Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. Description based on print version record. Includes bibliographical references (leaves 203-211).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1980. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Pectenotoxins (PTXs) are a group of large cyclic polyether compounds associated with diarrhetic shellfish poisoning (DSP) as they are often found in combination with other DSPs such as okadaic acid (OA) and dinophysis toxins (DTXs) in shellfish. Although classified and regulated with the DSPs, there is debate over whether these toxins should be classified with DSP toxins. To date, ten different analogues of PTXs have been identified from shellfish and algae, and of these, the pectenotoxin-2 seco acids (PTX2-SAs) are of particular interest as they have previously been implicated in a shellfish poisoning incident in Australia, but relatively little was known of their toxicology. One such incident occurred in December 1997, when approximately 200 people were reported with severe diarrhoetic shellfish poisoning in Northern New South Wales (NSW). Analysis of the shellfish associated with this incident revealed relatively high PTX2-SA concentrations (approx. 300 micrograms/kg shellfish meat), with only trace amounts of pectenotoxin-2 (PTX2) and OA. Following this incident, PTX2-SAs were considered a health threat and guidelines were implemented in the absence of toxicological data, which has caused a great economic burden to shellfish industries around the globe, in particular to Australia, New Zealand and Ireland. Such regulation created in the absence of scientific data demonstrated the need to determine the toxicology of PTX2-SAs in commercial shellfish. Thus a comprehensive study on the toxicology and possible health implications of the PTX2-SAs in Australian shellfish was conducted. PTX2-SAs were isolated in different batches from shellfish (pipis, oysters and mussels) and from algal bloom samples of Dinophysis caudata. Toxin extraction was conducted with several purification stages and chemical analysis was performed with high-performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS). The chemical stability of the PTX2-SAs was investigated to ensure consistency of doses between toxicology experiments. Acute dosing studies with mice were then performed and included toxicopathology investigations with light microscopy and electron microscopy, in addition to toxin distribution studies and investigation of in vivo lipid peroxidation. In vitro studies with HepG2 cells included cytotoxicity assays, cell cycle investigations using flow cytometry and gene expression profiling of cells exposed to PTX2-SAs employing cDNA microarray technology. Acute pathology studies demonstrated that the PTX2-SAs do not cause the characteristic symptoms or lesions associated with DSP toxins. No diarrhoea was observed at any dose level in mice and no deaths occurred up to the maximum dosing level of 1.6mg/kg PTX2-SA. Only one batch of PTX2-SA extract produced toxic lesions characteristic of a DSP toxin (batch 1-pilot study) but after follow up studies, it was determined that this first batch of shellfish most likely contained an additional unidentified shellfish toxin or contaminant that co-extracted with PTX2-SAs during toxin isolation and purification procedures. This finding highlighted the importance of supporting the inclusion of the mice bioassay in procedures for shellfish toxin testing to enable detection of new toxins, and also highlighted the importance of toxin purification for toxicology studies. A significant rise in malondialdehyde excretion was observed within 24 hours of dosing mice, indicating that the PTX2-SAs may cause damage by lipid peroxidation in vivo. In vitro studies showed HepG2 cells to have cell cycle and gene expression changes within 24 hours of a dose of 800ng/mL PTX2-SAs. Cell cycle arrest was observed at the G2/M checkpoint and gene expression changes included alterations in genes involved in cell cycle control, lipid metabolism and transport, lipid genesis and trace metal transport. Many genes involved in DNA repair processes were moderated at the 24 hour point, but as no apoptosis was observed up to 72 hours post dosing it is a promising indication that any DNA damage that may have been caused by the administration of PTX2-SAs was not lethal, and was able to be repaired. In light of the information provided by toxicology investigations in this PhD, with particular reference to evidence of in vivo lipid peroxidation by raised levels of MDA in mouse urine, and changes in cell cycle distribution and gene expression in a cultured human cell line, it is concluded that there is potential for these toxins to induce biological changes in mammalian cells in vivo and in vitro, and hence potential for PTX2-SAs to cause health effects in humans. During the course of this three-year study, developments in techniques for shellfish toxin identification within our laboratories have revealed that the shellfish responsible for the 1997 NSW poisoning incident contained significant concentrations of okadaic acid acyl esters that were not detected at the time of the NSW incident. Although reportedly less toxic than okadaic acid itself, the OA ester concentrations present may have been sufficient to cause the observed symptoms. It is also theorized that these esters could be hydrolyzed in the human gastro-intestinal tract to release okadaic acid. In the light of this new evidence and with no pathology lesions or symptoms of diarrhoea being observed in PTX2-SA dosing studies with mice, we now believe these OA acyl esters to be the causative agent in the 1997 NSW DSP incident and not the PTX2-SAs. Nothing is currently known of the chronic toxicology of PTX2-SAs and thus their potential implications to public health in the long term cannot determined. The toxicology investigations in this thesis were acute studies, and it has not been established if the observed changes could be repaired or returned within normal limits without the manifestation of illness or disease occurring. Utilizing the acute toxicology information in this thesis, a health risk assessment for consumption of PTX2-SA contaminated shellfish was performed. This risk assessment, employing numerous safety factors essential for an incomplete data set, produced guideline values that are lower than the current recommend concentrations. To date, there has been no solid evidence that PTX2-SAs cause illness in humans – all documented incidents involving the PTX2-SAs have also included other DSP contaminants that are known to cause human illness. Pathology has not unequivocally been demonstrated in animal studies and thus, in consideration of the epidemiological evidence, PTX2-SAs cannot be considered as high a risk to public health as was previously thought. For the reasons discussed above, and weighing up risk-benefit considerations of the economic burden the current guideline values are causing to shellfish industries around the globe, it is recommended that levels of PTX2-SAs be monitored in recognition of the precautionary principle, but no longer regulated as tightly with other DSPs until such a time that toxicological or epidemiological evidence can prove that the PTX2-SAs are a DSP and are a more considerable threat to human health than has been indicated by toxicology studies in this thesis. This study has produced a substantial amount of acute toxicology data and has provided a good basis for future chronic toxicology investigations with the PTX2-SAs for regulatory purposes.

Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references (leaves 118-130). Also available in electronic version. Access restricted to campus users.

No description available.

No description available.

With declining wild fisheries and increasing seafood demand from a growing population, attention has turned to aquaculture in general, and shellfish aquaculture in particular, to meet this demand. Aquaculture has grown dramatically in the last twenty years through intensification of operations and the expansion of the industry into new areas. This growth has been associated with environmental degradation and social conflict leading some to question its sustainability. However, those studying the problem point to significant opportunities for sustainable forms of aquaculture by focusing on the cultivation of species such as shellfish and the adoption of ecosystem-based management (EBM). Shellfish aquaculture has a long history in British Columbia (B.C.), Canada with an abundance of coastline and suitable water conditions. There is significant development potential for shellfish aquaculture in B.C., which creates an opportunity to ensure this development occurs in an ecologically sound way through the use of governance approaches like ecosystem-based management. Transitioning from conventional approaches to resource management to an ecosystem-based approach presents several challenges particularly for the management of one sector. This study highlights how an understanding of the industry and the existing governance context can inform the implementation of EBM. The specific research objectives include: (1) to understand the governance system for shellfish aquaculture in B.C.; (2) to understand the shellfish aquaculture industry within the context of EBM; and (3) to explore EBM as an approach to governance in the shellfish aquaculture industry in B.C. The main method of inquiry is a questionnaire survey (October 2006 to February 2008) of the shellfish aquaculture industry. Supporting methods include an analysis of industry data, an in-depth analysis of government documents, policies and regulations, and targeted interviews with federal and provincial government regulators. The empirical knowledge gained through the main research instrument was combined with the contextual knowledge gained through the supporting methods to achieve a more holistic understanding of the case study. The results show that the governance setting for the shellfish aquaculture industry is multi-lateral and the lack of comprehensive and targeted legal instruments, and the ill-use of marine spatial planning and conflicts with other coastal users have together contributed to an inefficient and costly site application process. EBM has the potential to address some of these challenges with the current governance process by making some decisions on an ecosystem-scale as opposed to an application-by-application basis, such as assessing the presence of fish habitat and consulting with stakeholders. The results of the survey of the shellfish aquaculture industry show that the industry is geographically diverse, and understands and values the connection between their business and the large ecosystem. This suggests that the industry may be supportive of EBM. However, the industry faces many economic challenges that may influence their capacity to participate, as such regulators should look towards the use of economic incentives to achieve policy objectives. Although this research provided several recommendations for management and the industry in moving forward with this new approach to governance, three fundamental elements are needed: • marine spatial planning that is integrated within the governance framework; • the integration science and management through adaptive management including an ongoing monitoring framework that informs governance strategies; and, • engaging the industry as active partners in this governance approach through co-management. This research makes significant contribution to understanding the shellfish aquaculture industry in B.C. Prior to this study there was little information available characterizing the structure and socio-economic make-up of the industry. The results of the survey and the in-depth analysis of the governance context for the shellfish aquaculture industry provide a previously unavailable base of information from which to build future studies. In addition this research contributes to the growing body of literature on EBM assessing the potential challenges and opportunities for moving the theoretical concept into practice. / Graduate

Graduation date: 1950

Thesis (M. Sc.)--Acadia University, 1997. / Includes bibliographical references. Also available on the Internet via the World Wide Web.

Thesis (M. Sc.)--Acadia University, 1997. / Includes bibliographical references. Also available on the Internet via the World Wide Web.