Increasing temperatures are expected to cause secondary salinisation in freshwater systems, such as the zooplankton community of Churchill, Manitoba. Salinity is a key environmental factor structuring these communities, thus, increasing salinity should cause these communities to change; however, previous research has shown that they are resilient. In order to ascertain how changing salinity will affect these communities I conducted toxicity tests for five crustacean species, individually and in a community setting. I sampled several pools throughout the season to ascertain the salinity level at which those same species were most abundant in the field. While the species had significantly different field distributions along the salinity gradient, the salinity levels associated with maximum densities did not correlate with the lab tolerances. However, lab tolerances were outside the field salinity range, thus providing an unexpected result. Local interactions appear to be very important in determining final community composition along this salinity gradient. / Northern Scientific Training Program, Northern Research Fund

Nanomaterial toxicity is a major concern and could potentially hamper the progress of biomedical nanotechnology development. Dispelling these concerns requires that the consequences of nanomaterial exposure are evaluated, and the findings will determine whether developmental hurdles can be overcome. This thesis evaluates the both in vivo and in vitro impact of quantum dots (QD , zinc sulphide capped cadmium selenide semiconductor nanocrystals) a fluorescent nanoparticle label with potential as an optical in vivo imaging agent. This work reviews nanoparticle characterization techniques and their importance to biological responses, and surveys QD interactions both in vivo and in vitro. We collected pharmacokinetic and toxicity data by a) quantitatively surveying the in vivo absorption, distribution , metabolism and excretion of QDs, and b) measuring the impacts of QDs on relevant organs (in vivo) and cells (in vitro). Neither of these areas had been explored when this thesis was started. In vivo, intravenous QD dosing in Sprague-Dawley rats showed uptake into reticuloendothelial cells with surface coating dependent kinetics, slow degradation, no excretion detected in feces or urine, and no indications of toxicity. The liver took up the majority of dose after 90 minutes and small amounts of QDs appeared in the spleen, kidney, and bone marrow. After 30 days, the cadmium concentration in the kidneys increased to 3µg/g without a proportional amount of zinc, indicating QD breakdown. In vitro we noted phagocytic capacity comparable to in vivo results, QD breakdown, and a retention of normal macrophage function thereby demonstrating that primary rat liver macrophages (Kupffer cells) are an appropriate in vitro system with which to investigate the cellular responses to quantum dots. Such an in vitro model will facilitate faster evaluation of individual nanotechnologies intended for in vivo use. This dissertation addresses a lack of in vivo background information needed to understand the consequences of QD exposure; though QD fail to demonstrate pharmacokinetics desirable for in vivo imaging agents, they are not toxic. Importantly, we provide in vitro data that will lead to the development of accurate and efficient in vitro primary screening methods that will be central to the further development of biomedical nanotechnologies.

No description available.

Manufactured nanoparticles (NPs) are a class of small ( ≤ 100 nm) materials that are being used for a variety of purposes, including industrial lubricants, food additives, antibacterial agents, as well as delivery systems for drug and gene therapies. Their unique characteristics due to their small size as well as their parent materials allow them to be exploited in convenience applications; however, some of these properties also allow them to interact with and invade biological systems. Few studies have been performed to determine the potential harm that NPs can inflict on reproductive and developmental processes in organisms. In this study, Drosophila melanogaster and CD-1 mice were orally exposed to varying doses of titanium dioxide (TiO2) NPs, silver (Ag) NPs, or hydroxyl-functionalized carbon nanotubes (fCNTs) and Drosophila were also exposed to microparticles (MPs) as a control for particle size. The subsequent effect of these materials on reproduction and development were evaluated. Strikingly, each type of NP studied negatively affected either reproduction or development in one or both of the two model systems. TiO2 NPs significantly negative effected both CD-1 mouse development (100 mg/kg or 1000 mg/kg) as well as Drosophila female fecundity (0.005%-0.5% w/v). Ag NPs significantly reduced mouse fetus viability after prenatal exposure to10 mg/kg. Ag NPs also significantly decreased the developmental success of Drosophila when they were directly exposed to these NPs (0.05% - 0.5% w/v) compared to both the vehicle and MP controls. fCNTs significantly increased the presence of morphological defects, resorptions and skeletal abnormalities in CD-1 mice, but had little effect on Drosophila. We speculate that the differences seen in the effects of NP types may be partially due to differences in reproductive physiology as well as each organism’s ability to internalize these NPs. Whereas the differing response of each organism to a NP type was likely due in part to varying durations of exposure. Since NPs are a popular commodity in today’s consumer world, the research presented here accentuates the need for further studies on the detrimental effects that these particles may have on a variety of developing organisms and on female reproductive health. / Thesis (Master, Environmental Studies) -- Queen's University, 2010-09-20 17:57:59.343

No description available.

No description available.

Nanomaterial toxicity is a major concern and could potentially hamper the progress of biomedical nanotechnology development. Dispelling these concerns requires that the consequences of nanomaterial exposure are evaluated, and the findings will determine whether developmental hurdles can be overcome. This thesis evaluates the both in vivo and in vitro impact of quantum dots (QD , zinc sulphide capped cadmium selenide semiconductor nanocrystals) a fluorescent nanoparticle label with potential as an optical in vivo imaging agent. This work reviews nanoparticle characterization techniques and their importance to biological responses, and surveys QD interactions both in vivo and in vitro. We collected pharmacokinetic and toxicity data by a) quantitatively surveying the in vivo absorption, distribution , metabolism and excretion of QDs, and b) measuring the impacts of QDs on relevant organs (in vivo) and cells (in vitro). Neither of these areas had been explored when this thesis was started. In vivo, intravenous QD dosing in Sprague-Dawley rats showed uptake into reticuloendothelial cells with surface coating dependent kinetics, slow degradation, no excretion detected in feces or urine, and no indications of toxicity. The liver took up the majority of dose after 90 minutes and small amounts of QDs appeared in the spleen, kidney, and bone marrow. After 30 days, the cadmium concentration in the kidneys increased to 3µg/g without a proportional amount of zinc, indicating QD breakdown. In vitro we noted phagocytic capacity comparable to in vivo results, QD breakdown, and a retention of normal macrophage function thereby demonstrating that primary rat liver macrophages (Kupffer cells) are an appropriate in vitro system with which to investigate the cellular responses to quantum dots. Such an in vitro model will facilitate faster evaluation of individual nanotechnologies intended for in vivo use. This dissertation addresses a lack of in vivo background information needed to understand the consequences of QD exposure; though QD fail to demonstrate pharmacokinetics desirable for in vivo imaging agents, they are not toxic. Importantly, we provide in vitro data that will lead to the development of accurate and efficient in vitro primary screening methods that will be central to the further development of biomedical nanotechnologies.

A series of acute (96h) toxicity tests were conducted on six species of crayfish inthe family Cambaridae. Toxicity values fell into a sensitive group comprising Orconectesplacidus and Procambarus acutus (LC 50= 0.368mg Cd/L - 0.487mg Cd/L; LC10= 0.048mg Cd/L - 0.092 mg Cd/L) and tolerant group comprising O. juvenilis, O. virilis, P.alleni, and P. clarkii (LC 50= 2.44 mg Cd/L - 3.30 mg Cd/L; LC10= 0.386 mg Cd/L -0.947 mg Cd/L). For juvenile crayfish, the LC50 and LC10 values were as follows: O.juvenilis, 0.060 and 0.014 mg Cd/L; O. placidus, 0.037 and 0.002 mg Cd/L; P. clarkii,0.624 and 0.283 mg Cd/L. Cd exposure decreased molting success highlighting theimportance of this sensitive process. Behavioral responses were assessed in O. placidus,O. virilis, P. acutus, P. alleni, and P. clarkii. The tail-flip predator avoidance behaviorwas significantly reduced by cadmium exposure. In most species tested, the claw raisedefensive behavior was significantly increased by Cd exposure. Between species, as bodymass increased, the tail-flip response frequency decreased, and the claw-raise responseincreased in frequency. P. clarkii was also analyzed for the effect of Cd exposure onheart rate and response to two stimuli. The data indicate that heart rate may be a usefulphysiological marker of Cd toxicity. The major organ systems were dissected fromsurvivors of four adult crayfish toxicity tests (O. juvenilis, O. placidus, P. acutus, P.clarkii) and analyzed for metal content. Cadmium tissue content correlated with Cdexposure. Cadmium accumulated more in the hepatopancreas, gills and green glands ofsensitive species than in tolerant species. Zn showed negative correlations with Cdexposure in the hepatopancreas. Cu increased in green glands, gills, and hemolymph and,in some cases, decreased in the hepatopancreas. Ca, Fe, Mg, and Zn also showedsignificant trends. Zn accumulated in the exposure water over 24h. These data indicatethat Cd may displace Cu and/or Zn in the hepatopancreas and the displaced metal thenmay move into other tissues, especially the gills and green glands, possibly to beexcreted.

Chapter 1 introduces the phenomenon of oxygen toxicity and the central role played by oxygen free radicals, most notably the superoxide radical anion. The technique of spin trapping, whereby reactive free radicals are studied and identified, is then introduced. The synthesis of improved spin traps for superoxide by the preparation of 1-pyrroline 1-oxides bearing a C-3 ester or alkyl halide substituent is then discussed. Chapter 2 describes the preparation of 2-(prop-2-enyl)-aldehydes, 2-dimethoxymethylaldehydes and a 2-phenylthiomethylaldehyde. Bromination of 5,5-dimethyl-1-(prop-2-enyl)-1-pyrroline 1-oxide did not give rise to addition at the C=C double bond but recovery of the nitrone and a hydroxamic acid. Similarly, hydrohalogenation of the alkenyl-nitrone did not lead to addition at the C=C double bond. The preparation and utility of 3-(ethoxycarbonylprop-2-enyl)-5,5-dimethyl-1-pyrroline 1-oxide is then described. Chapter 3 details the preparation of 3-dimethoxymethyl-1-pyrroline 1-oxides. Acid-catalysed deprotection of these nitrone acetals did not result in the formation of the expected 3-aldehydo-5,5-dimethyl-1-pyrroline 1-oxides. Chapter 4 deals with the preparation of 5,5-dimethyl-3-phenylthiomethyl-1-pyrroline 1-oxide. Conversion of the phenylthiomethyl group to an iodomethyl group led to the loss of the nitrone. Chlorination of the nitrone gave 4-methyl-4-nitro-2-phenylthiomethylpentanoic acid. Oxidation of 5,5-dimethyl-3-ethoxycarbonyl-1-hydroxypyrrolidine resulted in the dimeric nitrone 3,3'-bis(ethoxycarbonyl)-5,5,5',5'-tetramethyl-3,3'-bi-1-pyrrolinyl 1,1-dioxide being isolated. Chapter 5 concerns the synthetic utility of α-bromoaldehydes. The preparation of 5,5-dimethyl-3-benzenesulphonyl-1-pyrroline 1-oxide is then described. Alkylation of the nitrone in the presence of sodium hydride with methylbromoacetate gave the C-3 disubstituted nitrone, 3-benzenesulphonyl-5,5-dimethyl-3-methoxycarbonylmethyl-1-pyrroline 1-oxide. Chapter 6 concerns the spin trapping reactions of the nitrones prepared in this thesis. The ESR spectra of the hydrogen atom adducts showed the magnetic non-equivalence of the β-hydrogens owing to the presence of the C-3 substituent. Spin trapping of the <I>t</I>-butoxy radical was found to be stereospecific. Apparent selectivity for the hydroxyl radical was found as no spin adducts were detected with the superoxide radical anion.

The Canadian Council of Ministers of the Environment (CCME) developed guidelines for petroleum hydrocarbon (PHC) impacted field soils based on the “worst case” scenario of a fresh petroleum spill (CCME, 2001b; CCME, 2008b). Therefore, when these guidelines are applied as remedial benchmarks, they may be too conservative to be used as realistic targets as they do not account for weathering, which has been shown to decrease the toxicity of PHCs in soil. Chronic toxicity tests were performed using weathered PHC-impacted field soil from three different field sites (ON1, AB1 and BC1) and Folsomia candida. The highest PHC concentration of soil obtained from ON1 (635 mg/kg F2 and 12,000 mg/kg F3) and AB1 (610 mg/kg F2 and 2,900 mg/kg F3) did not affect F. candida survival and reproduction. However, when F. candida were exposed to PHC-impacted soil obtained from the BC1 site, a LC25 of 2,809 mg F2 + F3/kg was calculated for adult survival while an IC25 of 1,030 mg F2 + F3/kg was calculated for juvenile production. The toxicity at BC1 was postulated to be caused by the F2 concentration (it was the only site with high F2). Heat extraction and floatation methods were compared using the soil obtained from the ON1 field site. The number of adults obtained using the floatation method was always higher than the total number of adults obtained from the heat extraction method; however, only two of these results were statistically significant. This suggests that the floatation method is the best method to use to extract Folsomia candida and also indicates either method can be used with no significant effect on the conclusions. Chronic toxicity tests usually focus on measuring sub-lethal endpoints; however, only juvenile production was included in the Environment Canada protocol (Environment Canada, 2005; Environment Canada, 2007a). The endpoints of weight, length and width were added to chronic toxicity tests on AB1 and BC1 soils to determine if they were suitable endpoints. The highest concentration tested for AB1 (610 mg F2/kg and 2,900 mg F3/kg) had no effect on the weight, length or width of the adults. However, the toxicity data obtained for the BC1soils provided an EC25 of 421 mg F2 + F3/kg, 13,750 mg F2 + F3/kg and 17,425 mg F2 + F3/kg for weight, length and width, respectively. The EC25 of 421 mg F2 + F3/kg obtained for the weight of adults is lower than the IC25 of 1,030 mg F2 + F3/kg obtained for juvenile production which indicating that weight is a more sensitive endpoint than juvenile production. Avoidance-response tests involved placing a control and test soil on either side of a cylindrical container and adding 20 Folsomia candida to the midline (Environment Canada, 2007a; Liu et al., 2010). The results using soil obtained from AB1 showed no trend between soil avoidance and increasing PHC concentration. However, the avoidance-response test, using soil obtained from BC1, indicated that F. candida avoidance increased with increasing petroleum concentration. These results show that avoidance-response tests were able to predict the outcome of the chronic toxicity tests. Overall, the above results indicate that the CCME guidelines are too conservative to apply to weathered PHC-impacted field soil when the impacts are primarily F3. Results also indicate that F2 and F3 concentrations of 250 mg/kg and 2,900 mg/kg, respectively would not adversely affect F. candida adult survival, juvenile production or adult weight.