O presente trabalho objetivou avaliar a capacidade de um sal mineral rico em molibdênio (Mo) em prevenir a intoxicação cúprica acumulativa (ICA), analisando variáveis clínicas, sangüíneas e os teores de cobre (Cu) e Mo hepático. Foram utilizados 25 ovinos da raça Ilede-France, aleatoriamente distribuídos em cinco grupos de cinco animais de cada, sendo que o grupo 1 recebia dieta contendo 80% volumoso e 20% concentrado, os grupos 2 e 3 recebiam 50% volumoso e 50% concentrado, e os grupos 4 e 5 recebiam a mesma dieta dos grupos 2 e 3 com a adição diária de 150 mg de sulfato de Cu até o término do experimento (150 d). Os grupos 1, 3 e 5 recebiam sal mineral contendo 300 ppm de Mo. Foram realizadas três biópsias hepáticas para determinação da concentração de Cu, Mo e Zn neste órgão e três ensaios de retenção aparente de Cu e Mo (0 d, 75 d, 150 d). Quinzenalmente, foi realizado exame clínico e coleta de amostras de sangue e urina. Três ovinos do grupo 4 e um do grupo 5 manifestaram ICA. Não existiu diferença entre a freqüência de mortalidade entre os grupos (P = 0,56). Os teores de Cu hepático nos ovinos com ICA (2450 ppm) foram superiores aos que não intoxicaram (1518 ppm). Quanto maior a ingestão de Mo na dieta menor foi o acúmulo de Cu hepático ao término do experimento (r = -0,72). Ovinos com ICA aumentaram a concentração de Zn hepático nas fases finais da intoxicação. A presença de altas atividades de GGT (>56,5 U/L) e de AST (>120 U/L) indicaram de maneira efetiva a presença de destacado acúmulo de Cu nos tecidos hepáticos (1000 ppm). / The aim of this project is to evaluate the capacity of a molybdenum-rich mineral salt in the prevention of cumulative cooper poisoning (CCP) in sheep, through clinical and blood exams and hepatic copper and molybdenum concentrations. Twenty five Ile-de-France sheep were randomly distributed into five groups of five animals each, where group 1 received a 80% forrage and 20% concentrate diet, groups 2 and 3 received a 50% forrage and 50% concentrate diet, and groups 4 and 5 received the same diet as groups 2 and 3 with a daily supplementation of 150mg of copper sulphate until the end of the experiment (150 d). Groups 1, 3 and 5 received a mineral salt with 300 ppm of molybdenum. For three times during the experiment (day zero, 45th and 105th day) a liver biopsy was carried out to evaluate the degree of copper accumulation in this organ. Clinical examination was followed every two weeks, as far as blood and urine samples were withdrawn. Three sheep from group 4 and one sheep from group 5 presented clinical picture of CCP. There was no difference in the frequency of mortality between groups 4 and 5 (P = 0.56). The liver copper concentration was higher in sheep with CCP (2450 ppm) compared to sheep that not presented CCP (1518 ppm). The higher the ingestion of molybdenum in the diet the lower the liver copper concentration at the end of the experiment (r = -0.72). Sheep with CCP had higher liver zinc concentration. The presence of high activity of GGT (> 56.5 U/L) and AST (>120 U/L) indicated effectively the high accumulation of copper in liver (> 1000 ppm).

Para comparar o risco de intoxicação por uréia granulada (G) e extrusada (E) 24 garrotes, nunca alimentados com uréia, foram distribuídos em quatro grupos de seis animais, onde foi administrada, de uma só vez, (G) ou (E) em duas diferentes doses: alta (A; 0,5 g/kg PV) ou padrão (B; 0,22 g/kg PV). Em seguida, foram acompanhados o pH e os teores de amônia no rúmen, as concentrações sangüíneas de amônia, uréia, creatinina, glicose, lactato-L, potássio, as atividades de gama glutamiltransferase, aspartato aminotransferase e creatina quinase, perfil hemogasométrico e hematócrito, além de acompanhamento quadro clínico no decorrer de 240 min após as administrações de G ou E. Alguns animais dos grupos GB e EB tiveram um discreto quadro de intoxicação, se recuperando sem quaisquer tratamentos. Por outro lado, cinco garrotes de ambos grupos GA e EA tiveram severo quadro tóxico que exigiram tratamento, sendo que um animal GA sucumbiu. A velocidade de hidrólise ruminal da uréia G e E foi semelhante, embora as manifestações clínicas tenha sido iniciadas mais tardiamente no grupo EA. Quanto mais intensa foi a hiperamoniemia mais destacada foi o grau de acidose metabólica, desidratação, a glicólise anaeróbica e a gliconeogênese. Pela análise das atividades enzimáticas comprovou-se que os danos bioquímicos foram intensos na musculatura, mas não nos hepatócitos. Concluiu-se que tanto a uréia G como E quando oferecidas subitamente, em especial em doses altas, podem oferecer igual risco de intoxicação por amônia. / To compare the toxicity potential of prilled urea (G) and extruded grain with urea (E), both were administered all at once in two different doses, high (A; 0,5 g/kg BW) or standard (B; 0,22 g/kg BW), to 24 steers divided into four groups of six animals, which had never been fed nonprotein nitrogen compounds. For 240 min after the administration of urea the following variables were determined: rumen fluid pH and ammonia level, blood ammonia, urea, creatinine, glucose, L-lactate, potassium, and activities of gama glutamiltranspeptidase, aspartate aminotransferase and creatine kinase, haemogasometric profile and hematocrit. The clinical picture was also followed. Some steers from groups GB and EB showed slight signs of ammonia toxicity, overcoming it without treatment. On the other hand, five steers from either groups GA and EA showed severe signs of ammonia toxicity that required treatment; even though one animal from group GA succumbed. The speed of ruminal urea hydrolysis of G and E was similar, although the clinical signs started later in group EA. The higher the hyperammonemia, the higher the metabolic acidosis, dehydration, anaerobic glycolysis and gluconeogenesis. The enzymatic profile showed that biochemical damage occurred in the striated muscular tissue, but not in the hepatocytes. The results showed that both G and E had similar potential to cause ammonia poisoning, principally when high doses were administered all at once.

O desenvolvimento na área agroquímica associado as novas técnicas de plantio, asseguram ao país recordes anuais na produção agrícola. Entretanto, os defensivos agrícolas e fertilizantes utilizados para aumentar a produção das lavouras não são inertes a saúde humana. Exposições contínuas e inadequadas a esses compostos químicos podem causar sua absorção e resultar em intoxicações agudas ou crônicas. Com o objetivo de avaliar essas exposições, dosamos a atividade da enzima acetilcolinesterase, assim como, avaliamos os hemogramas e dosamos os níveis sanguíneos dos metais arsênio (As), cádmio (Cd), chumbo (Pb), manganês (Mn), zinco (Zn), cobre (Cu) e o não metal selênio (Se) em trabalhadores rurais e moradores da área urbana da região de Rio Verde-GO e comparamos esses resultados. A atividade média da enzima colinesterase eritrocitária nos trabalhadores rurais apresentou uma depressão significativa indicando uma exposição inadequada aos inseticidas inibidores das colinesterases. As concentrações sanguíneas médias dos metais As, Cd, Mn, e Zn nos trabalhadores rurais são maiores do que na população urbana, indicando que as exposições inadequadas aos fertilizantes e defensivos agrícolas podem causar absorção desses metais. A concentração sanguínea média de Se na população urbana é maior do que nos trabalhadores agrícolas. Esse fato pode estar ligado a alimentação, sendo que, uma provável causa seria o baixo consumo de alimentos ricos em selênio (castanha-do-pará, salmão, farelo de trigo, ostras e fígado bovino). Os hemogramas não apresentaram alterações, indicando que, sua utilização isolada na monitorização das exposições ocupacionais aos defensivos agrícolas e fertilizantes é inadequada. / Advancements in the agrochemical industry associated with new seeding techniques make it possible for the country to reach annual crop records in production. However, the chemicals and fertilizers used for increasing productions are by no means harmless to human health. Repeated and inadequate exposures to such chemicals may result in their absorption and cause acute and chronic poisoning. In order to assess these exposures, we measured the activity of the acetylcholinesterase enzyme and evaluated hemograms. In addition, we measured blood levels of metals such as arsine (As), cadmium (Cd), lead (Pb), manganese (Mn), zinc (Zn), copper (Cu), and the non metallic selenium in farm workers and urban residents in a region of Rio Verde- GO- Brazil and compared the results. Mean activity of the erythrocyte cholinesterase enzyme in the rural workers presented a significant decrease, indicative of inadequate exposure to cholinesterase inhibiting insecticides. Mean concentrations of the metals As, Cd, Mn, and Zn were higher in rural workers compared to urban residents, which suggests that inadequate exposure to fertilizers and agricultural chemicals may result in their absorption. Mean blood concentration of Se in urban residents was higher compared to rural workers. That can be associated with diet and a possible cause may be a low consumption of high Se foods (Brazils nuts, salmon, oysters, wheat bran, and bovine liver). The hemograms did not present any changes, indicating that its use for monitoring occupational exposures to fertilizers and agricultural chemicals is inadequate.

" This work investigated the long-term stability of sulfur tolerant Pd/Cu alloy membranes for hydrogen separation by performing characterizations lasting several thousand hours in H2, He and H2S/H2 atmospheres ranging in concentration from 0.2 – 50 ppm and temperatures ranging from 250 - 500ºC. Two methods were used for fabricating the Pd/Cu membranes so that the sulfur tolerant fcc alloy would remain on the surface and minimize the decrease in hydrogen permeance inherent with fcc Pd/Cu alloys. The first method consisted of annealing a Pd/Cu bi-layer at high-temperatures and the second consisted of depositing a Pd/Cu/Pd tri-layer with an ultra-thin surface alloy. High temperature X-ray diffraction (HT-XRD) was employed to study the kinetics of the annealing process and atomic adsorption spectroscopy (AAS) was used to investigate the kinetics of the Cu deposition and Pd displacement of Cu. Upon the introduction of H2S, the permeance decrease observed was dependent upon the H2S feed concentration, and not the time of poisoning. However, after the recovery in pure H2 there was a portion of the permeance which could not be recovered due to adsorbed sulfur blocking H2 adsorption sites. The amount of recoverable permeance was dependent on the time of exposure to H2S and reached a limiting value which decreased with temperature. X-ray photoemission spectroscopy (XPS) was used to investigate poisoned samples and it was observed that the permeance not recovered at a given temperature in H2 was caused mostly by Cu sulfides. Both bi-layer and tri-layer membranes had hydrogen permeances which were higher than homogeneous Pd/Cu membranes of the same surface concentration. However, the tri-layer membranes performed as well as Pd membranes thus eliminating the disadvantage of alloying Pd with Cu without sacrificing sulfur tolerance. "

Orientador: Mario Roberto Hatayde / Banca: Mirela Tinucci Costa / Banca: Wanderson Adriano Biscola Pereira / Resumo: O N. oleander é uma planta com ampla distribuição mundial, principalmente em regiões tropicais e subtropicais. Esses arbustos são frequentemente usados como plantas ornamentais e possuem mais de 30 glicosídeos cardíacos, causadores do quadro clínico de intoxicação em caninos. O objetivo deste trabalho foi avaliar as alterações clínicas, eletrocardiográficas, bioquímicas, hematológicas e histológicas do rim e avaliar o efeito do uso da frutose 1,6 difosfato e da glicose como alternativas de tratamento em cães intoxicados com 0,25g/Kg de folhas frescas trituradas e adicionadas à ração em única dose. Foram utilizados 10 cães adultos, hígidos, sem raça definida, com 10 a 25Kg de peso, de 4 a 8 anos de idade. Foram distribuídos em dois grupos (Gl e Gll) com 5 animais cada. Para o Gl o tratamento consistiu na administração de uma solução a 10 % de glicose a 50mg/Kg via intravenosa (IV) e em seguida uma infusão continua a 10% de glicose IV por uma hora a 10ml/kg e Gll recebeu frutose 1,6 difosfato, IV a 50mg/Kg, e em seguida uma infusão a 10% da mesma solução, durante uma hora a 10ml/kg. Nenhum dos animais do experimento veio a óbito e todos apresentaram sinais após a intoxicação como: vômito, sialorréia, náuseas, apatia, conjuntiva ocular congesta, desidratação, dor abdominal, tremores, diarréia, inapetência e tenesmo. Observou-se elevação principalmente da GGTU, CK e CKMB. Pela análise do eletrocardiograma encontrou-se arritmias como: bradicardia sinusal, bloqueios atrioventriculares de segundo grau, taquicardia ventricular paroxística e complexos ventriculares prematuros. Na histopatologia não se encontrou alterações no rim. Não observou-se diferença significativa entre tratamentos e na parte clínica houve melhora para Gll observada no consumo de alimento ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: N. oleander is a plant with worldwide distribution, mainly in tropical and subtropical regions. These shrubs are frequently used as ornamental plants and have more than 30 cardiac glycosides that can cause poisoning in dogs. The objective of this study was to evaluate alterations in clinical, electrocardiographic, biochemical, hematological parameters, as well as kidney histology, and to evaluate the effect of the use of fructose 1,6 diphosphate and glucose as alternative treatments in dogs poisoned by 0.25 g/kg of fresh ground leaves added to the kibble in a single dose. Ten adult, healthy, mongrel dogs weighing 10 to 25kg and 4 to 8 years old were selected for the study. They were distributed into two groups (GI and GII) of 5 animals each. For GI, treatment consisted of intravenous (IV) administration of 50 mg/kg of a 10% glucose solution followed by continuous IV infusion of 10% glucose at 10 ml/kg for one hour. GII received a solution of fructose 1,6 diphosphate at a dose of 50 mg/kg intravenously followed by infusion of 10 ml/kg of the same 10 % solution for one hour. None of the animals died and all exhibited signs of poisoning as: vomiting, sialorrhea, nausea, apathy, conjunctiva congestion, dehydration, abdominal pain, tremors, diarrhea, loss of appetite and tenesmus. An increase in values of biochemical parameters, especially urinary γ-glutamyl transpeptidase (GGTU), creatinine kinase (CK) and myocardial bound creatinine kinase (CKMB) were mainly. The electrocardiogram revealed arrhythmias such as: sinus bradycardia, second degree atrioventricular block, paroxysmal ventricular tachycardia and ventricular premature complexes. No alterations were found for kidney histology. No significant difference was seen when comparing treatments. Clinically, there was improvement in feed consumption observed for GII ... (Complete abstract click electronic access below) / Mestre

Typescript (photocopy). / Digitized by Kansas Correctional Industries

Para comparar o risco de intoxicação por uréia granulada (G) e extrusada (E) 24 garrotes, nunca alimentados com uréia, foram distribuídos em quatro grupos de seis animais, onde foi administrada, de uma só vez, (G) ou (E) em duas diferentes doses: alta (A; 0,5 g/kg PV) ou padrão (B; 0,22 g/kg PV). Em seguida, foram acompanhados o pH e os teores de amônia no rúmen, as concentrações sangüíneas de amônia, uréia, creatinina, glicose, lactato-L, potássio, as atividades de gama glutamiltransferase, aspartato aminotransferase e creatina quinase, perfil hemogasométrico e hematócrito, além de acompanhamento quadro clínico no decorrer de 240 min após as administrações de G ou E. Alguns animais dos grupos GB e EB tiveram um discreto quadro de intoxicação, se recuperando sem quaisquer tratamentos. Por outro lado, cinco garrotes de ambos grupos GA e EA tiveram severo quadro tóxico que exigiram tratamento, sendo que um animal GA sucumbiu. A velocidade de hidrólise ruminal da uréia G e E foi semelhante, embora as manifestações clínicas tenha sido iniciadas mais tardiamente no grupo EA. Quanto mais intensa foi a hiperamoniemia mais destacada foi o grau de acidose metabólica, desidratação, a glicólise anaeróbica e a gliconeogênese. Pela análise das atividades enzimáticas comprovou-se que os danos bioquímicos foram intensos na musculatura, mas não nos hepatócitos. Concluiu-se que tanto a uréia G como E quando oferecidas subitamente, em especial em doses altas, podem oferecer igual risco de intoxicação por amônia. / To compare the toxicity potential of prilled urea (G) and extruded grain with urea (E), both were administered all at once in two different doses, high (A; 0,5 g/kg BW) or standard (B; 0,22 g/kg BW), to 24 steers divided into four groups of six animals, which had never been fed nonprotein nitrogen compounds. For 240 min after the administration of urea the following variables were determined: rumen fluid pH and ammonia level, blood ammonia, urea, creatinine, glucose, L-lactate, potassium, and activities of gama glutamiltranspeptidase, aspartate aminotransferase and creatine kinase, haemogasometric profile and hematocrit. The clinical picture was also followed. Some steers from groups GB and EB showed slight signs of ammonia toxicity, overcoming it without treatment. On the other hand, five steers from either groups GA and EA showed severe signs of ammonia toxicity that required treatment; even though one animal from group GA succumbed. The speed of ruminal urea hydrolysis of G and E was similar, although the clinical signs started later in group EA. The higher the hyperammonemia, the higher the metabolic acidosis, dehydration, anaerobic glycolysis and gluconeogenesis. The enzymatic profile showed that biochemical damage occurred in the striated muscular tissue, but not in the hepatocytes. The results showed that both G and E had similar potential to cause ammonia poisoning, principally when high doses were administered all at once.

Made available in DSpace on 2016-04-28T20:16:24Z (GMT). No. of bitstreams: 1 2007- Flavio Augusto Soares Graca01.pdf: 782491 bytes, checksum: aca3b139eb03d06af06c5dd1c95ec3d7 (MD5) Previous issue date: 2007-04-26 / Crotalus poisoning was experimentally reproduced by inoculation of Crotalus durissus terrificus (South American Rattlesnake) venom by subcutaneous via in ten clinically healthy mixed breed bovine, weighing between 125 and 449 kg and aged 12 to 36 months. Two bovine of the same age range and breed standard were used as controls. The bovine that received a 0.03 mg/kg p.v. dose died 7h40min after inoculation. A 0.015 mg/kg p.v. dose provoked death in four out of seven inoculated bovine, while two bovine experimentally poisoned with 0.0075 mg/kg p.v. became mildly sick and recovered. Onset of symptoms occurred between 1h30min and 13h45min after inoculation. Evolution oscillated between 5h25min and 44h59min for bovine deaths and between 33h15min and 17 days for bovine that recovered. The principal nervous signs observed were diminished response to external stimuli, hypotonic reflexes, dragging of hooves along the ground, apparent lethargy, difficulties in moving around obstacles, ocular globe paralysis, lateral and sternal decubitus and tongue paralysis. Constant adypsia and petechiae in the conjunctival and vaginal mucosa was also verified. A discrete to moderate increase in bleeding time was verified in six bovine and a moderate increase in partial thromboplastin time was activated in seven bovine. Moderate leukocytosis with neutrophilia, relative lymphopenia, eosinopenia and monocytosis occurred and a discrete increase in the number of rods. A significant increase in creatine kinase serum levels was observed, of a ten-fold order. No significant alterations were observed at urinalysis. At necropsy there were minimal edema at the inoculation site, discrete petechiae and suffusions in the epicardium, omentum, biliary vesicle and bladder mucosa. Histopathological examination revealed necrosis (hyalinization) of groups or isolated myocytes in ten different muscles examined, both close and distant from the inoculation site. Faced with the clinic-pathological picture, observations were made regarding the diagnosis of crotalus envenomation and its differentiation from deseases which course with paralysis and muscular necrosis in cattle in Brazil. / Reproduziu-se experimentalmente o envenenamento crot?lico, atrav?s da inocula??o, por via subcut?nea, do veneno de Crotalus durissus terrificus (Cascavel sul-americana) em dez bovinos mesti?os, com peso variando entre os 125 e 449 quilogramas e idade entre 12 e 36 meses. Dois animais na mesma faixa et?ria e padr?o racial foram utilizados como controle. O animal que recebeu dose de 0,03 mg/kg p.v. foi a ?bito 7h40min ap?s a inocula??o. A dose de 0,015 mg/kg p.v. induziu o ?bito em quatro de sete bovinos inoculados, enquanto os dois animais que receberam 0,0075 mg/Kg, adoeceram discretamente e se recuperaram. Os sintomas tiveram in?cio entre 1h30min e 13h45min ap?s a inocula??o. A evolu??o oscilou entre 5h25min e 44h59min para os animais que morreram e entre 33h15min e 17 dias entre os animais que se recuperaram. Os principais sinais nervosos observados foram diminui??o da resposta aos est?mulos externos, reflexos hipot?nicos, arrastar dos cascos no solo, aparente letargia, paralisia do globo ocular e da l?ngua, dec?bito esternal e lateral. Verificou-se tamb?m adipsia constante e pet?quias nas mucosas vaginal e conjuntival. Observaram-se discreto a moderado aumento do tempo de sangramento em seis animais e moderado aumento do tempo de tromboplastina parcial ativada em sete bovinos. Houve moderada leucocitose com neutrofilia, linfopenia relativa, eosinopenia, monocitose e discreto aumento do n?mero de bast?es. Foi evidenciado significativo aumento dos n?veis s?ricos de creatinaquinase, da ordem de dez vezes. N?o foram observadas altera??es significativas atrav?s da urin?lise. ? necropsia constataram-se edema quase impercept?vel no local da inocula??o, discretas pet?quias e sufus?es no epic?rdio, omento, ves?cula biliar e mucosa da bexiga. Os exames histopatol?gicos revelaram necrose (hialiniza??o) de grupos de mi?citos ou em mi?citos isolados em dez diferentes m?sculos esquel?ticos examinados, pr?ximos ou distantes do local de inocula??o. Diante do quadro cl?nico-patol?gico foram feitas observa??es sobre o diagn?stico do envenenamento crot?lico e sua diferencia??o com enfermidades que cursam com paralisia e necrose muscular em bovinos do Brasil.

This thesis investigates the use of single Cooper-pair transistor (SCPT) for fast and sensitive detection of quasiparticle dynamics. This investigation is motivated by the possibility of quantum information processing using superconducting nanoscale circuits, such as the SCPT and the Cooper-pair-box (CPB). In the SCPT coherent charge transport can be temporarily halted due to quasiparticle tunnelling, known as quasiparticle poisoning. Quasiparticle poisoning can be reduced by the use of engineered island and lead gap energies. The thesis begins by reporting measurements of the superconducting gap in aluminium - aluminium-oxide - aluminium tunnel junctions, as a function of film thickness. We have observed an increase in the superconducting energy gap of aluminium with decreasing film thickness. This method is used to engineer the island and gap energies in a SCPT and consequently we observe reduced poisoning and a modification of the thresholds for finite bias transport processes. Radio-frequency reflectometry is used to perform high-bandwidth measurements of quasiparticle tunnelling in a gap engineered SCPT. A model for the radio-frequency (rf) operation of the SCPT is presented and shows close agreement with experiment. Thermal activation of the quasiparticle dynamics is investigated, and consequently, we are able to determine energetics of the poisoning and unpoisoning processes. This enables an effective quasiparticle temperature to be determined, allowing the poisoning to be parametrised. An investigation of the use of normal metal quasiparticle traps for suppression of quasiparticle poisoning in SCPT devices is performed. To date, there has been little quantitative information about the behaviour of quasiparticle traps even though they have been used extensively. The work presented serves to clarify the nature of quasiparticle trap performance. Finally the single-quasiparticle sensitivity of the SCPT is employed to directly probe a few quasiparticle gas in a small superconducting volume. The quasiparticle population is monitored both in the steady-state and under non-equilibrium conditions of injection. In the non-equilibrium regime the quasiparticle recombination time is accessed from the response of the SCPT to pulsed injection. Agreement to previous experimental studies of recombination times in aluminium is found.

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.