<p>The rapidly increasing use of silver nanoparticles (Ag NPs) in consumer products and medical applications has raised ecological and human health concerns. Significant progress has been made in understanding the toxicity of silver nanoparticles (Ag NPs) under carefully controlled laboratory conditions. The goals of this dissertation were to investigate the mechanism of Ag NP toxicity under both laboratory conditions and environmental backgrounds, using <italic>Caenorhabditis elegans</italic> (<italic>C. elegans</italic>) as a model system. A key question for addressing these concerns is whether Ag NP toxicity is mechanistically unique to nanoparticulate silver or if it is a result of the release of silver ions. Ag NPs are produced in a large variety of monomer sizes and coatings, and since their physicochemical behavior depends on the media composition, it is important to understand how these variables modulate toxicity.</p><p> In order to test the hypothesis of a particle-specific effect, multiple techniques were used, including analytical chemistry, pharmacological rescue, and genetic analysis. Results suggested that dissolution was important for all tested Ag NPs and oxidative stress (a particle-specific effect) was important only for some Ag NPs, especially the citrate-coated Ag NPs (CIT-Ag NPs). The hypothesis of the particle-specific effect was further tested by investigating the cellular uptake and damage co-localization upon exposures to CIT-Ag NPs. I found that Ag NPs crossed all layers, including the pharynx, gut, and also embryos through trans-generational transfer. Sites of damage were examined through transmission electron microscopy (TEM), and CIT-Ag NPs showed a more severe and deeper level of damage compared to ionic Ag. In addition, pharmacological inhibitors in parallel with genetic mutants (deficient in both endocytosis and lysosomal function) were used to explore the impact of those pathways on Ag NP uptake and associated toxicity. I found that endocytosis was important for CIT-Ag NP uptake and toxicity. Most intriguingly, one of the lysosomal deficient mutants was much more sensitive than wild type to reproductive inhibition after exposure to CIT-Ag NPs but not ionic Ag, constituting a clear nanoparticle-specific toxic effect.</p><p> These laboratory mechanistic studies, however, cannot be directly extrapolated to complicated environmental conditions, including variable amounts of natural organic matter (NOM), different temperatures and salinities, surface sulfidation, etc. My general hypothesis was that complex environmental medium would reduce Ag NP toxicity. In support of this, the environmental conditions present in mesocosms resulted in a loss of toxicity one week after dosing/spiking. In laboratory studies, I found that that increasing temperature and salinity tended to increase Ag NP toxicity, while sulfidation reduced Ag NP toxicity, acting as a &ldquonatural antidote&rdquo. I studied two types of NOM, Suwannee River and Pony Lake fulvic acids (SRFA and PLFA respectively). PLFA rescued toxicity more effectively than SRFA. Therefore, CIT-Ag NP-NOM interactions were explored in depth using PLFA. Using hyperspectral dark field microscopy, I was able to detect the formation of Ag NP-PLFA complexes and the limited tissue uptake of Ag NPs (with and without PLFA). Consistent with the reduced acute toxicity of Ag NPs by PLFA, I also found a rescue effect of PLFA on Ag NP-induced ultrastructural damage.</p><p> In conclusion, Ag NP toxicity resulted largely from dissolution and in some cases also from a particle-specific effect. However, Ag NP toxicity was strongly altered by environmental matrices. Continued in depth elucidation of Ag NP behavior, cellular uptake pathways and trafficking, and their interactions with other environmental factors will be invaluable in predicting, designing, and remediating the potential/existing environmental implications of silver-related nanotechnology.</p> / Dissertation

Ibogainas yra indolo grupės alkaloidas, išskiriamas iš augalo Tabernanthe iboga Baill. (Apocynaceae). Šis alkaloidas mažina priklausomybę nuo opiatų bei lengvina abstinencijos požymius. Noribogainas – ibogaino aktyvusis metabolitas, sukeliantis mažiau nepageidaujamų reiškinių. Darbo tikslas: ištirti ibogaino ir noribogaino toksiškumą ir farmakokinetines savybes taikant eksperimentinį laboratorinių pelių modelį. Uždaviniai: Nustatyti ibogaino ir noribogaino toksiškumą, apskaičiuojant šių medžiagų vidutinę mirtinąją dozę (LD50) laboratorinėms pelėms. Pritaikyti ir validuoti efektyviosios skysčių chromatografijos (ESC) metodiką ibogaino ir noribogaino analizei laboratorinių pelių kraujo plazmoje ir vidaus organuose. Išskirti ibogainą ir noribogainą iš laboratorinių pelių kraujo plazmos ir vidaus organų mėginių ir atlikti kiekybinį įvertinimą. Nustatyti ibogaino ir noribogaino farmakokinetinius parametrus pelių kraujo plazmoje ir organuose. Ištirti vienkartinės ir kartotinių ibogaino ir noribogaino dozių įtaką šių medžiagų kaupimuisi pelių organuose. Nustatyti farmakokinetiniai parametrai atskleidžia kiekybinius ibogaino ir noribogaino kitimus organizme, įtakojančius biologiškai aktyvios medžiagos veiksmingumą, o medžiagų kaupimasis pelių organuose padeda įvertinti toksinio poveikio riziką. Gauti tyrimų rezultatai naudingi ir informatyvūs siekiant toliau atlikti klinikinius tyrimus su žmonėmis. / Ibogaine is a psychoactive alkaloid extracted from the Tabernanthe Iboga Baill. (Apocynaceae). This alkaloid reduces dependence on opiates and attenuates withdrawal symptoms. Ibogaine is metabolized to metabolite – noribogaine. Noribogaine appears less likely to produce the adverse effects associated with ibogaine. The aim of work is to test the toxicity and pharmacokinetic properties of ibogaine and noribogaine by conducting tests with white laboratory mice. The objectives of the research work are as follows: To determine the toxicity of ibogaine and noribogaine by calculating the median lethal dose (LD50) in laboratory mice. To adapt and validate the methodology of high-performance liquid chromatography (HPLC) for the analysis of ibogaine and noribogaine in the blood plasma and internal organs of laboratory mice. To determine ibogaine and noribogaine in plasma and organs of mice. To determine pharmacokinetic parameters of ibogaine and noribogaine in mice blood plasma and organs. To test the influence of repeated doses of ibogaine and noribogaine on the accumulation of these substances in organs of mice. Pharmacokinetic properties reveal quantitative variation of ibogaine and noribogaine in the body, influencing the effectiveness of biologically active substances. Accumulation test of these substances helps to assess the risk of toxicity. The obtained results are useful and informative in order to continue to carry out clinical trials with humans.

The current work determined whether there is a constant tissue residue associated with narcotic compounds. In this investigation, the cladoceran, Daphnia magna was exposed to lethal levels (48h LC50) of ten, $ sp{14}$C-labelled, narcotic organic chemicals in a closed system. Exposure times, ambient concentrations, and body sizes were varied to evaluate their effects. The $ sp{14}$C-method developed in current work can detect chemicals in single D. magna in concentrations ranging from 0.02 to 6310 mmol/kg. Moreover, the technique detected phobic and lipophilic chemicals equally well. The technique's sensitivity (nmol/kg) allowed for detection of differences in the internal concentrations of pollutants among the unaffected, immobilized, and dead D. magna. Immobilized D. magna contained between 0.14 mmol/kg and 200 mmol/kg of narcotics. On the average, however, the internal residues were 3.1 mmol/kg (95%CL = 3.1 $ pm$ 2.0). This agreed with literature values. The effects of time of exposure, ambient concentration, and body size on the tissue residues of narcotics varied with the chemical compound.

Quaternary ammonium compounds (QACs) are ubiquitous contaminants found worldwide in both engineered and natural systems. QACs are toxic to aquatic organisms and cause co-selection for antibiotic resistance, thus providing a reservoir of antibiotic-resistant bacteria, as well as antibiotic resistance genes in QAC-polluted environments. The objectives of the research presented here were to: a) systematically assess the fate and toxicity of QACs using quantitative structure-activity relationships (QSAR); b) evaluate the biotransformation potential of QACs under aerobic, anoxic and anaerobic conditions; and c) assess the potential toxicity of QACs biotransformation products. Nine QACs, belonging to three homologous groups -- monoalkonium, dialkonium and benzalkonium chlorides -- were the target QACs. The QACs critical micelle concentration (CMC) was determined. Then, the CMC was used as a descriptor to derive relationships between QAC structure and partitioning to biosolids as well as acute Microtox® toxicity. QACs with low CMCs had a relatively high adsorption affinity for biosolids and a lower toxicity than QACs with higher CMCs, which suggests that QACs that are more mobile and more (bio)available are more toxic. The biotransformation potential of benzalkonium chlorides (BAC) -- the most commonly used QACs found in engineered and natural biological systems -- under aerobic, methanogenic, nitrate reducing, and fermentative conditions was evaluated using bioenergetics and batch bioassays. The aerobic BAC biotransformation involved sequential dealkylation and debenzylation steps resulting in the formation of benzyl dimethyl amine, and dimethyl amine, respectively. The bacterial community involved in the aerobic BAC degradation was mainly composed of species belonging to the Pseudomonas genus. All QACs tested were recalcitrant under methanogenic conditions and inhibited methanogenesis at and above 25 mg QAC/L. Under nitrate reducing and fermentative conditions, BAC was transformed to alkyldimethyl amines via an abiotic reaction known as modified Hofmann degradation and a biotic reaction known as fumarate addition, respectively. Both reactions are based on a mechanism known as nucleophilic substitution. The discovery of BAC transformation by the above mentioned two reactions is the first ever report to document QAC transformation under anoxic/anaerobic conditions and delineate the transformation pathway.

Mucositis manifesting as diarrhoea is a common side effect of chemotherapy which remains poorly understood. It is one of a number of manifestations of alimentary mucositis, which affects the entire gastrointestinal tract. The exact number of patients that are affected by diarrhoea as a result of treatment is uncertain, although it is believed that approximately 10% of patients with advanced cancer will be afflicted. Despite advances in the understanding of oral and small intestinal mucositis over recent years, large intestinal mucositis, including diarrhoea, has not been well defined and the underlying mechanisms of the condition are yet to be established. The majority of the literature available concerning diarrhoea is based on clinical observations, with very little basic research existing. However, from the research conducted, it is likely that the intestinal microflora and mucins play a role in the development of chemotherapy-induced diarrhoea. This thesis will examine in detail what is known about the mechanisms of chemotherapy-induced diarrhoea (CID). Furthermore it will explore the potentially important relationship between intestinal microflora, the luminal environment and the subsequent development of chemotherapy-induced mucositis and diarrhoea. 5-Fluorouracil (5-FU) is a commonly used chemotherapy agent in clinical oncology practice. Two of its major side effects are mucositis and diarrhoea. The structure of mucins offers mucosal protection, and allows maintenance of intestinal flora by providing attachment sites and preventing bacterial overgrowth and/or penetration. Following treatment with 5-FU, we showed decreases in Clostridium spp., Lactobacillus spp. and Streptococcus spp., and an increase in Escherichia spp. in the jejunum. In the colon, 5-FU caused decreases in Enterococcus spp., Lactobacillus spp. and Streptococcus spp. Real time PCR of faecal samples showed decreasing trends in Lactobacillus spp. and Bacteroides spp., and an increasing trend in E. coli. Significant increases (p<0.05) were seen in Clostridium spp. and Staphylococcus spp. at 24 h. Goblet cell numbers decreased significantly in the jejunum from 24-72 h, with a significant increase in the percentage of cavitated goblet cells, suggesting 5-FU treatment causes significant changes in intestinal flora and mucin secretion in rats. These changes could result in systemic effects, and in particular may contribute to the development of chemotherapy-induced mucositis. Irinotecan causes cholinergic and delayed onset diarrhoea in patients, in which β-glucuronidase produced by gut bacteria is thought to be involved. Diarrhoea was observed in treated rats, as expected, following irinotecan treatment. β-glucuronidase expression increased in the jejunum and colon. Faecal flora changed quantitatively after treatment also, with increases in E. coli, Staphylococcus spp., and Clostridium spp. (all β-glucuronidase producing), and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (β-glucuronidase producing, major component of intestinal flora), suggesting that irinotecan-induced diarrhoea may be caused by an increase in β-glucuronidase producing bacteria. However, the increase in bacteria may also be caused by irinotecan, further exaggerating the toxicity of the drug, and emphasising the need for these specific bacteria to be therapeutically targeted for successful treatment regimens to be accomplished. Mucus production appears to be increased after irinotecan treatment, which may contribute to the development of diarrhoea. Goblet cells were demonstrated to decrease significantly after irinotecan treatment. However, mucin secretion increased. Mucin expression changed significantly after treatment. Muc2 and Muc4 decreased significantly in the villi of the jejunum after treatment, Muc2 and Muc4 decreased significantly in the crypts. Muc2 decreased significantly in the colon. This indicates that irinotecan causes an increase in mucin secretion and a net decrease in mucin-producing goblet cells, and the expression of Muc2 and Muc4 in the gastrointestinal tract is altered following treatment. Increased mucin secretion is likely to be related to altered mucin expression, and may contribute to chemotherapy-induced diarrhoea. To determine if the changes to the intestinal microflora caused by chemotherapy could be translated to the clinic, a pilot clinical study was carried out. Sixteen patients experiencing CID were recruited to the study with two control subjects. A large proportion of patients (75%) demonstrated a reduced anaerobic component of their faecal microflora. A reduced diversity of species was also observed in patients. The majority of patients exhibited decreases in Clostridium spp., Lactobacillus spp. and Bifidobacterium spp., whilst all patients exhibited decreases in Bacteroides spp. and Enterococcus spp. Patients receiving antibiotics did not exhibit any marked differences to patients not receiving antibiotics. This indicates that the results observed in the animal studies are clinically relevant, and further research into this area should be undertaken. CID is associated with marked changes in the intestinal microflora. These changes may result in diminished bacterial functions within the gut, altering gut function and initiating intestinal damage, resulting in the onset of diarrhoea. In conclusion, there is clear evidence demonstrating chemotherapy treatment results in changes to the intestinal microflora and mucin secretion, which may be responsible in part for the development of severe mucositis and diarrhoea. Irinotecan toxicity may be compounded by the increase in β-glucuronidase producing bacteria. The intestinal flora of cancer patients experiencing CID is also noticeably different to that of healthy subjects. Irinotecan causes changes to mucin secretion, and the specific expression of Muc2, Muc4 and Klf4, suggesting that secretory control by the enteric nervous system may also be affected by chemotherapy. This research has extended the understanding of chemotherapy-induced mucositis and diarrhoea, complex side effects of chemotherapy. However, new areas for future research have also been identified. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352119 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2009

Mucositis manifesting as diarrhoea is a common side effect of chemotherapy which remains poorly understood. It is one of a number of manifestations of alimentary mucositis, which affects the entire gastrointestinal tract. The exact number of patients that are affected by diarrhoea as a result of treatment is uncertain, although it is believed that approximately 10% of patients with advanced cancer will be afflicted. Despite advances in the understanding of oral and small intestinal mucositis over recent years, large intestinal mucositis, including diarrhoea, has not been well defined and the underlying mechanisms of the condition are yet to be established. The majority of the literature available concerning diarrhoea is based on clinical observations, with very little basic research existing. However, from the research conducted, it is likely that the intestinal microflora and mucins play a role in the development of chemotherapy-induced diarrhoea. This thesis will examine in detail what is known about the mechanisms of chemotherapy-induced diarrhoea (CID). Furthermore it will explore the potentially important relationship between intestinal microflora, the luminal environment and the subsequent development of chemotherapy-induced mucositis and diarrhoea. 5-Fluorouracil (5-FU) is a commonly used chemotherapy agent in clinical oncology practice. Two of its major side effects are mucositis and diarrhoea. The structure of mucins offers mucosal protection, and allows maintenance of intestinal flora by providing attachment sites and preventing bacterial overgrowth and/or penetration. Following treatment with 5-FU, we showed decreases in Clostridium spp., Lactobacillus spp. and Streptococcus spp., and an increase in Escherichia spp. in the jejunum. In the colon, 5-FU caused decreases in Enterococcus spp., Lactobacillus spp. and Streptococcus spp. Real time PCR of faecal samples showed decreasing trends in Lactobacillus spp. and Bacteroides spp., and an increasing trend in E. coli. Significant increases (p<0.05) were seen in Clostridium spp. and Staphylococcus spp. at 24 h. Goblet cell numbers decreased significantly in the jejunum from 24-72 h, with a significant increase in the percentage of cavitated goblet cells, suggesting 5-FU treatment causes significant changes in intestinal flora and mucin secretion in rats. These changes could result in systemic effects, and in particular may contribute to the development of chemotherapy-induced mucositis. Irinotecan causes cholinergic and delayed onset diarrhoea in patients, in which β-glucuronidase produced by gut bacteria is thought to be involved. Diarrhoea was observed in treated rats, as expected, following irinotecan treatment. β-glucuronidase expression increased in the jejunum and colon. Faecal flora changed quantitatively after treatment also, with increases in E. coli, Staphylococcus spp., and Clostridium spp. (all β-glucuronidase producing), and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (β-glucuronidase producing, major component of intestinal flora), suggesting that irinotecan-induced diarrhoea may be caused by an increase in β-glucuronidase producing bacteria. However, the increase in bacteria may also be caused by irinotecan, further exaggerating the toxicity of the drug, and emphasising the need for these specific bacteria to be therapeutically targeted for successful treatment regimens to be accomplished. Mucus production appears to be increased after irinotecan treatment, which may contribute to the development of diarrhoea. Goblet cells were demonstrated to decrease significantly after irinotecan treatment. However, mucin secretion increased. Mucin expression changed significantly after treatment. Muc2 and Muc4 decreased significantly in the villi of the jejunum after treatment, Muc2 and Muc4 decreased significantly in the crypts. Muc2 decreased significantly in the colon. This indicates that irinotecan causes an increase in mucin secretion and a net decrease in mucin-producing goblet cells, and the expression of Muc2 and Muc4 in the gastrointestinal tract is altered following treatment. Increased mucin secretion is likely to be related to altered mucin expression, and may contribute to chemotherapy-induced diarrhoea. To determine if the changes to the intestinal microflora caused by chemotherapy could be translated to the clinic, a pilot clinical study was carried out. Sixteen patients experiencing CID were recruited to the study with two control subjects. A large proportion of patients (75%) demonstrated a reduced anaerobic component of their faecal microflora. A reduced diversity of species was also observed in patients. The majority of patients exhibited decreases in Clostridium spp., Lactobacillus spp. and Bifidobacterium spp., whilst all patients exhibited decreases in Bacteroides spp. and Enterococcus spp. Patients receiving antibiotics did not exhibit any marked differences to patients not receiving antibiotics. This indicates that the results observed in the animal studies are clinically relevant, and further research into this area should be undertaken. CID is associated with marked changes in the intestinal microflora. These changes may result in diminished bacterial functions within the gut, altering gut function and initiating intestinal damage, resulting in the onset of diarrhoea. In conclusion, there is clear evidence demonstrating chemotherapy treatment results in changes to the intestinal microflora and mucin secretion, which may be responsible in part for the development of severe mucositis and diarrhoea. Irinotecan toxicity may be compounded by the increase in β-glucuronidase producing bacteria. The intestinal flora of cancer patients experiencing CID is also noticeably different to that of healthy subjects. Irinotecan causes changes to mucin secretion, and the specific expression of Muc2, Muc4 and Klf4, suggesting that secretory control by the enteric nervous system may also be affected by chemotherapy. This research has extended the understanding of chemotherapy-induced mucositis and diarrhoea, complex side effects of chemotherapy. However, new areas for future research have also been identified. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1352119 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2009

Exposure to air contaminants is significantly associated with both short-term and long-term health effects. However, the precise mechanisms that derive such effects are not always understood. While an extensive background database from in vivo toxicological studies have been developed, most toxicity data is from oral and dermal chemical exposures rather than inhalation exposure. There is a need to explore new alternative approaches to provide toxicity information particularly on this technically demanding area. This research explores the potential of in vitro methods for toxicity assessment of workplace air contaminants. A tiered approach for in vitro toxicity testing of workplace contaminants was designed in which appropriate air sampling and exposure techniques were developed. A diversified battery of in vitro assays including the MTS (tetrazolium salt, Promega), NRU (neutral red uptake, Sigma) and ATP (adenosine triphosphate, Promega) and a multiple human cell system including: A549- lung derived cells; HepG2-liver derived cells, and skin fibroblasts were used. Primarily the application and merits of in vitro methods for prediction of toxicity of selected workplace contaminants including Ammonium hydroxide, Cadmium chloride, Cobalt chloride, Formaldehyde, Glutaraldehyde, Manganese chloride, Mercuric chloride, Sodium dichromate, Sulphureous acid and Zinc chloride was confirmed. To study the toxicity of airborne contaminants an indirect exposure method was established using air sampling techniques followed by static and dynamic direct exposure methods by culturing cells on porous membranes to reveal representative data relating to human airborne exposures. The static method enabled the measurement of an airborne IC50 (50% inhibitory concentration) value for selected volatile organic compounds (VOCs) including: Xylene (IC50 = 5,350-8,200 ppm) and Toluene (IC50 = 10,500- 16,600 ppm) after 1 hr exposure. By implementing the dynamic method, airborne IC50 values were calculated for gaseous contaminants including: NO2 (IC50 = 11 ?? 3.54 ppm; NRU), SO2 (IC50 = 48 ?? 2.83 ppm; ATP) and NH3 (IC50 = 199 ?? 1.41 ppm; MTS). A higher sensitivity of in vitro methods was observed compared to in vivo published data. A range of in vitro bioassays in conjunction with exposure techniques developed in this thesis may provide an advanced technology for a comprehensive risk assessment of workplace air contaminants.

Bibliography: leaves 116-138 / [14], 138 leaves, 5 leaves of plates : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Clinical & Experimental Pharmacology, 1988

Pesticide runoff from agricultural applications poses a potential threat to water quality in the world heritage listed Great Barrier Reef (GBR) and sensitive monitoring tools are needed to facilitate effective monitoring of these pollutants. This thesis has worked to advance passive sampling tools for monitoring trace organic pollutants and their potential impacts on the GBR. The suitability of several available passive sampling tools for detecting trace concentrations of target pesticide analytes was investigated in a laboratory calibration chamber before experiments were conducted to further understanding of the response of Chemcatcher passive samplers in environmental conditions likely to be experienced in the GBR. Passive samplers were deployed in a survey of pesticides in the GBR environment and extracts were applied in bioassays to investigate their application for predicting mixture toxicity to GBR biota. When employed and interpreted appropriately, passive sampling tools have been shown to provide for sensitive and reproducible detection of organic pollutants in relatively pristine environments. While considerable research has been conducted into the performance and theory of analyte uptake by a range of passive sampling devices, several key knowledge gaps existed and were addressed in this study. The applicability of the performance reference compound (PRC) concept as an in situ calibration method for passive samplers using Empore Disk sampling phases (Chemcatchers) to monitor polar compounds was investigated. This experiment showed that while uptake of pesticides was linear and reproducible, PRC loss was not linear, meaning that the dissipation rates of these PRCs cannot be used to estimate the effect of field exposure conditions on uptake rates. An alternative in situ calibration technique using PRC loaded polydimethylsiloxane (PDMS) disks deployed alongside the Chemcatchers as a surrogate calibration phase has been tested and shows promise for future applications. Pesticide concentrations in waters flowing to the GBR have been shown to undergo dramatic fluctuations over short time periods and the potential for these conditions to limit the integrative period of sampling was investigated by simulating a changing concentration event in a calibration chamber. The ability for samplers to predict average concentrations was dependant on the deployment configuration (with or without membrane) used and the period of deployment relative to the changing concentration event. Passive samplers were employed in a survey of pesticides in GBR waters during a wet and dry season at river mouths, two nearshore regions and an offshore region. The nearshore marine environment was shown to be contaminated with pesticides in both the dry and wet seasons (average water concentrations of 1.3-3.8 ng L-1 and 2.2-6.4 ng L-1, respectively), while no pesticides were detected further offshore. Continuous monitoring of two rivers over 13 months showed waters flowing to the GBR were contaminated with herbicides (diuron, atrazine, hexazinone) year round, with highest average concentrations present during summer months (350 ng L-1). The use of passive samplers has enabled identification of insecticides in GBR waters which have not been reported in the literature previously. Extracts from passive samplers deployed at three sites in the GBR were applied to bioassays targeting integral life stages or functions of coral reef biota: scleractinian coral larvae, sea urchin larvae, a marine diatom and marine bacteria. The results demonstrate the utility of pairing passive sampling with bioassays and reveal that mixtures of organic pollutants in the GBR have the potential to cause detrimental effects to coral reef biota. This research outlines an approach that reduces one of the levels of simplification of risk assessment of pollutants to ecosystems by incorporating mixtures of chemicals present in the environment. The use of passive sampler extracts in toxicity testing allows pollutant mixtures to be assessed at a range of enrichment factors and, with the inclusion of biota from the ecosystem of concern, improves the relevance of results for predicting real world effects. The findings of this thesis are intended to be used to improve the application of passive sampling tools for routine monitoring to provide managers with understanding of the pesticides present, the potential effects of those pollutant mixtures and feedback on the efficacy of implemented land management practices in halting and reversing the impacts of pesticides on the GBR.

The current application of low persistence pesticides is unreliable for protecting wooden structures from termite attack. These applications may also pose an environmental and public health risk. Consequently, there is a need for the development of alternative systems to protect wooden structures from termites. Investigated here is the interaction between Australian termites, Coptotermes acinaciformis Froggatt, and to a lesser extent, Mastotermes darwiniensis Froggatt and Schedorhinotermes seclusus Hill, and a barrier system for protection of wooden structures. The aim was to develop an improved barrier for the protection of wooden structures that maximizes protection and minimizes environmental and health risks. Specifically, the performance of a barrier to protect wood against termite attack that incorporates a synthetic pyrethroid into polyurethane formulations is investigated. This research was conducted in parallel with other project contributors focusing on material science aspects of the research goals. A fundamental problem in assessing the value of termite barrier strategies lies in developing and interpreting laboratory assays that can deliver reasonable predictions of performance in the field. This is particularly the case with respect to the behaviour of termites over much longer periods in the field than can be undertaken in the laboratory. The approach to laboratory trials presented here is to define individual termite capabilities and, in combination with behavioural studies, to develop an understanding of factors which affect termite performance. The key experimental approach involved various laboratory based assays to evaluate termite foraging behaviour and performance against a range of barrier materials, progressing to field trials with the best performing material. Various species of termites; M. darwiniensis (Mastotermitidae), Cryptotermes primus (Hill) (Kalotermitidae), C. acinaciformis , Coptotermes frenchi Hill and S. seclusus (Rhinotermitidae), Microcerotermes serratus (Froggatt), Microcerotermes turneri (Froggatt) and Nasutitermes walkeri (Hill) (Termitidae) and Porotermes adamsoni (Froggatt) (Termopsidae); were investigated to determine the force that they can develop at their mandible tips. Larger termites can generate higher pressures on their mandible tips than smaller termites. By quantifying the mandible strength of a termite it was possible to contrast the capabilities of various economic termite species. Damage caused by an individual termite biting on synthetic materials was measured using electron microscope generated three dimensional models of indentations caused to the material. This was successful in quantifying the immediate capabilities of individual termites of different species. Most species were found to inflict a similar amount of damage to high density polyethylene. However M. darwiniensis caused much more damage than other species examined. Micro hardness testing was utilized to determine the relative hardness of pest termite mandibles. Termites were found to have mandibles much harder than any tested synthetic material. It was therefore found to be unrealistic to aim to develop barrier technology based on “harder than termite mandible material”. Trials using groups of termites in the laboratory demonstrated large differences in the performance of termites against various synthetic materials. There was a tendency for harder materials to suffer less damage. Mechanical properties of the barrier alone were found to be insufficient to stop termite damage. The resistance of polyurethane formulations incorporating insecticides to termite attack in the laboratory demonstrated a potential suitability for termite barrier technology. In behaviour trials, persistence of termite attack at the barrier face was found to be due not only to deterrent chemicals, but also to physical characteristics. Softer materials are not only easier for termites to remove but termites attack softer materials with greater tenacity, more termites spend more time attacking softer materials. Laboratory toxicity trials confirmed the bioavailability of Bifenthrin when incorporated within the barrier material and enabled the establishment of expected concentrations for effective protection. Termites were found to require direct contact with the barrier for mortality to occur. Trials designed to quantify repellence of the Bifenthrin in the barrier found that termites did not escape mortality by avoiding contact with the barrier material. As such pure Bifenthrin is shown to protect the barrier material directly by causing mortality rather than by repelling live termites away from the barrier. Field trials were conducted in northern Queensland where colonies of economic termites could be directly targeted. Wooden blocks were coated in polyurethane containing a range of Bifenthrin concentrations and trialed over an eight month period. Combination of the pyrethroid Bifenthrin in a polyurethane barrier at concentrations as low as 0.07% proved successful in preventing damage by the economically important termites M. darwiniensis and C. acinaciformis under high pressure field conditions. Only very small amounts of Bifenthrin migrated into adjacent soil, concentrations reached were in the order of 100 µg/kg of soil. For comparison the MLR for Bifenthrin in bananas for human consumption is 100 µg/kg. Bifenthrin in a polyurethane barrier could be used for the protection of houses and other wooden structures in the same manner as existing barrier film technology in order to minimise environmental and health risks associated with direct pesticide application techniques.