indicator dyes: Alamar Blue (AB) for metabolism, 5-carboxyfluorescein diacetate acetoxymethyl (CFDA AM) for cell membrane integrity, and Neutral Red (NR) for lysosomal activity. The concentrations causing a 50 % reduction in viability (EC50) as measured with these three dyes were used to compare the relative cytotoxicity of these chemicals. For both cell lines and with all viability endpoints, TBBPA was the most cytotoxic, with EC50s ranging from 2.33 to 3.11 ug/ml. BPA, BrBPA, Br2BPA, and Br3BPA also caused dose-dependent declines in cell viability but showed no consistent order of potency. None of the six compounds induced EROD activity, which suggests that they do not activate the aryl hydrocarbon receptor (AhR). Regardless of the endpoint or cell line, TBBPA-DBPE was not cytotoxic. This suggests that, from a toxicological perspective, this compound may be a suitable replacement for TBBPA as a BFR. BPA stood out from the other compounds in two regards. BPA caused a dose-dependent decline in cell viability for cultures in L-15 with FBS, whereas for the other compounds, little or no change in viability was seen in cultures with FBS. BPA elicited a decline in the ability of cells to reduce AB almost immediately upon its addition to cultures in a simple buffer, whereas as for other compounds a decline took time to develop. These results suggest that BPA exerts its cytotoxicity by a different mechanism different from the other compounds.

Brominated flame retardants (BFR) such as hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO), bis(2-ethylhexyl)tetrabromophthalate (BEHTBP), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and decabromodiphenylethane (DBDPE) are contaminants of environmental concern. These BFRs are replacement alternatives for some of the major production BFRs, which have been restricted from the marketplace due to their adverse health effects. Their presence in environmental matrices, including wild birds, suggests they should be tested for possible toxic effects. BFR alternatives have been detected in the eggs of colonial fish-eating birds, suggesting maternal transfer during ovogenesis and the potential for these chemicals to bioaccumulate through the food chain. However, information regarding the toxicity of HCDBCO, BEHTBP, BTBPE and DBDPE exposure in birds is lacking. This thesis consisted of a combined in vitro/in ovo approach to determine: 1) the concentration-dependent effects of these four BFR alternatives in chicken embryonic hepatocytes (CEH), and 2) the dose-dependent effects of HCDBCO and BTBPE in chicken embryos following injection into the air cell of eggs prior to incubation. Changes in the mRNA expression levels of genes previously found to be responsive to other BFRs were assessed in CEH and liver tissue, in addition to examining overt toxicity (i.e. cytotoxicity, pipping success). None of the BFRs tested were cytotoxic up to 60 µM HCDBCO, 60 µM BEHTBP, 1.4 µM BTBPE or 0.2 µM DBDPE in CEH. Injection doses up to 50 µg/g egg HCDBCO and 10 µg/g egg BTBPE had no effect on embryonic pipping success. The accumulation of HCDBCO and BTBPE was variable in liver and did not follow a linear uptake pattern with respect to injection dose, due in part to difficulties with the solubility of these chemicals in the dimethyl sulfoxide (DMSO) vehicle. In, CEH, HCDBCO caused a decrease in CYP1A4/5 mRNA at all concentrations tested, while CYP2H1 and CYP3A37 were induced only at 10 µM. In contrast, only TTR mRNA was down-regulated in hepatic tissue at all injection concentrations of HCDBCO. The highest concentration of BTBPE induced CYP1A4/5 mRNA to 115- and 18-fold in CEH, and 6.5- and 1.8-fold in liver tissue. In vitro and in ovo exposure to BTBPE caused a concentration-dependent decrease in DIO3 mRNA, while CYP3A37 was down-regulated 2-fold at 10 µg/g in liver tissue. In CEH, DBDPE induced CYP1A4/5 mRNA to a maximum of 29- and 59-fold at 0.2 µM, and increases in DIO1 mRNA and decreases in CYP3A37 mRNA were also observed. None of the gene targets were responsive to BEHTBP exposure in CEH. This is the first study to report on the toxicological and molecular effects of HCDBCO, BEHTBP, BTBPE and DBDPE in an avian species. Using this combined in vitro/in ovo approach has permitted the characterization of these four BFR alternatives by defining possible mechanisms of biological action in a model avian species, the chicken.