In our modern society we are exposed to many natural and synthetic chemicals. The assessment of chemicals with regard to human safety is difficult but nevertheless of high importance. Beside clinical studies, which are restricted to potential pharmaceuticals only, most toxicity data relevant for regulatory decision-making are based on in vivo data. Due to the ban on animal testing of cosmetic ingredients in the European Union, alternative approaches, such as in vitro and in silico tests, have become more prevalent. In this thesis existing non-testing approaches (i.e. studies without additional experiments) have been extended, e.g. QSAR models, and new non-testing approaches, e.g. in vitro data supported structural alert systems, have been created. The main aspect of the thesis depends on the determination of data quality, improving modelling performance and supporting Adverse Outcome Pathways (AOPs) with definitions of structural alerts and physico-chemical properties. Furthermore, there was a clear focus on the transparency of models, i.e. approaches using algorithmic feature selection, machine learning etc. have been avoided. Furthermore structural alert systems have been written in an understandable and transparent manner. Beside the methodological aspects of this work, cosmetically relevant examples of models have been chosen, e.g. skin penetration and hepatic steatosis. Interpretations of models, as well as the possibility of adjustments and extensions, have been discussed thoroughly. As models usually do not depict reality flawlessly, consensus approaches of various non-testing approaches and in vitro tests should be used to support decision-making in the regulatory context. For example within read-across, it is feasible to use supporting information from QSAR models, docking, in vitro tests etc. By applying a variety of models, results should lead to conclusions being more usable/acceptable within toxicology. Within this thesis (and associated publications) novel methodologies on how to assess and employ statistical data quality and how to screen for potential liver toxicants have been described. Furthermore computational tools, such as models for skin permeability and dermal absorption, have been created.

No description available.

Objective: In order to introduce automated vehicles on public roads, it is necessary to ensure that these vehicles are safe to operate in traffic. One challenge is to prove that all physically possible variations of situations can be handled safely within the operational design domain of the vehicle. A promising approach to handling the set of possible situations is to identify a manageable number of logical scenarios, which provide an abstraction for object properties and behavior within the situations. These can then be transferred into concrete scenarios defining all parameters necessary to reproduce the situation in different test environments. Methods: This article proposes a framework for defining safety-relevant scenarios based on the potential collision between the subject vehicle and a challenging object, which forces the subject vehicle to depart from its planned course of action to avoid a collision. This allows defining only safety-relevant scenarios, which can directly be related to accident classification. The first criterion for defining a scenario is the area of the subject vehicle with which the object would collide. As a second criterion, 8 different positions around the subject vehicle are considered. To account for other relevant objects in the scenario, factors that influence the challenge for the subject vehicle can be added to the scenario. These are grouped as action constraints, dynamic occlusions, and causal chains. Results: By applying the proposed systematics, a catalog of base scenarios for a vehicle traveling on controlled-access highways has been generated, which can directly be linked to parameters in accident classification. The catalog serves as a basis for scenario classification within the PEGASUS project. Conclusions: Defining a limited number of safety-relevant scenarios helps to realize a systematic safety assurance process for automated vehicles. Scenarios are defined based on the point of the potential collision of a challenging object with the subject vehicle and its initial position. This approach allows defining scenarios for different environments and different driving states of the subject vehicle using the same mechanisms. A next step is the generation of logical scenarios for other driving states of the subject vehicle and for other traffic environments.

No description available.

Moisture induced damages to building envelopes can result in microbial growth possibly affecting the health and wellbeing of occupants. Recent failing structures and damaged buildings indicate a lack of tools to estimate risk of mould growth and moisture damage. In this work a so-called mould resistance design (MRD) model has been applied for mapping the risk for mould growth on a number of wood-containing wall structures. The MRD model introduces an engineering approach to moisture safety design in a similar way as for structural design, where load and resistance is compared. The MRD model introduces and quantifies the concepts of climatic exposure and material resistance and compares them through an MRD index. This MRD index incorporates a limit state, which gives the critical dose of exposure for a given resistance to initiate onset of mould growth.   Three conceptual wall structures were evaluated and analyzed in terms of MRD index: two wall systems with an air gap and one wall system without. A parametric study investigating the effect of parameter variation on MRD index was conducted. Evaluated parameters were: climate (geographic location), orientation, air changes per hour in the air gap, driving rain penetrating the facade layer, exterior plaster properties and wood type. The simulations were performed using the hygrothermal calculation software WUFI. The results indicate that the wall systems with a ventilated air gap performs better in terms of MRD index i.e. suggests a lower risk of initiation of mould growth than the wall system without air gap. The results of orientation variation show that wall systems perform differently dependent on layering structure. The inherent water sorption properties of the exterior plaster are shown to have a large effect on the results. In addition, uncertainties were found on how to accurately include hydrophobicity as a parameter in the model. The report concludes that geographical location and its specific climate is the most important parameter to consider when designing for moisture safety. The MRD model is recommended to be used in combination with traditional moisture safety evaluation.

In September 2000 the DAfStb issued a technical recommendation for the experimental assessment of structural safety and usability of concrete structures. By now, the influence of pavement or floor layers and of other factors on the load carrying capacity is not known exactly. In this thesis, it has been investigated how road pavements, the geometry and bridge caps reduce the actions on concrete bridge structures and how these influences should be taken into account in the experimental evaluation of the bending capacity by an additional test load increment. In co-operation with a local authority in Stralsund, Germany, comprehensive loading test could be performed at an abandoned concrete bridge with prefabricated girders. Between loading cycles, the pavement has been stepwise disassembled. In addition, the ultimate load of the structure as well as of an individual girder has been determined in fracture tests. By means of a hybrid analysis, i.e. a numerical simulation supported by experimental data, the influences of the pavement layers have been determined. These results were verified by experimental observations obtained in past bridge tests. The influence of the pavement layers on the load carrying capacity appeared to be as high as 28% at the maximum for the bridges investigated. Since the loading vehicle BELFA has been completed in March 2001, test loads can be applied now self-securing to bridges in the so-called large load circuit, i.e. the structure is loaded including supports and foundation. The technical concept, the principle and possible applications of the BELFA are described. The results presented will allow to determine the additional test load increment for compensating the influence of pavement layers, structural geometry and bridge caps in future experimental safety evaluations. For this analysis, the exact geometry of the structure, the thickness of the pavement layers as well as their material properties, especially the modulus of elasticity, have to be known. Guidelines for the analysis procedure as well as for simplifying assumptions are given. / Experimentelle Nachweise der Tragsicherheit und Gebrauchstauglichkeit von Betonbauwerken sind seit September 2000 in einer DAfStb-Richtlinie geregelt. Der Einfluss mittragender Aufbauschichten und anderer Faktoren war bisher quantitativ unbekannt. In der vorliegenden Arbeit wurde untersucht, wie Straßenbeläge, Bauwerksgeometrie und Kappen die Beanspruchung der Tragkonstruktion von Massivbrücken mindern und im experimentellen Nachweis der Biegetragsicherheit durch eine Überlast zu berücksichtigen sind. In Zusammenarbeit mit dem Straßenbauamt Stralsund konnten an einer Fertigteilträgerbrücke Belastungsversuche mit sukzessivem Rückbau des Fahrbahnaufbaus sowie Bruchversuche am Gesamtsystem und an ausgebauten Fertigteilträgern mit Ortbetonergänzung erfolgen. Mit Hilfe der hybriden Statik, also der Modifikation und Evaluation von Rechnungen anhand experimentell erlangter Messwerte, wurden die Einflüsse der Aufbauschichten quantifiziert und durch Auswertung weiterer Brückenbelastungsversuche verifiziert. Der Einfluss der Aufbauschichten betrug bei den untersuchten Brücken bis zu 28%. Seit der Inbetriebnahme des Belastungsfahrzeuges BELFA im März 2001 können Versuchlasten auch im großen Kräftekreislauf, d.h. am Gesamtsystem einschließlich Auflager- und Gründungssituation, selbstsichernd aufgebracht werden. Die Entwicklung des BELFA, seine Funktionsweise und seine Einsatzmöglichkeiten werden erläutert. Mit den Ergebnissen dieser Arbeit ist es zukünftig möglich, die notwendige Überlast bei Belastungsversuchen zur Kompensation der Einflüsse aus Straßenbelag, Bauwerksgeometrie und Kappen mit genauem Aufmaß der Bauwerksgeometrie und der Schichtdicken sowie mit ingenieurmäßigem Abschätzen der Materialkennwerte (E-Moduli) hinreichend genau zu bestimmen. Handlungsempfehlungen geben Hinweise zur generellen Vorgehensweise sowie für vereinfachte Rechenannahmen.

In September 2000 the DAfStb issued a technical recommendation for the experimental assessment of structural safety and usability of concrete structures. By now, the influence of pavement or floor layers and of other factors on the load carrying capacity is not known exactly. In this thesis, it has been investigated how road pavements, the geometry and bridge caps reduce the actions on concrete bridge structures and how these influences should be taken into account in the experimental evaluation of the bending capacity by an additional test load increment. In co-operation with a local authority in Stralsund, Germany, comprehensive loading test could be performed at an abandoned concrete bridge with prefabricated girders. Between loading cycles, the pavement has been stepwise disassembled. In addition, the ultimate load of the structure as well as of an individual girder has been determined in fracture tests. By means of a hybrid analysis, i.e. a numerical simulation supported by experimental data, the influences of the pavement layers have been determined. These results were verified by experimental observations obtained in past bridge tests. The influence of the pavement layers on the load carrying capacity appeared to be as high as 28% at the maximum for the bridges investigated. Since the loading vehicle BELFA has been completed in March 2001, test loads can be applied now self-securing to bridges in the so-called large load circuit, i.e. the structure is loaded including supports and foundation. The technical concept, the principle and possible applications of the BELFA are described. The results presented will allow to determine the additional test load increment for compensating the influence of pavement layers, structural geometry and bridge caps in future experimental safety evaluations. For this analysis, the exact geometry of the structure, the thickness of the pavement layers as well as their material properties, especially the modulus of elasticity, have to be known. Guidelines for the analysis procedure as well as for simplifying assumptions are given. / Experimentelle Nachweise der Tragsicherheit und Gebrauchstauglichkeit von Betonbauwerken sind seit September 2000 in einer DAfStb-Richtlinie geregelt. Der Einfluss mittragender Aufbauschichten und anderer Faktoren war bisher quantitativ unbekannt. In der vorliegenden Arbeit wurde untersucht, wie Straßenbeläge, Bauwerksgeometrie und Kappen die Beanspruchung der Tragkonstruktion von Massivbrücken mindern und im experimentellen Nachweis der Biegetragsicherheit durch eine Überlast zu berücksichtigen sind. In Zusammenarbeit mit dem Straßenbauamt Stralsund konnten an einer Fertigteilträgerbrücke Belastungsversuche mit sukzessivem Rückbau des Fahrbahnaufbaus sowie Bruchversuche am Gesamtsystem und an ausgebauten Fertigteilträgern mit Ortbetonergänzung erfolgen. Mit Hilfe der hybriden Statik, also der Modifikation und Evaluation von Rechnungen anhand experimentell erlangter Messwerte, wurden die Einflüsse der Aufbauschichten quantifiziert und durch Auswertung weiterer Brückenbelastungsversuche verifiziert. Der Einfluss der Aufbauschichten betrug bei den untersuchten Brücken bis zu 28%. Seit der Inbetriebnahme des Belastungsfahrzeuges BELFA im März 2001 können Versuchlasten auch im großen Kräftekreislauf, d.h. am Gesamtsystem einschließlich Auflager- und Gründungssituation, selbstsichernd aufgebracht werden. Die Entwicklung des BELFA, seine Funktionsweise und seine Einsatzmöglichkeiten werden erläutert. Mit den Ergebnissen dieser Arbeit ist es zukünftig möglich, die notwendige Überlast bei Belastungsversuchen zur Kompensation der Einflüsse aus Straßenbelag, Bauwerksgeometrie und Kappen mit genauem Aufmaß der Bauwerksgeometrie und der Schichtdicken sowie mit ingenieurmäßigem Abschätzen der Materialkennwerte (E-Moduli) hinreichend genau zu bestimmen. Handlungsempfehlungen geben Hinweise zur generellen Vorgehensweise sowie für vereinfachte Rechenannahmen.

Indiana University-Purdue University Indianapolis (IUPUI) / Safety researchers have devoted extensive attention to safety performance behaviors. However, current safety performance models have yet to differentiate between safety citizenship behaviors directed towards the organization and those directed towards individuals. This might be a potential oversight, considering that citizenship behaviors targeted at different beneficiaries might be associated with different antecedents. As such, the purpose of the present study was to develop and validate a new safety performance scale. Items from existing measures formed the item pool and those tapping into the proposed dimensions were selected. Next, items were pilot tested using an online panel of 333 employees from various safety-related industries. A 4-factor structure emerged after exploratory factor analysis and the scale was further refined using reliability analysis and item response theory analysis. Finally, confirmatory factor analysis was conducted to replicate the factor structure using data from 137 employees. Theoretically related variables were correlated with the safety performance dimensions to establish the nomological network. Results supported the 4-factor structure of the new safety performance scale and construct validation hypotheses were largely supported. Implications, study limitations, and directions for future research are discussed.

Traffic safety has been considered one of the most important issues in the transportation field. Crashes have caused extensive human and economic losses. With the objective of reducing crash occurrence and alleviating crash injury severity, major efforts have been dedicated to reveal the hazardous factors that affect crash occurrence. With these consistent efforts, both fatalities and fatality rates from road traffic crashes in many countries have been steadily declining over the last ten years. Nevertheless, according to the World Health Organization, the world still lost 1.24 million lives from road traffic crashes in the year of 2013. And without action, traffic crashes on the roads network are predicted to result in deaths of around 1.9 million people, and up to 50 million more people suffer non-fatal injuries annually, with many incurring a disability as a result of their injury by the year 2020. To meet the transportation needs, the use of expressways (toll roads) has risen dramatically in many countries in the past decade. In fact, freeways and expressways are considered an important part of any successful transportation system. These facilities carry the majority of daily trips on the transportation network. Although expressways offer high level of service, and are considered the safest among other types of roads, traditional toll collection systems may have both safety and operational challenges. The traditional toll plazas still experience many crashes, many of which are severe. Therefore, it becomes more important to evaluate the traffic safety impacts of using different tolling systems. The main focus of the research in this dissertation is to provide an up-to-date safety impact of using different toll collection systems, as well as providing safety guidelines for these facilities to promote safety and enhance mobility on expressways. In this study, an extensive data collection was conducted that included one hundred mainline toll plazas located on approximately 750 miles of expressways in Florida. Multiple sources of data available online maintained by Florida Department of Transportation were utilized to identify traffic, geometric and geographic characteristics of the locations as well as investigating and determination of the most complete and accurate data. Different methods of observational before-after and Cross-Sectional techniques were used to evaluate the safety effectiveness of applying different treatments on expressways. The Before-After method includes Naive Before-After, Before-After with Comparison Group, and Before-After with Empirical Bayesian. A set of Safety Performance Functions (SPFs) which predict crash frequency as a function of explanatory variables were developed at the aggregate level using crash data and the corresponding exposure and risk factors. Results of the aggregate traffic safety analysis can be used to identify the hazardous locations (hot spots) such as traditional toll plazas, and also to predict crash frequency for untreated sites in the after period in the Before-After with EB method or derive Crash Modification Factors (CMF) for the treatment using the Cross-Sectional method. This type of analysis is usually used to improve geometric characteristics and mainly focus on discovering the risk factors that are related to the total crash frequency, specific crash type, and/or different crash severity levels. Both simple SPFs (with traffic volume only as an explanatory variable) and full SPFs (with traffic volume and additional explanatory variable(s)) were used to estimate the CMFs and only CMFs with lower standard error were recommended. The results of this study proved that safety effectiveness was significantly improved across all locations that were upgraded from Traditional Mainline Toll Plazas (TMTP) to the Hybrid Mainline Toll Plazas (HMTP) system. This treatment significantly reduced total, Fatal-and-Injury (F+I), and Rear-End crashes by 47, 46 and 65 percent, respectively. Moreover, this study examined the traffic safety impact of using different designs, and diverge-and-merge areas of the HMTP. This design combines either express Open Road Tolling (ORT) lanes on the mainline and separate traditional toll collection to the side (design-1), or traditional toll collection on the mainline and separate ORT lanes to the side (design-2). It was also proven that there is a significant difference between these designs, and there is an indication that design-1 is safer and the majority of crashes occurred at diverge-and-merge areas before and after these facilities. However, design-2 could be a good temporary design at locations that have low prepaid transponder (Electronic Toll Collection (ETC)) users. In other words, it is dependent upon the percentage of the ETC users. As this percentage increases, more traffic will need to diverge and merge; thus, this design becomes riskier. In addition, the results indicated significant relationships between the crash frequency and toll plaza types, annual average daily traffic, and drivers* age. The analysis showed that the conversion from TMTP to the All-Electronic Toll Collection (AETC) system resulted in an average reduction of 77, 76, and 67 percent for total, F+I, and Property Damage Only (PDO) crashes, respectively; for rear end and Lane Change Related (LCR) crashes the average reductions were 81 and 75 percent, respectively. The conversion from HMTP to AETC system enhanced traffic safety by reducing crashes by an average of 23, 29 and 19 percent for total, F+I, and PDO crashes; also, for rear end and LCR crashes, the average reductions were 15 and 21 percent, respectively. Based on these results, the use of AETC system changed toll plazas from the highest risk sections on Expressways to be similar to regular segments. Therefore, it can be concluded that the use of AETC system was proven to be an excellent solution to several traffic operations as well as environmental and economic problems. For those agencies that cannot adopt the HMTP and the AETC systems, improving traffic safety at traditional toll plazas should take a priority. This study also evaluates the safety effectiveness of the implementation of High-Occupancy Toll lanes (HOT Lanes) as well as adding roadway lighting to expressways. The results showed that there were no significant impact of the implementation of HOT lanes on the roadway segment as a whole (HOT and Regular Lanes combined). But there was a significant difference between the regular lanes and the HOT lanes at the same roadway segment; the crash count increased at the regular lanes and decreased at the HOT lanes. It was found that the total and F+I crashes were reduced at the HOT lanes by an average of 25 and 45 percent, respectively. This may be attributable to the fact that the HOT lanes became a highway within a highway. Moreover adding roadway lighting has significantly improved traffic safety on the expressways by reducing the night crashes by approximately 35 percent. Overall, the proposed analyses of the safety effectiveness of using different toll collection systems are useful in providing expressway authorities with detailed information on where countermeasures must be implemented. This study provided for the first time an up-to-date safety impact of using different toll collection systems, also developed safety guidelines for these systems which would be useful for practitioners and roadway users.