INTRODUCTION: Chemical exposures to US pregnant women have been shown to have adverse health impacts on both mother and fetus. A prior paper revealed that US pregnant women in 2003-2004 had widespread exposure to multiple chemicals. The goal of this research is to examine how environmental chemical exposures to US pregnant women have changed from 2003 to 2010 and to look further at the extent of simultaneous exposure to multiple chemicals in US pregnant women using biomonitoring data available through NHANES (the National Health and Nutritional Examination Survey). METHODS: Using available NHANES data from the following cycles (2003-2004, 2005-2006, 2007-2008, 2009-2010), we analyzed how environmental chemical exposures changed over time. Covariates were used and data was weighted to reflect the population of pregnant US women. Each cycle was then compared to the 2003-2004 cycle in order to assess how exposures have changed over time. We then looked at the data in an entirely different fashion. We examined the total number of chemicals detected in a given pregnant woman by chemical group. Finally, we looked at the total number of detects across various chemical groups and used the Fisher Exact Test to study how the distribution of detections changed in 2009-2010 compared to 2003-2004. RESULTS: While at least one-third of the chemicals analyzed showed one cycle that differed, exposure rates of individual chemicals were generally not increasing from 2003-2010. Median number of detections over chemical groups also did not show much difference over time. However, analysis of the change in frequency distributions revealed that, for some chemical groups, the frequency of detects in US pregnant woman significantly increased in 2010 compared to 2003. CONCLUSIONS: Widespread chemical exposures were seen in US pregnant women from 2003 through 2010. The number of chemical analytes detected in US pregnant women’s bodies is rising. Many chemicals studied had similar mechanisms of action and/or similar adverse health outcomes upon exposure which is known to result in a cumulative health effect. This research suggests that we need to focus not only on exposure rates of individual chemicals but also on the overall number of chemicals detected when assessing the overall picture of environmental chemical exposures to pregnant women in the US.

Presented is a study of persistent organic pollutants in Australian sewage sludge, focusing on environmental monitoring and a sewage sludge land application human health risk contaminated with these compounds. The chemicals of concern were: • Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and

Understanding the transport of particulate and gaseous indoor air pollutants from source to exposure is paramount to improve our understanding of the complexities of the built environments in which we spend the majority of our time. This dissertation offers new insights on particle resuspension from indoor surfaces, infant exposure to organic contaminants released from crib mattresses, and the dynamics of pollutant transport and human exposure while sleeping. Particle resuspension is the physical process by which settled particles detach from a surface and become airborne through application of various aerodynamic and mechanical removal forces. Resuspension is an important indoor source of coarse mode particles (> 1 µm in diameter) and can be a source mechanism for biological matter and organic contaminants that accumulate in house dust. Settled dust deposits on indoor surfaces can vary considerably in their structure and mass loading, yet little is known as to how these parameters affect resuspension. Through wind tunnel experiments, this research demonstrates that the deposit structure (monolayer or multilayer) can have a significant impact on the number of particles that aerodynamically resuspend. Furthermore, this dissertation presents the first full-scale experimental chamber study to show that human body movements in bed can resuspend settled mattress dust particles. An indoor aerosol model was utilized to provide a mechanistic understanding of the impact of movement intensity, surface vibrations, bedroom ventilation rate, and dust loading on the resuspension flux and intake fraction of resuspended particles. Infants spend most of their time sleeping and are likely to be exposed to elevated concentrations of chemicals released from their crib mattresses. Through a combination of chamber experiments and solvent extractions, this research shows that infant crib mattresses can emit a variety of volatile organic compounds (VOCs) and contain numerous chemical additives, including phthalate and alternative plasticizers, flame retardants, and unreacted isocyanates. Additionally, this study discovered that infants are exposed to approximately twice the concentrations of VOCs in their breathing zones as compared to the bulk bedroom air, due to their close proximity to the source.

Human health depends on a well-functioning endocrine system to regulate hormone release for normal bodily functions. Endocrine disrupting chemicals (EDCs) constitutes a group of chemicals, included in many commonly used products, (e.g., PVC flooring), with properties proven or suspected to interact with the natural hormone system in humans and animals. EDCs are manmade compounds (there are also natural compounds with such properties) that can bind to cell receptors and mimic or block the functions of natural hormones potentially resulting in adverse human health effects. One type of widely concerning EDC is phthalates. Since phthalates create weak chemical bonds when they are added into different products, they readily leach into the surrounding environment. Phthalate metabolites can therefore be frequently measured in human biological samples. Major public health concerns regarding EDCs over the past three decades have focused on phthalates. According to the World Health Organization, EDCs are suspected to be associated with altered reproductive function in males and females, increased incidence of breast cancer, abnormal growth patterns and neurodevelopmental delays in children, as well as changes in immune function. The thesis shows that PVC flooring in the home is a source for human uptake of phthalates, that replacement of phthalates in soft PVC products have an impact on human uptake of these chemicals, and that exposure for phthalates in early life increase the risk for airway disorders in children. As we have shown, ongoing regulations on phthalates is of importance for human uptake. Ultimately, individuals can make small changes in their consumer product choices that can lead to changes in uptake of chemicals with endocrine disrupting properties. Philosophically, we all have a responsibility to protect future generations from dangerous chemicals. / Human health depends on a well-functioning endocrine system to regulate hormone release for normal bodily functions. Endocrine disrupting chemicals (EDCs) constitutes a group of chemicals, included in many commonly used products, (e.g., PVC flooring), with properties proven or suspected to interact with the natural hormone system in humans and animals. One type of widely concerning EDC is phthalates. Since phthalates create weak chemical bonds when they are added into different products, they readily leach into the surrounding environment. Phthalate metabolites can therefore be frequently measured in human biological samples. Major public health concerns regarding EDCs over the past three decades have focused on phthalates resulting in implementation of regulations. The thesis shows that PVC flooring in the home is a source for human uptake of phthalates, that replacement of phthalates in soft PVC products have an impact on human uptake of these chemicals, and that exposure for phthalates in early life increase the risk for airway disorders in children. This means that regulation and consumers’ product choices can lead to changes in uptake of EDCs of importance for human health. Philosophically, we all have a responsibility to protect future generations from dangerous chemicals.

The overall objective of the research presented in this dissertation was to assess exposure to endocrine disrupting chemicals (EDCs), polychlorinated biphenyls (PCBs), phthalates, and bisphenol A (BPA) in the general population and evaluate their associations with adverse reproductive health effects, including cancers, in women. Given the proven contribution of unopposed estrogens to the risk for endometrial neoplasia or breast cancer, renewed health concerns have aroused about estrogen mimicking EDCs found in food, personal care products or as environmental contaminants. Our meta-analysis showed that exposure to estrogen mimicking PCBs increased summary risk of breast cancer and endometriosis. We further evaluated the relationship between endometriosis and breast cancer, and EDCs using a bioinformatics method. Our bioinformatics approach was able to identify genes with the potential to be involved in interaction with PCB, phthalates and BPA that may be important to the development of breast cancer and endometriosis. Therefore, we hypothesized that exposure to EDCs such as PCBs, phthalates, and BPA, results in adverse reproductive health effects in women. Using subject data and biomarkers available from the Center for Disease Controls National Health and Nutrition Examination Survey database we conducted a cross-sectional study of EDCs in relation to self-reported history of endometriosis, uterine leiomyomas, breast cancer, cervical cancer, ovarian cancer, and uterine cancer. Significantly higher body burdens of PCBs were found in women diagnosed with breast cancer, ovarian cancer, and uterine cancer compared to women without cancer. PCB 138 was significantly associated with breast cancer, cervical cancer, and uterine cancer, while PCBs 74 and 118 were significantly associated with ovarian cancer. The sum of dioxin-like PCBs were significantly associated with ovarian cancer (OR of 2.02, 95% CI: 1.06-3.85) and the sum of non-dioxin-like PCBs were significantly associated with uterine cancer (OR of 1.12, 95%CI: 1.03-1.23). Significantly higher body burdens of PCBs were also found in women diagnosed with endometriosis and uterine leiomyomas. Documenting the exposure to EDCs among the general U.S. population, and identifying agents associated with reproductive toxicity have the potential to fill research gaps and facilitate our understanding of the complex role environmental chemicals play in producing toxicity in reproductive organs.

Using critical feminist theories and methodologies, my research investigates the power relations and influences at play within the field of children's environmental health. I begin with the research question of how a parent's everyday purchase of a toy or other children's product is "hooked into" extra-local governance (agenda-setting, rule-making and monitoring). Focusing on Bisphenol A and phthalates as an example, in-depth interviews were conducted with six government officials (three federal and three municipal), three non-governmental organization (NGO) representatives, a politician, six higher education faculty members and a parent, as well as two focus groups of 23 parents. Legislation and other relevant documents from governments, NGOs, industry and media were analyzed together with reports of their activities and attitudes to theorize "how things work" in the identification and management of toxic substances in products for sale, with a special interest in how this affects children's environmental health. My research revealed the influence of neo-liberalism, corporate power and over-reliance on strictly evidence-based biomedical reductionism in slowing down assessment and regulation of chemicals while many health professionals and grassroots activists have called for swifter responses based on the precautionary principle, as favoured by European governments. That is, politics and bureaucracy, with the approval of industry, over the past two decades, have clung to reductionist science as the only paradigm for understanding toxicity, thus slowing down regulatory processes. Although the historical and epistemological power relations mapped in my research work together to legitimize scientific certainty rather than the precautionary principle, I argue that the resulting regulatory logjam has been and could be addressed by reference to European examples, knowledge produced by collectives and the establishment of upstream and equity-based public health strategies with public input into the process.

Using critical feminist theories and methodologies, my research investigates the power relations and influences at play within the field of children's environmental health. I begin with the research question of how a parent's everyday purchase of a toy or other children's product is "hooked into" extra-local governance (agenda-setting, rule-making and monitoring). Focusing on Bisphenol A and phthalates as an example, in-depth interviews were conducted with six government officials (three federal and three municipal), three non-governmental organization (NGO) representatives, a politician, six higher education faculty members and a parent, as well as two focus groups of 23 parents. Legislation and other relevant documents from governments, NGOs, industry and media were analyzed together with reports of their activities and attitudes to theorize "how things work" in the identification and management of toxic substances in products for sale, with a special interest in how this affects children's environmental health. My research revealed the influence of neo-liberalism, corporate power and over-reliance on strictly evidence-based biomedical reductionism in slowing down assessment and regulation of chemicals while many health professionals and grassroots activists have called for swifter responses based on the precautionary principle, as favoured by European governments. That is, politics and bureaucracy, with the approval of industry, over the past two decades, have clung to reductionist science as the only paradigm for understanding toxicity, thus slowing down regulatory processes. Although the historical and epistemological power relations mapped in my research work together to legitimize scientific certainty rather than the precautionary principle, I argue that the resulting regulatory logjam has been and could be addressed by reference to European examples, knowledge produced by collectives and the establishment of upstream and equity-based public health strategies with public input into the process.

Modern indoor environments contain a vast array of contaminating sources. Emissions from these sources produce contaminant concentrations that are substantially higher indoors than outside. Because we spend most of our time indoors, exposure to indoor pollutants may be orders-of-magnitude greater than that experienced outdoors. Phthalate esters have been recognized as major indoor pollutants. They are mainly used as plasticizers to enhance the flexibility of polyvinylchloride (PVC) products, as well as in humectants, emollients, and antifoaming agents. Phthalates are found in a wide range of consumer products including floor and wall coverings, car interior trim, floor tiles, gloves, footwear, insulation on wiring, and artificial leather. Because these phthalate additives are not chemically bound to the polymer matrix, slow emission from the products to the surrounding air or other media usually occurs. Biomonitoring data suggest that over 75% of the U.S. population is exposed to phthalates. The ubiquitous exposure to phthalates is of concern because toxicological investigations have demonstrated considerable adverse health effects of phthalates and their metabolites. Studies have shown that exposure to phthalates results in profound and irreversible changes in the development of the reproductive tract, especially in males, raising the possibility that phthalate exposures could be the leading cause of reproductive disorders in humans. In addition, effects such as increases in prenatal mortality, reduced growth and birth weight, skeletal, visceral, and external malformations are possibly associated with phthalate exposure. Epidemiologic studies in children also show associations between phthalate exposure in the home and the risk of asthma and allergies. Given the ubiquitous nature of phthalates in the environment and the potential for adverse human health impacts, there is a critical need to understand indoor emissions of phthalates and to identify the most important sources and pathways of exposure. In this study, a model that integrates the fundamental mechanisms governing emissions of semi-volatile organic compounds (SVOCs) from polymeric materials and their subsequent interaction with indoor surfaces and airborne particles was developed. The emissions model is consistent with analogous mechanistic models that predict emission of volatile organic compounds (VOCs) from building materials. Reasonable agreement between model predictions and gas-phase di-2-ethylhexyl phthalate (DEHP) concentrations was achieved for data collected in a previously published experimental study that measured emissions of DEHP from vinyl flooring in two very different chambers. The analysis showed that while emissions of highly volatile VOCs are subject to “internal“ control (through the material-phase diffusion coefficient), emissions of the very low volatility SVOCs are subject to “external“– control (through partitioning into the gas phase, the convective mass transfer coefficient, and adsorption onto interior surfaces). Because of the difficulties associated with sampling and analysis of SVOCs, only a few chamber studies quantifying their emissions from building materials and consumer products are available. To more rigorously validate the SVOCs emission model and more completely understand the mechanisms governing the release of phthalate from polymeric building materials, the emission of DEHP from vinyl flooring was studied for up to 140 days in a specially-designed stainless steel chamber. In the duplicate chamber study, the gas-phase concentration in the chamber increased slowly and reached a steady state level of 0.9 µg/m3 after 30 days. By increasing the area of vinyl flooring and decreasing that of the stainless steel surface in the chamber, the time to reach steady state was significantly reduced, compared to the previous study (1 month vs. 5 months). The adsorption isotherm of DEHP on the interior stainless steel chamber surface was explicitly measured using two different methods (solvent extraction and thermal desorption). Strong adsorption of DEHP onto the stainless steel surface was observed and found to follow a simple linear relationship. In addition, parameters measured in the experiments were then applied in the fundamental SVOCs emission model. Good agreement was obtained between the predictions of the model and the gas-phase DEHP chamber concentrations, without resorting to fitting of model parameters. These chamber studies have shown that the tendency of SVOCs to adsorb strongly to interior surfaces has a very strong influence on the emission rate. Compared to the experimental chamber systems, however, the real indoor environment has many other types of surface that will adsorb phthalates to different extents. The emission rate measured in a test chamber may therefore be quite different to the emission rate from the same material in the indoor environment. For this reason, both a two-room model and a more representative three-compartment model were developed successively to estimate the emission rate of DEHP from vinyl flooring, the evolving gas-phase and adsorbed surface concentrations, and human exposures (via inhalation, dermal absorption and oral ingestion of dust) in a realistic indoor environment. Adsorption isotherms for phthalates and plasticizers on interior surfaces, such as carpet, wood, dust and human skin, were derived from previous field and laboratory studies. A subsequent sensitivity analysis revealed that the vinyl flooring source characteristics, as well as mass-transfer coefficients and ventilation rates, are important variables influencing the steady-state DEHP concentration and resulting exposures. A simple uncertainty analysis suggested that residential exposure to DEHP originating from vinyl flooring may fall somewhere between about 5 µg/kg/d and 180 µg/kg/d. The roughly 40-fold range in exposure reveals the inherent difficulty in using biomonitoring results to identify specific sources of exposure in the general population. This research represents the first attempt to explicitly elucidate the fundamental mechanisms governing the release of phthalates from polymeric building materials as well as their subsequent interaction with interior surfaces. The mechanistic models developed can most likely be extended to predict concentration and exposure arising from other sources of phthalates, other sources of other semi-volatile organic compounds (such as biocides and flame retardants), as well as emissions into other environmental media (food, water, saliva, and even blood). The results will be of value to architects, governments, manufacturers, and engineers who wish to specify low-emitting green materials for healthy buildings. It will permit health professionals to identify and control health risks associated with many of the SVOCs used in indoor materials and consumer products in a relatively inexpensive way. / Ph. D.

Cette thèse porte sur l’évaluation de l’impact de certains composés environnementaux sur la fécondité féminine, tel que mesuré par le délai de conception (« time to pregnancy » en anglais, ou TTP). Cette recherche a été réalisée dans le cadre de l’Étude mère-enfant sur les composés chimiques de l’environnement (MIREC), une cohorte de grossesse de 2001 femmes recrutées durant le premier trimestre dans dix villes canadiennes de 2008 à 2011. Les données des questionnaires et les échantillons biologiques ont servi à évaluer l’effet de deux groupes de composés : les persistants [composés perfluorés – perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA) et perfluorohexane sulfonate (PFHxS)] et les non persistants (bisphénol A, triclosan et phtalates). Cette thèse comprend également une analyse du potentiel du ratio index-annulaire (2D:4D) comme mesure de sensibilité endocrinienne. À ce jour, des mesures anthropométriques ont été collectées sur environ 800 mères-enfants dans le cadre de l’Étude mère-enfant sur les composés chimiques de l’environnement : biomonitoring et neurodéveloppement à la petite enfance (MIREC CD Plus), un suivi de la cohorte MIREC portant sur la croissance et le développement des enfants jusqu’à 5 ans. Sur l’ensemble, les résultats de cette thèse permettent d’étoffer les preuves concernant les effets adverses potentiels de plusieurs contaminants environnementaux sur la fécondité féminine, telle que mesurée par le TTP. Dans le premier article, nous avons montré une association entre les PFOA et les PFHxS et une baisse de fécondité, ce que d’autres recherches avaient déjà révélé. Dans le deuxième article, nous avons évalué l’effet du triclosan sur le TTP, ce qui n’avait jamais été examiné, pour montrer un délai plus élevé chez les femmes du quartile supérieur d’exposition. De plus, nos résultats sont en accord avec ceux de la seule étude ayant évalué l’effet du Bisphénol A sur la fécondité féminine, qui n’avait pas détecté d’effet. Finalement, nos données semblent indiquer une association entre l’exposition des femmes aux phtalates et un TTP plus court, mais ces résultats ne sont pas statistiquement significatifs. En ce qui a trait au potentiel du ratio index-annuaire (2D:4D) pour mesurer la sensibilité endocrinienne chez les femmes, nos données ne permettent pas d’établir une association entre ce ratio et le TTP. Pour ce qui est des enfants, nous n’avons pas trouvé d’effet adverse entre le tabagisme de la mère durant la grossesse et leur ratio 2D:4D. Par conséquent, nos données ne semblent pas justifier l’utilisation du ratio 2D:4D pour mesurer la sensibilité endocrinienne en lien avec le potentiel reproducteur (basé sur le TTP) ou l’exposition des enfants au tabac durant le premier trimestre de grossesse. / In this thesis, we aimed to evaluate the impact of selected environmental compounds on female fecundity as measured by time to pregnancy (TTP). This research was conducted in the framework of the Maternal-Infant Research on Environmental Chemicals (MIREC) study, a pregnancy cohort of 2001 women recruited during the first trimester of pregnancy in ten cities across Canada between 2008 and 2011. Questionnaire data and biological samples were analyzed to assess the effect of two groups of compounds: persistent [perfluorinated compounds - perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexane sulfonate (PFHxS)-] and nonpersistent chemicals (Bisphenol A, Triclosan, and phthalates). In addition, this thesis aimed to examine the potential of the second to fourth finger digit ratio (2D:4D) as a sensitive-endocrine endpoint. To this end, anthropometric measurements were obtained in about 800 children and their mothers during the Early Childhood Biomonitoring and Neurodevelopment Study (MIREC-CD Plus), a MIREC follow-up conducted to measure growth and development up to age five. Overall, the results of this thesis have contributed to the evidence regarding the potential adverse effect of several environmental contaminants (ECs) on female fecundity as measured by TTP. In the first article, we found that PFOA and PFHxS were associated with diminished fecundity, supporting previous evidence that suggested a similar effect. In the second article, we assessed for the first time the effect of Triclosan on TTP, presenting evidence of delayed fecundity at the highest quartile of exposure. In addition, our findings agreed with those of the only study that has assessed the effect of Bisphenol A on female fecundity, and which showed no effect. Finally, we found some indication that female exposure to phthalates might be associated with a shorter TTP, although this finding did not reach statistical significance. With regard to the potential of the digit length ratio (2D:4D) as an endocrine-sensitive endpoint in women, our data do not support a strong association between 2D:4D and TTP. In children, we did not find an adverse impact of maternal smoking during pregnancy on children’s 2D:4D. Thus, our data do not support evidence to suggest that 2D:4D could be used as a potential reproductive endocrine-sensitive endpoint in women as measured by TTP, and in their offspring as measured by exposure to maternal smoking during the first trimester of pregnancy.

The overall objective of this dissertation was to examine exposures to the estrogenic endocrine disrupting chemicals (EEDCs), phthalates, bisphenol-A (BPA), and the metalloestrogens cadmium (Cd), arsenic (As), and manganese (Mn) in an older geriatric aged-population and examine associations with brain health. Given the evidence that EEDCs affect brain health and play a role in the development of cognitive dysfunction and neurodegenerative disease, and the constant environmental exposure through foods and everyday products has led this to becoming a great public health concern. Using a bioinformatic approach to find nuclear respiratory factor 1 (NRF1) gene targets involved in mitochondrial dysfunction, that are both estrogen and EEDC-sensitive, we found several genes involved in the gene pathways of Alzheimer’s disease (AD): APBB2, EIF2S1, ENO1, MAPT, and PAXIP1. Using the Center for Disease Control and Prevention (CDC), National Health and Nutrition Examination Survey (NHANES) 2011-2014 datasets to assess EEDC bioburden and associations with surrogate indicators of brain health, which include cognitive scores, memory questions, and taste and smell data, we found phthalate bioburden to be significantly higher in those with adverse brain health vii and significantly higher in females. In our logistic regression model when controlling for all known and suspected covariates in AD, in females, the phthalates in females ECP, MBP, MOH, MZP, and MIB in males and the phthalates COP, ECP, MBP, MC1, MEP, MHH, MOH, and MIB were significantly associated with poor cognitive test scores, poor memory, and taste and smell dysfunction. Among the metalloestrogens, Cd bioburden was higher in those with poor cognitive performance, poor memory, and taste and smell dysfunction, with the trend more significant in males. Among oral contraceptive (OC) and HRT (hormone replacement therapy) use, in our logistic regression model when controlling for all known and suspected covariates in AD, past OC and HRT use was associated with better cognitive test scores. The study provides further evidence of the complex role EEDCs play in overall brain health through other biological mechanisms and fills a gap in knowledge that demonstrates EEDCs effects on brain health in a geriatric age population.