Tesi sul tema "Exposure"

Le cancer du sein est le cancer le plus fréquent chez la femme et son incidence a doublé ces 30 dernières années. Les facteurs environnementaux à effet perturbateur endocrinien, tels que les dioxines émises par les activités de combustion industrielle, sont suspectés d'augmenter le risque de cancer du sein. L'alimentation et l'inhalation sont les deux voies majeures d'exposition aux dioxines chez l'Homme. Les données épidémiologiques sur le sujet sont non concluantes, et il existe des limites méthodologiques. Ce travail doctoral avait pour objectif d'étudier l'impact de l'exposition aux dioxines sur le risque de cancer du sein dans la cohorte E3N, en répondant aux limites des études existantes.Nous avons évalué l'exposition alimentaire aux dioxines puis estimé le risque de cancer du sein associé parmi les femmes de la cohorte E3N. Nous avons ensuite développé un score d'exposition basé sur un système d'information géographique, associant la distance à la source, la durée d'exposition et la fréquence de vent dominant, afin d'évaluer l'exposition environnementale aux dioxines à chaque adresse des femmes entre 1990 et 2008. Le risque de cancer du sein associé au score d'exposition cumulé a été estimé dans une étude cas-témoins nichée dans la cohorte E3N, parmi les femmes ayant résidé en Rhône-Alpes. Aucune association n'a été observée, à l'exception d'une diminution du risque de cancer du sein hormono-indépendant, retrouvée de façon significative dans l'étude alimentaire. Cette dernière observation est cohérente avec des données expérimentales. Dû à un manque de puissance statistique pour l'exposition aérienne, nos résultats demandent confirmation au niveau national
Breast cancer (BC) is the first malignancy among women. Its incidence has doubled over the past 30 years. Environmental factors with endocrine disruptive properties, such as dioxins emitted from industrial combustion processes, are suspected to affect BC risk. Ingestion of contaminated food and inhalation are the major exposure routes in humans. Epidemiological evidence on the association between dioxin exposure and BC risk remains inconclusive due to methodological limitations. The aim of the thesis was to investigate the association between dioxin exposure and BC risk in the E3N prospective cohort, filling current methodological gaps.First, we assessed the association between estimated dietary dioxin exposure and BC risk among women from the E3N cohort. Second, we developed a geographic information system (GIS)-based metric to assess airborne dioxin exposure at the individual address level, including proximity to and technical characteristics of industrial sources, exposure duration and prevailing wind frequency. The metric was then applied to each E3N women’s addresses from 1990 to 2008, and airborne dioxin exposure was estimated for cases and matched controls from a cohort sub-population (the Rhône-Alpes region). Third, we estimated BC risk associated with cumulative airborne dioxin exposure. Overall, no statistically significant association was observed, except for a decrease in hormone-independent BC risk. The latter was significant for dietary dioxin exposure. For airborne exposure, we might have lacked statistical power and confirmation at the national level is required. The inverse association with ER-negative BC risk is consistent with experimental evidence

This study reviews available methods of exposure assessment, examines the effects of exposure misclassification on the ability to identify an association, and focuses on recent progress in subjective exposure modelling. Subjective exposure modelling utilises a framework of parameters identified as likely to control personal exposure levels together with detailed guidance and expert judgement in order to estimate exposure concentrations. As part of a case-control study, the Neurotoxicity of Paint Solvents (NPS) study, the process of evaluating subjects' lifetime exposure to solvents was reviewed. A training program and detailed guidance material was produced and the ability of assessors to reconstruct inhalation exposures from textual data was tested. In the training study, assessors were shown to estimate exposures that were well correlated with measured levels (correlation coefficients for log estimate compared to log measured values ranging from 0.73 to 0.85). The assessors tended to overestimate levels with the estimates ranging from 1.6 to 3.5 times the measured results. A series of painting simulation exercises was carried out to validate the use of certain guidance values for the model parameters. Using different paint application methods and different paint types, the influence of these variables on exposure levels was assessed. The results agreed closely with the guidance produced for the inhalation exposure model. Analysis of the solvent exposure histories of the NPS study group suggested that dermal exposure and uptake of solvents was important. To this end a novel dermal exposure model was developed for spray painting tasks. Using a conceptual model of the process, a method to describe both the likely dermal solvent exposure and solvent uptake through the skin was created. Mechanisms for combining exposures from the dermal and inhalation exposure pathways are described. Using occupational history information together with workplace monitoring records and data from paint manufacturers, both inhalation and dermal exposure to solvents was estimated for the one-hundred and twenty NPS study subjects. Two solvent exposure metrics were calculated. Cumulative exposure was the product of exposure level and time, while average annual intensity was the cumulative exposure figure divided by the number of years in solvent using employment.

Video exposure monitoring (VEM) consists of taking video recording of a worker performing a task at the same time while personal monitoring is performed using a direct-reading instrument. The video and the exposure data are then merged and synchronized and analyzed together. The industrial hygienist conducting the VEM is able to identify any high level of exposure and note the time when the excessive level happened. The corresponding task of the worker is then identified based from the video shot taken at the same time as the exposure data. The objective of this thesis was to study the implementation of a low cost means of conducting VEM in workplaces with hazardous chemicals in use, by utilizing commercially-available direct reading instruments, a digital video camera, and either off-the-shelf software or freeware downloadable from the internet. It was intended that VEM done by such means would still have the same ability of conveying workplace exposure results and, at the same time, capable of pinpointing work areas where controls could be initiated to reduce excessive levels of contaminants.

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.

Glyphosate is a leaf-absorbed, systemic herbicide against a wide range of problem annual and perennial weeds that is widely used in crop production, general land management and home gardens. Though glyphosate is the most heavily used herbicide in Australia, its use is not monitored (ATSE, 2002). Controlled residue studies show that residues of glyphosate persist in food crops, creating the potential for a large number of people to be exposed (FAO/WHO, 1986; 2006b; U.S. EPA, 1993). Regulatory studies show that glyphosate per se is practically harmless to humans, wildlife and the environment; however, recent research indicates other ingredients in the formulation increase the toxicity and availability of glyphosate in animal cells, tissues and organs, raising concern for the safety of glyphosate on human health. While dietary exposure of the general population to glyphosate has been predicted, it has not been measured in regional surveillance or national total diet studies; neither has an exposure assessment been conducted in the residential setting (FSANZ, 2003; personal communication Cook (FSANZ), 2007; U.S. EPA, 1993; WHO, 1994).

Organophosphate (OP) pesticides, as a group, are the most widely used insecticides in Australia. Approximately 5 000 tonnes of active ingredient are used annually (Radcliffe, 2002). The OP pesticide group consists of around 30 identifiably distinct chemicals that are synthesised and added to approximately 700 products (Radcliffe, 2002). OP pesticides are used on fruit, vegetable, grain, pasture seed, ornamental, cotton, and viticultural crops, on livestock and domestic animals, as well as for building pest control. OP pesticides all act by inhibiting the nervous system enzyme acetylcholinesterase (AChE) and as such are termed anticholinesterase insecticides. The phosphorylation of AChE and the resultant accumulation of acetylcholine are responsible for the typical symptoms of acute poisoning with OP compounds. In addition to acute health effects, OP compound exposure can result in chronic, long-term neurological effects. The traditional method of health surveillance for OP pesticide exposure is blood cholinesterase analysis, which is actually biological effect monitoring. However, there are several drawbacks associated with the use of the blood cholinesterase test, including its invasive nature, the need for baseline levels and a substantial exposure to OP pesticide before a drop in cholinesterase activity can be detected. OP pesticides are metabolised fairly rapidly by the liver to form alkyl phosphates (DAPs). Approximately 70% of OP pesticides in use in Australia will metabolise into one or more of six common DAPs. During the last 30 years, scientists have developed a urine test that detects these six degradation products. However, unlike the blood cholinesterase test, there is currently no Biological Exposure Index (BEI) for the urine DAP metabolite test. Workers in the agricultural industry - particularly those involved with mixing, loading and application tasks - are at risk of exposure to OP pesticides. It is therefore important that these workers are able to assess their risk of health effects from exposure to OP pesticides. However, currently in Queensland, workplace health and safety legislation exempts the agricultural industry from hazardous substance legislation that incorporates the requirement to perform risk assessments and health surveillance (blood cholinesterase testing) for OP pesticide exposure. The specific aim of this research was to characterise OP pesticide exposure and to assess the feasibility of using urine DAP metabolite testing as a risk assessment tool for agricultural and related industry workers exposed to OP pesticides. An additional aim among farmers was to conduct an in-depth evaluation of their knowledge, attitudes and behaviours related to handling OP pesticides and how they assess the risks associated with their use of OPs. A cross-sectional study design was used to assess exposure to OP pesticides and related issues among four groups: fruit and vegetable farmers, pilots and mixer/loaders, formulator plant staff and a control group. The study involved 51 farmers in the interviewer-administered questionnaire and 32 in urine sample provision. Eighteen pilots and mixer/loaders provided urine samples and 9 exposed formulation plant staff provided urine and blood samples. Community controls from Toowoomba Rotary clubs provided 44 urine samples and 11 non-exposed formulation plant staff provided blood and urine samples; all groups also provided responses to a self-administered questionnaire. Participant farmers were drawn from the main cropping areas in south-east Queensland - Laidley/Lowood, Gatton, and Stanthorpe. The farmer group was characterised by small owner-operators who often had primary responsibility for OP pesticide mixing and application. Farmers had good knowledge of pesticide-related safety practices; however, despite this knowledge, use of personal protective equipment (PPE) was low. More than half of the farmers did not often wear a mask/respirator (56%), gloves (54%) or overalls (65%). Material Safety Data Sheets were never or rarely read and 88.2% of farmers never or rarely read OP pesticide labels before application. There were also problems with chemical suppliers providing farmers with MSDSs. The majority of farmers (90.2%) reported that they had never had any health surveillance performed and three-quarters had never read about or been shown how to perform a formal risk assessment. The main inhibitors to the use of PPE in the farmers' group included the uncomfortable and cumbersome nature of PPE, especially in hot weather conditions, and the fear of PPE use triggering neighbours' complaints to Government authorities. Factors associated with better PPE use included having positive attitudes and beliefs toward PPE use, higher knowledge scores and low risk perception. Farmers' use of OP pesticides was infrequent, of short duration and involved application via a boom on a tractor, a lower risk application method. Consequently, urine DAP metabolite levels in this group were generally low, with 36 out of 96 samples (37.5%) containing detectable levels. Detectable results ranged from 9.00-116.00 mol/mol creatinine. Formulators exposed to OP pesticides were found to have the highest urine DAP metabolite levels (detectable levels 13.20-550.00 mol/mol creatinine), followed by pilots and mixer/loaders (detectable levels 8.40-304.00 mol/mol creatinine) and then farmers. Despite this, pilots and mixer/loaders (particularly mixer/loaders) had the greatest number of samples containing detectable levels (94.4% of samples). The DAP metabolite most frequently detected across all groups was DMTP, which was the only metabolite found in control samples. Levels found in this study are similar to those reported in international research (Takamiya, 1994, Stephens et al., 1996, Simcox et al., 1999, Mills, 2001, Cocker et al., 2002). The observed DAP levels were not associated with a drop in cholinesterase activity among the formulation plant workers, as expected from the literature. Such exposure also is unlikely to be associated with acute health effects. In contrast, there is insufficient scientific knowledge to know whether levels recorded in this study and elsewhere may be associated with long-term, chronic health effects. Notably, DMTP levels also were observed among the presumably 'unexposed' comparison groups. Environmental background level exposures to OPs producing the DAP metabolite DMTP are therefore of potential significance and may be related, at least in part, to consumption of contaminated fruit and vegetables. There is also emerging evidence to suggest that exposure to DAP metabolites themselves through diet and other sources may contribute to the concentration of DAPs, including DMTP in urine, potentially complicating assessment of occupational exposures. Nevertheless, the urine DAP metabolite test was a useful, sensitive indicator of occupational OP pesticide exposure among agricultural workers and may be of use to the industry as part of the risk assessment process. Future research should aim to establish a BEI for the urine DAP test.

Organophosphate (OP) pesticides, as a group, are the most widely used insecticides in Australia. Approximately 5 000 tonnes of active ingredient are used annually (Radcliffe, 2002). The OP pesticide group consists of around 30 identifiably distinct chemicals that are synthesised and added to approximately 700 products (Radcliffe, 2002). OP pesticides are used on fruit, vegetable, grain, pasture seed, ornamental, cotton, and viticultural crops, on livestock and domestic animals, as well as for building pest control. OP pesticides all act by inhibiting the nervous system enzyme acetylcholinesterase (AChE) and as such are termed anticholinesterase insecticides. The phosphorylation of AChE and the resultant accumulation of acetylcholine are responsible for the typical symptoms of acute poisoning with OP compounds. In addition to acute health effects, OP compound exposure can result in chronic, long-term neurological effects. The traditional method of health surveillance for OP pesticide exposure is blood cholinesterase analysis, which is actually biological effect monitoring. However, there are several drawbacks associated with the use of the blood cholinesterase test, including its invasive nature, the need for baseline levels and a substantial exposure to OP pesticide before a drop in cholinesterase activity can be detected. OP pesticides are metabolised fairly rapidly by the liver to form alkyl phosphates (DAPs). Approximately 70% of OP pesticides in use in Australia will metabolise into one or more of six common DAPs. During the last 30 years, scientists have developed a urine test that detects these six degradation products. However, unlike the blood cholinesterase test, there is currently no Biological Exposure Index (BEI) for the urine DAP metabolite test. Workers in the agricultural industry - particularly those involved with mixing, loading and application tasks - are at risk of exposure to OP pesticides. It is therefore important that these workers are able to assess their risk of health effects from exposure to OP pesticides. However, currently in Queensland, workplace health and safety legislation exempts the agricultural industry from hazardous substance legislation that incorporates the requirement to perform risk assessments and health surveillance (blood cholinesterase testing) for OP pesticide exposure. The specific aim of this research was to characterise OP pesticide exposure and to assess the feasibility of using urine DAP metabolite testing as a risk assessment tool for agricultural and related industry workers exposed to OP pesticides. An additional aim among farmers was to conduct an in-depth evaluation of their knowledge, attitudes and behaviours related to handling OP pesticides and how they assess the risks associated with their use of OPs. A cross-sectional study design was used to assess exposure to OP pesticides and related issues among four groups: fruit and vegetable farmers, pilots and mixer/loaders, formulator plant staff and a control group. The study involved 51 farmers in the interviewer-administered questionnaire and 32 in urine sample provision. Eighteen pilots and mixer/loaders provided urine samples and 9 exposed formulation plant staff provided urine and blood samples. Community controls from Toowoomba Rotary clubs provided 44 urine samples and 11 non-exposed formulation plant staff provided blood and urine samples; all groups also provided responses to a self-administered questionnaire. Participant farmers were drawn from the main cropping areas in south-east Queensland - Laidley/Lowood, Gatton, and Stanthorpe. The farmer group was characterised by small owner-operators who often had primary responsibility for OP pesticide mixing and application. Farmers had good knowledge of pesticide-related safety practices; however, despite this knowledge, use of personal protective equipment (PPE) was low. More than half of the farmers did not often wear a mask/respirator (56%), gloves (54%) or overalls (65%). Material Safety Data Sheets were never or rarely read and 88.2% of farmers never or rarely read OP pesticide labels before application. There were also problems with chemical suppliers providing farmers with MSDSs. The majority of farmers (90.2%) reported that they had never had any health surveillance performed and three-quarters had never read about or been shown how to perform a formal risk assessment. The main inhibitors to the use of PPE in the farmers' group included the uncomfortable and cumbersome nature of PPE, especially in hot weather conditions, and the fear of PPE use triggering neighbours' complaints to Government authorities. Factors associated with better PPE use included having positive attitudes and beliefs toward PPE use, higher knowledge scores and low risk perception. Farmers' use of OP pesticides was infrequent, of short duration and involved application via a boom on a tractor, a lower risk application method. Consequently, urine DAP metabolite levels in this group were generally low, with 36 out of 96 samples (37.5%) containing detectable levels. Detectable results ranged from 9.00-116.00 mol/mol creatinine. Formulators exposed to OP pesticides were found to have the highest urine DAP metabolite levels (detectable levels 13.20-550.00 mol/mol creatinine), followed by pilots and mixer/loaders (detectable levels 8.40-304.00 mol/mol creatinine) and then farmers. Despite this, pilots and mixer/loaders (particularly mixer/loaders) had the greatest number of samples containing detectable levels (94.4% of samples). The DAP metabolite most frequently detected across all groups was DMTP, which was the only metabolite found in control samples. Levels found in this study are similar to those reported in international research (Takamiya, 1994, Stephens et al., 1996, Simcox et al., 1999, Mills, 2001, Cocker et al., 2002). The observed DAP levels were not associated with a drop in cholinesterase activity among the formulation plant workers, as expected from the literature. Such exposure also is unlikely to be associated with acute health effects. In contrast, there is insufficient scientific knowledge to know whether levels recorded in this study and elsewhere may be associated with long-term, chronic health effects. Notably, DMTP levels also were observed among the presumably 'unexposed' comparison groups. Environmental background level exposures to OPs producing the DAP metabolite DMTP are therefore of potential significance and may be related, at least in part, to consumption of contaminated fruit and vegetables. There is also emerging evidence to suggest that exposure to DAP metabolites themselves through diet and other sources may contribute to the concentration of DAPs, including DMTP in urine, potentially complicating assessment of occupational exposures. Nevertheless, the urine DAP metabolite test was a useful, sensitive indicator of occupational OP pesticide exposure among agricultural workers and may be of use to the industry as part of the risk assessment process. Future research should aim to establish a BEI for the urine DAP test.

Indoor microenvironments can have a relevant contribution towards the total exposure to pollutants. The biomarkers of exposure and effect were analysed in general population, to evaluate the impact of VOCs, PAHs and tobacco smoke exposure in everyday life. We designed a model for toxicological studies, as proof of concept for future studies. We analysed airborne personal exposure to air pollutants, the urinary and oxidative stress biomarkers of three exposure level groups in a non-smoking population from Birmingham, UK, a subset with high exposures to tobacco smoke, and a subset of schoolchildren in Saudi Arabia, living in high pollution areas. A significant correlation was observed between low concentration urinary cotinine and urinary VOCs. Urinary VOCs were found suitable for exposure assessment of general population, although the correlations with oxidative stress biomarkers were weak. No significant correlation between urinary PAHs and oxidative stress was observed in schoolchildren from Saudi Arabia, although certain areas showed a significant increase in urinary PAHs and oxidative stress biomarker. The cell exposure system was designed and tested so it could be applied in future toxicological studies. The observed ROS generation and DNA damage in the cells after exposure, proved the validity of the model for benzene exposure.

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2006.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references (p. 73-79).
A technology is presented for exposing the contents of microfabricated cavities in a substrate. These contents are hermetically sealed until exposure is triggered by an electronic signal. The exposure mechanism uses electrothermal heating to rupture a metal membrane at one end of the cavity. The device's capability for storing a variety of contents and exposing them on demand makes it well suited for periodic exposure of new sensors as old ones degrade. Two commercialization possibilities are investigated: biowarfare agent detection and in vivo glucose sensing. Both applications employ sensing mechanisms that can be miniaturized and packaged in an array. These sensors are susceptible to fouling or degradation over time from environmental factors. The controlled-exposure technology addresses this problem by periodically exposing fresh sensors. The two applications are thought to be especially favorable markets because of the need for reliable, continuous sensing. The engineering aspects of the technology are investigated by identifying key material properties for each component of the device.
(cont.) The key properties for the substrate material are suggested to be its vapor permeability and suitability for cavity formation. The most important properties of the membrane are its electrical requirements (the current and voltage required to expose or "activate" the device), its strength and hermeticity, and its stability in the intended working environment. Design and materials selection approaches for optimizing these properties are presented.
by John Mapes Maloney.
M.Eng.

The main aim of this thesis is a development of ILF curves that can be used in the insurance industry when pricing general third party liability on the Czech market. Based on available data there are first estimated size of loss distribution functions used for following generating process. From generated data the increased limit factors are estimated and with a usage of Riebesell's parameterization ILF curves are derived. A substantial part of the thesis is a compilation of literature and the expansion of the statistical approach for estimating fair ILFs based on these data. Besides, the basis for the curves derivation are chapters describing basic theoretical knowledge in the field of reinsurance - in particular, the description of the basic types of reinsurance contracts, as well as the most common methods of a pricing. There is the whole mechanism of curves derivation described; their own use is then demonstrated with the example based on pseudoreal data.

The primary objective of this research was to investigate exposure to formaldehyde. There has been very little research on personal exposure to pollutants in the community and none on personal exposure to formaldehyde. In Australia, there are very little data on indoor formaldehyde concentrations. This is despite the fact that in Europe and in the United States, formaldehyde is one of the most frequently found indoor air contaminants, and is known to cause both acute and chronic health effects. The results of this research generally support the hypothesis that fixed site monitoring in indoor environments is able to explain a substantial portion of the personal exposure to formaldehyde. However, the study also provided results in cabinet making factories which are not consistent with this hypothesis. The results did not support the hypothesis that time weighted models will improve the accuracy of personal exposure predictions relative to linear regression models of indoor and outdoor concentrations. The research was divided into two areas. Firstly, the spatial and temporal changes in concentrations of formaldehyde in indoor environments, and the factors affecting these levels were investigated. This resulted in a comprehensive documentation of the concentrations found in typical indoor environments, and in indoor environments likely to experience elevated concentrations of formaldehyde. Secondly, an assessment of personal exposure to formaldehyde, and a comparison of these results to formaldehyde concentrations recorded at fixed sites was conducted. This enabled the comparison of different models to understand personal exposure. Formaldehyde exposure assessment was conducted in 186 Australian homes and 60 occupied caravans and indoor measurements recorded in 132 unoccupied caravans. There were no significant differences between levels recorded in winter or summer for conventional homes monitored during different seasons, however a significant seasonal difference occurred in concentrations recorded in caravans. The highest concentrations were recorded in winter. In conventional homes a significant decrease in formaldehyde concentrations was found in levels recorded 6 months after the initial monitoring. The decrease was greatest in homes less than 10 years of age. In 13 multi-storey office buildings, levels ranged from 4 ppb to 90 ppb, with the highest concentrations being recorded in new buildings. A new four floor building was assessed for formaldehyde over fourteen months. Formaldehyde concentrations increased as the building progressed through its construction phase, and with the introduction of furnishings and carpet. After occupation, fluctuations in formaldehyde concentrations in the building were closely correlated with outdoor temperatures. The results from 24 hour personal exposure of people, non-occupationally exposed to formaldehyde, in conventional homes and caravans suggest that the home environment is the most important predictor of formaldehyde exposure. Measurements in conventional homes were able to account for between 54% and 61% of the variation of personal exposure. Measurements in caravans were able to account for 71% of the variation in personal exposure. For people occupationally exposed to elevated concentrations of formaldehyde, personal exposure in the workplace is the most significant exposure in accounting for variation in 24 hour personal exposure. Time weighted models were not found to improve the explanation of variation in personal exposure. This research derived models of formaldehyde exposure for people occupationally exposed to formaldehyde and identified concentrations in the home as the major determinant of personal exposure to people nonoccupationally exposed to formaldehyde. It also highlighted the complexity of personal exposure and the need to use time weighted models with some caution. The next step in research should be aimed at expanding these tests with different population sub-groups and the use of real time personal monitoring when the equipment is developed. This would facilitate a more complete description of personal exposure to formaldehyde and more accurate exposure models to assess the potential impact of formaldehyde on public health.

Hypospadias is a congenital malformation that occurs in 0.3-1% of live births, in which the meatus (the urethral opening) is dorsally malpositioned. Uncorrected hypospadias can cause difficulties in urination, abnormal sexual function, and adverse psychological consequences; surgical correction, though generally successful, constitutes an economic burden for families. Several common classes of pesticides have demonstrated potential to disrupt normal endocrine hormones that regulate fetal genitourinary development. Past epidemiologic studies of pesticide exposure and risk of hypospadias have been limited by limited available data, small sample sizes, or poor ascertainment of pesticide exposure. The objective of this study was to examine the relationship between parental occupational pesticide exposure and risk of hypospadias in their offspring; and further, to assess whether addition of residential pesticide exposure data is feasible and contributes to overall pesticide exposure. We began by conducting a meta-analysis of the current literature, in which summary measures of occupation (such as census occupation code) had been used to assign pesticide exposure. We found elevated but marginally significant risks of hypospadias were associated with maternal occupational exposure (PRR of 1.36, CI = 1.04-1.77), and paternal occupational exposure (PRR of 1.19, CI= 1.00-1.41) in the previously published literature. We then used industrial hygienist review of occupational histories to estimate the relationship between pesticide exposure and risk of hypospadias. We found that maternal occupational exposure to any pesticides (yes/no) was not associated with an increased risk of hypospadias (OR = 0.83, 95% CI = 0.6-1.1), cumulative insecticide (OR = 1.09; 95% CI = 0.9- 1.3), herbicide (OR = 1.05; 95% CI = 0.9- 1.2), or fungicide (OR = 0.91; 95% CI = 0.7-1.2) exposure. These negative findings might be explained by a lack of relationship at the low levels of exposure observed in this study population, in which case another farm exposure could be related to hypospadias; or this negative finding may be due to exposure misclassification. Finally, we evaluated the feasibility and relevance of collecting residential pesticide exposure and direct reports of occupational exposure from fathers. Residential pesticide use during the six months prior to pregnancy and during pregnancy was common among control mothers: 45% reported that their home had been treated for insect or rodent pests; 47% reported that their lawn or garden had been treated for weeds or insect pests; 16% used a lawn service; 26% reported that a pet had been treated for fleas, ticks, or mites (including flea and tick preventives); 17% reported community-wide sprayings for pests; and 16% reported that their workplaces were treated for pests. Case mothers were more likely to report that their home had been treated of insect or rodent pests (50%) or that a pet had been treated for fleas, ticks, or mites (36.5%). Our results suggest that collection of information on residential pesticide use is feasible, and the impact of residential pesticide use on birth defects risk should be assessed in future studies.

Les égoutiers sont exposés à une grande variété de mélanges de produits chimiques beaucoup ce sont des substances génotoxiques ou cancérigènes. Le but de cette étude transversale était d'explorer des biomarqueurs intégrés d’exposition et des effets précoces chez les égoutiers afin de mieux apprécier leur risque cancérogène (article I-protocole). L'article II expose l'étape de validation préalable effectuée sur la lignée cellulaire pour nos objectifs. Avec un recueil en 10 mois et sur une base hebdomadaire, nous avons, a) évalué l'exposition personnelle des égoutiers (n=34) et administratifs (n=30) (groupe témoin) à des hydrocarbures aromatiques polycycliques (HAP) et composés organiques volatils (COV) dans l'air des lieux de travail, b) évalué la génotoxicité de leurs extraits organiques urinaire par des tests in vitro : tests des comète et des micronoyaux sur les cellules Hep G2, c) évalué la réponse à un stress oxydatif de l'ADN par la mesure du 8 oxo 2' deoxyguanosine urinaire (8 oxodG) dans les urines de 24h (Article III). Les tests ont montré la présence de plus de génotoxiques dans les urines des égoutiers (P <0,001). La moyenne du 8 oxodG urinaire chez les égoutiers était plus élevée (non significatif, P = 0,28) que les administratifs et ses valeurs moyennes ont été associées (P = 0,04) avec les années de travail dans le système des égouts. Les concentrations des HAP et COV dans l'atmosphère professionnelle des égoutiers étaient élevées par rapport à celles des administratifs (P <0,01) et il a été montré une augmentation de risque du cancer en utilisant les facteurs d'équivalence de toxicité et de risque unitaire de cancer. En conclusion, les biomarqueurs intégrés urinaire d’exposition et non spécifiques montrent que les égoutiers sont professionnellement exposés aux mélanges des substances génotoxiques. Il n’est pas possible de relier nos résultats avec l’accroissement du risque cancérogène chez les égoutiers
Sewage workers are exposed to a wide variety of mixtures of chemicals many were shown to be genotoxicants or carcinogens. The aim of this cross sectional study was to explore integrated biomarkers of exposure and of early effects among sewage workers in order to better assess their carcinogenic risk (Paper I-protocol). Paper II, describes the validation step performed prior to choose the cellular line that meet our objectives. Over 10 months and on weekly basis, we, a) assessed the personal exposure of sewage (n=34) and office (n=30) workers (control group) to polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) in the air of workplaces, b) evaluated the genotoxicity of organic urine extracts by in vitro comet and micronucleus assays on Hep G2 cells, c) assessed the DNA oxidative stress by the 24h urinary 8 oxo 2' deoxyguanosine (8 oxodG) (Paper III). The tests showed greater genotoxicity in the urine extracts of sewage workers (P<0.001). The 24hr urinary 8 oxodG mean level in sewage workers was higher (nonsignificant, P=0.28) than office workers and its mean values were associated (P=0.04) with working years in sewage system. Workplace air concentrations of PAHs and VOCs were elevated in sewage compared to office workplaces (P<0.01) and resulted in an increased lifetime cancer risk using toxicity equivalent factors and inhalation unit risk of cancer. In conclusion, the applied integrated and non-specific urinary biomarkers show that sewage workers experience exposure to multiple genotoxicants at the workplace. It is not possible to simply link our results with the increased cancer risk in sewage workers

European Project INDEX-UPRIC 2009 In 2009, DG SANCO funded an update of the 2005 project INDEX “Critical Appraisal of the Setting and Implementation of Indoor Exposure Limits in the EU”. DG SANCO required a particular focus on formaldehyde, on the basis of new papers published following its re-classification in Group 1 (sufficient epidemiological and scientific evidence for an association with nasopharyngeal cancer) by IARC. INDEX-UPRIC 2009 (“UPdate of PRIority Compounds”) aimed at reviewing recent scientific data, but also at re-examining previous studies and re-considering the reference values proposed in 2005. From selected results of scientific literature and an innovative approach in applying uncertainty factors, making the best use of chemical specific data on toxicodynamics and toxicokinetics, new reference limits have been proposed for exposure to formaldehyde in indoor settings. The reference range of values for short-term exposure (30 minutes) proposed at EU level is 70-100 ppb (or 90-120 µg/m3); it is comparable to most of exposure limits set by other national or international organisation. WHO in particular, in the latest version of IAQ guidelines (just published in December 2010), even if resulting from a different calculation, recommends a limit of 100 µg/m3 (~80 ppb) for short-term exposure. The reference values proposed by INDEX UPRIC 2009 should be used for the risk characterisation of situations related to acute exposure to formaldehyde indoors. In the light of scientific data available, it can be considered protective from carcinogenic effects in relation to short-term exposure, although it is derived from an irritation endpoint. Always looking at the scientific evidence available so far, there is no indication of cumulative effects following exposure to low concentrations (below 1 ppm), as adverse effects seem to recover shortly after exposure period. Current knowledge allows to reasonably assume that the proposed reference range of concentrations is also protective from long-term health effects due to repetitive short-term exposures. However, attention must be paid at the outcomes of genotoxicity studies (currently inconclusive), particularly with concern to a potential association of formaldehyde with increased incidence of tumours other than those located in the site of exposure (airways tissues). Exposure characterisation and Exposure Scenarios in hospitals The hazard characterisation of formaldehyde carried out in INDEX UPRIC project indicates that recurrent, short-term, peak exposures, rather than exposure to constant levels, are expected to adversely affect eyes and upper airways in exposed subjects, posing also a potential risk for more severe health outcomes. Exposure to formaldehyde in occupational settings, and particularly in Pathology labs, appears to be characterised by concentration fluctuations and peaks. To perform a correct exposure assessment in Pathology Units, and to eventually associate exposure levels with health effects, an in-depth understanding of determinant factors of exposure and actual air levels, is a requirement. The project aimed to reach this goal through the development of detailed Exposure Scenarios and the characterisation of concentration fluctuations during specific tasks in Pathology Units of two different hospitals. Three monitoring methods have been adopted: passive, active and in-continuous techniques have been tested and their outcomes analysed. Potential hazards for operators’ health have been identified during the performance of several tasks, being measured formaldehyde levels clearly above the TLV-C set by US ACGIH (0.3 ppm). From circumstances observed during monitoring, some misuses have been identified as well as inappropriateness of some organisational, logistic, and mitigation factors leading to high level of exposure (even above 1 ppm). Exposure Scenarios for critical tasks have been presented, including operational conditions, formaldehyde levels detected by the three techniques, possible causes of rises above the TLV-C, and proposed RMMs . Due to intrinsic properties of formaldehyde, its release from formalin solution is unavoidable, thus the implementation of RMMs is particularly crucial to avoid excessive exposure of operators. Much can be done in order to reduce critical situations, but measures to put into practice must be shared within all personnel working in the Unit. Less problematic alternatives (i.e. glutaraldehyde) should be also taken into account, considering the current debate on carcinogenicity and being formaldehyde in revision of classification at EU level as a consequence of a French request to place it among Carcinogens Category 1. Proposed RMMs have started to be put into place by Prevention and Protection Service of both hospitals. Very soon after their implementation another monitoring survey is foreseen, in order to check their effectiveness and appropriateness.

La radio FM reste populaire chez toutes les catégories du grand public. Les antennes FM sont généralement placées sur des structures métalliques, aussi appelées pylônes, que les travailleurs doivent escalader pour effectuer des travaux de maintenance. La législation exige le contrôle de l’exposition lorsque les travailleurs sont exposés à des émetteurs à haute puissance. L’objectif de cette recherche est de caractériser les champs électromagnétiques dans les environnements des pylônes et d’évaluer l’exposition. Les champs électromagnétiques dans les environnements des pylônes sont généralement dans le champ proche des antennes, mais la caractérisation et la compréhension du champ proche dans la littérature est limitée à des cas spécifiques d’exposition. Cette recherche s’est donc focalisée sur la définition d’une nouvelle méthodologie en généralisant l’évaluation de l’exposition en champ proche. Cette étude a examiné l’environnement des champs proches en analysant des indicateurs de champs électromagnétiques que l’on peut trouver dans les pylônes, pour ensuite générer des champs incidents aléatoires aux caractéristiques similaires. Les champs aléatoires ont été validés et sélectionnés par un procédé, pour ensuite effectuer des simulations FDTD pour évaluer le débit d’absorption spécifique (DAS) .Cinq cents simulations FDTD pour l’évaluation du DAS ont été effectuées. Les résultats montrent une forte corrélation entre le DAS local/corps entiers et le champ électrique moyen. Des modèles de substitution permettant de lier le DAS au champ électrique ont été trouvés en utilisant des techniques de Machine Learning. L’incertitude des résultats de DAS et des modèles de substitution a été quantifiée
FM radio is still popular among all segments of the general population. FM antenna arrays are usually placed on metallic structures known as pylons that workers have to climb in order to do maintenance and repair work. Exposure monitoring is required by regulation when workers are exposed to high-power emitters. The purpose of this research is to characterize electromagnetic fields (EMF) in pylon environments and to assess EMF exposure in such cases.EMF in pylon environments tend to be in the near-field region of the antenna arrays, but the characterization and understanding of such environments in the literature is limited to specific exposure cases. This research has therefore focused on defining a new methodology by generalizing exposure assessment in the near-field.Using field metrics analysis in human-sized volumes, this study analyzed the near-field environments found in the transmission pylons and generated random incident fields that have the same characteristics. The random incident fields were subjected to a validation and selection process in order to be used in FDTD simulations for specific absorption rate (SAR) assessment.Five hundred FDTD simulations for SAR assessments were performed. The results showed a high correlation between local & whole-body SAR and averaged electric field strength. Surrogate models linking SAR to electric field strength were built using machine learning techniques. The uncertainty of the SAR results and the surrogate models was quantified

Excess exposure to solar ultraviolet radiation (UVR) is the only readily modifiable skin cancer risk factor, and childhood exposure is implicated in melanoma aetiology. To assist the design and evaluation of child sun protection interventions in the school and community context, this first comprehensive study used electronic monitors to record time-stamped, second-by-second UVR exposure of 325 children (from 28 randomly selected New Zealand primary schools) who kept a diary record of concurrent activities and sun-protective practices and completed a sun-related knowledge, attitudes and usual behaviours questionnaire. School principals and Health promoters (HPs) were interviewed about school and community sun protection efforts. Using the Haddon matrix and Ottawa Charter of Health Promotion to guide research, four potential domains of influence were identified: the physical and social environments, protective products, and host (child). Two key outcomes identified were child UVR exposure and sun-protective practices. A path model was developed where potential influences on these outcomes included school, community, host factors (demographics, skin type, sun-related attitudes, and sun-related knowledge), and pattern of concurrent outdoor activity. Seven specific hypotheses were defined to investigate the effects of host, school and community factors on UVR exposure, sun-protective practices, and sun-related knowledge, attitudes and behaviours. To test for the effects of host factors, day of the week and activity on UVR exposure and sun-protective practices, linear mixed models containing these factors and interactions between Year level-sex, activity-Year level and activity-sex, accounting for clustering within schools and allowing for repeated measures, were applied. Logistic regression with a random school effect was used to assess differences in scored student questionnaire items. Structural equation modelling was implemented to consider associations between sun-related knowledge, attitudes and behaviours, and other explanatory factors for variations in UVR exposure and sun-protective practices. Three of the seven specific hypotheses were supported. There were statistically significant differences in UVR exposure by sex, skin type, day of the week and activity, and sex-activity and Year level-activity interactions. Passive pursuits were associated with the highest UVR exposure rates compared to outdoor active, travel and unclassified pursuits. There were statistically significant differences in sun-protective practices by sex, ethnicity and skin type, and sex-activity and Year level-activity interactions. Girls tended to have higher sun protection scores than boys, but were more likely to sunbathe and use sunscreen. Children identifying with Pacific Island ethnicities had higher scores than children with other ethnicities, and children with Fitzpatrick skin types I and II had higher scores than children with skin types III, IV and V. School and community factors were not associated with UVR exposure, sun-protective practices, sun-related knowledge, attitudes and behaviours, but school and HPs� scores were relatively high, reflecting the significant time and effort spent promoting youth sun protection. Trends for Year level indicated that whereas child sun-related knowledge increased with Year level, attitudes and behaviours supportive of sun protection declined. When considering sun-related knowledge, attitudes and behaviours simultaneously, knowledge was only significantly associated with behaviours when mediated by attitudes. The study findings have implications for child sun protection interventions.

HIV infection remains a worldwide concern and new drug treatments are required to tackle drug resistance and to reduce drug-associated host toxicity. Raltegravir, a new anti-HIV drug which targets the HIV integrase enzyme, is now being used in anti-HIV treatment and has shown impressive efficacy and low toxicity. However, the drug shows high pharmacokinetic (PK) variability between subjects and it has been difficult to associate PK parameters with treatment outcome. The aim of this thesis was to improve the current understanding of the factors influencing raltegravir PK and cellular exposure using in vitro and in silico techniques.

This thesis consists of three substantive essays on exchange rate exposure, each constituting a separate chapter. These essays address three questions to improve our knowledge on exchange rate exposure. First, do exchange rates matter to firms? Secondly, which companies are more likely to be affected by exchange rate changes? Finally, does exchange rate exposure play a role in cross-sectional return variation? The first essay (Chapter 2) addresses the first two questions for the UK market by utilising a detailed and novel dataset drawn from a variety of sources, including hand collected data from company financial reports. This permits a robust examination of exchange rate exposure and its determinants in the UK market. The chapter analyses monthly firm characteristics data for a sample of 168 non-financial companies for the 2000-2011 period. The empirical results indicate that firms with more foreign sales, less foreign assets and higher growth opportunities exhibit more exposure to exchange rate changes. The second essay (Chapter 3) adopts a novel quantile regression approach to examine exchange rate exposure in the UK market. This is able to provide a more nuanced picture of the relationship between exchange rate changes and stock returns. A puzzling finding in the exchange rate exposure literature is that often empirical researchers are led to conclude that exchange rate changes have no impact on stock returns. By adopting the quantile regression approach, the results show that exchange rate exposure is significant and negative for the firms which underperform and positive for the firms which overperform. The final essay (Chapter 4) investigates the relation between exchange rate exposure and stock returns. Specifically we use Fama-Macbeth regressions and focus on a sample of 251 UK non-fmancials over the years 2002-2011. We opt for a quantile regression estimation method which provides robust and more efficient estimates than OLS does particularly for data samples with heterogeneity and outliers. Our fmdings show that exposure is economically meaningful and is an important contributor to the cross-sectional variation in returns. We reveal substantial heterogeneity in the effects of exchange rate exposure on future stock returns

Background Violence is a global public health problem and violence among youth is a matter of high priority. Adolescence and young adulthood are important periods for the foundation of future health. Youth victimization may have serious health consequences, making it important to address the occurrence and socio-medical context for possible interventions against violence. Aims To analyze prevalence, risk patterns and gender differences in emotional, physical, sexual, and multiple-violence victimizations and the associations between violence victimization and sexual ill health, sexual risk behaviors and mental health in Swedish youth. Methods A cross sectional study using two samples, a national sample from nine youth health centers in Sweden and a population-based sample from a middle-sized Swedish city. The questionnaire included standardized instruments addressing violence exposure (NorAQ), socio-demographics, mental and sexual ill-health and sexual risk behaviors, alcohol and substance use. Proportions and crude and adjusted odds ratios with a 95% CI were calculated. Results A total of 2,250 young women and 920 men, aged 15-23, answered the questionnaire at the youth health centers. In upper secondary school, 1,658 women and 1,589 men, aged 15-22, answered the questionnaire. High prevalence rates with gendered differences both in rates and in co-occurrence of different types of violence were found. Women were more often exposed to emotional violence and sexual violence than men, while men were more often physically victimized. For both women and men, violence victimization before the age of 15 was strongly associated with all types of violence victimizations during the past year. Strong associations were found between multiple-violence victimization and poor mental health in both genders. Among the sexually experienced students, consistent associations between lifetime multiple-violence victimization and various sexual ill-health and sexual risk behaviors were found in both genders, except for non-contraceptive use. Conclusions High prevalence of violence victimization in youth and strong associations between victimization, especially multiple victimization, and poor mental and sexual health were found. This needs to be recognized and addressed in social and medical settings.

Two optimisation problems were considered, in which market exposure is indirectly controlled. The first one models the capital of a company and an independent portfolio of new businesses, each one represented by a Cram\'r-Lundberg process. The company can choose the proportion of new business it wants to take on and can alter this proportion over time. Here the objective is to find a strategy that maximises the survival probability. We use a point processes framework to deal with the impact of an adapted strategy in the intensity of the new business. We prove that when Cram\'{e}r-Lundberg processes with exponentially distributed claims, it is optimal to choose a threshold type strategy, where the company switches between owning all new businesses or none depending on the capital level. For this type of processes that change both drift and jump measure when crossing the constant threshold, we solve the one and two-sided exit problems. This optimisation problem is also solved when the capital of the company and the new business are modelled by spectrally positive L\'vy processes of bounded variation. Here the one-sided exit problem is solved and we prove optimality of the same type of threshold strategy for any jump distribution. The second problem is a stochastic variation of the work done by Taylor about underwriting in a competitive market. Taylor maximised discounted future cash flows over a finite time horizon in a discrete time setting when the change of exposure from one period to the next has a multiplicative form involving the company's premium and the market average premium. The control is the company's premium strategy over a the mentioned finite time horizon. Taylor's work opened a rich line of research, and we discuss some of it. In contrast with Taylor's model, we consider the market average premium to be a Markov chain instead of a deterministic vector. This allows to model uncertainty in future conditions of the market. We also consider an infinite time horizon instead of finite. This solves the time dependency in Taylor's optimal strategies that were giving unrealistic results. Our main result is a formula to calculate explicitly the value function of a specific class of pricing strategies. Further we explore concrete examples numerically. We find a mix of optimal strategies where in some examples the company should follow the market while in other cases should go against it.

We study whether exposure to poverty can induce affective states that decrease productivity. In a controlled laboratory setting, we find that subjects randomly assigned to a treatment, in which they view a video featuring individuals that live in extreme poverty, exhibit lower subsequent productivity compared to subjects assigned to a control treatment. Questionnaire responses, as well as facial recognition software, provide quantitative measures of the affective state evoked by the two treatments. Subjects exposed to images of poverty experience a more negative affective state than those in the control treatment. Further analysis shows that individuals in a more positive emotional state exhibit less of a treatment effect. Also, those who exhibit greater attentiveness upon viewing the poverty video are less productive. The results are consistent with the notion that exposure to poverty can induce a psychological state in individuals that adversely affects productivity.

Thesis (M.S.) -- University of Maryland, College Park, 2008.
Thesis research directed by: Dept. of Electrical and Computer Engineering. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.

ABSTRACT Occupational exposure to wood dust and biohazards associated with wood dust (endotoxins, (1->3)-b-D-glucans, Gram (-)ve bacteria and fungi), their correlation to respiratory function, and symptoms among woodworkers have been investigated in the present study. Wood dust, endotoxins, and allergenic fungi are the main hazards found in woodworking environments. Relatively very few studies have been done on wood dust exposure. The present study was designed to comprehensively investigate the health effects of wood dust exposure, and in particular provide new information regarding: Exposure to (1->3)-b-D-glucans in an occupational environment; Levels of exposure to wood dust and biohazards associated with wood dust in different woodworking environments; Correlations among personal exposures, especially correlations between (1->3)-b-D-glucans and fungi exposures, and endotoxins and Gram (-)ve bacteria exposures; Effects of personal exposure to biohazards on lung function; Effects of personal exposure to biohazards on work-related symptoms; and Determinants of inhalable exposures (provide which factors in the environment influence the personal inhalable exposures). Workers at four different woodworking processes; two logging sites, four sawmills, one major woodchipping operation and five joineries situated in the state of New South Wales in Australia were studied for personal exposure to inhalable dust (n=182) and respirable dust (n=81), fungi (n=120), Gram (-)ve bacteria (n=120), inhalable endotoxin (n=160), respirable endotoxin (n=79), inhalable (1->3)-b-D-glucan (n=105), and respirable (1->3)-b-D-glucan (n=62). The workers (n=168) were also tested for lung function. A questionnaire study (n=195) was carried out to determine the prevalence of work-related symptoms. The geometric mean inhalable exposure at logging sites was 0.56 mg/m3 (n=7), sawmills 1.59 mg/m3 (n=93), the woodchipping mill 1.86 mg/m3 (n=9) and joineries 3.68 mg/m3 (n=66). Overall, sixty two percent of the exposures exceeded the current standards. Among joineries, 95% of the hardwood exposures and 35% of the softwood exposures were above the relevant standards. Compared with green mills, the percentage of samples, which exceeded the hardwood standard was high for dry mills (70% in dry mills, 50% in green mills). The respirable dust exposures were high at the joineries compared with the other worksites. Exposure levels to fungi at logging sites and sawmills were in the range 103-104 cfu/m3, woodchipping 103-105 cfu/m3 and joineries 102-104 cfu/m3. The predominant fungi found at sawmills were Penicillium spp. High exposure levels of Aureobasidium pullulans were also found at two sawmills. At the woodchipping mill the predominant species were Aspergillus fumigatus, Penicillium spp., and Paecilomyces spp. The sawmills, which employed kiln drying processes, had lower exposure levels of fungi compared with the green mills. Those workplaces which had efficient dust control systems showed less exposure to fungi and bacteria. Although mean endotoxin levels were lower than the suggested threshold value of 20 ng/m3, some personal exposures at sawmills and joineries exceeded the threshold limit value. The mean inhalable (1->3)-b-D-glucan level at the woodchipping mill was 2.32 ng/m3, at sawmills 1.37 ng/m3, at logging sites 2.02 ng/m3, and at joineries 0.43 ng/m3. For the respirable size fraction, mean endotoxin and mean (1->3)-b-D-glucan concentrations were much lower, being similar to observed dust concentrations. Significant correlations were found between mean inhalable endotoxin and Gram (-)ve bacteria levels (p<0.0001), and mean airborne inhalable (1->3)-b-D-glucan and fungi levels (p=0.0003). The correlations between mean respirable endotoxin levels vs Gram (-)ve bacteria exposure levels (p=0.005), and respirable (1->3)-b-D-glucan exposure levels vs total fungi levels (p=0.005) were also significant. Significant correlations were found between lung function and personal exposures. Multivariate analyses showed that the effect of all the personal exposures on cross-shift decrements in lung function was more prominent among sawmill and chip mill workers compared with joinery workers. Woodworkers had markedly high prevalence of cough, phlegm, chronic bronchitis, frequent headaches, throat and eye irritations, and nasal symptoms compared with controls. Among the woodworkers, smokers had a high prevalence of chronic bronchitis (20%) compared with non-smokers (10%). Some workers also reported a variety of allergy problems due to exposure to various types of wood dust. Both joinery workers and sawmill and chip mill workers revealed significant correlations between work-related symptoms and personal exposures. Chronic bronchitis was significantly correlated with personal exposure to wood dust, endotoxin, (1->3)-b-D-glucan, fungi, and Gram (-)ve bacteria among joinery workers. Whereas among sawmill workers chronic bronchitis was significantly correlated with personal exposure to endotoxin, (1->3)-b-D-glucan, and fungi. Woodworkers showed significant positive correlations between percentage cross-shift change (decrease) in lung function and respiratory symptoms. Significant inverse correlations were also found among percentage predicted lung function and respiratory symptoms. The elevated inhalable dust exposures observed in this study can be explained by a combination of factors, including: lack of awareness of potential health effects of wood dust exposure among both management and workers, aging equipment, inadequate and ineffective dust extraction systems or usually none especially for hand held tools, poor maintenance of the ventilation system in some, non-segregation of dusty processes, dry sweeping, and the use of compressed air jets. The determinant-of-exposure analysis confirmed the field observations. The significant determinants of personal inhalable dust exposures (n=163) were found to be: local exhaust ventilation, job title, use of hand-held tools, cleaning method used, use of compressed air, and green or dry wood processed. Type of wood processed was not found to be statistically significant. A majority of workers (~90%) did not wear appropriate respirators approved for wood dust, while the workers who did wear them, used them on average less than 50% of the time. Workers should be protected by controlling dust at its source. When exposure to wood dust cannot be avoided, engineering controls should be supplemented with the use of appropriate personal protective equipment.

ABSTRACT Occupational exposure to wood dust and biohazards associated with wood dust (endotoxins, (1->3)-b-D-glucans, Gram (-)ve bacteria and fungi), their correlation to respiratory function, and symptoms among woodworkers have been investigated in the present study. Wood dust, endotoxins, and allergenic fungi are the main hazards found in woodworking environments. Relatively very few studies have been done on wood dust exposure. The present study was designed to comprehensively investigate the health effects of wood dust exposure, and in particular provide new information regarding: Exposure to (1->3)-b-D-glucans in an occupational environment; Levels of exposure to wood dust and biohazards associated with wood dust in different woodworking environments; Correlations among personal exposures, especially correlations between (1->3)-b-D-glucans and fungi exposures, and endotoxins and Gram (-)ve bacteria exposures; Effects of personal exposure to biohazards on lung function; Effects of personal exposure to biohazards on work-related symptoms; and Determinants of inhalable exposures (provide which factors in the environment influence the personal inhalable exposures). Workers at four different woodworking processes; two logging sites, four sawmills, one major woodchipping operation and five joineries situated in the state of New South Wales in Australia were studied for personal exposure to inhalable dust (n=182) and respirable dust (n=81), fungi (n=120), Gram (-)ve bacteria (n=120), inhalable endotoxin (n=160), respirable endotoxin (n=79), inhalable (1->3)-b-D-glucan (n=105), and respirable (1->3)-b-D-glucan (n=62). The workers (n=168) were also tested for lung function. A questionnaire study (n=195) was carried out to determine the prevalence of work-related symptoms. The geometric mean inhalable exposure at logging sites was 0.56 mg/m3 (n=7), sawmills 1.59 mg/m3 (n=93), the woodchipping mill 1.86 mg/m3 (n=9) and joineries 3.68 mg/m3 (n=66). Overall, sixty two percent of the exposures exceeded the current standards. Among joineries, 95% of the hardwood exposures and 35% of the softwood exposures were above the relevant standards. Compared with green mills, the percentage of samples, which exceeded the hardwood standard was high for dry mills (70% in dry mills, 50% in green mills). The respirable dust exposures were high at the joineries compared with the other worksites. Exposure levels to fungi at logging sites and sawmills were in the range 103-104 cfu/m3, woodchipping 103-105 cfu/m3 and joineries 102-104 cfu/m3. The predominant fungi found at sawmills were Penicillium spp. High exposure levels of Aureobasidium pullulans were also found at two sawmills. At the woodchipping mill the predominant species were Aspergillus fumigatus, Penicillium spp., and Paecilomyces spp. The sawmills, which employed kiln drying processes, had lower exposure levels of fungi compared with the green mills. Those workplaces which had efficient dust control systems showed less exposure to fungi and bacteria. Although mean endotoxin levels were lower than the suggested threshold value of 20 ng/m3, some personal exposures at sawmills and joineries exceeded the threshold limit value. The mean inhalable (1->3)-b-D-glucan level at the woodchipping mill was 2.32 ng/m3, at sawmills 1.37 ng/m3, at logging sites 2.02 ng/m3, and at joineries 0.43 ng/m3. For the respirable size fraction, mean endotoxin and mean (1->3)-b-D-glucan concentrations were much lower, being similar to observed dust concentrations. Significant correlations were found between mean inhalable endotoxin and Gram (-)ve bacteria levels (p<0.0001), and mean airborne inhalable (1->3)-b-D-glucan and fungi levels (p=0.0003). The correlations between mean respirable endotoxin levels vs Gram (-)ve bacteria exposure levels (p=0.005), and respirable (1->3)-b-D-glucan exposure levels vs total fungi levels (p=0.005) were also significant. Significant correlations were found between lung function and personal exposures. Multivariate analyses showed that the effect of all the personal exposures on cross-shift decrements in lung function was more prominent among sawmill and chip mill workers compared with joinery workers. Woodworkers had markedly high prevalence of cough, phlegm, chronic bronchitis, frequent headaches, throat and eye irritations, and nasal symptoms compared with controls. Among the woodworkers, smokers had a high prevalence of chronic bronchitis (20%) compared with non-smokers (10%). Some workers also reported a variety of allergy problems due to exposure to various types of wood dust. Both joinery workers and sawmill and chip mill workers revealed significant correlations between work-related symptoms and personal exposures. Chronic bronchitis was significantly correlated with personal exposure to wood dust, endotoxin, (1->3)-b-D-glucan, fungi, and Gram (-)ve bacteria among joinery workers. Whereas among sawmill workers chronic bronchitis was significantly correlated with personal exposure to endotoxin, (1->3)-b-D-glucan, and fungi. Woodworkers showed significant positive correlations between percentage cross-shift change (decrease) in lung function and respiratory symptoms. Significant inverse correlations were also found among percentage predicted lung function and respiratory symptoms. The elevated inhalable dust exposures observed in this study can be explained by a combination of factors, including: lack of awareness of potential health effects of wood dust exposure among both management and workers, aging equipment, inadequate and ineffective dust extraction systems or usually none especially for hand held tools, poor maintenance of the ventilation system in some, non-segregation of dusty processes, dry sweeping, and the use of compressed air jets. The determinant-of-exposure analysis confirmed the field observations. The significant determinants of personal inhalable dust exposures (n=163) were found to be: local exhaust ventilation, job title, use of hand-held tools, cleaning method used, use of compressed air, and green or dry wood processed. Type of wood processed was not found to be statistically significant. A majority of workers (~90%) did not wear appropriate respirators approved for wood dust, while the workers who did wear them, used them on average less than 50% of the time. Workers should be protected by controlling dust at its source. When exposure to wood dust cannot be avoided, engineering controls should be supplemented with the use of appropriate personal protective equipment.

Studies on repeated exposure to opioids have been carried out for decades yet the mechanisms for certain phenomena such as tolerance are still not fully understood. Furthermore, different medications, such as frequently prescribed benzodiazepines, or different disease states, such as HIV, have their own effects and interactions with chronic opioid exposure that are not fully understood. The overall objective of this dissertation was to investigate the complexities of chronic opioid exposure and how different disease states and medications may modulate the effects of chronic opioids. Our findings demonstrate that the administration of diazepam, at doses that are not antinociceptive or have any motor effects, reverse both antinociceptive and locomotor tolerance to orally active opioids. These doses of diazepam did not potentiate the acute effects of these prescription opioids. We also found that HIV-1 Tat expression significantly attenuated the antinociceptive potency of acute morphine in non-tolerant mice while not significantly altering the antinociceptive tolerance to morphine. Consistent with this, Tat attenuated withdrawal symptoms among morphine-tolerant mice. Pretreatment with maraviroc, a CCR5 antagonist blocked the effects of Tat, reinstating morphine potency in non-tolerant mice and restoring withdrawal symptomology in morphine-tolerant mice. Protein array analyses revealed only minor changes to cytokine profiles whether morphine was administered acutely or repeatedly; however, 24 h post repeated morphine administration, the expression of several cytokines was greatly increased. Tat further elevated levels of several cytokines and maraviroc pretreatment attenuated these effects. With the understanding that gap junctions may be involved in both HIV-Tat effects on opioid antinociception as well as tolerance, we investigated the role of gap junctions in opioid antinociceptive tolerance. We observed that carbenoxolone, a gap junction inhibitor, administered systemically attenuated the development of opioid antinociceptive tolerance. Furthermore, we observed a small percentage of carbenoxolone in brain tissue compared to the amount found in blood, suggesting a peripheral site of action. Finally, we show preliminary evidence that in vivo administration of carbenoxolone is able to attenuate tolerance to morphine in DRG neurons.

Ultraviolet radiation (UVR) is a by-product of the welding process and is emitted by the arc formed between the electrode and the base metal. Exposure to UVR can produce acute and chronic effects on the eyes and skin, including photokeratitis and erythema (acute), and pterygium and skin cancer (chronic). The measurement of UVR can be used to determine the level of hazard posed by a particular source. The personal UVR exposure levels of a group of welders and nearby workers was estimated using a photosensitive polymer film, polysulphone. The polysulphone film was attached to eye protection, the workers clothing and also placed throughout the workarea. The estimated ocular exposures of all subjects were found to exceed the eight-hour maximum permissible exposure limit. As the main UVR protective measure for welders is a welding helmet, the degree of protection afforded by a range of helmets was investigated in a laboratory experiment. Radiation was found to be reflected off the filter and toward the eye after entering through: (1) an opening between the edge of the shield and the side of the face, and (2) an opening between the top lip of the shield and the top of the head. The results of this study suggest that welders require ocular protection in addition to welding helmets, and that all exposed skin surfaces of workers in a welding environment should also be protected.

Exposure to particulate matter in work environments has been linked to ischemic heart, cardiovascular and respiratory-related disease risk increase due to inhalation. Increased adverse health effects have been linked to nanoparticles (< 100 nm) due to their ability to reach the deepest sections of the respiratory tract and their longer retention time. Exposure monitoring is widely used method to assess worker exposure to airborne particles. However, other prediction tools have been explored such as the use of the dustiness index, mass-balance models, and health risk assessment tools. Discussions regarding the use and application of the latter tools are ongoing due to their relatively novelty for worker exposure assessment, the need to test their performance under real- world scenarios, and the need to understand the uncertainties related to critical parameters and limitations. The main objectives of this PhD Thesis are to 1) assess worker exposure to particles (4 nm - 35 μm) in ceramic industry real-world workplace scenarios; 2) evaluate currently used exposure assessment metrics and decision-making approaches; 3) understand the relationship between material dustiness and worker exposure; 4) evaluate the performance of mass-balance models, and 5) compare health risk assessment tools. Worker exposure was assessed during mechanical handling of powders in 6 different scenarios and for 15 materials as well as thermal spraying of ceramic coatings. Exposure monitoring was conducted using online and offline instruments which allowed for the characterization of particle mass and number concentrations, particle size and size distribution, particle morphology and chemical composition. In addition, some of these scenarios were also selected to assess relationship between the dustiness index and exposure concentrations as well as the ability of different particle metrics to represent worker exposure. Finally, decision making approaches, and the performance of mass- balance models and risk assessment tools were tested. Results evidenced clear impacts of industrial activities on workplace exposure to coarse, fine and nanoparticles. Significant increases of inhalable and respirable particle mass concentrations (inhalable mass concentration 80-4000 μg m-3) were observed during mechanical handling of raw materials (d50 2.7-40 µm), when compared to background concentrations. The highest mean inhalable mass concentration (3700 μg m-3) was monitored during packing of ceramic materials, when mitigation strategies were inefficiently implemented. Conversely, particle number concentrations were not influenced by mechanical handling of powders, but by driving of diesel-powdered forklifts, leading to concentrations up to 70000 cm-3. Thermal spraying, on the other hand, increased particle number concentration up to 105 cm-3 in the worker area. After the application of the ICRP respiratory tract deposition model, airborne particles in the workplaces studied were seen to deposit mainly in the alveolar region (51-64%) during packing of powder materials and (54-70%) during thermal spraying by means of surface area. Source enclosure and modification of the energy settings were pointed out as useful strategies to minimize worker exposure. The validity, performance and comparability of tools for exposure assessment were evaluated. Several decision-making approaches were tested to determine statistically significant impacts on exposure. Among them, the ARIMA models were seen to be the least conservative while the nanoGEM approach confirmed its usefulness for particle number but slightly underestimated exposure for particle mass concentrations when compared to traditional statistical tests. High degree of correlation was found between dustiness and measured exposure concentrations during mechanical handling of powders in a pilot plant (R2 up to 0.97) and at industrial scale (R2 up to 0.80). This correlation was stronger when material characteristics dominated over process characteristics, and an adequate methodology is applied, using the dustiness method which best mimics the activity under study. Finally, one- and two-box models were used to model particles under high and low concentrations in terms of mass and particle number concentrations. Ratios between modelled and measured concentrations were 0.82-1.22 when modelling inhalable particle mass in the mechanical handling scenario, whereas ratios of 0.2-0.7 were obtained when modelling thermal spraying particles. Thus, model performance was poorer for the high nanoparticle concentration scenario. The addition of background and outdoor concentrations as input improved model performance. Risk assessment and control banding tools (ART, Stoffenmanager and NanoSafer) were tested for the scenarios under study, and it was concluded that the mechanical processes were estimated with higher accuracy and lower variability by Stoffenmanager (64% of the cases). Conversely, ART and NanoSafer showed higher flexibility for introducing more case-specific input data. A clear need for harmonization between risk assessment tools was evidenced.
L’exposició per inhalació de material particulat en ambients de treball ha estat relacionat amb l’augment del risc de patir malalties cardiovasculars y respiratòries. En el cas específic de les nanopartícules (< 100 nm), els efectes adversos han estat relacionats amb la seva capacitat per arribar a les regions més profundes del aparell respiratori i al seu major temps de retenció. Per tal de determinar els nivells d’exposició a material particulat, un mètode experimental àmpliament utilitzat és l’ús d’equips de mesura en continu de les concentracions. No obstant això, altres eines estan sent actualment explorades com per exemple l’ús del poder d’emissió de pols dels materials, models basats en balanços de masses per a la predicció de l’exposició, així com eines per a l’avaluació del risc per a la salut degut a l’exposició d’agent químics. No obstant això, degut a la seva relativa novetat, existeix la necessitat d’avaluar la validesa de totes aquestes eines en escenaris reals, així com de comprendre les incerteses relacionades amb els paràmetres i les seves limitacions. Per tant, el seu us i aplicació es troben actualment en debat. Els principals objectius d’aquesta tesi doctoral són: 1) avaluar els nivells d’exposició laboral a material particulat d’entre 4 nm i 35 μm en escenaris de treball reals, 2) avaluar les diferents mètriques existents per a l’avaluació dels nivells d’exposició i els mètodes de presa de decisions utilitzats en la actualitat; 3) comprendre la relació existent entre el poder d’emissió de pols dels materials i els nivells d’exposició dels treballadors durant la seva manipulació; 4) avaluar la validesa del models basats en balanços de massa; i 5) comparar diferents eines d’avaluació dels riscos de l’exposició a agents químics. En aquesta tesi s’han avaluat els nivells d’exposició laborals a material particulat, tant durant manipulació mecànica, concentradament de 15 materials pulverulents en 6 escenaris diferents, com durant projecció tèrmica de recobriments ceràmics, amb l’estudi de 2 escenaris amb tres materials per a l’obtenció de recobriments ceràmics sobre peces metàl·liques. El control experimental dels nivells d’exposició es va realitzar mitjançant l’ús d’equips de mesura de partícules en temps real i de la recol·lecció de mostres gravimètriques del material particulat emes, que va ser posteriorment analitzat per microscòpia electrònica. Tot això va permetre la caracterització de la concentració del material particulat en massa, numero de partícules, mida i distribució de mida de les partícules, la morfologia de les partícules i la seva composició química. Addicionalment, en els processos mecànics es va avaluar la relació entre el poder d’emissió de pols dels materials i els nivells d’exposició, així com la capacitat de diferents mètriques, generalment utilitzades per a l’ anàlisis de l’exposició a partícules (massa i numero), de representar l’exposició dels treballadors. Finalment, es van estudiar diferents mètodes per a la presa de decisions, es va avaluar la aplicabilitat en condicions industrials dels models basats en balanços de massa, així com de tres eines per a l’avaluació dels riscs per exposició a agents químics. Els resultats van evidenciar un clar impacte de les activitats industrial estudiades sobre els nivells d’exposició dels treballadors en els escenaris estudiats a partícules grolleres, fines i nanopartícules. Durant la manipulació mecànica de matèries primeres (d50 2.7-40 µm) es van observar augments significatius de les fraccions màssiques de pols inhalable i respirable (concentració de massa inhalable 80-4000 μg m-3) en comparació amb les concentracions de fons. La concentració mitjana més elevada per a la fracció màssica inahlable (3700 μg m-3) va ser mesurada durant l’ensacat de materials ceràmics amb una implementació ineficient de mesures de mitigació. Per el contrari, les concentracions en numero de partícules no es van veure influenciades per la manipulació mecànica dels materials pulverulents, però si que es van registrar concentracions de numero de partícules de fins 7x104 cm-3 degut a l’ús de carretons elevadors dièsel. Per una altra banda, en els escenaris de projecció tèrmica es va observar un augment de la concentració en numero de partícules de fins a valors del ordre de 105 cm-3 en l’àrea de treball. Mitjançant l’aplicació del model de deposició de partícules ICRP, es va observar que les partícules en suspensió en els llocs de treball estudiats es depositaven principalment en la regió alveolar tant durant l’ensacat (51-64%), com durant la projecció tèrmica (54-70%). L’aïllament de la font d’emissió així com la modificació de l’energia aplicada durant el procés es van detectar com a estratègies útils per a minimitzar l’exposició dels treballadors. També es va avaluar la validesa, el rendiment i la comparabilitat de varies eines estadístiques per a avaluar la significança estadística de les dades d’exposició. D’entre els mètodes avaluats, els models ARIMA van ser considerats com als menys conservadors, mentre que la metodologia nanoGEM va confirmar la seva utilitat per a l’anàlisis de les concentracions en numero de partícules, però va subestimar lleugerament la significança estadística de les concentracions en massa en comparació amb les proves estadístiques tradicionals. Es van trobar alts graus de correlació entre el poder d’emissió de pols del materials i les concentracions d’exposició mesurades durant la manipulació mecànica dels materials en planta pilot (R2 fins a 0.97) i en escala industrial (R2 fins a 0.80). Aquesta correlació s’ha vist reforçada quan les característiques dels materials dominen sobre les característiques del procés, i quan una metodologia adequada per a la determinació del poder d’emissió de pols va ser utilitzada, aquella que millor simula el procés d’estudi. Finalment, es van utilitzar els models basats en balanços de massa de una i dos caixes per a modelar dos escenaris diferents, un de baixa exposició a partícules grolleres (manipulació mecànica, ensacat de materials) y un altre d’altes concentracions de numero de partícules (projecció tèrmica). Les proporcions entre les concentracions modelades/mesurades van ser de 0.82-1.22 per a la modelització de la fracció màssica de pols inahalble en el cas de la manipulació mecànica, mentre que les proporcions van ser de 0.2-0.7 per a la modelització de la concentració en numero de partícules durant la projecció tèrmica. Per tant, la bondat dels models basats en balanços de massa va ser menor en l’escenari d’altes concentracions de numero de partícules. Al considerar les concentracions de fons i de l’aire ambient en els models, la bondat i la precisió dels models va augmentar. De les tres eines per a l’avaluació de riscos per exposició a agents químics (ART, Stoffenmanager i NanoSafer) que van ser provades, les concentracions mesurades durant els processos de manipulació mecànica van ser estimats amb una major precisió i menor variabilitat per Stoffenmanager (64% dels cases). Per el contrari, ART i NanoSafer van mostrar tenir una major flexibilitat per a introduir dades d’entrada especifiques per a cada cas.

Nanomaterials (NMs) can be defined as having at least one external dimension between 1-100nm. Due to their small size, NMs have a large surface area giving them characteristics that differ from bulk material. NMs are incorporated into numerous applications making environmental exposure to NMs likely. Increased reliance on plastic results in accumulation of nano-plastics in fresh waters. Polystyrene (PS) acts as a representative of both nano-plastic and NMs. The deposition of gold (Au) NMs is also likely due to their use in medical applications so that both PS and Au have a potential to interact with environmental organisms. Daphnia manga (D. magna) is an ideal candidate in fresh water toxicity testing. Toxicity, uptake and retention of NMs by organisms is dependent on several factors such as NM charge, shape, chemical composition and the absorption of natural biomolecules binding to the surface of the NM creating an eco-corona, altering stability of the NMs thereby changing their toxicity. This work investigates the toxicity of PS and Au NMs and explores the effects of charge, shape, presence of a corona and the impact of realistic modes of presentation of NMs to D. magna and how these factors impact toxicity, uptake, retention and depuration.