Les mycotoxines sont de métabolites secondaires produits par de nombreuses espèces fongiques. Les effets sanitaires induits par l’ingestion de ces substances sont bien documentés et certaines mycotoxines font désormais l’objet de réglementations quant à leurs teneurs maximales tolérables dans les aliments. Cependant, d’autres voies d’exposition à ces contaminants sont possibles. Si l’action irritante ou allergisante liée à l’inhalation de spores fongiques ou de fragments mycéliens a été démontrée, l’inhalation de mycotoxines est aussi suspectée d’induire certains troubles respiratoires ou certaines pathologies. En effet, les mycotoxines peuvent être retrouvées dans les spores mais également sur des particules plus fines facilement aérosolisables et donc susceptible d’être inhalées. Cependant, les données concernant le danger associé à l’exposition humaine aux mycotoxines par inhalation sont encore très parcellaires. Dans ce contexte, nos travaux ont eu comme objectif principal la caractérisation de l’aérosolisation des mycotoxines lors de la colonisation de différents matériaux rencontrés dans les environnements intérieurs par des moisissures toxinogènes. Tout d’abord nous avons étudié la croissance et la production de mycotoxines lors de la colonisation de matériaux de construction (papier peint, toile de verre peinte, papier peint vinyle, sapin) par trois espèces fongiques d’intérêt: Aspergillus versicolor, Penicillium brevicompactum, Stachybotrys chartarum. Ces espèces ont été choisies à cause de leur présence fréquente dans les environnements intérieurs et de leur diversité d’organisation mycélienne. De plus, ces trois espèces produisent des toxines différentes: stérigmatocystine, acide mycophénolique et trichothécènes macrocycliques pour A. versicolor, P. brevicompactum et S. chartarum, respectivement. Ces travaux ont démontré que, pendant leur développement sur les matériaux testés, les trois espèces produisent des mycotoxines. Le matériau le plus favorable au développement fongique et à la toxinogénèse est le papier peint. L'acide mycophénolique, la stérigmatocystine et les trichothécènes macrocycliques peuvent ainsi être produits à des niveaux de 1.8, 112.1 et 27.8 mg/m2, respectivement, sur ce matériau. Ces toxines peuvent ensuite être partiellement aérosolisées. Nous avons montré que l’aérosolisation dépend des espèces et de leur structure mycélienne mais aussi des conditions de culture et du flux d’air. Ce transfert dans l'air est observé après des sollicitations aérauliques qui peuvent être rencontrées facilement dans les environnements intérieurs car elles correspondent au mouvement de personne dans une pièce (0.3 m/s), à la vitesse de l'air dans les diffuseurs de plafond (2 m/s), à des coutants d’air ou des claquements de porte (6 m/s). P. brevicompactum est l’espèce la plus facile à aérosoliser. La majeure partie de la charge toxique des aérosols est retrouvée dans des particules dont la taille correspond à celle de spores ou de fragments de mycélium. Cependant, pour les trichothécènes macrocycliques, des toxines ont également été trouvées sur des particules plus petites que les spores, qui pourraient être facilement inhalées par les habitants et pénétrer profondément dans les voies respiratoires. Afin de mieux caractériser le danger réel associé à l’inhalation de ces composés, des études de cytotoxicité ont été réalisés en utilisant des cellules pulmonaires et en comparant avec les résultats observés sur cellules digestives. La toxicité sur cellules pulmonaires est comparable à celle observée sur cellules digestives. Les trichothécènes macrocycliques sont beaucoup plus toxiques que les autres toxines testées avec des IC50 de l’ordre du ng/ml. Au final, nous avons évalué la persistance de ces contaminants lors de l’application d’eau de javel, procédé de décontamination le plus fréquemment utilisé. Nous avons montré qu’une procédure de nettoyage normale ne permet qu’une élimination partielle des moisissures. / Mycotoxins are secondary metabolites produced by many fungal species. Health effects induced by the ingestion of these substances are well documented and some mycotoxins are now regulated for their maximum tolerable levels in foods. However, other routes of exposure to these contaminants are possible. Thus, if irritating or allergenic reactions related to the inhalation of fungal spores or mycelial fragments have been demonstrated, inhalation of mycotoxins is also suspected to be causing certain respiratory disorders or certain pathologies. Indeed, mycotoxins can be found in spores but also on finer particles which are easily aerosolized and therefore likely to be inhaled. However, data on the hazard associated with human exposure to mycotoxins by inhalation are still very fragmented. In this context, our main objective was to characterize the aerosolization of mycotoxins during the colonization of different materials encountered in indoor environments by toxinogenic molds. First we studied growth and production of mycotoxins during the colonization of building materials (wallpaper, painted fiberglass wallpaper, vinyl wallpaper, fir, fiberglass) by three fungal species of interest: Aspergillus versicolor, Penicillium brevicompactum, Stachybotrys chartarum. These species were chosen because of their frequent presence in indoor environments and their diverse mycelial organization. In addition, these three species produce different toxins: sterigmatocystin, mycophenolic acid and macrocyclic trichothecenes for A. versicolor, P. brevicompactum and S. chartarum, respectively. These studies have shown that, during their development on tested materials, three species produce mycotoxins. The most favorable material for fungal development and toxinogenesis is wallpaper. Mycophenolic acid, sterigmatocystin and macrocyclic trichothecenes can thus be produced at levels of 1.8, 112.1 and 27.8 mg/m2, respectively, on this material. These toxins can then be partially aerosolized. We have shown that aerosolization depends on species and their mycelial structure, but also on culture conditions and airflow. This transfer to air is nevertheless observed after aeraulic solicitations which can be easily encountered in indoor environments because theycorrespond to the movement of people in a room (0.3 m/s), speed of air in ceiling diffusers (2 m/s), slamming doors or air drafts when opening windows(6 m/s). P. brevicompactum showed to be the easiest to aerosolize. The major part of the aerosols’ toxic charge is found in particles whose size corresponds to that of spores or mycelial fragments. However, for macrocyclic trichothecenes, toxins were also found in particles smaller than spores, which could easily be inhaled by occupants and penetrate deep into the respiratory tract. In order to better characterize the actual hazard associated with inhalation of these compounds, cytotoxicity studies have been performed using lung cells and comparing with results observed on digestive cells. Pulmonary toxicity is comparable to that observed in digestive cells. Macrocyclic trichothecenes are much more toxic than other tested toxins with IC50 in order of ng/ml. In parallel, we analyzed the VOCs specifically produced during active mycotoxinogenesis in order to identify potential biomarkers of the actual production of mycotoxins that could be used as tools for monitoring of indoor environments. Unfortunately, this approach has not, for the moment, led to the identification of specific targets. In the end, we evaluated the persistence of these contaminants during application of bleach, the most frequently used decontamination process. We have shown that a normal cleaning procedure allows only partial removal of mold.

With increasing knowledge about the indoor climate in recent years, preventive methods to avoid health problems caused by deficient building performance may become preferable to reactive methods. Benefits from preventive actions have been suggested for late building design phases, construction, and building operations, however, few data are available that demonstrate the benefits of preventive actions in early planning phases. In a case study, expected building performance in respect to indoor air quality and thermal conditions in a large judicial facility in North America was evaluated retrospectively at the end of the schematic design and substantial completion phases. A process for evaluation of building performance at schematic design is developed from existing procedures for building diagnostics in operating buildings. Criteria for evaluation of expected building environmental quality at schematic design as available from standards and guidelines are presented. The results of the study show that building diagnostics at schematic design can be an effective mean of prevention of occupant health problems. Further findings indicate that the assurance of indoor environmental quality can be improved, if the criteria for expected building performance are defined and complied with from early on. It is concluded that implementation of building diagnostics in early project phases can reduce the likelihood of adverse health effects in operating buildings. / Master of Science

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京都大学 / 新制・論文博士 / 博士(工学) / 乙第13492号 / 論工博第4201号 / 新制||工||1785(附属図書館) / (主査)教授 米田 稔, 教授 高野 裕久, 教授 松井 康人 / 学位規則第4条第2項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

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The purpose of this study was to perform an indoor air quality (IAQ) investigation at the Center for Applied Reproductive Science (CARS) to assess whether VOCs exist at levels dangerous to embryo. Formaldehyde, n-hexane, benzene, and styrene concentrations were measured at six locations. Formaldehyde concentrations were comparable to office and residential indoor air. N-hexane, benzene, and styrene were not detected. In addition, acetaldehyde, ethanol, and isopropyl alcohol were detected. IAQ parameters (carbon dioxide, temperature, humidity, pressure, and particulates) were measured at 22 sites monthly for one year. Temperature and humidity readings were within Environmental Protection Agency recommendations. Particulate concentrations were below Occupational Safety and Health Administration standards. Pressure readings indicated the facility was under a negative pressure. Carbon dioxide concentrations exceeded recommendations established by American Society for Heating, Refrigeration, and Air Conditioning Engineers (ASHRAE). Recommendations include assessing air intakes to assure dampers are adjusted to allow 15 ft3/min/person of fresh air established by ASHRAE.

Co-firing is a combustion process in which more than one type of fuel is used. In many cases, co-firing reduces fuel costs and/or reduces the environmental impact. The objective of this research was to test the hypothesis that adding biogas to be co-fired with biomass in a traditional cookstove reduces indoor air pollution and increases the combustion efficiency. The impact of co-firing on indoor air pollution is assessed by comparing the concentrations of carbon monoxide and particulate matter in the exhaust stream of a co-fired cookstove to a cookstove fueled with biomass alone. The concentrations of each of these pollutants were measured using a portable emissions monitoring system. Combustion efficiency is defined as the ratio of energy released by combustion to energy in the fuel. Instead of combustion efficiency, the impact of co-firing was assessed on the modified combustion efficiency, which is defined as CO2/(CO2+CO) on a molar basis. This is because CO and CO2 concentrations can be measured. In addition, the impact of cofiring on other parameters such as thermal efficiency, specific fuel consumption rate, and specific emission of CO, CO2, and PM were assessed. Previous investigation of biomass combustion in traditional cookstoves indicates that power harvested using a thermoelectric generator can be used to drive a fan and increase the amount of air flowing into the combustion zone. The impact of using a fan on indoor air pollution and combustion efficiency was also assessed. It was found that co-firing biomass with optimum amount of biogas reduced the emission of CO by 32 % and PM by 33 % and increased the modified combustion efficiency by 1.3 %. It was found that using a fan reduced the emission of CO by 35 % and PM by 39 % and increased the modified combustion efficiency by 1.1 %. Finally, the combination of co-firing and use of a fan reduced the emission of CO by 58 % and PM by 71 % and increased the modified combustion efficiency by 2.8 %.

Many applied statistical applications face the potential problem of model contamination and measurement error. The form and degree of contamination as well as the measurement error are usually unknown and sample-specific, which brings additional challenges for researchers. In this thesis, we have proposed several Bayesian inference models to address these issues, with the application to one type of special data for allergen concentration measurement, which is called serial dilution data and is self-calibrated. In our first chapter, we address the problem of model contamination by using a multilevel model to simultaneously flag problematic observations and estimate unknown concentrations in serial dilution data, a problem where the current approach can lead to noisy estimates and difficulty in estimating very low or high concentrations. In our second chapter, we propose the Bayesian joint contamination model for modeling multiple measurement units at the same time while adjusting for differences between experiments using the idea of global calibration, and it could account for uncertainty in both predictors and response variables in Bayesian regression. We are able to get efficacy gain by analyzing multiple experiments together while maintaining robustness with the use of hierarchical models. In our third chapter, we develop a Bayesian two-step inference model to account for measurement uncertainty propagation in regression analysis when the joint inference model is infeasible. We aim to increase model inference reliability while providing flexibility to users by not restricting the type of inference model used in the first step. For each of the proposed methods, We also demonstrate how to integrate multiple model building blocks through the idea of Bayesian workflow. In extensive simulation studies, we show that our proposed methods outperform other commonly used approaches. For the data applications, we apply the proposed new methods to the New York City Neighborhood Asthma and Allergy Study (NYC NAAS) data to estimate indoor allergen concentrations more accurately as well as reveal the underlying associations between dust mite allergen concentrations and the exhaled nitric oxide (NO) measurement for asthmatic children. The methods and tools developed here have a wide range of applications and can be used to improve lab analyses, which are crucial for quantifying exposures to assess disease risk and evaluating interventions.

Energy calculations are used for many purposes, for example during the design andconstruction phase to comply with Boverket’s building regulations, energy declarations or toachieve energy saving in a building. A main problem in the design process of a new building,is to accurately predict the energy performance. The energy calculations require data fromdifferent interacting components, which have been shown to be challenging to measure. Thisproblem arises in particularly for complex buildings, notably office buildings. Due to the lackof detailed energy models and analyses of the differences between the model and reality foroffice buildings in Sweden, this report aims to answer the question: What are the causes ofdeviations between the models and the measurements of energy usage and indoor airtemperature for the studied office building? The office building Sthlm New 04 was modeledas a whole-building within IDA ICE and the simulated data was compared with measureddata from 2021 that was provided by Skanska Fastigheter.During the design of the model, the simulation model was fed with external source files (withmeasured data) to make the model operate at the same time as the real system. Since therewas no logged occupancy data for this office building, it was assumed that occupancy wasdistributed equally in all office zones. The model has a detailed HVAC system to make themodel as accurate as possible.The result showed overall a good agreement with the measured data, especially for thesimulated district heating and cooling. However, a closer look revealed that there were somedifferences that the model did not account for. The building’s three Air-handling units alsoshowed a good agreement with an average of -0.3 °C, -0.2 °C and +0.2 °C. The resultshighlight several problems with modeling and measured data. Under the influence ofassumptions and hard to define input data, there may be misinterpretation by the modeler.Other reasons could be sensor errors or manufacturing errors by most of the errors could becorrected by a more detailed occupancy in the model. However, this study has shown thatthe detailed model can be used for a fair comparison between the simulated model and thereal building, although there may be some discrepancies. Undoubtedly, it is difficult to createa model that exactly matches the real building, but this model is a good representation thatcan be used for future research such as digital twin.