Abstrakt Bei Frauen wurde der Zusammenhang zwischen berufsbedingten Expositionen und dem primären Leberzellkarzinom (HCC) bisher nur sehr eingeschränkt diskutiert, das heißt, es gibt bisher kaum Forschungsergebnisse. Diese Arbeit zeigt die Ergebnisse einer internationalen Fall-Kontroll-Studie bei Frauen. Es wurden 317 HCC-Fälle und 1789 Kontrollen ohne diese Erkrankung untersucht. Grenzwertig signifikant erhöhte, adjustierte Risikoschätzer (Odds Ratio=OR)konnten für Beschäftigte in der Landwirtschaft (OR=2.50, 95% Konfidenzintervall: 1.28-4.88) und der chemischen Industrie (2.37 (1.04-5.41)) gefunden werden. Andere, nicht-signifikant erhöhte Werte fanden sich bei Frauen, die in der pharmazeutischen Industrie, in der Plastik- und PVC-Produktion, in der Schlachterei und in der Textilindustrie beschäftigt waren. Allerdings zeigten die jeweiligen Risikoschätzer nur eine geringe Konsistenz zwischen drei verschiedenen Analyseverfahren. Desweiteren zeigte keine der Analysen einen linearen Trend mit zunehmender Zeitdauer der Exposition. Die Anzahl der exponierten Fälle und Kontrollen waren aber in vielen der Berufsgruppen sehr klein, und damit auch die Studien-Power und die Präzision. Wir konnten keinen ernstzunehmenden und konsistenten Beleg für eine Beziehung zwischen HCC bei Frauen und berufsbedingten Expositionen aufzeigen. Nichtsdestotrotz, auch schwache Hinweise auf berufsbedingte Risiken rechtfertigen weitere sorgfältige Betrachtungen in zukünftigen Studien. / Abstract The association of occupational variables and hepatocellular cancer (HCC) is discussed with particular reference to women, as little research has been undertaken on their behalf. This paper reports the results of an international case-control study concerning women and involves 317 cases of HCC and 1789 controls without HCC. Working in the chemical industry and in farming was shown to have only a marginally significant risk associated with HCC: adjusted occupational risk (OR) and 95% confidence interval 2.37 (1.04-5.41) for the chemical industry and 2.50 (1.28-4.88) for farming. Other non-significantly elevated ORs were observed in the pharmaceutical, plastics, PVC-producing, textile-producing and butchery industries. Little consistency was found among the risk estimates for HCC, based on three different analytical approaches. None of the analyses showed a linear trend of risk with increasing duration of exposure. However, the numbers of exposed cases and controls were small for many of the occupations and therefore the study power and precision were low. We failed to find important and consistent evidence for a relationship between HCC in women and occupational variables. However, even weak evidence of occupational risk warrants careful consideration in future studies.

Thesis (M. Tech.) -- Central University of Technology, Free State, 2008

Background: Only few studies deal with the workload of physical therapists and the health consequences, although this occupational group is quite important for the health care system in many industrialized countries (e.g. ca. 136 000 people are currently employed as physical therapists in Germany). Therefore, the current state of knowledge of work-related diseases and disorders of physical therapists is insufficient. The aim of the "Physical Therapist Cohort" (PTC) study is to analyze the association between work-related exposures and diseases among physical therapists in Germany. This article describes the protocol of the baseline assessment of the PTC study. Methods/Design: A cross-sectional study will be conducted as baseline assessment and will include a representative random sample of approximately 300 physical therapists employed in Germany (exposure group), and a population-based comparison group (n = 300). The comparison group will comprise a sample of working aged (18–65 years) inhabitants of a German city. Variables of interest will be assessed using a questionnaire manual including questions regarding musculoskeletal, dermal, and infectious diseases and disorders as well as psychosocial exposures, diseases and disorders. In addition to subjective measures, a clinical examination will be used to objectify the questionnaire-based results (n = 50). Discussion: The study, which includes extensive data collection, provides a unique opportunity to study the prospective association of work-related exposures and associated complaints of physical therapists. Baseline results will give first clues with regard to whether and how prevalent main exposures of physiotherapeutic work and typical work areas of physical therapists are associated with the development of work-related diseases. Thereby, this baseline assessment provides the basis for further investigations to examine causal relationships in accordance with a longitudinal design.

Ce travail s'inscrit dans le cadre de l'amélioration de la connaissance sur la mesure de la surface des aérosols ultrafins. En effet, l'essor des nanotechnologies peut être à l'origine de situations d'exposition professionnelle aux particules nanostructurées dispersées dans l'air, ce qui soulève une problématique nouvelle de prévention. Si à ce jour aucun des trois indicateurs (masse, surface, nombre) ne fait l'objet d'un consensus, il semble que le paramètre de surface des particules permet une bonne corrélation avec les effets biologiques observés lorsqu'elles sont inhalées. Un travail théorique original a donc été mené afin de positionner le paramètre de surface vis-à-vis d'autres grandeurs caractéristiques des aérosols. En vue de caractériser des méthodes de mesure de la surface des aérosols nanostructurés, le banc d'essais CAIMAN (CAractérisation des Instruments de Mesure des Aérosols Nanostructurés) a été dimensionné et réalisé. Celui-ci permet la production d'aérosols nanostructurés de propriétés variables et maîtrisées (taille, concentration, nature chimique, morphologie, état de charge), offrant une très bonne stabilité dans le temps. Les aérosols générés en laboratoire ont été utilisés en vue d'évaluer expérimentalement la réponse des instruments de mesure étudiés (NSAM & AeroTrak 9000 TSI, LQ1-DC Matter Engineering). Les fonctions de réponse expérimentales établies sur des aérosols monodispersés présentent un bon accord avec les courbes théoriques, dans une large gamme d'étude de 15 à 520 nm. Par ailleurs, des hypothèses ont été avancées en vue d'expliquer les écarts raisonnables observés lors des mesures effectuées sur des aérosols polydispersés / This work aims at improving knowledge on ultrafine aerosols surface-area measurement. Indeed, the development of nanotechnologies may lead to occupational exposure to airborne nanostructured particles, which involves a new prevention issue. There is currently no consensus concerning what parameter (mass, surface-area, number) should be measured. However, surface-area could be a relevant metric, since it leads to a satisfying correlation with biological effects when nanostructured particles are inhaled. Hence, an original theoretical work was performed to position the parameter of surface-area in relation to other aerosol characteristics. To investigate measurement techniques of nanostructured aerosols surface-area, the experimental facility CAIMAN (ChAracterization of Instruments for the Measurement of Aerosols of Nanoparticles) was designed and built. Within CAIMAN, it is possible to produce nanostructured aerosols with varying and controlled properties (size, concentration, chemical nature, morphology, state-of-charge), stable and reproducible in time. The generated aerosols were used to experimentally characterize the response of the instruments in study (NSAM & AeroTrak 9000 TSI, LQ1-DC Matter Engineering). The response functions measured with monodisperse aerosols show a good agreement with the corresponding theoretical curves in a large size range, from 15 to 520 nm. Furthermore, hypotheses have been formulated to explain the reasonable biases observed when measuring polydisperse aerosols

Introdução: A exposição ocupacional ao ruído tem sido um tema estudado para diferentes ocupações. Na atividade de teleatendimento também tem sido referido como um fator de risco com repercussões à saúde. Objetivo: Identificar a presença de perdas auditivas em operadores de teleatendimento da central de reservas de uma empresa aérea. Métodos: Realizado estudo epidemiológico transversal e longitudinal. O estudo transversal compreendeu os últimos audiogramas de 589 operadores distribuídos de acordo com o sexo, faixa etária (18 a 30, 31 a 43, mais de 44 anos), e tempo na função (01 a 35, 36 e 60, mais 61 meses). Foram avaliados os audiogramas de 387 operadores que estavam na empresa há mais de 3 anos, através de um estudo longitudinal, comparando os audiogramas referenciais e finais no período de 1999 a 2006. Resultados: Identificou-se o predomínio do sexo feminino, prevalência de perdas auditivas de 6,0% com 3,1% de PAIR e 2,9% por outras causas. Para as perdas auditivas sexo não se mostrou um fator de risco significativo (p>0,05). Observa-se um risco maior para as faixas etárias de 31 a 43 e de 41 a 55 anos de idade e tempo de serviço maior de 61 meses com chance de 3,35 (IC95%: 1,31 8,57) quando comparados com o tempo de serviço menor do que 36 meses. A comparação entre as médias mostrou um aumento significante dos limiares com exceção da freqüência de 1K na orelha direita. Conclusões: Operadores de teleatendimento na empresa estudada apresentaram rebaixamento dos limiares auditivos em todas as freqüências. A exposição ocupacional por ruído ambiental e uso de headset dos operadores de teleatendimento necessita de estudos longitudinais detalhados para definição das repercussões auditivas e extra-auditivas / Introduction: Occupational noise exposure has been a subject studied for various occupations. At call centers, it has also been referred to as a healthhazardous risk factor. Aim: Identify the presence of hearing loss in operators of an airline company call center. Methodology: Cross-section and longitudinal epistemological study has been carried out. The cross-section study considered the latest audiograms of 589 operators divided according to gender, age (18 to 30, 31 to 43, over 44), and employment time (01 to 35, 36 to 60, over 61 months). The longitudinal study considered the audiograms of 387 operators who have been with the company for over 3 years, comparing referencial and final audiograms of the period between 1999 and 2006. Results: A predominance of 6.0% hearing loss, with 3.1% of NIHL and 2.9% by other causes, has been noticed in females. For hearing losses, gender has not turned out to be a significant risk factor (p>0.05). There is a greater risk for ages between 31 and 43, and 41 and 55, having been with the company for over 61 months, of 3.35 (IC95%: 1.31 - 8.57) when compared to those who have been with the company for less than 36 months. The comparison between the averages has shown a significant rise of threshold with the exception of 1K frequency in the right ear. Conclusions: Call center operators in the airline company at stake have shown lowering of hearing threshold in all frequencies. Noise-induced occupational exposure and the use of headsets by call center operators demand further, more detailed longitudinal studies to define the hearing and extra-hearing repercussions

O benzeno é um hidrocarboneto aromático produzido pela combustão de produtos naturais. A exposição ocupacional ao benzeno é caracterizada por ambientes industriais que o empregam em seus processos produtivos. Nos laboratórios de indústria do petróleo ele é utilizado em forma pura para análise, e está presente como contaminante em derivados, como gasolina, hexano, querosene, tolueno, entre outros. No Brasil o valor recomendado pela legislação como limite de exposição ambiental ao benzeno é de 1ppm. O câncer hematológico é considerado um dos principais fatores de risco para a saúde dos trabalhadores expostos ao benzeno e a utilização de biomarcadores no monitoramento destes profissionais tem sido sugerida em diferentes países. O presente trabalho teve como objetivo avaliar diferentes biomarcadores em sangue periférico de trabalhadores homens, cronicamente expostos ao benzeno em refinarias e siderurgia (18 deles com diagnóstico de intoxicação), que estavam afastados de suas funções por períodos que variaram de cinco meses a 27 anos, com idade média de 46,8 ± 9,33 anos comparado com um grupo controle composto também de 20 homens, selecionados em Bancos de Sangue (idade média de 45,7 ± 8,00 anos), com diferentes ocupações não correlacionadas ao agente em estudo. Em ambos os grupos foram realizados hemograma completo, teste do micronúcleo em linfócitos com bloqueio da citocinese (CBMN), teste de FISH em linfócitos para a translocação t(15;17), bem como testes moleculares para avaliação de polimorfismos em genes envolvidos na metabolização do benzeno (MPO, NQO1, CYP1A1 e CYP2E1) e na eliminação de xenobióticos (GSTM1/GSTT1). Quanto ao hemograma à análise estatística realizada pelo teste t-Student revelou que os expostos ao benzeno apresentavam leucopenia com diferença altamente significante na contagem de leucócitos (p<0,001), neutrófilos (p<0,001), segmentados (p<0,001), linfócitos (p=0,013) e monócitos (p=0,010). A avaliação da série eritrocitária também revelou diferenças estatísticas entre os grupos para os índices de RDW-CV (p= 0,031) e RDW-SD (p=0,008), assim como para o VPM (p=0,001). Não foi verificada diferença entre os grupos quanto à frequência de polimorfismos nos genes CYP1A1, CYP2E1, MPO, NQO1, GSTM1, GSTT1. No teste do CBMN a contagem de células com MN e pontes núcleoplasmáticas foi três vezes maior nos expostos (1,95 ± 2,37) que nos controles (0,65 ± 0,75), diferença essa considerada estatisticamente significante (t=2,33; 38gl; p=0,024). Na análise de FISH para o rearranjo PML/RAR? os trabalhadores expostos também apresentaram frequência três vezes maior de células com pelo menos uma fusão gênica (9,79 ± 9,54) em comparação aos controles (3,95 ± 3,17), diferença essa considerada estatisticamente significante pelo teste t-Student (p=0,019). Os resultados obtidos na presente investigação parecem estar de acordo com os dados da literatura que revelam alteração nas células primordiais da medula, decorrente da exposição ocupacional ao benzeno, bem como ação genotóxica, identificada pelos testes do CBMN e FISH em linfócitos de sangue periférico. Embora o número de trabalhadores estudados seja reduzido, e a exposição ocupacional possivelmente inclua outros agentes potencialmente genotóxicos que não só o benzeno é interessante ressaltar que os resultados positivos foram observados após em média nove anos de afastamento profissional. A utilização do teste do CBMN e o estudo de outras translocações, que não só a PML/ RAR?, em linfócitos de trabalhadores expostos pode representar um biomonitoramento importante e menos invasivo no acompanhamento destes trabalhadores. A análise de um grupo maior de trabalhadores, inclusive expostos a baixas concentrações de benzeno pode ser fundamental na validação destes biomarcadores. / Benzene is an aromatic hydrocarbon produced by the burning of natural products. The occupational exposure to benzene is characterized by industrial environments that use in their production processes. In the laboratories of Petroleum industry it is used in the pure form for analysis, and it is present as a contaminant in other products like gasoline, hexane, kerosene, toluene, etc. In Brazil the threshold limit value recommended by law in environmental exposure to benzene is 1 ppm. The hematological cancer is considered one of the main risk factors for the health of workers occupationally exposed to benzene and the use of biomarkers in monitoring these professionals has been suggested in different countries. The aim of this study was to assess different biomarkers in peripheral blood lymphocytes from 20 men workers chronically exposed to benzene in Petroleum Refinery and Steel Industry (18 workers with poisoning diagnosis), who were removed from workplace for periods ranging from five months to 27 years, with average age 46.8 ± 9.33 years old compared to a control group consisting also of 20 men, selected in Blood Banks (average age 45.7 ± 8.00 years old), with different occupations unrelated to the agent under study. In both groups were performed blood cell counts, cytokinesis-block micronucleus assay (CBMN), FISH assay in peripheral blood lymphocytes for translocation t(15;17), and molecular tests for evaluation of genetic polymorphisms in genes involved in benzene metabolism (MPO, NQO1, CYP1A1 e CYP2E1) and detoxification (GSTM1/GSTT1). Despite blood cell counts the statistical analysis performed by t-Student test revealed that workers exposed to benzene had leukopenia with a highly significant difference in leukocyte count (p<0.001), neutrophils (p<0.001), segmented (p<0.001), lymphocytes (p=0.013) and monocytes (p=0.010). The evaluation of red blood cells also revealed statistically significant differences between groups for RDW-CV (0.031), RDW-SD (0.008) and MPV (0.001). There were no differences between groups regarding the frequency of genetic polymorphisms in CYP1A1, CYP2E1, MPO, NQO1, GSTM1, and GSTT1. In the CBMN test the cell counts with MN and nucleoplasmic bridges was three times higher in exposed (1.95 ± 2.37) than in controls (0.65 ± 0.75), and the difference was considered statistically significant (t=2.33;38gl;p=0.024). In the FISH analysis for the PML/RAR? rearrangement the exposed workers also showed three times higher frequency of cells with at least one signal fusion (9.79 ± 9.54) in comparison to controls (3.95 ± 3.17), and the difference was statistically significant by the t-Student test (p=0.019). The results obtained in this study seem to agree with the literature data that show alterations in the stem cells of the bone marrow, resulting from occupational exposure to benzene, as well genotoxicity, identified by CBMN and FISH assay in peripheral blood lymphocytes. Although the number of subjects evaluated is reduced, and the occupational exposure includes other potentially genotoxic agents not only benzene, it is interesting to note that positive results were observed after an average of nine years of removal professional. The use of the CBMN test and the study of other translocations, not only PML/ RAR?, in lymphocytes of workers exposed may represent an important biomonitoring and less invasive monitoring of workers. The analysis of a major number of individuals, including those exposed to low concentrations of benzene, may be essential in validation of these biomarkers.

A artrite idiopática juvenil (AIJ) constitui um grupo heterogêneo de doenças que se caracteriza por inflamação crônica em uma ou mais articulações, com diagnóstico em menores de 16 anos de idade. A poluição atmosférica tem sido responsabilizada pelo aumento da morbidade e mortalidade em doenças cardiorrespiratórias, mas poucos estudos avaliaram os efeitos da exposição prolongada sobre doenças inflamatórias crônicas. Alguns estudos demonstram associação entre fumo e início da doença reumatológica em adultos e outros mostram associação de mães fumantes durante a gravidez com desenvolvimento de AIJ nos filhos. Entretanto, existem poucos estudos na literatura avaliando a exposição à poluição do ar e AIJ. Objetivo: avaliar a influência de poluentes ambientais inalatórios como fatores de risco no desenvolvimento da AIJ em pacientes residentes na Região Metropolitana de São Paulo, acompanhados em um serviço terciário de Reumatologia Pediátrica. Metodologia: Este foi um estudo retrospectivo, do tipo caso-controle, que incluiu 66 pacientes com AIJ e 124 controles saudáveis, semelhantes em idade e gênero, residentes na Região Metropolitana de São Paulo, desde a gestação até o diagnóstico da doença. Um questionário estruturado e com alto índice de confiabilidade (índice kappa para teste-reteste 0,80) avaliou dados demográficos, fatores relacionados à gestação e ao período perinatal, exposição ocupacional materna durante a gravidez a partículas inaláveis e/ou vapor volátil, exposição ao tabaco e exposição à inalação ambiental durante a gravidez e após o nascimento (presença de atividades industriais, pedreiras ou postos de gasolina perto do domiícilio/ trabalho/ creche/ escola). Foram também analisados poluentes troposféricos nos dois períodos: material particulado (PM10), dióxido de enxofre (SO2), dióxido de nitrogênio (NO2), ozônio (O3) e monóxido de carbono (CO). Resultados: Durante a gravidez, o fumo fetal (OR= 3,43, IC 95%: 1,45-8,12, p=0,005) e a exposição ocupacional materna (OR= 13,69, IC95%: 4,43-42,27, p < 0,001) se mostraram fatores de risco independentes para AIJ. Em contrapartida, o fato de a mãe trabalhar fora de casa (OR= 0,06, IC 95%: 0,02- 0,16, p < 0,001) e o ganho de peso ideal da mãe (OR = 0,36, IC 95%: 0,16-0,83, p= 0,017) apresentaram associação negativa. Para o período após o nascimento até o diagnóstico de AIJ, fumo passivo (OR= 3,6, IC 95%: 1,76- 7,31, p < 0,0001) e exposição ao ozônio durante o segundo ano de idade (OR= 2,76, IC 95%: 1,20-6,37, p= 0,017) foram fatores de risco independentes e significativos para o diagnóstico da AIJ. Conclusão: O fumo passivo, a exposição ao ozônio no segundo ano de vida e a exposição ocupacional materna são destacados como importantes fatores de risco para a AIJ / Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases characterized by chronic inflammation in one or more joints with onset in children under 16 years of age. Air pollution has been blamed for increased morbidity and mortality in cardiorespiratory diseases, but few studies have evaluated the effects of prolonged exposure on chronic inflammatory diseases. Some studies show an association between smoking and onset of rheumatologic illness in adults, and others show an association of smoking mothers during pregnancy with the development of JIA in children. However, there are few studies in the literature to date evaluating exposure to air pollution and JIA. Objective: To evaluate the influence of exposure to inhalable environmental factors during pregnancy and after birth until JIA diagnosis in residents of the São Paulo metropolitan area. Methods: Case-control study comprising 66 JIA patients and 124 healthy controls matched by age and gender, living in the Sao Paulo metropolitan area until JIA diagnosis, and whose mothers had resided in this region during pregnancy. A structured and reliable questionnaire (kappa index for test-retest was 0.80) assessed demographic data, gestational and perinatal-related factors, mothers\' work-related exposure during pregnancy to inhalable particles and / or volatile vapor, exposure to inhalable elements during pregnancy and after birth (work-related exposure to inhalable particles and/or volatile vapor, exposure to tobacco and the presence of industrial activities, quarries or gas stations near the home/ work/ daycare/ school). Tropospheric pollutants included: particulate matter (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO). Results: During pregnancy, fetal smoking (OR=3.43, 95%CI: 1.45-8.12, p=0.005) and mothers\' work-related exposure (OR=13.69, 95%CI: 4.43-42.27, p < 0.001) were independent significant risk factors for JIA diagnosis. In contrast, working mother (OR=0.06, 95% IC: 0.02-0.16, p < 0.001) and ideal mother weight gain (OR=0.36, 95% IC:0.16-0.83, p=0.017) presented a negative association. After birth until JIA diagnosis, secondhand smoking (OR=3.6, 95% IC: 1.76-7.31, p < 0.0001) and exposure to O3 during the second year of age (OR=2.76, 95% IC: 1.20-6.37, p=0.017) were independent and significant risk factors for JIA diagnosis. Conclusion: Secondhand smoking, exposure to O3 during the second year of age and mothers\' work-related exposure are highlighted as important risk factors to JIA

De nombreuses études de biométrologie sont menées à l’INRS, pour évaluer l’exposition professionnelle à des substances chimiques, en France, et pour compléter les connaissances en proposant des valeurs de références destinées à protéger des salariés exposés à ces substances. Ces études consistent à mesurer simultanément l’imprégnation biologique et l’exposition atmosphérique à une substance, chez des salariés exposés à celle-ci. La relation entre ces mesures biologiques et atmosphériques est ensuite estimée à travers un modèle de régression linéaire. Lorsque que cette relation existe et que la voie d’absorption du toxique est essentiellement inhalatoire, il est ensuite possible de dériver une Valeur Limite Biologique (VLB) à partir de la Valeur Limite d’Exposition Professionnelle (VLEP-8h) du toxique. Deux aspects de ces données ont été identifiés, qui ne sont pas ou seulement partiellement prises en compte dans les modélisations statistiques courantes : la censure due aux limites de détection (LD)/quantification (LQ) des mesures biologiques et atmosphériques et la variabilité inter-individuelle. Ignorer ces deux particularités lors de la modélisation mène à une perte de puissance statistique et à de potentielles conclusions biaisées. Les travaux menés dans le cadre de cette thèse ont permis d’adapter le modèle de régression à ces deux caractéristiques, dans un cadre bayésien. L’approche proposée repose sur la modélisation des mesures atmosphériques à l’aide de modèles à effets aléatoires prenant en compte les valeurs inférieures à la LD/LQ, et sur la modélisation simultanée des mesures biologiques, supposée être linéairement dépendantes sur une échelle logarithmique, de l'exposition atmosphérique, tout en tenant compte de la variabilité inter-individuelle. Ce travail a donné lieu à une publication scientifique dans une revue à comité de lecture. L’application de cette méthodologie a été réalisée sur des jeux d’exposition professionnelle au béryllium et au chrome, après avoir été cependant adaptée aux caractéristiques toxicocinétiques de ces deux substances. Il a ainsi été possible de proposer une VLB pour le béryllium (0,06 µg/g créatinine). L’exploitation de mesures de chrome dans deux secteurs d’activités différents (exposition professionnelle aux peintures de chromates, et exposition professionnelle dans le secteur du chromage électrolytique) a permis de mettre en évidence que le chrome urinaire dépend essentiellement de l’exposition au chrome VI, le chrome non VI ayant moins d’impact. Nous n’avons pas pu montrer de relation entre la solubilité du CrVI et le chrome urinaire. Une VLB de 0,41 µg/g créatinine, de l’ordre de la Valeur Biologique de Référence (VBR) proposée par l’ANSES (0,54 µg/g créatinine), a été estimée pour l’exposition professionnelle aux peintures de chromates, et une VLB de 1,85 µg/g créatinine a été estimée pour l’exposition professionnelle dans le secteur du chromage électrolytique, qui est en cohérence avec la VLB proposée par l’ANSES dans ce secteur, à savoir 1,8 µg/g créatinine / Many biomonitoring studies are conducted at INRS, in order to assess occupational exposure to chemicals in France, and to propose reference values to protect workers exposed to these substances. These studies consist in measuring simultaneously biological and airborne exposure of workers exposed to a toxic substance. The relationship between these biological and airborne measurements is then estimated through a linear regression model. When this relationship exists and the route of absorption of the toxic is essentially inhalatory, it is possible to derive a Biological Limit Value (BLV) from the Occupational Exposure Limit Value (OEL) of the toxic substance. However, two characteristics of these data have been identified, which are not or only partially taken into account in the current statistical modelling: the left-censoring due to limits of detection (LoD)/quantification (LoQ) of biological and airborne measurements, and the between-individual variability. Ignoring both of these features in modelling leads to a loss of statistical power and potentially biased conclusions. The work carried out in this thesis allowed us to adapt the regression model to these two characteristics, in a Bayesian framework. The proposed approach is based on the modelling of airborne measurements using random effects models adapted for values below the LoD / LoQ, and on the simultaneous modelling of biological measurements, assumed to depend linearly on a logarithmic scale, on the airborne exposure, while taking into account between-subject variability. This work resulted in a scientific publication in a peer-reviewed journal. This methodology has been applied on beryllium and chromium occupational exposure datasets, after adaptation to the toxicokinetic characteristics of these two substances. It has thus been possible to propose a BLV for beryllium (0.06 μg / g creatinine). The analysis of chromium measurements in two different sectors of activity (occupational exposure to chromate paints, and occupational exposure in the electroplating sector) made it possible to show that urinary chromium depends mainly on airborne exposure to VI chromium, non-VI chromium having less impact. We were not able to show a relationship between the solubility of airborne VI chromium and urinary chromium. A BLV of 0.41 μg / g creatinine, close to the Biological Guidance Value (BGV) proposed by ANSES (0.54 μg / g creatinine), was estimated for occupational exposure to chromate paints, and a BLV of 1.85 μg/g creatinine was obtained for occupational exposure in the electrolytic chromium plating sector, which is consistent with the ANSES proposed BLV in this sector, i-e 1.8 μg / g creatinine

estudo da variabilidade da frequência cardíaca (VFC) é um método que vem sendo usado para a análise da função autonômica cardiovascular frente aumentos da poluição atmosférica por material particulado (MP) em diversas populações, porém esse efeito em controladores de tráfego e taxistas permanece pouco compreendido especialmente durante o exercício. Objetivos: O presente estudo teve o objetivo de avaliar a resposta autonômica, ao repouso e ao exercício, frente variações da concentração de poluição (MP2,5) em indivíduos cronicamente expostos. Métodos: Foram estudados 75 trabalhadores da cidade de São Paulo divididos em grupo trabalhadores do tráfego (GTT; n=57) e grupo de trabalhadores florestais (GTF; n=18), posteriormente os 75 sujeitos foram novamente divididos pela presença ou ausência de comorbidades dando origem ao grupo hipertensão e/ou diabetes (GHD; n=21) e grupo sem comorbidades (GSC; n=54). As medidas de MP2,5 foram realizadas por monitoramento individual da exposição ao poluente e as avaliações ambulatoriais da VFC foram realizadas em 4 dias diferentes, tanto ao repouso quanto durante o exercício leve. Resultados: Foi observado que aumentos de 10g/m3 de PM2,5 levam a redução de HFms2 ao repouso no GTT sem nenhuma alteração durante o exercício. Por outro lado o GTF não apresentou mudanças durante o repouso, entretanto, durante o exercício o aumento do poluente leva a redução parassimpática (RMSSD), além disso, uma variável observada como interveniente nessa mudança foi a carga horária diária de trabalho exercida. Quando separados por comorbidades o GHD apresentou redução parassimpática ao repouso (HFms2 e HFnu) além de aumento simpático (LFnu) e ao exercício redução predominantemente parassimpática (RMSSD, LFms2, HFms2), já o GSC apresentou somente redução do LFms2 ao repouso sem alterações no exercício. Conclusão: Pequenos aumentos nas concentrações de MP2,5 levaram a alterações autonômicas em sujeitos cronicamente expostos, além disso essas alterações são mais evidentes nos sujeitos portadores de hipertensão e diabetes do que nos indivíduos saudáveis / The study of heart rate variability (HRV) is a method that has been used for the analysis of cardiovascular autonomic function front air pollution increases by particulate matter (PM) in many populations, but the effect on traffic controllers and taxi drivers remains poorly understood especially during exercise. Objectives: This study aimed evaluate the autonomic response, at rest and during exercise, compared to variations in the pollution concentration (PM2, 5) in chronically exposed subjects. Methods: We studied 75 workers of the city of São Paulo divided into group traffic workers (GTT, n=57) and group of forest workers (GTF, n=18), subsequently the 75 subjects were again divided by comorbidities presence or absence leading the group hypertension and/or diabetes (GHD, n=21) and group without comorbidities (GSC, n=54). PM2,5 measures were performed by individual monitoring of pollutants exposure and ambulatory HRV ratings were performed on 4 different days, both at rest and during light exercise. Results: We found that 10g/m3 of PM2,5 increases lead to HFms2 reduction at rest in GTT with no change during exercise. Moreover GTF showed no changes at rest, however, during exercise, pollutant increased leads to parasympathetic reduction (RMSSD) and the daily workload performed also observed as a intervener variable in this change. When separated by the comorbidities, GHD decreased parasympathetic at rest (HFms2 and HFnu) as well as increased sympathetic (LFnu) and exercise predominantly parasympathetic (RMSSD, LFms2, HFms2), the GSC has had only reduced LFms2 at rest without changes in exercise. Conclusion: Small increases in the PM2,5 concentrations led autonomic changes in subjects chronically exposed furthermore these changes are more evident in subjects with hypertension and diabetes than in healthy individuals

Introdução: A Perda Auditiva Induzida por Níveis de Pressão Sonora Elevados (PAINPSE) é a doença auditiva mais encontrada no ambiente de trabalho. A exposição a níveis elevados de pressão sonora pode causar perdas auditivas irreversíveis e outros danos à saúde em geral, tornando-se imprescindível sua redução e controle. Para combater o ruído que ameaça a saúde e induz à perda de audição, tem-se utilizado desde a década de cinquenta os dispositivos de proteção auditiva (protetores auditivos). Com o objetivo de avaliar a eficácia dos protetores auditivos, alguns métodos estão sendo criados. Um deles, ainda em fase de estudo, é o método objetivo do microfone em ouvido real (do inglês MIRE - Microphone In Real Ear). Objetivo: Avaliar a eficácia de um protetor auditivo do tipo concha em uma população exposta a ruído ocupacional, por meio do método objetivo MIRE e aplicação de questionário. Método: Participaram do estudo 30 indivíduos do sexo masculino expostos a ruído ocupacional. Os procedimentos realizados incluíram: aplicação de questionário, meatoscopia e método de avaliação individual objetivo MIRE. Resultados: Ao comparar as médias do nível de ruído no microfone lapela e no MIRE, foi observada diferença estatisticamente significante para todas as frequências avaliadas. Verificou-se que 30% dos indivíduos estavam subprotegidos (Dose_8h acima de 100%), com diferença estatisticamente significante entre os grupos, sendo que a maioria recebia proteção adequada. A atenuação verificada para a amostra deste estudo foi semelhante, em muitas frequências e para a atenuação média, aos valores fornecidos pelo fabricante do protetor auditivo, com diferença estatisticamente significante apenas para as frequências de 4000Hz e 8000Hz (com maiores valores para o fabricante). Conclusões: o PA do tipo concha avaliado não se mostrou eficaz para a totalidade dos trabalhadores participantes do estudo, pois 30% da amostra apresentaram subproteção. A atenuação fornecida pelo PA concha variou aproximadamente de 12 a 36 dB entre as bandas de frequência avaliadas, com média de 22,9 dB. / Introduction: The Noise Induced Hearing Loss is the hearing disease most commonly found in the work environment. Exposure to high sound pressure levels can cause permanent hearing loss and other damages to health in general, making their reduction and control indispensable. Hearing protection devices have been used since the fifties to combat the noise that threatens the health and induces hearing loss. Some methods are being created in order to evaluate the effectiveness of hearing protection. One of them, still under study, is the Microphone In Real Ear (MIRE). Objective: Evaluate through the objective method MIRE and a questionnaire the effectiveness of an earmuff in a population exposed to occupational noise. Methods: The study enrolled 30 male subjects exposed to occupational noise. The procedures performed included: questionnaire, otoscopy and objective individual evaluation method MIRE. Results: When comparing the average noise level in the lapel microphone and MIRE, it has been observed statistically significant difference at all the frequencies. It was found that 30% of individuals were under protected (Dose_8h over 100%), with statistically significant difference between the groups, in which the majority has received adequate protection. The observed attenuation for the sample of this study was similar in many frequencies and the average attenuation to the values provided by the manufacturer of hearing protectors, with statistically significant difference only for the frequencies of 4000 Hz and 8000 Hz (with higher values for the manufacturer). Conclusions: The evaluated earmuff was not effective for all the workers participating in the study, since 30% of the sample had under protection. The attenuation provided by the earmuff ranged approximately from 12 to 36 dB between the measured frequency bands, with an average of 22.9 dB