Introduction Lead exposure continues to be a major public health issue in South Africa, and other low and middle income countries. Environmental lead exposure has been associated with detrimental health effects in children. The aim of this thesis was to assess the prevalence of lead exposure and its association with various risk factors, its effects on puberty and socio-behavioural adjustment in adolescents. Methods The Birth to Twenty (Bt20) cohort study started in 1990, and is a long-term prospective follow-up study of children’s health and well-being. Mothers were recruited from antenatal clinics in the Johannesburg-Soweto metropolitan area between April and June 1990 (n=3273). Lead levels were analysed in samples of cord blood collected at birth (n=618) and whole venous blood collected at 13 years of age (n=1546). Data on selected child, maternal and household factors were collected using a structured questionnaire in the third trimester of pregnancy and at 13 years of age. Additional data on puberty (attainment of menarche and self-reported Tanner staging for breast and pubic development) and behaviour using the Youth Self Report was obtained at 13 years of age. Results In the Bt20 cohort the mean blood lead level at birth was 5.9 μg/dl, and at 13 years of age it was 5.7 μg/dl. The majority of children had blood lead levels above 5.0 μg/dl (52% at birth and 56% at 13 years). At birth, being a teenage mother and having low educational status were strong predictors for elevated cord blood lead levels. Being a male child, having an elevated cord blood level, and lack of household ownership of a phone were significant risk factors for high blood lead levels at 13 years. In 13 year old females with pubertal data (n= 682) the mean blood lead level was 4.9 μg/dl. Fifty percent had blood lead levels < 5.0 μg/dl, 49 % were ≥5.0 μg/dl and 1% was > 10.0 μg/dl. The average age of menarche was 12.7 years. At 13 years, 4% and 7% had reached Tanner stage 5 for pubic hair and breast development, respectively. Analyses showed that higher blood lead levels were significantly associated with delays in all measures of puberty (p <0.001). In the 13 year old sample with data on the Youth Self Report (n= 1041), the geometric mean blood lead level was significantly (P value<0.001) higher in boys (6.0 μg/dl) compared to girls (4.5 μg/dl). The bivariate analyses stratified by gender showed that boys’ blood lead levels were significantly associated with four types of aggressive behaviour. There were no significant associations found in girls. A multivariate analysis was conducted in the sample of boys and after adjusting for socio-economic factors ”Attacking People” remained significantly associated with blood lead levels. Conclusion Significant associations found in the study point to the low socio-economic status of lead exposed children. These poor circumstances frequently persist into adolescence resulting in continued high lead levels. Higher blood lead levels were associated with a delay in the onset of puberty in girls, and with anti-social behaviour among boys in early adolescence. Lead exposure in low and middle countries is generally higher compared to high income countries, and thus the effects of high blood levels are much greater and have larger personal and public health significance.

<p>A computer technique for the optimization of thermal waste destruction systems for various design modes, with emphasis on satisfying the air pollution limitations is discussed. The approach considers the incineration of wastes by addition of fuels to permit the thermal destruction of waste materials which are potential pollutants. The computer optimizing package developed utilizes a modified form of a NASA chemical equilibrium program, the Pasquill-Gifford gas diffusion equation and an optimization routine. </p><p>The method employed incorporates the mathematical modeling of elementary incineration systems, with consideration of the practical aspects of the problem. The final computer design and assessment package is flexible and is developed in a way that permits upgrading and modification for realistic systems. </p> / Thesis / Master of Engineering (ME)

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Ph.D.

In recent years, there has been growing concern about the effect of environmental pollutants on the immune system. In the current study, we investigated the toxicity induced by certain environmental pollutants on the immune systems of fish, amphibians, and mice. Fish in the laboratory were tested for susceptibility to immunosuppression by treatment with 1,3-Bis (chloroethyl)-1-nitrosourea (BCNU). Immunotoxicity of the tilapian immune system was detectable using mitogen-induced proliferation assay and cell-mediated toxicity assay. Fish from various streams of the Roanoke River were tested for immunotoxicity and parasitic infection. Fish from the more polluted North Fork of the Roanoke River exhibited a stronger mitogenic response when compared to fish from the South Fork of the Roanoke River. The effect of perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), commonly referred to as dioxin, a highly toxic environmental pollutant, was tested in C57BL/6 mice. TCDD was administered on gestational day 14 and pup thymocytes were studied for apoptosis on postnatal days 2, 4, 7, 14, and 21. Perinatal exposure to TCDD decreased thymic cellularity and induced apoptosis in the thymocytes of the pups. Amphibians from polluted areas of Bermuda were similarly tested for immunotoxicity and compared with amphibians from less polluted areas. The lymphocyte responsiveness of toads from the more polluted Bermuda Biological Station of Research (BBSR) to mitogens such as lipopolysaccarhide (LPS) was significantly less than in toads from less polluted areas of Bermuda. Histological studies revealed differences in the liver and spleen tissues of the two groups. Melanomacrophage centers were prevalent in the livers of amphibians from the more polluted BBSR when compared to the less polluted Zoo site. These data taken together encompass a broad study on the effect of environmental pollutants across species. In each study, immunotoxicity is the end result of contact with contamination, whether occurring in the environment or induced in the laboratory. These data suggest that the immune system may serve as a biomarker for pollutants present in the environment. / Master of Science

The UPPER (Unified Physicochemical Property Estimation Relationships) model uses additive and non-additive parameters to estimate 21 biologically and environmentally important physicochemical properties of organic compounds. Thermodynamically sound relationships are used to predict boiling and melting points, aqueous and octanol solubilities, vapor pressure and the air-octanol, air-water and octanol-water partition coefficients. These properties determine the distribution and fate of organic compounds in biological and environmental systems. The model has been validated on a data set of 2000 hydrocarbons and polyhalogenated hydrocarbons, provides a simple and accurate method to predict the properties studied.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2006. / Härtill 4 uppsatser.

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.

In externally fertilizing fishes, multiple factors of the spawning environment may affect the sperm viability, and thus the fertilization rate. In this thesis, the sperm activation effect of osmolality of non-electrolytes and electrolytes activation media, pH and ion channel inhibitors on Nile tilapia, Oreochromis niloticus, and the effect of environmentally relevant pollutants (cadmium, malathion and rotenone) on sperm fitness (motility and morphology) were investigated. Seminal fluid samples collected from male fishes (200-250g) were subjected to activation treatments, then analyzed for sperm motility using motility score, and motility variables using Hobson sperm tracker for straight line velocity (VSL), beat cross frequency (BCF) and percentage of motile cells (MOT). For the ion channel inhibitors and pollutants, the effect on sperm motility variables of VSL, VCL (curvilinear velocity) and LIN (linearity) were determined. Multivariate analysis was also carried out to determine the effects of ion channel inhibitors and pollutants on sperm subpopulations. The effects of pollutants on sperm morphology were observed using microscopy techniques, namely, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Sperm motility was initiated when the sperm were exposed to hypoosmotic electrolytes and non-electrolytes solution. We also found that sperm show optimal activity at pH range of 6-8 which depicts that the effect of pH on sperm motility is negligible. Lanthanum (calcium channel blocker) and flunarizine (sodium-calcium exchanger pump blocker) were found to inhibit sperm motility at 25 and 5 µM, respectively, suggesting that both ion channels play a significant role in sperm activation in O. niloticus. In contrast amiloride, ouabain and quinine showed no effects on activation, indicating that epithelial sodium channels, sodium-potassium ATPase and voltage gated potassium channels respectively are unlikely to have major roles in sperm activation or motility. The spermatozoa of Oreochromis niloticus were uniflagellate with clearly differentiated oval-shaped head, midpiece and flagellum. Sperm exposed to hypoosmotic shock showed swelling of the midpiece and sleeve structure. The pollutants showed dose- and time-dependent effect on sperm motility of the fast linear sperm subpopulation. Sperm morphology was not affected. Sperm motility was inhibited at 0.44, 0.03 and 0.063 µM, cadmium, malathion and rotenone respectively. Both cadmium and malathion exerted effects very quickly after exposure. The effect of cadmium, which can exert toxicity by calcium antagonism, is consistent with the effects of calcium channel blockes and further supports an important role for calcium in sperm activation and motility. Malathion had effects at relatively low, environmentally relevant concentrations, suggesting the presence of functionally important acetylcholinesterase activity in sperm, and also the presence of activation cytochrome P450 activity. Rotenone, a well known mitochondrial poison, affected motility only after 15 min of pretreatment. The alteration of sperm trajectories in fast linear spermatozoa subpopulation by pollutants at submicromolar concentrations as demonstrated in our study implies potentially serious consequences for fish populations in polluted environments. Furthermore the results indicate that fish sperm motility as assessed by CASA could be an ecologically relevant, sensitive, and ethically acceptable method for toxicity testing in environmental risk assessment.