DDT, an extremely widely used organochlorine pesticide, was banned in most developed countries more than 30 years ago. However, DDT residues, including 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (DDE), still persist in the environment and have been identified as priority pollutants due to their toxicity and their ability to bioaccumulate and biomagnify in the food chain. In particular, DDE was long believed to be &quotenon-biodegradable&quote, however some microorganisms have now been isolated that are able to metabolise DDE in pure culture. Terrabacter sp. strain DDE-1 was enriched from a DDT-contaminated agricultural soil from the Canterbury plains and is able to metabolise DDE to 4-chlorobenzoic acid when induced with biphenyl. The primary objective of this study was to identify the gene(s) responsible for Terrabacter sp. strain DDE-1�s ability to metabolise DDE and, in particular, to investigate the hypothesis that DDE-1 degrades DDE cometabolically via a biphenyl degradation pathway. Catabolism of biphenyl by strain DDE-1 was demonstrated, and a biphenyl degradation (bph) gene cluster containing bphDA1A2A3A4BCST genes was identified. The bphDA1A2A3A4BC genes are predicted to encode a biphenyl degradation upper pathway for the degradation of biphenyl to benzoate and cis-2-hydroxypenta-2,4-dienoate and the bphST genes are predicted to encode a two-component signal transduction system involved in regulation of biphenyl catabolism. The bph gene cluster was found to be located on a linear plasmid, designated pBPH1. A plasmid-cured strain (MJ-2) was unable to catabolise both biphenyl and DDE, supporting the hypothesis that strain DDE-1 degrades DDE cometabolically via the biphenyl degradation pathway. Furthermore, preliminary evidence from DDE overlayer agar plate assays suggested that Pseudomonas aeruginosa carrying the strain DDE-1 bphA1A2A3A4BC genes is able to catabolise DDE when grown in the presence of biphenyl. A second objective of this study was to characterise pBPH1. The complete 84,054-bp sequence of the plasmid was determined. Annotation of the DNA sequence data revealed seventy-six ORFs predicted to encode proteins, four pseudogenes, and ten gene fragments. Putative functions were assigned to forty-two of the ORF and pseudogenes. Besides biphenyl catabolism, the major functional classes of the predicted proteins were transposition, regulation, heavy metal transport/resistance, and plasmid maintenance and replication. It was shown that pBPH1 has the terminal structural features of an actinomycete invertron, including terminal proteins and terminal inverted repeats (TIRs). This is the first report detailing the nucleotide sequence and characterisation of a (linear) plasmid from the genus Terrabacter.

This thesis describes a study undertaken between 1992 and 2001 to explore the possible health impacts of human exposure to pesticides. The study followed the health outcomes of approximately 4000 outdoor workers over a period of up to sixty-one years. These workers comprised two subcohorts of approximately even size, one composed of agricultural workers with high insecticide exposures, and the other made up of outdoor staff from local councils in the same area with little or no occupational exposure to insecticides. Mortality and morbidity were compared between the two groups, and with the general Australian community. The study identifies significantly increased mortality among both exposed and control subjects when compared to the Australian population. The major cause of this increase was mortality from smoking related diseases. The study also identifies significant increases in mortality among exposed subjects for a number of conditions that do not appear to be the result of smoking patterns, both when compared to the control group and the Australian population. These include pancreatic cancer in some DDT exposed subjects and asthma, diabetes, and leukaemia in subjects working with more modern chemicals. There was also an increase in self reported chronic illness and asthma, and lower neuropsychological functioning scores among surviving exposed subjects when compared to controls. Diabetes was also reported more commonly by subjects reporting occupational use of herbicides.

Thesis (Ph.D.)--University of Adelaide, Dept. of Soil and Water, 2001. / Bibliography: leaves 177-191.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1967. / Typescript. Vita. Description based on print version record. Includes bibliographical references (leaves 208-226).

Orientador: Lineu Cesar Werneck / Dissertação (mestrado) - Universidade Federal do Paraná. Curso de Pós-Graduação em Medicina Interna / Sem resumo e abstract

Ph.D. / This study consisted of a two-tiered approach to assessment of the effects of EDCs on aquatic organisms, and heavy metal accumulation in the aquatic environment, by integrating field work and laboratory-based experiments. In the last three decades a considerable portion of research in aquatic health and aquatic toxicology has been largely focused on endocrine disruptors, aiming to establish how certain chemicals discharged into the environment, especially organochlorine pesticides (OCs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), surfactants and plasticisers, can mimic endogenous hormones and thereby induce reproductive abnormalities. The rationale behind the present study was the growing interest in the study of endocrine disrupting chemicals (EDCs) internationally and the aspects of this field of research that are relevant to South Africa’s aquatic environment and its endemic aquatic organisms. The field work was carried out in the Rietvlei Wetland System and consisted of a combination of plant root analysis and application of the South African Scoring System 5 (SASS5) macroinvertebrate index. Three characteristic wetland macrophytes used in the study were Typha capensis, Phragmites australis and Persicaria lapathifolia. Samples of plants, sediment and water were taken from predetermined locations along the wetland system in the Rietvlei Nature Reserve and analyzed for heavy metals by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The heavy metals analyzed in this study; lead, arsenic and cadmium, have also been implicated as endocrine disruptors. The results of heavy metal accumulation in the plant roots reflected a pollution trend along the wetland, suggesting that plant roots are useful bioindicators of contamination in freshwater systems.

No description available.

<div>Nitrous oxide (N₂O) has gained popularity as a unique oxidizer due to its ability to decompose exothermically, producing nitrogen and oxygen. Additionally, there are concerns about the safety of nitrous oxide in the nuclear industry where it has been observed that stored nuclear waste generates and retains large amounts of flammable</div><div>gases such as hydrogen and ammonia along with nitrous oxide. These gases are at risk of explosion even in the presence of a weak ignition source which can result in detonations more violent than those initiated directly. Nitrous oxide is also finding an application in the geothermal industry where it is being tested in combination with ethylene as a stimulant mixture to fracture rock. The detonations initiated in this mixture have the ability to produced a network of fractures in the rock formation. In the rocket industry, nitrous oxide has been used for propulsion in multiple systems, but never in a detonative mode. In order to use nitrous oxide in these areas, its detonation properties in combination with a fuel require quantification. Available literature on nitrous oxide-hydrocarbon detonations is mainly restricted to initial pressures below one atm or with dilution. Therefore, detonations with nitrous oxide as the oxidizer are far from being completely characterized. In addition to this lack of general knowledge, understanding of nitrous oxide-fuel detonations at higher pressures, more typical of practical combustion systems is either extremely limited or</div><div>non-existent.</div><div><br></div><div>In the current work, the flame acceleration, deflagration-to-detonation transition (DDT), and detonation properties of a bipropellant mixture of ethylene (C₂H₄) and N₂O are studied as a function of initial pressures. These properties are compared to those in mixtures of ethylene-oxygen (O₂). these detonations are investigated in a combustion tube designed and fabricated in-house. The performances of these two mixtures are also investigated using theoretical Chapman-Jouguet detonation calculations as a basis of comparison with the measured properties. Additionally, detonation properties in a mixture of acetylene (C₂H₂) and nitrous oxide are also investigated to compare the two fuels. While C₂H₂ is a highly energetic fuel with theoretically high performance, it presents serious practical storage concerns when considered for propulsion applications. These practical issues motivates the investigation of C₂H₄as a potential alternative fuel, which is relatively easy to manage. </div><div><br></div><div>A critical requirement for the application of bipropellant mixtures to detonation systems is rapid flame acceleration to achieve significant chamber pressure rise in a short distance with the potential for a prompt transition to detonation. This DDT behavior of mixtures using N₂O and O₂ with C₂H₄ and C₂H₂ is investigated for increasing initial pressures in the experimental portion of this work. This behavior is quantified by measuring the run-up distances leading to DDT. The pre-compression of the bipropellant mixtures during flame acceleration caused by the accelerating flame is also estimated and directly measured using appropriate instrumentation. These direct measurements of pre-compression are further used to estimate the path of the</div><div>accelerating flame in the combustion tube. These estimates are compared with the flame tracked by high-speed imaging in an optically accessible combustion tube.</div>

MEnvSC / Department of Ecology and Environmental Science

In vitro testing includes both cell-based and cell-free systems that can be used to detect toxicity induced by xenobiotics. In vitro methods are especially useful in rapidly gathering intelligence regarding the toxicity of compounds for which none is available such as new chemical entities developed in the pharmaceutical industry. In addition to this, in vitro investigations are invaluable in providing information concerning mechanisms of toxicity of xenobiotics. This type of toxicity testing has gained popularity among the research and development community because of a number of advantages such as scalability to high throughput screening, cost-effectiveness and predictive power. Hepatotoxicity is one of the major causes of drug attrition and the high cost associated with drug development poses a heavy burden on the development of new chemical entities. Early detection of hepatotoxic agents by in vitro methods will improve lead optimisation and decrease the cost of drug development and reduce drug-induced liver injury. Literature highlights the need for a cellbased in vitro model that is capable of assessing multiple toxicity parameters, which assesses a wider scope of toxicity and would be able to detect subtle types of hepatotoxicity. The present study was aimed at developing an in vitro procedure capable of mechanistically profiling the effects of known hepatotoxin dichlorodiphenyl trichloroethane (DDT) and its metabolites, dichlorodiphenyl dichloroethylene (DDE) and dichlorodiphenyl dichloroethane (DDD) on an established liver-derived cell line, HepG2, by evaluating several different aspects of cellular function using a number of simultaneous in vitro assays on a single 96 well microplate. Examined parameters have been suggested by the European Medicines Agency and include: cell viability, phase I metabolism, oxidative stress, mitochondrial toxicity and mode of cell death (apoptosis vs. necrosis). To further assess whether the developed method was capable of detecting hepatoprotection, the effect of the known hepatoprotectant, N-acetylcysteine, was determined. Viability decreased in a dose-dependent manner yielding IC50 values of 54 μM, 64 μM and 44 μM for DDT, DDE and DDD, respectively. Evaluation of phase I metabolism showed that cytochrome P4501A1 activity was dose-dependently induced. Test compounds decreasedlevels of reactive oxygen species, and significantly hyperpolarised the mitochondrialmembrane potential. Assessment of the mode of cell death revealed a significant elevation of caspase-3 activity, with DDD proving to be most potent. DDT alone induced dosedependent loss of membrane integrity. These results suggest that the tested compounds produce apoptotic death likely due to mitochondrial toxicity with subsequent caspase-3 activation and apoptotic cell death. The developed in vitro assay method reduces the time it would take to assess the tested parameters separately, produces results from multiple endpoints that broadens the scope of toxicity compared to single-endpoint methods. In addition to this the method provides results that are truly comparable as all of the assays utilise the same batch of cells and are conducted on the same plate under the exact same conditions, which eliminates a considerable amount of variability that would be unavoidable otherwise. The present study laid a solid foundation for further development of this method by highlighting the unforeseen shortcomings that can be adjusted to improve scalability and predictive power. / Thesis (PhD)--University of Pretoria, 2011. / Pharmacology / unrestricted