Mycotoxin contamination in food commodities is an age-old problem. Due to the detrimental impact of mycotoxins on human health, exposure to mycotoxins and their health implications have been increasingly recognized. Ochratoxin A (OTA), one of the mycotoxins, has been found to cause diverse toxicities in animals, with potential impact on human health. OTA has been reported to be teratogenic and interfere with steroidogenesis in vivo. Chronic exposure of pregnant women to OTA may be hazardous for the human foetus, especially when endocrine and developmental toxicities are taken into consideration. Accordingly, in the first part of this project, I hypothesized that OTA may interfere with enzymes involved in human placental steroidogenesis. By evaluation of human placental 3β–hydroxysteroid dehydrogenase/isomerase (3β-HSD) at both mRNA and protein (hormonal) levels, my results showed that OTA could up-regulate 3β-HSD1 expression in human placental cells with concentration relevant to human exposure. This study is the first to report the endocrine disruption potential of OTA in human placental cells. As several mycotoxins have been demonstrated previously to cross human placental barrier and OTA has been associated with developmental toxicity in vivo, I further hypothesized that OTA may be transferred through human placenta and accumulate in foetal compartment. In the second part of this project, human perfused placenta was used to investigate the placental toxicokinetics of OTA using concentrations found in serum of pregnant women. Findings from this study clearly showed that the transfer of OTA through term human placenta was minimal, contradicting the existing epidemiological studies reporting higher foetal OTA levels than maternal. This is the first study where transplacental kinetics of OTA has been studied in human perfused placenta. To assess the relevance of the study findings, it is very important to provide information on maternal OTA exposure during pregnancy. Currently there is limited information regarding OTA exposure of pregnant women. The third part of this project aimed at evaluating the frequency and level of exposure to OTA in pregnant women from Egypt, where exposure to dietary mycotoxins is common due to the environmental conditions. Biomonitoring of both serum and urinary OTA levels showed that more than 70% of pregnant women were exposed to OTA with a geometric mean of 0.27 ng/ml in serum and 37.21 pg/mg creatinine in urine indicating frequent exposure of this subpopulation. As an ultimate aim, maternal-foetal risk assessment served as a conclusive part of this project to predict and evaluate both maternal and foetal risk of exposure to OTA during pregnancy. Data from the exposure of pregnant women in Egypt to OTA were further ultilized to conduct maternal-foetal risk assessment in relation to OTA exposure. Based on the refined Klaassen equation for exposure estimation during pregnancy and the benchmark dose approach for risk assessment, this subpopulation of pregnant women generally was not exposed to OTA in a high-risk manner. However, considering the suspected chronic exposure beginning from early pregnancy with high foetal susceptibility and diverse toxic effects, and in particular the potential endocrine disruption of OTA, keeping OTA exposure to a minimum is recommended. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

Not available / text

Thesis (M.S.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains viii, 69 p. : ill., maps. Includes abstract. Includes bibliographical references.

Thesis (M. S.)--Civil and Environmental Engineering, Georgia Institute of Technology, 2006. / Ching-Hua Huang, Committee Co-Chair ; F. Michael Saunders, Committee Member ; Jae-Hong Kim, Committee Chair.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2003. / Bibliography: leaves 101-113. Also available online.

Title from PDF of title page (University of Missouri--Columbia, viewed on Feb 15, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Raymond D. Semlitsch Vita. Includes bibliographical references.

Thesis (M.S.)--Texas State University-San Marcos, 2007. / Vita. Appendices: leaves 45-65. Includes bibliographical references (leaves 66-68).

Thesis (M.S.)--Texas State University-San Marcos, 2007. / Vita. Appendices: leaves 45-65. Includes bibliographical references (leaves 66-68).

Thesis (M.Med.(Community Health))--University of Pretoria, 2004. / Summary in English and Afrikaans. Includes bibliographical references (leaves 66-73). Also available online.

Nanofiltration (NF) and ultrafiltration (UF) membranes were tested in cross-flow configuration for removal of the natural estrogenic hormone 17Beta-estradiol (E2). The NF membranes, FilmTec NF270 and NF90 and Saehan NE-70 and NE-90, showed significant adsorption of E2 during the initial stage of filtration followed by relatively high steady-state rejection. The rejection ranged from 70% for the NF270 to greater than 97% for the NF90 and NE-90. UF membranes, such as Saehan UE2010 and Sterlitech GH, showed relatively low rejection (0-20 %) at steady-state, but did show significant adsorption during the initial time period. In both NF and UF, adsorbed hormone was released into the permeate stream when the feed solution was replaced with pure water. The rate of desorption was approximately the same as that of adsorption. Similar results were observed at both high concentrations (100 microgram/L), and at lower, environmentally-relevant concentrations (100 ng/L). Fouling of membranes by natural organic matter improved rejection, as did operation at higher permeate flux and higher pH. These results indicate that the high initial rejection of hormones due to adsorption on membranes may not accurately reflect true rejection of hormones by these membranes at steady state.