A análise de fármacos é fundamental nas diversas fases do desenvolvimento farmacêutico, tais como estudos de formulação, estabilidade e controle de qualidade do produto. A rivaroxabana (RIV) é um anticoagulante de uso oral indicado para prevenção da formação de coágulos venosos. A literatura pesquisada apresenta poucos relatos de determinação quantitativa e de estudos de estabilidade do fármaco em comprimidos. E ainda nenhum método analítico em compêndios oficiais Diante do exposto, o objetivo deste trabalho foi desenvolver e validar métodos analíticos para determinação qualitativa e quantitativa da RIV por cromatografia líquida de alta eficiência com detecção por UV e de ultra eficiência com detecção por espectrometria de massas (CLAE-UV e CLUE-EM) e eletroforese capilar (EC). Os resultados encontrados foram adequados conforme o preconizado nos guias oficiais nacionais e internacionais. Foi avaliada também a viabilidade da técnica de eletroforese capilar em microchip para análise de RIV. Através de método desenvolvido por CLAE foi realizado estudo de cinética de degradação e posterior avaliação do potencial tóxico in vitro das amostras de degradação forçada da RIV. A identificação de três produtos de degradação majoritários da RIV, formados a partir de estresse ácido, alcalino e fotolítico, foi realizada por CLUE-EM/EM, possibilitando a proposição da estrutura molecular de cada produto de degradação. O potencial tóxico da RIV antes e depois da exposição à degradação forçada foi avaliado através dos métodos in vitro MTT, Vermelho Neutro, Ensaio Cometa e DNA de baixo peso molecular. Não foram encontrados sinais de dano ao DNA celular, contudo, amostras de RIV expostas ao meio alcalino apresentaram maior redução da viabilidade celular. O trabalho avaliou ainda o perfil de dissolução da RIV em comprimidos baseado nos dados de absorção in vitro conforme modelagem in silico dos dados, estabelecendo uma correlação linear entre a fração absorvida e fração dissolvida. As diferentes metodologias e técnicas desenvolvidas e aplicadas nesse trabalho contribuem para o desenvolvimento do controle de qualidade farmacêutico na direção de ensaios mais confiáveis que garantam a segurança e eficácia de medicamentos. / Drug analysis is critical at various stages of pharmaceutical development, such as formulation studies, stability and quality control products. Rivaroxaban (RIV) is an oral anticoagulant indicated for prevention of thromboembolism. Literature contains few reports of quantitative determination and drug stability studies of RIV on pharmaceutical formulation. Analytical method for RIV quality control are not evaluable on official guides yet. This research work aimed to develop and validate analytical methods for qualitative and quantitative determination of RIV by high and ultra performance liquid chromatography with UV detection mass spectrometry detection (HPLC -UV and UPLC-MS) and capillary electrophoresis (CE). The results were adequate as recommended in national and international official guides. Reliability of RIV analysis by microchip capillary electrophoresis was also assessed. Through the method developed by HPLC degradation kinetic studies were performed, zero order kinetic has better description of RIV degradation behaviour. RIV toxic potential before and after exposure to forced degradation was assessed by in vitro methods of MTT, Neutral Red, Comet Assay, and Low Molecular Weight DNA. There were no signals of DNA damage however, RIV samples exposed to alkaline medium showed increased reduction in cell viability. Identification of RIV degradation products formed after exposure to acid and alkaline media and UVC radiation was performed by UPLC-MS / MS. It was possible to elucidate molecular structures of three major degradation products. This study also assessed the dissolution profile of RIV tablets based on in vitro absorption data, a linear point-to-point correlation was found for fraction absorbed and dissolved. Different methodologies and techniques developed and applied in this work can contribute to the development of pharmaceutical quality towards more reliable tests to ensure safety and efficacy of medicines.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study aims to validate an analytical multi-mycotoxin method using UPLC-MS/MS for 12 mycotoxins determination in wheat and maize matrices. The parameters evaluated for the validation were: calibration curve and linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy (recovery%), precision (RSD %) and matrix effect. The extraction of mycotoxins was performed using the modified QuEChERS method, whereby were used 12.5 g of slurry (suspension between sample and water), 4.5 g MgSO4 anhydrous and 10 ml of acidified acetonitrile at 1% acetic acid. After method validation, it was used to search, quantitatively, the occurrence of mycotoxins in 646 samples, 476 samples of wheat (the field trials, exported and imported grain type, grain processing and their fractions (flour and bran) and flour collected in supermarkets) and 170 samples of maize (grain exported type, flour collected in supermarkets, grains and brewer for the manufacture of animal feed). The results were satisfactory for all evaluated parameters, thus showing that the method validated for the matrices of wheat and maize, it is effective to determine these 12 mycotoxins studied. The matrix effect for some mycotoxins was outside the range -20 to +20%. These results for some analytes were compensated by matrix-mached calibration. All were contaminated by at least one of 12 mycotoxins in the study, regardless of origin. The mycotoxin DON was predominantly found in wheat samples, while fumonisin were determined in maize. In the field trials, factors such as genotype, environment and fungicide treatment had influence on DON concentration. Wheat grain for exportation and imported from Argentina had DON contamination in all samples. In wheat for exportation, also been determined contamination for FB1, FB2, ZEN and OTA. There is evidence that this is the first study to report the presence of fumonisins in Brazilian wheat, since it was not found other reports in the literature. In the sub-products of milling was observed redistribution of DON, a decreased concentration in white flour and increased in bran fraction when compared to the initial concentration in the grain, showing that this process is not effective for mycotoxins removal. It was determined DON and ZEN mycotoxins in flour samples purchased either in the city of Cruz Alta as Santa Maria as well. In maize samples for exportation was observed concomitant contamination by DON, ZEN, FB1 and FB2 and AFLA B1. In maize flour samples collected from supermarkets all samples were contaminated with fumonisins. Besides fumonisins evidenced the presence of DON, ZEN and AFLA B1 in some samples. Samples destined for the production of animal feed were determineted with aflatoxins (B1, B2, G1, G2), fumonisins (B1 and B2), DON and ZEN, and in some samples, the concentrations were higher than Brazilian MRL. The extraction method combined with modern chromatographic technique for the determination of analytes, were effective for the analysis of mycotoxins in wheat and maize. Even in concentrations below the legal limits, human been exposure to mycotoxins can occur constantly. Monitoring of mycotoxins in foods is extremely important for public health, seeking quality to make healthy products available at all points of the supply and commercial chain. / O trabalho teve por finalidade validar um método analítico multimicotoxinas empregando UPLC-MS/MS para determinação simultânea de 12 micotoxinas em matrizes de trigo e milho. Os parâmetros avaliados para validação do método foram: curva analítica e linearidade, limite de detecção (LOD), limite de quantificação (LOQ), exatidão (recuperação%), precisão (RSD%) e efeito matriz. A extração das micotoxinas foi realizada empregando o método QuEChERS modificado, no qual foram utilizados 12,5 g de slurry (suspensão entre amostra e água), 4,5 g MgSO4 anidro e 10 mL de acetonitrila acidificada a 1% com ácido acético. Após a validação do método, o mesmo foi empregado para pesquisar, quantitativamente, a ocorrência de micotoxinas em 646 amostras, sendo 476 amostras de trigo (ensaios a campo, grãos tipo exportação e importação, grãos para processamento e respectivas frações (farinha e farelo) e farinhas comercializados em supermercados) e 170 amostras de milho (grãos tipo exportação, farinhas coletadas em supermercados, grãos e quirera destinados à fabricação de ração animal). Os resultados obtidos foram satisfatórios para todos os parâmetros avaliados, mostrando desta forma, que o método validado para as matrizes de trigo e milho, é eficaz para determinar as 12 micotoxinas em estudo. O efeito matriz, para algumas micotoxinas ficou fora da faixa de -20 a +20%. Esse efeito pronunciado para alguns analitos foi compensado pela calibração por superposição da matriz. Este método pode então ser utilizado para avaliação das amostras, em que todas apresentaram contaminação por pelo menos uma das 12 micotoxinas estudadas, independente da origem. A micotoxina DON foi predominantemente encontrada em amostras de trigo, enquanto fumonisinas foram as micotoxinas predominante determinadas em milho. Nos ensaios a campo, fatores como genótipo, ambiente e tratamento fungicidas tiveram influência sobre as concentrações de DON. Grãos de trigo tipo exportação e importados da Argentina apresentaram contaminação por DON em todas as amostras. Em trigo tipo exportação, também foi determinado contaminação por FB1, FB2, ZEN e OTA. Há evidências de que este seja o primeiro trabalho a relatar a presença de fumonisinas em trigo brasileiro, visto que não foi encontrado outros relatos na literatura. Nos subprodutos derivados da moagem foi verificado redistribuição de DON, com redução das concentrações na farinha branca e incremento na fração farelo, quando comparados a concentração inicial no grão, evidenciando que tal processo não é eficaz para eliminação de micotoxinas. Foram determinadas as micotoxinas DON e ZEN em amostras de farinhas adquiridas tanto na cidade de Cruz Alta quanto de Santa Maria. Nas amostras de milho tipo exportação foi evidenciada contaminação concomitante por DON, ZEN, FB1 e FB2 e AFLA B1. Nas amostras de farinha de milho coletadas em supermercados todas estavam contaminadas por fumonisinas. Além de fumonisinas foi evidenciado a presença de DON, ZEN e AFLA B1 em algumas amostras. Em amostras destinadas a fabricação de ração animal foi determinada aflatoxinas (B1, B2, G1, G2), fumonisinas (B1 e B2), DON e ZEN, sendo que em alguns casos, as concentrações foram superiores aos limites tolerados pela legislação brasileira. O método de extração, aliado com a técnica cromatográfica para determinação dos analitos mostraram-se eficientes para a análise de micotoxinas em trigo e milho. Mesmo em concentrações abaixo dos limites legais, a exposição humana a micotoxinas pode ocorrer constantemente. O monitoramento de micotoxinas em alimentos é de extrema importância para a saúde pública, visando a disponibilização de produtos de qualidade em todos os pontos da cadeia produtiva e comercial.

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第15364号 / 工博第3243号 / 新制||工||1488(附属図書館) / 27842 / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 田中 宏明, 教授 藤井 滋穂, 教授 米田 稔 / 学位規則第4条第1項該当

The aim of this study was to examine if perfluorinated alkylated substances (PFASs) reaches north of Sweden by long-range atmospheric transport. This was done by monitoring the levels of PFASs in reindeer livers at two locations in 2002 and 2010, respectively. The reindeers have lived all of their lives in the mountains and therefore the main source of exposure for PFASs is through air. The samples were extracted and analysed for 24 different PFASs using ultra performance liquid chromatography tandem mass spectrometer (UPLC-MS/MS). The most significant change concerns perfluorooctane sulfonic acid (PFOS) which decreased significantly from 6.1 ng/g at the most northern location (Ammarnäs/Biergenis) in 2002 to 0.87 ng/g 2010. At the other sampling location, Glen, PFOS decreased from 5.0 to 3.2 ng/g during the eight years. Mainly PFOS and longer chain carboxylates were found. The results revealed that the levels of many compounds decreased in time. The location seems to have an impact on the level of perfluorinated compounds present and most likely the distribution of them in the air, since certain PFASs have increased and decreased differently in time between the two locations. Since PFASs are non-volatile, they are believed to be degradation products of volatile compounds such as fluorotelomer alcohols (FTOHs) and perfluoroalkylated sulfonamido alcohols (FOSEs). FTOHs and FOSEs are released, translocated by long-range atmospheric transport and degraded to perfluorinated compounds in organisms or atmosphere.

Cocoa beans (Theobroma cacao) are a highly concentrated source of dietary flavanols- bioactive compounds associated with the health protective properties of cocoa. Cocoa beans undergo processing steps, such as fermentation, roasting, winnowing, grinding, pressing, etc., to produce a final product with specific desirable sensory attributes. It is well established that these processing steps, specifically fermentation and roasting, result in dramatic degradation of cocoa's native flavanols, but it is possible that these processing steps may generate compounds with novel activities, potentially preserving or enhancing bioactivity. Raw unfermented cocoa beans were processed by way of a partial factorial approach to produce cocoa powders from the same batch of raw beans using various combinations of fermentation [unfermented, cool fermented (maximum 46°C), hot fermented (maximum 60°C))] and roasting [unroasted, cool roasted (120°C), hot roasted (170°C)]. To simulate cocoa fermentation in a highly controlled environment, a pilot-scale fermentation model system was employed to eliminate many external unknowns and ensure that the differences between our cocoa powders were due to our various treatments, rather than unknown factors occurring during fermentation and roasting. Low and high molecular weight fractions (8-10 kDa cutoff) were produced from cocoa powder extracts (CPE) of each treatment to quantify Maillard reaction products (MRP). A HILIC-UPLC MS/MS method was developed to more efficiently and sensitively quantify cocoa flavanols with high degrees of polymerization (DP) produced during processing. Overall, cocoa processing significantly (p<0.05) decreased the total phenolic and total flavanol concentrations of CPEs. Hot roasting had the greatest impact on native flavanol degradation yet produced CPEs with the highest mean degree of polymerization (mDP). All CPEs dose-dependently inhibited α-glucosidase enzyme activity, with cool fermented/cool roasted cocoa powder exhibiting the best inhibition (IC50 of 62.2 µg/mL). Increasing flavanol mDP was correlated with decreasing IC50 values, suggesting that the complex flavanols produced during processing enhance cocoa's bioactivity (or their production is associated with other products that enhance bioactivity). Alternatively, high molecular weight CPE fractions were correlated with increasing IC50 values, suggesting that MRPs interfere with enzyme inhibition or are associated with other products (polyphenols, macronutrients, etc.) that interfere with enzyme inhibition. Overall, the data presented within this work indicate that the components of processed cocoa powders are promising inhibitors of α-glucosidase, despite a significant reduction in native flavanol composition induced by processing, and moreover that fermentation and roasting conditions can positively influence the bioactivity of cocoa despite losses of native flavanols. / Master of Science in Life Sciences / According to the Centers for Disease Control and Prevention, obesity-related chronic conditions such as cardiovascular disease and type 2 diabetes mellitus (T2D) are the leading cause of preventable and/or premature death, with 51% of the American population predicted to be obese by 2030. Cocoa (Theobroma cacao) is a highly concentrated source of polyphenols, and these compounds have been shown to interact with and inhibit digestive enzymes responsible for carbohydrate breakdown. By inhibiting the activity of these digestive enzymes, it is possible to slow down carbohydrate absorption after a meal and ultimately reduce large spikes in blood glucose levels, being a promising strategy in the prevention and maintenance of T2D. Cocoa beans undergo processing steps to produce a final product, such as cocoa powder, and it is known that these processing steps reduce the levels of beneficial polyphenols. Yet, how this processing-induced degradation effects the health protective activities of cocoa is still widely unknown and is the focus of this work. Through highly controlled cocoa bean processing, cocoa powders of different processing conditions were produced and used to assess how various processing parameters impacted digestive enzyme activity. Overall, processing steps did reduce levels of native polyphenols. However, these losses did not demonstrate a reduction in enzyme inhibition and certain processing conditions actually enhanced digestive enzyme inhibition. This research shows promise for the potential use of processed cocoa powder as an effective strategy in the prevention and maintenance of T2D and further work must be done to understand the mechanisms behind this relationship.

Ces travaux ont pour but d’identifier des métabolites dans des teintures-mères (TMs) utilisées en homéopathie et en phytothérapie pour mieux contrôler la qualité des TMs et de mieux comprendre leur mode d’action sur la santé humaine. Nous avons étudié, par une approche de métabolomique globale, 19 TMs et un produit leader : le L52, fabriqués par les Laboratoires Lehning. Premièrement, nous avons utilisé des approches non-ciblées en construisant des banques de données GC-MS et UPLC-MS/MS, afin d’identifier un maximum de molécules dans chaque extrait. Puis, nous avons fractionné certaines TMs et purifié des métabolites inconnus pour une identification fine en HRMS. Nous avons identifié de nombreuses molécules dans chaque TM, montrant que ces dernières sont très riches en molécules pouvant être utilisées pour le contrôle-qualité des TMs et valorisées pour la santé humaine. / Tinctures defined as hydro-alcoholic extracts have been used from centuries in homeopathy and phytotherapy, but their chemical compositions remain still unknown. During my PhD, metabolomics analyses of nineteen tinctures and one leader product, L52, made by Laboratoires Lehning, were conducted using untargeted metabolomic approach. We build GC-MS and UPLC-MS/MS databases to identify a large amount of metabolites. Then, we used semi-preparative HPLC with both UV and mass detection to isolate some compounds from tinctures. We used UPLC-HRMS to obtain chemical formula, a prerequisite for metabolites identification. Finally, we identified a broad range of different metabolites in each tincture, highlighting the metabolic complexity of the TMs. These molecules can now be used for quality-control and valued for a better understanding of these products on human health.

Afin d’étudier la santé d’un écosystème marin et le potentiel toxique d’une contamination telle que celle liée à la présence d’hydrocarbures aromatiques polycycliques (HAP), il est nécessaire, outre de connaître les niveaux de contamination du milieu, de pouvoir accéder à la fraction toxique à laquelle les organismes aquatiques ont été exposés et de connaître les effets toxiques des contaminants incriminés. L’exposition et la contamination des organismes aquatiques aux HAP ont généralement été évaluées par le dosage des HAP bioaccumulés dans les tissus. Or, cette approche est critiquable si l'on tient compte des capacités de biotransformation des organismes, notamment des vertébrés, et des propriétés toxiques des produits de transformation formés. Dans ce contexte, l’objectif de cette thèse est d’étudier les phénomènes de bioccumulation et de biotransformation des HAP chez les organismes marins via l’étude des métabolites de HAP. Un effort de validation de biomarqueurs pertinents pour évaluer la génotoxicité des HAP en lien avec la contamination chimique des tissus et la production de métabolites est nécessaire. Des méthodes de dosage des métabolites de HAP dans les matrices biologiques ont tout d’abord été mises au point. Ces outils analytiques sensibles, innovants et performants ont ensuite été appliqués lors d’expositions de poissons à des HAP via différentes voies de contamination en milieu contrôlé. Ils ont permis une meilleure connaissance des phénomènes de biotransformation des HAP. Enfin, des études de terrain ont été réalisées, notamment dans le cadre de l’étude de la contamination de la Baie de Seine, montrant l’applicabilité du dosage des métabolites de HAP dans l’évaluation de l’exposition des organismes aux HAP en milieu naturel. Dans le cadre d’une approche intégrée chimie/biologie, ces travaux ont permis d’apporter une contribution dans le transfert méthodologique des biomarqueurs de génotoxicité des HAP pour des applications en surveillance de l’Atlantique Nord et notamment dans la Manche. / In order to study the health of a marine ecosystem and the toxic potential of a contamination such as that related to the presence of polycyclic aromatic hydrocarbons (PAHs), it is necessary, in addition to the determination of environmental contamination levels, to have access to the fraction for aquatic organisms have been exposed to and to identify the toxic effects of the contaminants. The exposure and contamination of aquatic organisms to PAHs have generally been evaluated by the quantification of bioaccumulated PAHs in tissues. However, this approach is criticable when taking into account the biotransformation capabilities of organisms such as vertebrates and the toxic properties of biotransformation products. In this way, the aim of this study is to study PAH bioaccumulation and biotransformation phenomena through the PAH metabolites study. An effort for the validation of relevant biomarkers to evaluate the link between the genotoxicity of PAHs, PAHs body burden and PAH metabolites production, is necessary. Analytical techniques to quantify PAH metabolites in biological matrices have first been set up. Then, these sensible, innovating and powerful analytical tools have been applied to the study of fish exposures to PAHs through differents contamination sources in controlled conditions. This allowed to have a better understanding of PAH biotransformation phenomena. Finally, field studies have been led, notably to study the contamination of the Seine bay, demonstrating the applicability of the quantification of PAH metabolites to evaluate the exposure and the contamination of organisms to PAHs in natural environment. Within the framework of an integrated approach chemistry/biology, this work led to a contribution in the methodological transfer of biomarkers of PAH genotoxicity

The hip-flask defence is a common claim in drunkdrinking cases. In Sweden and Norway two different models are used to determinethese cases. In Sweden one blood and two urine samples taken 60 minutes apartare used for analysis. In Norway two blood samples taken 30 minutes apart areused. Sweden focuses on the rise or fall of alcohol concentration in urine(UAC), and the ratio between UAC and blood alcohol concentrations (BAC). Norwayfocuses on the rise or fall of the alcohol metabolite ethylglucuronide (EtG) and the ratio between BAC and EtG. The aim of this study wasto test the models for multiple intakes and with different alcoholic beverages.Thirtyfive participants ingested two doses, first0.51 g/kg of beer and later either 0.25, 0.51 or 0.85 g/kg of beer, wine orvodka. Blood and urine samples were obtained before and after alcoholingestion. Alcohol was measured by GC-HS, and the alcohol metabolite byUPLC-MS/MS. The results showed that there are kineticdifferences between single and repeated intakes, that there are no significantdifferences in kinetics from different alcoholic beverages and thatthe Norwegian model appears to be the stronger one in hip-flask determination.

<p>Entomophagy, which is the habit of eating insects, has become relevant in the past few years as it could potentially help reduce current and future food insecurity, due to the highly nutritious and sustainable characteristics of edible insects. In addition to the nutritional content of insects, research on the potential bioactive components of insect extracts has also gained popularity. In this study, extracts from house cricket (<i>Acheta domesticus</i>) from two farms and their corresponding feeds were obtained using a microwave-assisted extraction. Further phenolic characterization led to the identification and quantification of 4-hydroxybenzoic acid, <i>p</i>-coumaric acid, ferulic acid and syringic acid as major phenolic compounds in both <i>A. domesticus </i>extracts as well as both feed extracts. Additionally, <i>in vitro</i> antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical cation (DPPH) and 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical assays. In both <i>in vitro</i> assays, <i>A. domesticus</i> extracts showed higher antioxidant activity compared to the feeds. Antibacterial activity against <i>E. coli</i> and <i>L. innocua</i> was also evaluated using the microwell method. The <i>A. domesticus </i>extracts showed a selective inhibition (p<0.05) towards the gram-positive bacteria <i>L. innocua </i>between a period of 4 to 8 h. This inhibition is thought to have occurred as a result of the presence of phenolic acids and antimicrobial peptides, while the feed extracts did not exhibit any inhibitory activity towards any of the bacteria. The finding of the same phenolic acids in <i>A. domesticus</i> and their corresponding feed could imply the capacity of <i>A. domesticus</i> to absorb and sequester dietary phenolics that may provide additional health benefits when the insect is consumed, unveiling new benefits of entomophagy. </p>

Per- and polyfluorinated substances (PFAS) are used in the production of ski wax to reduce the friction between the snow and the ski. In this occupational study of ski wax technicians’ exposure to PFAS and particulate aerosol we have collected whole blood (wb) (n =94), air (n =84) and aerosol (n =159) samples at World Cup events from 2007-2011. We have analysed the blood, air and aerosol with respect to 13 perfluorocarboxylic acids (PFCAs), 4 perfluorosulfonic acids (PFSAs), 3 fluorotelomer alcohols (FTOHs), 3 fluorotelomer acids (FTCAs) and 3 unsaturated fluorotelomer acids (FTUCAs). Further, we assessed the exposure to 3 particulate aerosol fractions (inhalable, respirable and total aerosol) in air. In comparison to a general population, several of the PFCA blood levels are elevated in the technicians’, primarily  erfluorooctanoate (PFOA) and perfluorononate (PFNA) with concentrations up to 628 and 163 ng/mL wb, respectively. Further,  we detected FTUCAs and FTCAs in the blood, suggesting biotransformation of FTOHs to PFCAs. The metabolites 5:3 and 7:3 FTCA were detected in all blood samples at levels up to 6.1 and 3.9 ng/mL wb. Levels of perfluorohexadecanoic acid PFHxDA) and perfluorooctadecanoic acid (PFOcDA) were detected in the technician’s blood at mean concentration up to 4.22 ng/mL wb and 4.25 ng/mL wb. The FTOH levels in air of the wax cabin during work ranged up to 997 000 ng/m3 (average=114 000 ng/m3 ) and PFOA up to 4 890 ng/m3 (average= 526 ng/m3 . FTOHs were not detected in aerosols but PFOA showed average levels of 12 000 ng/m3 (range=1 230- 46 900 ng/m3 ). The occupational exposure limit (OEL) of 2 mg/m3 was exceeded in 37% of the personal measurements with aerosol  concentrations up to 15 mg/m3 . Keywords : Perfluorinated, polyfluorinated, FIS, occupational exposure, ski wax,  iotransformation, metabolism, fluorotelomer alcohol, fluorotelomer acid, aerosol, dust, UPLC/MS-MS, GC/MS-MS