Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

Wet-work exposure has been recognized as a main risk factor for developing Irritant contact dermatitis of the hand. Duration and frequency of wet-work exposure are the key risk determinants, but there is still no reliable objective method to assess these factors in the workplace. The current study aimed to further validate a newly invented wet-work exposure monitor (WWEM) among four high risk occupational groups of hairdressers, florists, caterers and nurses. The WWEM, which consists of two similar thermocouples provides a real-time indication of the wetness of the finger by measuring the temperature changes when the finger is wet and subsequent cooling when the water evaporates from the skin. A suitable data analysis routine was constructed and direct observation was employed as the gold standard. Receiver Operating Characteristic (ROC) analysis was used to compare the results. In laboratory experiments, the most suitable wet-event threshold value, as a criterion to distinguish the wet and dry exposure periods was identified as 1.6°C (Mean+5SD of the “dry” data). Using this value sensitivity and specificity were 70% and 78%, respectively. An area under the curve (AUC) of 0.78 demonstrated a “high” accuracy for WWEM in lab experiments. Field testing in real occupational fields identified varying degrees of user acceptability and different wet-event threshold values to produce maximal sensitivity and specificity of the instrument. Among hairdressers, the WWEM showed a “moderate” accuracy at the threshold value of 1.37°C with an AUC of 0.62. For florists, the most suitable threshold value in the range of examined thresholds was 1.14°C with a “good” accuracy. Among a cohort of caterers, a threshold value of 1.6°C demonstrated a “hi gh” accuracy with an AUC of 0.72. The WWEM demonstrates the minimum value of the largest AUC for nurses. This is the minimum amount of accuracy among the four occupational groups. The figure is 0.52, achieved at a threshold value of 2.5°C. The WWEM enables the frequency and duration of wet-work exposure to be assessed in an objective manner rather than the current costly and unreliable subjective methods of direct observation and questionnaire. The results indicate that the WWEM has good sensitivity and high specificity in detecting exposure to wet-work. This device provides new experimental data on wetwork exposure and may be used in future as an educational tool to highlight the importance of wet-work exposure to both employees and employers.

Environmental exposure and outcomes assessment is a great challenge to scientists. Increasingly more and more detailed data are becoming available to understand the nature and complexity of the relationships involved. The methodology of mixture models provides a means to understand, quantify and describe features and relation- ships within complex data sets. In this thesis, we focussed on a number of applied problems to characterise complex environmental exposure and outcomes, including: assessing the interaction between environmental exposures as risk factors for health outcomes; identifying di®ering environmental outcomes across a region; and estab- lishing patterns in the size and concentration of aerosol particles over time. Mixture model approaches to address these problems are developed and examined for their suitability in these contexts.

Human biomonitoring aims to measure the amount of certain substances in all aspects of the environment, how much of this that reach humans and in what way, and finally how this affects our health. In all aspects of this process lays challenges that must be overcome. When measuring substances in the environment, one must make sure that one is measuring the biomarker which gives the most precise results according to what one seeks to find. Dependent on the biomarker in question, multiple factors can potentially affect the measurements. When the most suitable biomarker has been found, one must make sure that all possible sources are located and taken into consideration, in order to provide a sufficient exposure assessment. The next challenge is to gather accurate epidemiologic data, and link this to the exposure in question, and make a reliable risk assessment. As the examples in this paper highlights, within each step are challenges, and possible limitations. For most substances, there are data gaps and incomplete understanding. There is now much work done globally, on how to further improve the process. Based on today's experiences and knowledge, new guidelines are put down. In Europe there was recently launched a program, that will coordinate the cooperation between the member states. Though it is already a...

Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 6 uppsatser.

Thesis (Ph. D.)--University of Adelaide, Faculty of Health Sciences, Dept. of Public Health, 2005. / "November 2004." Includes bibliographical references (leaves 149-179).

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [148]-164).

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 68-74).

Abstract The tumour suppressor gene TP53 is the most commonly mutated gene in human cancers. The protein it codes, p53, becomes activated as a response to stress signals. When activated, p53 binds to DNA and affects the transcription of its target genes. They then cause cell cycle arrest, DNA repair and/or induction of programmed cell death, thus preventing mutations and cancer. Specific mutations in TP53 are associated with exposure to certain carcinogens, such as polycyclic aromatic hydrocarbons (PAHs). These environmental chemical carcinogens are formed through incomplete combustion of organic material. Benzo(a)pyrene (BP) is commonly used as a model compound for PAH carcinogenesis. BP causes accumulation of p53, but the mechanism of accumulation is not known. The aim of this study was to gain more insight into the p53 protein in the first phases of PAH carcinogenesis in vivo in mouse, using BP as the model compound. Mice from the inbred C57BL/6 strain were treated topically or intraperitoneally with BP or were exposed to cigarette smoke inhalation. The amount of p53 protein was studied by immunoblotting, immunohistochemistry and immuno electron microscopy, and the mdm2, p21 and p19ARF proteins were studied by immunoblotting. The binding of BP to DNA was measured by synchronous fluorescence spectrophotometry. The p53 protein was induced in vivo in skin and lung after BP treatment and in lung after cigarette smoke treatment. An increase in p53 was associated with an increase in the amount of BP-DNA adducts. In skin, the induction of p53 was accompanied by induction of the p21 and mdm2 proteins, which are transcriptional targets of p53. This indicates that the in vivo induced p53 is a wild-type protein and functional. In lungs, the induction of p53 was accompanied by a decrease of mdm2 and an increase of p19ARF. These results confirm that BP is metabolized and binds to DNA in mouse tissues and indicate that BP-DNA adducts are the trigger for p53 protein induction. The in vivo regulation of the p53 protein is different in different tissues of C57BL/6 mouse.