In the early 1990s polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) contamination of fish was widely associated with bleached kraft pulp mills. Regulations were put into place in Canada and elsewhere to reduce or eliminate the presence of these chemicals in pulp mill effluents. The industry quickly introduced treatment and process changes such as elemental (ECF) and total chlorine free (TCF) bleaching, which resulted in dramatically reduced PCDD/F concentrations in pulp mill effluents. However, PCDD/Fs may remain a concern for the receiving environment near bleached kraft pulp mills due to their tendency to persist in sediments and bioaccumulate in aquatic biota. Several studies conducted in the early 1990s reported significantly elevated levels of PCDD/Fs in white sucker (Catostomus commersoni) exposed to bleached kraft mill effluent (BKME). Particularly high concentrations were observed in the receiving environment of two mills in northern Ontario. The first mill, located in the town of Terrace Bay, discharges effluent into Jackfish Bay, Lake Superior. The second mill is located in Smooth Rock Falls, Ontario and discharges effluent into the Mattagami River where effects have been observed in fish collected downstream of the pulp mill. Over time, both mills have undergone a number of process upgrades, including a transition to 100% chlorine dioxide (ClO2) substitution. In 2006 the Tembec Smooth Rock Falls Pulp and Paper Mill closed permanently, while the mill in Terrace Bay has gone through a number of temporary shutdowns and is currently in the process of transitioning to a dissolving pulp process. Temporal changes in PCDD/F contamination was examined in white sucker historically exposed to BKME in Jackfish Bay and the Mattagami River, following mill process changes and closures. Historical data was summarized from studies conducted in the 1990s and analyzed along with liver tissue of male white sucker collected from each location in 2011 and 2012. The body burden of each fish was analysed using Toxic Equivalency (TEQ) calculations to account for concentration and relative toxicity of 2,3,7,8??? substituted PCDD/F congeners. At Jackfish Bay, concentrations of PCDD/Fs in surface sediment and dated sediment cores were used to document the spatial and temporal pattern of PCDD/F contamination in relation to historical process upgrades and operational changes at the mill. PCDD/Fs measured in white sucker liver samples collected from Jackfish Bay during gonadal recrudescence in the fall illustrate a decrease in mean TEQ from 74.2 ?? 20.9 pg???g-1 in 1991 to 3.34 ?? 2.05 pg???g-1 in 2012. These values were slightly elevated compared to the remote reference location at Mountain Bay, Lake Superior, which exhibited a mean TEQ of 1.88 ?? 0.45 pg???g-1 and 1.06 ?? 0.69 pg???g-1 in white sucker collected in fall 2011 and 2012, respectively. Although below consumption guidelines, trace levels of PCDD/Fs persist in fish collected from Jackfish Bay and these concentrations are suspected to reflect sediment contamination in Moberly Bay (part of Jackfish Bay). A unique PCDD/F contaminant profile, dominated by 2,3,7,8??? tetrachlorodibenzo???p???dioxin (TCDD) and dibenzofuran (TCDF), was observed in white sucker and sediment collected from Jackfish Bay. Analysis of surface sediment collected throughout Jackfish Bay revealed elevated PCDD/F concentrations, compared to reference areas in Lake Superior. TEQ values measured in surface sediment from the depositional areas of Moberly Bay exceeded the Canadian Council of Ministers of the Environment (CCME) guidelines. In 1991 PCDD/F contamination, reported as mean TEQ, of white sucker collected downstream of the pulp mill outfall in Smooth Rock Falls reached levels of 111 ?? 86.2 pg???g-1. At the time, the mill utilized molecular chlorine (Cl2) in the bleaching sequence and employed primary effluent treatment. A dramatic decline was observed in PCDD/F concentrations of fish collected in 1993 and 1995, corresponding to implementation of 100% ClO2 substitution in the bleaching process. PCDD/F contamination in white sucker collected from the Mattagami River in 2011 and 2012 were similar upstream (0.53???1.49 pg TEQ???g-1) and downstream (0.75???2.87 pg TEQ???g-1) of the historical pulp mill outfall at Smooth Rock Falls, suggesting a return to background condition following the 2006 mill closure. Levels of 2,3,7,8???TCDD and 2,3,7,8???TCDF in liver tissue of fish collected downstream declined drastically compared to concentrations measured in 1991. The PCDD/F congener profile observed in white sucker downstream in 2011 and 2012 was more similar to fish collected from the reference site upstream than exposed fish collected in 1991. No sediment depositional areas suitable for taking a core sample were found on the river downstream of Smooth Rock Falls due to the nature of the system. This study supports the conclusion that particulate (POM) and dissolved organic matter (DOM) from continuous inputs of effluent were likely the primary source of PCDD/Fs to fish in these receiving environments, with only a small contribution from surface sediment. Results indicate a decreasing trend in PCDD/F contamination of white sucker historically exposed to bleached kraft pulp mill effluent in the receiving environments of Jackfish Bay and the Mattagami River, consistent with mill process upgrades to eliminate the use of elemental chlorine from the bleaching sequence. Current levels of PCDD/Fs measured in white sucker collected from these locations suggest a return to background condition.

This thesis examines the discourses of human health and synthetic chemicals that emerged in New Zealand, focusing specifically on the 1970s dioxin controversy. Dioxins were highly toxic contaminants in the herbicide 2,4,5-T, one of the country’s most widely used agricultural chemicals from 1948 to 1987. The theoretical framework of the thesis is grounded in poststructural notions about power/knowledge and ideas from sociology and science studies that highlight the inevitable uncertainties that surround human exposure to chemicals. Archival material from the Agricultural Chemicals Board and the Department of Health, chemical industry publications and a range of other textual materials were analysed using a discourse methodology that focused on intertextuality. To better understand the discursive construction of dioxins in New Zealand, the role of the chemical industry, government and opposition groups in constructing, resisting and politicising dioxins is described. The thesis reconceptualizes environmental (in)justices as not exclusively local, but as boundless, discursive and socio-historic in character. It also reflects on how resolving contemporary dioxin injustices in New Zealand, themselves the result of historical exposures, are problematically still being approached primarily through a reductionist approach to health and chemicals.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic environmental pollutant and is well known for its immunotoxic effects, particularly on the thymus. The exact mechanism by which TCDD induces thymic atrophy is not known. In the current study, we investigated whether TCDD triggers apoptosis in the thymocytes and whether Fas and Fas ligand play a role in TCDD-mediated immunotoxicity. Administration of a single dose of TCDD at 0.1, 1, 5 or 50 mg/kg body weight intraperitoneally into C57BL/6 +/+ mice caused a significant dose-dependent decrease in the thymic cellularity; whereas, in the C57BL/6 lpr/lpr (lpr) (Fas-deficient) and C57BL/6 gld/gld (gld) (Fas ligand-defective) mice, TCDD failed to induce a decrease in thymic cellularity at doses of 0.1-5 mg/kg body weight. In the lpr and gld mice, thymic atrophy was seen only at 50 mg/kg body weight of TCDD. Significant apoptosis was detected within 8-12 hours after injection in the wild type mice, whereas, in the lpr and gld mice apoptosis could not be detected. Upon culturing the thymocytes from TCDD-treated mice for 24 hours in vitro, the wild-type cells showed increased apoptosis when compared to the control; whereas, similar cells from lpr and gld mice did not show apoptosis. Furthermore, TCDD-treatment caused significant alterations in the expression of surface molecules on the thymocytes in the wild-type mice and minimal changes in the lpr or gld mice. Sera from TCDD-treated wild-type mice also exhibited increased levels of soluble Fas ligand. Also, TCDD-induced apoptosis was inhibited both in vitro and in vivo by caspase inhibitors and other inhibitors of apoptosis. Together, the current study demonstrates that TCDD-induced apoptosis plays an important role in thymic atrophy caused by TCDD in vivo. Furthermore, phenotypic changes in the density of thymocyte surface molecules may serve as a useful biomarker for chemical toxicity involving apoptosis. The current study also demonstrates that Fas-Fas ligand interactions play an important role in the induction of apoptosis and immunotoxicity by TCDD. / Ph. D.

Remediation of weathered petroleum hydrocarbons, polycyclic aromatic hydrocarbons (PAHs), dioxins, and polychlorinated biphenyls (PCBs) through monitored natural attenuation, in-situ biostimulation, and/or bioaugmentation was assessed using laboratory-scale microcosms. These contaminants of interest (COIs) have persisted in Santa Susana Field Laboratory (SSFL) soils for over 40 years in some cases. The objective of this United States Department of Energy (DOE)-funded study was to determine the potential of the aforementioned remediation methods to reduce COI concentrations in soil and estimate potential biodegradation rates of COIs in SSFL soils. Several types of soil microcosms were established: one set of microcosms was run without amendments to estimate natural attenuation rates at the site; biostimulation was tested by addition of nitrogen and phosphorus, rice hulls, and biosurfactant (soya lecithin), another set was augmented with the white-rot fungus Phanerochaete chrysosporium, and gamma-irradiated microcosms served as sterilized controls. Soil samples were collected and analyzed for dioxins, PCBs, PAHs, and extractable fuel hydrocarbons (EFH) after 0, 4, and 8 months of incubation. Soil contamination in the microcosms initially consisted of primarily heavily chlorinated dioxins and PCBs, longer petroleum hydrocarbons (21-40 equivalent carbon chain length), and PAHs with 4-6 aromatic rings. Small decreases in PAH, PCB, and dioxin soil concentrations were observed, but these decreases were not statistically significant. EFH concentrations were inflated at the final sampling event, but they appeared to reduce for two of three soils (Soils A and C) tested at the second sampling event. No COI concentration reductions were statistically significantly during 8 months of incubation. Because petroleum hydrocarbons were primarily longer-chain hydrocarbons in the C21 to C40 EFH range, it is likely that lighter hydrocarbons had been preferentially degraded, leaving the more recalcitrant longer-chain hydrocarbons in the soil. Dioxin concentrations appeared to decrease in some cases, but these reductions were not statistically significant at the 95% confidence level. Larger PAHs (4-6 rings) comprise the majority of residual PAH soil contamination. Given that concentrations of these PAHs have not decreased significantly during this 8-month long study, it is likely that these larger PAH contaminants are somewhat recalcitrant and will take a long time to biodegrade. Similarly, little or no PCB biodegradation was observed which is not surprising because the PCBs are heavily chlorinated, and bacterial biodegradation of these highly chlorinated compounds is reported to occur only under anaerobic conditions. The primary dioxin congener present in soils was octachlorodibenzodioxin (OCDD), which is the heaviest-chlorinated dioxin congener. Like PCBs, this compound requires anaerobic conditions for reductive dechlorination, and these are not present at the site. Total dioxin concentrations decreased in the microcosms amended with Phanerochaete chrysosporium, although this decrease was not statistically significant due to variability of dioxin concentrations measured in the soil. No decrease in tetrachlorodibenzodioxin toxicity equivalence was observed with P. chrysosporium bioaugmentation, and this parameter is important in terms of dioxin toxicity. Soil vapor analyses performed at the site indicate highly aerobic soil conditions. To mimic site conditions as closely as possible, experimental microcosms were maintained incubated in aerobic conditions. Although fungi have been reported to degrade PCBs and dioxins under aerobic conditions, the microcosms augmented with Phanerochaete chrysosporium did not show statistically significant biodegradation of PCBs. Contaminant sequestration in the soil may also have contributed to the lack of observed biodegradation because the COIs at this site are highly weathered. However, even microcosms augmented with a surfactant (soya lecithin), which would be expected to solubilize sequestered COIs, did not show significant biodegradation.

No description available.

Aryl Hydrocarbon Receptor (AhR) is a ligand-actviated receptor known as the dioxin receptor. Environmental pollutants called dioxin-like toxicants are found in food, cigarette smoke, automobile exhaust and air. Therefore, they could chronically amplify the pathology of numerous chronic inflammatory diseases. AhR is a well known target of these environmental chemicals that disrupt endocrine signaling. By the year 2020, the number of people older than 60 years is expected to top 1 billion. The burden of treating chronic disease is significant both in dollars spent and in lost productivity. The need to identify risk factors for chronic diseases must be evaluated along with diet and lifestyle factors that will promote healthy aging. The studies presented in this dissertation tested the hypothesis that habitual exposure to dioxin-like contaminants contributes to chronic inflammatory disease states through activation of AhR pathway. Due to their lipophilicity, dioxin like toxicants (like PCB 77) accumulated in mice' visceral adipose tissue and induced adipocytes maturation and ectopic fat deposition. Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCB 77) can cause endothelial cells activation and inflammation by inducing pro-inflammatory signaling pathways. In our studies, PCB 77 had cumulative effects in Angiotensin II - induced Abdominal Aortic Aneurysm (AAA) by exacerbating inflammation in and around the aortic wall. More, PCB 77 increased mortality in mice that developed AAA. In order to appreciate the AhR involvement in inflammation we used a mouse model of Inflammatory Bowel Disease(IBD). Mice that had a reduced Ahr Receptor expression developed a less severe colitis and had a decreased general inflammatory status. These data provide evidence that exposure to environmental toxicants could augment inflammation and contribute to the social burden of obesity and obesity related chronic inflammatory diseases.

Sawmills which conducted dipping operations is a breach where previously used chemicals mean that you generally can expect to find contaminated areas. To investigate contaminated areas the Swedish environmental protection agency developed a method for investigation of polluted areas (MIFO). The purpose of a MIFO analysis is to provide a unified approach and risk classification system for polluted areas. The aim of this thesis it to perform a soil survey according to MIFO phase 2 (general investigations) at the former sawmill in Lövsele, Västerbotten county. The study is based on assumptions about the presence of dioxins in the area, due to the previous use of the wood preservative Ky-5. Dioxins are dangerous substances and are considered poisonous for both humans and the environment. The field study was conducted 30 September 2016 in 8 selected points where the greatest risk to find dioxins were considers to exist after completion of background investigations. 9 samples were the chosen for analysis by ALS Scandinavia AB. The completed analysis shows that pollution levels above the guideline values of both sensitive land use (KM) and less sensitive land use (MKM) were discovered in 7 out of 9 analyzed samples. The MIFO analysis was conducted to answer questions about the pollution hazards, pollution level, distribution conditions and the sensitivity and protection value in the area. The result of the MIFO-analysis is evaluated as class 1, very high risk to human health and the environment. Further studies should therefore be conducted to determine the pollution situation in the area and to provide data for remediation measures to reduce the risk to human health and the environment.

The main goal of this thesis was to develop new methods and knowledge that will explain and predict species differences in sensitivity to dioxin-like compounds (DLCs) in birds. The important achievements and results obtained from the four experimental chapters of this thesis are summarized as follow: (1) an efficient luciferase reporter gene (LRG) assay was developed for use with 96-well cell culture plates; (2) the results obtained from LRG assay were shown to be highly correlated to available in ovo toxicity data; (3) amino acids at positions 324 and 380 within the aryl hydrocarbon receptor 1 ligand binding domain (AHR1 LBD) were shown to be responsible for reduced Japanese quail (Coturnix japonica) AHR1 activity to induce a dioxin-responsive reporter gene in comparison to chicken (Gallus gallus domesticus), and ring-necked pheasant (Phasianus colchicus) AHR1 in response to different DLCs; (4) AHR1 LBD sequences of 86 avian species were studied and differences at amino acid sites 256, 257, 297, 324, 337 and 380 were identified. It was discovered that only positions 324 and 380 play a role in AHR1 activity to induce a dioxin-responsive gene; (5) in COS-7 cells expressing chicken AHR1, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) are equipotent inducers of the reporter gene and bind with similar affinity to chicken AHR1, however, in the cells expressing pheasant, Japanese quail and common tern (Sterna hirundo) AHR1, PeCDF is a stronger inducer than TCDD. PeCDF also binds with higher affinity to pheasant and quail AHR1 than TCDD. The results of this thesis show that embryo lethal effect of DLCs in avian species can be predicted by use of two new non-lethal methods: (1) the LRG assay and (2) determination of the identity of the amino acids at positions 324 and 380. The findings and methods described in this thesis will be of use for environmental risk assessments of DLCs.

The aryl hydrocarbon receptor (AHR) mediates the toxic effects of halogenated aromatic hydrocarbons (HAHs), including 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran and 2,3,7,8-tetrachlorodibenzofuran. Y322 is believed to play a role in binding-independent activation of AHR by atypical inducers, such as omeprazole. I examined AHR-mediated regulation of and coactivator recruitment to CYP1A1, CYP1B1, HES1 and TiPARP in T-47D and HuH7 cells. All compounds induced expression of each gene in both cell lines, with some temporal differences between the HAHs and omeprazole. Chromatin immunoprecipitation assays demonstrated activator-, cell line- and gene-selectivity in AHR coactivator recruitment. Omeprazole induced AHR degradation which was prevented by MG-132 pre-treatment. Y322 was found to be important for maximal AHR activation by 2,3,7,8-TCDD and 2,3,4,7,8-PeCDF, but required for 2,3,7,8-TCDF and Omp in an AHR-deficient MCF-7 cells. My findings provide further evidence for cell-, gene- and ligand-dependent differences in AHR-mediated gene expression and coactivator recruitment, and a role for Y322 in AHR activation.

The aryl hydrocarbon receptor (AHR) mediates the toxic effects of halogenated aromatic hydrocarbons (HAHs), including 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran and 2,3,7,8-tetrachlorodibenzofuran. Y322 is believed to play a role in binding-independent activation of AHR by atypical inducers, such as omeprazole. I examined AHR-mediated regulation of and coactivator recruitment to CYP1A1, CYP1B1, HES1 and TiPARP in T-47D and HuH7 cells. All compounds induced expression of each gene in both cell lines, with some temporal differences between the HAHs and omeprazole. Chromatin immunoprecipitation assays demonstrated activator-, cell line- and gene-selectivity in AHR coactivator recruitment. Omeprazole induced AHR degradation which was prevented by MG-132 pre-treatment. Y322 was found to be important for maximal AHR activation by 2,3,7,8-TCDD and 2,3,4,7,8-PeCDF, but required for 2,3,7,8-TCDF and Omp in an AHR-deficient MCF-7 cells. My findings provide further evidence for cell-, gene- and ligand-dependent differences in AHR-mediated gene expression and coactivator recruitment, and a role for Y322 in AHR activation.