Adverse health effects from exposure to air pollution, although at present only partly understood, are a global challenge and of widespread concern. Quantifying human exposure to air pollutants is challenging, as ambient concentrations of air pollutants at potentially harmful levels are ubiquitous and subject to high spatial and temporal variability. At the same time, individuals have their very own unique activity-patterns. Hence exposure results from intertwined relationships between environmental and human systems add complexity to the assessment process. It is essential to develop a deeper understanding of individual exposure pathways and situations occurring in people’s everyday lives. This is important especially with regard to exposure and health impact assessment which provide the basis for public health advice and policy development. This thesis describes the development and application of a personal monitoring method to assess exposure to fine particulate matter in a variety of microenvironments. Tools and methods applied are tested with respect to feasibility, intrusiveness, performance and potential for future applications. The development of the method focuses on the application in everyday environments and situations in an attempt to capture as much of the total exposure as possible, across a complete set of microenvironments. Seventeen volunteers took part in the pilot study, collected data and provided feedback on methodology and tools applied. The low-cost particle counter applied showed good agreement with reference instruments when studied in two different environments. Based on the assessment of the two instruments functions to derive particle mass concentration from the original particle number counts have been defined. The application of the devices and tools received positive feedback from the volunteers. Limitations are mainly related to the non-weatherproof design of the particle counter. The collection of time-activity patterns with GPS and time-activity diaries is challenging and requires careful processing. Resulting personal exposure profiles highlight the influence of individual activities and contextual factors. Highest concentrations were measured in indoor environments where people also spent the majority of time. Differences between transport modes as well as between urban and rural areas were identified.

Much research has gone into noise-induced hearing loss (NIHL) and the effects of high intensity noise levels on the hearing mechanism of individuals. A study by the National Institutes of Health has established that high intensity sounds can cause hearing damage of either a temporary, or worse, a permanent nature; regardless of the age of the person. While sound levels below 75 decibels are considered comparatively harmless and have been found not to cause any kind of permanent hearing loss; sound levels greater than 85 decibels and regular exposure of approximately 8 hours per day, on an average, has been found to cause permanent loss of hearing (Bulla, 2003). The purpose of this research study was to assess excessive noise exposure of music-oriented nightclub employees, with music playing. Two employees were used as candidates for the purpose of this study, which was conducted on three days during a work week. Data on personal noise exposure was collected using personal noise dosimeters on a server and a promoter. For purposes of the study, a sound level meter was used to collect the noise levels in the working area, and prepare a sound map. The study was conducted in a nightclub in Tampa, Florida, with music playing. Data was collected on Wednesday, Friday, and Saturday. In total, the data was collected over six sampling nights. The data on noise levels was collected for both personal noise data levels and area noise levels during the period of study. In addition to the personal dosimeters, a sound level meter was also used for data collection. The results of this study indicate that noise levels were highest on nights with live entertainment. The days with performance of live entertainment were random and followed no particular order. The highest TWA noise exposure of 97.3 dB, for the server, occurred on Saturday, when a live entertainer performed in the establishment. The highest TWA noise exposure of 94.3 dB, for the promoter, occurred on Wednesday. Using the OSHA PEL and OSHA Hearing Conversation measurement methods, the server was exposed to excessive noise levels, greater than 85 dBA, on every night of the study (6 nights), while the promoter had three exposures that were greater than 90 dBA, using the OSHA PEL method, and exposures greater than 85 dBA on every night of the study, using the OSHA Hearing Conservation method. However, using the ACGIH measurement method, both the Server and the Promoter were exposed to excessive noise levels every night of the study (six nights).

Background: As more women of childbearing age engage in the workforceand a lot of new chemicals are available, a growing interest of diagnosing andpreventing reproductive disorders due to occupational and environmentalexposure has occurred. The source location of this thesis is the Rönnskärcopper smelter which is situated in the north of Sweden, in the municipality of Skellefteå. Emissions from the smelter, which have diminished during theperiod 1975-1990 include sulphur dioxide and heavy metals, especially lead,arsenic, cadmium, copper, mercury and zinc. Reproductive studies from the1970s in and around the smelter reported increased risks of spontaneousabortions, malformations and lower birth weight. The aim of this thesis wasto perform a broad and long-term epidemiological assessment of adversereproductive outcome in and around the smelter and to determine if theexposed population suffered from reproductive disturbances during the recentdecades. Subjects and methods: The study involve two main sources of data. Onewas a retrospective cohort formed through record linkage of populationregisters, the medical birth register (1961-90), the register of congenitalmalformations (1973-90) and the cancer register (1961-90). As another source,information on reproductive history, life-style and work related factors wasobtained from a questionnaire study in 1992. An exposed population wasdefined as smelter workers and their children, and also neighbours to thesmelter and their children. Results: In the register study, compared to the reference population, nooverall significant increased risk of malformations, childhood cancer, low birthweight or perinatal death was found in the exposed group. In thequestionnaire study, regarding infertility, no environmental effects were found.Also, no increased risk of a prolonged waiting time to pregnancy or increasedrisk of spontaneous abortions were associated with occupational or environmentalfactors. Conclusion: With the lack of a high statistical power in mind, due to smallsample sizes in some of the studies, the summary of our findings includingseveral outcomes, different epidemiological study designs and studies coveringa long period of time gives no evidence for any increased risk of reproductivehazards due to occupational or environmental exposure. / digitalisering@umu

L’exposition prolongée par inhalation à des poussières de taille respirable contenant de la silice cristalline est reconnue pour causer des maladies respiratoires dont le cancer du poumon et la silicose. De nombreuses études ont relevé la surexposition des travailleurs de la construction à la silice cristalline, puisque ce composé est présent dans de nombreux matériaux utilisés sur les chantiers. L’évaluation de l’exposition à la silice cristalline dans cette industrie constitue un défi en raison de la multitude de conditions de travail et de la nature éphémère des chantiers. Afin de mieux cerner cette problématique, une banque de données d’exposition professionnelle compilée à partir de la littérature a été réalisée par une équipe de l’Université de Montréal et de l’IRSST, et constitue le point de départ de ce travail. Les données présentes dans la banque ont été divisées en fonction de la stratégie d’échantillonnage, résultant en deux analyses complémentaires ayant pour objectif d’estimer les niveaux d’exposition sur le quart de travail en fonction du titre d’emploi, et selon la nature de la tâche exécutée. La méthode de Monte Carlo a été utilisée pour recréer les échantillons provenant de données rapportées sous forme de paramètres de synthèse. Des modèles Tobit comprenant les variables de titre d’emploi, tâche exécutée, durée, année et stratégie d’échantillonnage, type de projet, secteur d’activité, environnement et moyens de maîtrise ont été développés et interprétés par inférence multimodèle. L’analyse basée sur le quart de travail a été réalisée à partir de 1346 données d’exposition couvrant 11 catégories de titre d’emploi. Le modèle contenant toutes les variables a expliqué 22% de la variabilité des mesures et la durée, l’année et la stratégie d’échantillonnage étaient d’importants prédicteurs de l’exposition. Les chantiers de génie civil et les projets de nouvelle construction étaient associés à des expositions plus faibles, alors que l’utilisation de moyens de maîtrise diminuait les concentrations de 18% à l’extérieur et de 24% à l’intérieur. Les moyennes géométriques les plus élevées prédites pour l’année 1999 sur 8 heures étaient retrouvées chez les foreurs (0.214 mg/m3), les travailleurs souterrains (0.191 mg/m3), les couvreurs (0.146 mg/m3) et les cimentiers-applicateurs (0.125 mg/m3). 1566 mesures réparties en 27 catégories de tâches étaient contenues dans la seconde analyse. Le modèle contenant toutes les variables a expliqué 59% des niveaux d’exposition, et l’ensemble des variables contextuelles étaient fortement prédictives. Les moyennes géométriques prédites pour l’année 1998 et selon la durée médiane par tâche dans la banque de données étaient plus élevées lors du bouchardage du béton (1.446 mg/m3), du cassage de pièces de maçonnerie avec autres outils (0.354 mg/m3), du décapage au jet de sable (0.349 mg/m3) et du meulage de joints de brique (0.200 mg/m3). Une diminution importante des concentrations a été observée avec les systèmes d’arrosage (-80%) et d’aspiration des poussières (-64%) intégrés aux outils. L’analyse en fonction des titres d’emploi a montré une surexposition généralisée à la valeur guide de l’ACGIH et à la norme québécoise, indiquant un risque à long terme de maladies professionnelles chez ces travailleurs. Les résultats obtenus pour l’évaluation en fonction de la tâche exécutée montrent que cette stratégie permet une meilleure caractérisation des facteurs associés à l’exposition et ainsi de mieux cibler les priorités d’intervention pour contrôler les niveaux d’exposition à la silice cristalline sur les chantiers de construction durant un quart de travail. / Chronic inhalation of respirable inorganic dusts containing crystalline silica is linked to occupational respiratory diseases such as lung cancer and silicosis. Several studies have documented the overexposure to respirable crystalline silica in construction workers, as this compound is found in several building materials and many operations can release fine suspended particles. Comprehensive quantitative exposure assessment in this industry is challenging due to the variety in tasks performed, materials used and environmental conditions between work sites, the mobile workforce and the temporary nature of construction sites. An occupational exposure database of silica exposure was compiled from the literature by a research group from the Université de Montréal and the Institut de recherche en santé et en sécurité du travail (IRSST) to address this issue. The exposure data contained in the database were separated on the basis of sampling strategies, which resulted in two separate – but complementary – analyses. The first analysis was restricted to samples collected to compare levels with an occupational exposure limit, in order to estimate work-shift respirable crystalline silica exposure by construction trade. The second analysis used measurements collected under a task-based sampling strategy in order to estimate the exposure levels associated with specific activities. Monte-Carlo simulation was used to recreate individual exposures from measurements reported as summary statistics. Modeling was performed using Tobit models within a multimodel inference framework, with construction trade, task, sampling duration, year and strategy, project type, construction sector, workspace and control methods as potential predictors. The dataset for the analysis by construction trade was comprised of 1346 exposure measurements and included 11 trade categories. The model containing all the variables explained 22% of the exposure variability and the sampling duration, year and strategy were identified as important predictors. Civil engineering and roadwork sites as well as new construction projects were associated with lower exposure levels, while the use of control methods reduced silica concentrations by 18% outdoors and 24% indoors. Predicted geometric means (GM) for year 1999 were the highest for drillers (0.214 mg/m3), underground workers (0.191 mg/m3), roofers (0.146 mg/m3) and cement grinders/finishers (0.125 mg/m3), based on a 8-hour shift. Heavy equipment operators (0.041 mg/m3) and foremen (0.047 mg/m3) had the lowest predicted GMs. 1566 task-based measurements, representing 27 task categories, were included in the activity-specific dataset. The proportion of variance explained by the model containing all the variables was 59%, and all the variables investigated had a strong influence on the exposure levels. Predictions were made based on the year 1998 and the median duration by task in the dataset. The largest predicted GMs were associated with the following operations: scabbling concrete (1.446 mg/m3), chipping with other tools (0.354 mg/m3), abrasive blasting (0.349 mg/m3) and tuck point grinding (0.200 mg/m3). Important reductions in exposure levels were found with the use of tool-integrated water sprays (-80%) and local exhaust ventilation (-64%). Important overexposure to the ACGIH Threshold Limit Value and the Québec exposure limit was found for all the trades investigated, indicating a long-term risk of silica-related occupational diseases. The results of the task-based analysis suggest that this sampling strategy provides a better characterization of the factors affecting exposure and the impacts of engineering dust control methods to control long-term exposure levels.

No description available.

O trato gastrointestinal (TGI) é a principal rota de exposição ao fluoreto (F) e o seu mais importante sítio de absorção. Acredita-se que a toxicidade do F comprometa a fisiologia do intestino, devido à relevante sintomatologia gastrointestinal relatada em consequência da exposição excessiva ao F. A função intestinal é controlada por uma complexa rede neuronal interligada e incorporada à parede deste órgão, denominada Sistema Nervoso Entérico (SNE). Embora os efeitos tóxicos do F sobre o Sistema Nervoso Central sejam descritos na literatura, não há estudos relacionados à sua toxicidade sobre o SNE. Neste estudo realizado em ratos, foi avaliado o efeito da exposição aguda ou crônica ao F, sobre a população geral de neurônios entéricos e sobre as subpopulações que expressam os principais neurotransmissores entéricos: Acetilcolina (ACh), Óxido Nítrico (NO), Peptídeo Vasoativo Intestinal (VIP), Peptídeo Relacionado ao Gene da Calcitonina (CGRP) e Substância P (SP). Os animais foram divididos em 5 grupos: 3 destinados à exposição crônica (0 ppm, 10 ppm ou 50 ppm de F na água de beber) e 2 à exposição aguda (0 ou 25 mgF/Kg por gavagem gástrica). Foram coletados os 3 segmentos do intestino delgado (duodeno, jejuno e íleo) e processados para a detecção da HuC/D, ChAT, nNOS, VIP, CGRP e SP, através de técnicas de imunofluorescência, no plexo mioentérico. Foram obtidas imagens para a realização da análise quantitativa dos neurônios da população geral (HuC/D) e nitrérgicos (imunorreativos à nNOS); e morfométrica dos neurônios imunorreativos à HuC/D ou nNOS; e das varicosidades imunorreativas à ChAT, VIP, CGRP ou SP. Amostras dos 3 segmentos intestinais foram preparadas e coradas em Hematoxilina e Eosina para análise histológica da morfologia básica. O segmento intestinal considerado mais afetado na análise morfométrica da população geral de neurônios, o duodeno, foi selecionado para a realização da análise proteômica, com o objetivo de oferecer o seu perfil proteico e determinar diferenças na expressão proteica em decorrência da exposição crônica ou aguda ao F. A análise da concentração de F no plasma sanguíneo foi realizada para a confirmação da exposição. Na análise quantitativa, o grupo de 50 ppm F, apresentou uma diminuição significativa na densidade da população geral de neurônios do jejuno e do íleo e na densidade dos neurônios imunorreativos à nNOS no duodeno e no jejuno. Quanto à análise morfométrica, a população geral e as subpopulações neuronais entéricas avaliadas apresentaram alterações morfológicas significativas, tanto após a exposição crônica quanto a aguda. Para a análise proteômica do duodeno, verificou-se que da associação de seus genes a um termo, e assim classificadas de acordo com diferentes processos biológicos. No caso do grupo da dose aguda, o processo biológico com a maior porcentagem de genes associados foi a geração de metabólitos precursores e energia (27% das proteínas); enquanto para os grupos de 10 e 50 ppm F foram o processo metabólico da piridina (41%) e a polimerização proteica (33%), respectivamente. / The gastrointestinal tract (GIT) is the main route of fluoride (F) exposure, and the most important site of its absorption. It is believed that F toxicity compromises the intestine physiology, due to the relevant gastrointestinal symptomatology reported in consequence to excessive exposure. The intestinal function is controlled by a complex neuronal net, which is interconnected and embedded in the wall of this organ, named Enteric Nervous System (ENS). Although the toxic effects of F on the Central Nervous system are described in the literature, there are no studies related to its toxicity on the ENS. Therefore, in this study performed in rats, the effects of chronic and acute F exposure were evaluated, on the general population of enteric neurons and on the subpopulations that express the main enteric neurotransmitters: Acetylcholine (Ach), Nitric Oxide (NO), Vasoactive Intestinal Peptide (VIP), Calcitonin gene related peptide (CGRP), and Substance P (SP). The animals were divided into 5 groups: 3 designed to the chronic exposure (0 ppm, 10 ppm ou 50 ppm de F in the drinking water) and 2 to the acute exposure (0 ou 25 mgF/Kg - gastric gavage). Three intestinal segments were collected (duodenum, jejunum, and ileum) and processed for the immunofluorescence techniques to detect HuC/D, ChAT, nNOS, VIP, CGRP and SP, on the myenteric plexus. Images were obtained for the quantitative analysis of the general population of neurons (HuC/D immunoreactive) and the nitrergic neurons (nNOS immunoreactive), for the morphometric analysis of the general population and nitrergic neurons and also for the immunoreactive varicosities to ChAT, VIP, CGRP or SP. Samples of the 3 intestinal segments were prepared and stained with hematoxylin and eosin for histological analysis of the basic morphology. Duodenum, the intestinal segment considered the most affected in the morphological analysis of the general population of neurons, was selected for the proteomic analysis, with the objective to offer the entire protein profile and to determine differences in the protein expression due to chronic or acute F exposure. Plasma F concentration was analyzed to confirm the exposure. In the quantitative analysis, the 50 ppm F group presented a significant decrease in the density of the general population of neurons in the jejunum and ileum, and in the density of the nitrergic neurons in the duodenum and jejunum. Regarding the morphometric analysis, the general population of neurons and all the neuronal subpopulations evaluated presented significant morphological alterations, for both exposures, chronic and acute. In the proteomic analysis of the duodenum, it was verified that both exposures caused alterations in the expression of intestinal proteins. These proteins identified with differential expression were distributed according the association of their genes to a specific term, and by this term classified in different biological process. In the group that received the acute dose the biological process with the highest percentage of associated genes was the generation of precursor metabolites and energy (27% of proteins), and for the 10 and 50 ppm F groups, they were pyridine nucleotide metabolic process (41%) and protein polymerization (33%), respectively.

En France, deux bases de données d’exposition professionnelle, COLCHIC et SCOLA, coexistent avec des objectifs différents (prévention et réglementation). Leur représentativité par rapport à la population générale est cependant inconnue, et fait l’objet de ce travail. Après avoir effectué une analyse descriptive comparative, l’étude de l’association entre les niveaux d’exposition et les éléments contextuels a été réalisée par modélisation statistique pour chaque agent, séparément pour COLCHIC et SCOLA, puis dans un jeu de données commun. La synthèse à travers les agents s’est faite par Méta analyse. COLCHIC et SCOLA contiennent respectivement 929 700 (670 agents chimiques) et 429 104 données (105). Trois forts prédicteurs « Durée de prélèvement », « Equipement de protection individuelle » et « Année » sont systématiquement associés aux niveaux dans les deux bases et 3 autres sont spécifiques à chacune d’elles. Avec des niveaux deux fois plus élevés dans COLCHIC comparés à SCOLA en 2007, leurs concentrations deviennent comparables entre 2012 et 2015. COLCHIC et SCOLA représentent une source importante d’informations. La prise en compte des descripteurs associés aux mesures et l’utilisation de méthodes prédictives permettront d’en améliorer l’interprétation / Two occupational exposure databases of occupational exposures to chemicals, COLCHIC and SCOLA, coexist in France with different objectives (prevention and compliance). Little is known about their representativeness of exposures in the general population. We explored to what extent COLCHIC and SCOLA adequately reflect occupational exposures in France. After performing a descriptive and comparative analysis, associations between exposure levels and ancillary information were explored for each agent, separately for COLCHIC and SCOLA and in a common dataset, using statistical modelling. Modelling results were synthesized across agents using Meta analysis. COLCHIC and SCOLA contain, respectively, 929 700 (670 chemicals) and 429 104 records (105). Three predictors "Sample Time", "Personal protective equipment" and "Year" are strongly associated with exposure levels across a large majority of chemicals in both databases, and 3 others are specific to each one. Exposure levels are in average twice higher in COLCHIC compared to SCOLA in 2007, but become comparable from 2012-2015. COLCHIC and SCOLA are an important source of information. Inclusion of descriptors associated with exposure levels in our study and the use of predictive methods should help to improve their interpretation.

La veille sanitaire dans le champ de la santé au travail est cruciale pour détecter l’apparition de nouveaux risques. Le réseau National de Vigilance et de Prévention des Pathologies Professionnelles (RNV3P), réseau national d’experts opérationnel depuis 2011, y participe activement. Pour cela, le RNV3P a déployé plusieurs méthodes pour détecter les nouveaux risques : émergence clinique et émergence statistique. La méthode des mesures de disproportion couramment utilisée dans le domaine de la pharmacovigilance a déjà été appliquée avec succès aux données du RNV3P. Néanmoins, une limite importante peut être soulevée. Les professionnels de santé déclarant les expositions qui leur semble liées à la pathologie déclarée, nous pouvons légitimement suspecter l'existence d'un biais de sélection de ces expositions : l'exposition la plus reconnue par le monde professionnel sera forcément déclarée. Pour tenter de maîtriser ce biais, nous avons proposé d’appliquer les matrices emploi / exposition (MEE) sur les données du RNV3P et d’examiner leur impact sur les mesures de disproportion. Dans un premier temps, nous avons testé la faisabilité de l’application des MEE au RNV3P et leur apport. Pour cela, 3 MEE issues du programme Matgéné ont été appliquées (benzène, poussières respirables de silice cristalline libre et solvants chlorés). Les données d’exposition rapportées respectivement par les experts et par la MEE ont été comparées en particulier pour des associations bien connues comme la silicose/silice ou les maladies hématopoïétiques/benzène, et pour des associations moins connues ou douteuses comme la sclérose systémique/silice et les maladies hématopoïétiques/solvants chlorés (trichloréthylène). Dans un second temps, nous avons appliqué les mesures de disproportion de type fréquentielle et bayésienne en comparant les résultats obtenus par les experts et les MEE pour trois nuisances : silice, trichloroéthylène et tétrachloroéthylène. Au final, les MEE permettent de rapporter plus d’expositions que les experts pour chaque nuisance testée et ce d’autant plus que l’association est peu connue. Cet apport d’information permet la génération de nouveaux signaux avec les mesures de disproportion qu’il est intéressant de discuter et d’explorer avec des experts / Health surveillance in the field of occupational health is crucial to detect the emergence of new risks The National Network of Vigilance and Prevention of Occupational Pathologies (RNV3P), a national network of experts operating since 2011, actively participates in. The RNV3P has deployed several methods to detect new risks: clinical emergence and statistical emergence. In the latter case, the disproportionate measures used in the field of pharmacovigilance have been successfully applied to RNV3P. Nevertheless, an important limitation can be raised. As health professionals report exposures associated with the declared pathology, we can legitimately suspect the existence of a selection bias: the most well known exposures of the professional community inevitably are most liable to be more frequently declared. To try to control this bias, we proposed to apply job / exposure matrices (JEM) on the data of the RNV3P and to examine their impact on the measures of disproportion. Initially, we tested the feasibility of applying MEE to the RNV3P data and their contribution. For this, 3 JEMs from the Matgéné program were applied (benzene, free crystalline silica breathing dusts and chlorinated solvents). The exposure data reported by the experts and the JEM were compared in particular for well-known associations such as silicosis / silica or hematopoietic / benzene diseases, and for less known or doubtful associations such as systemic sclerosis and hematopoietic diseases / chlorinated solvents (trichloroethylene). Secondly, we applied the frequency and Bayesian disproportion measures by comparing the results obtained for experts and JEM and for three nuisances: silica, trichloroethylene and tetrachloroethylene. In summary, MEE help to provide more exposure than the experts for each tested chemicals and especially if the association is little known. These new data allow the generation of new signals with the disproportion measures that it is interesting to discuss and explore with experts

Os efeitos tóxicos decorrentes da exposição ambiental e ocupacional ao benzeno são amplamente descritos na literatura. Seus produtos de biotransformação fenólicos, entre os quais os compostos hidroxilados como FE e hidroquinona HQ, são indutores importantes de efeitos citotóxicos e genotóxicos responsáveis pela toxicidade ao sistema imune. No entanto, a contribuição de cada metabólito e os mecanismos envolvidos não estão completamente esclarecidos. Desta forma, o presente trabalho teve por objetivo estudar a capacidade da resposta inflamatória em ratos expostos à HQ, ao FE, ou a ambos simultaneamente (HQ+FE). Para tanto, ratos Wistar machos foram expostos aos agentes químicos por período de tempo prolongado (doses diárias de 5 ou 10mg/kg; i.p.; com 5 doses/semana no período de 17 ou 23 dias). Animais controles receberam o veículo pela mesma via. As respostas inflamatórias foram induzidas 24 horas após a última dose administrada. Foram avaliadas a resposta inflamatória inespecífica, decorrente da instilação intranasal de LPS de Salmonella abortus e a resposta inflamatória específica em animais previamente sensibilizados e desafiados pela OVA. Na resposta inflamatória inespecífica, as exposições à HQ e à HQ+FE provocaram redução acentuada no influxo de leucócitos para o pulmão inflamado, pelo menor número de leucócitos no LBA e pela atividade enzimática da MPO reduzida no tecido pulmonar. O efeito não é dependente de modificações no número de leucócitos circulantes nem de alterações nas expressões de moléculas de adesão nos leucócitos circulantes (L-selectina e β2 integrina) e no endotélio pulmonar (ICAM-1 , VCAM-1 e PECAM-1) envolvidas na interação leucócito-endotélio. Na vigência de resposta inflamatória específica, as exposições à HQ, FE ou HQ+FE reduziram significativamente a migração de leucócitos para o LBA e para o tecido pulmonar. Da mesma forma que a RI induzida pelo LPS, não foram detectados alterações nos número de leucócitos circulantes e na expressão de moléculas de adesão. No entanto, os resultados obtidos em ensaios de anafilaxia passiva cutânea e reação anafilática in vitro mostraram que o efeito é dependente, pelo menos em parte, da menor concentração de imunoglobulinas anafiláticas circulantes e, consequentemente, da menor habilidade de desgranulação mastocitária. Em conjunto, os dados obtidos demonstram que as exposições à HQ, ao FE ou à HQ+FE prejudicam a migração de leucócitos para o foco de lesão na vigência de respostas inflamatórias de origem inata ou adquirida. / The toxic effects of the ambiental and occupational exposures to benzene is widely described in the literature. Phenolic hydroxylated compounds obtainded from its biotransformation, such as phenol (PHE) and hydroquinone (HQ), induce important of cytotoxic and genotoxic effects responsible for the immunotoxicity. However, the role of each metabolite and mechanisms of toxicity are unknown. Then, the present work aimed to study the inflammatory response in rats exposed to HQ, PHE, ar both simultaneously (HQ+PHE). Male Wistar rats were exposed to they chemical agents for extended period of time (5 or 10mg/kg/day; ip.; during 17 or 23 days; 2 days intervals each 5 doses). Control animais received the vehicle. Inflammatory reactions were induced 24 hours after the last dose by they intranasal instillation of lipopolysaccharide of Salmonella aborlus (non-specific response) or by inhalation of ovalbumin in animals previously sensitized to the same antigen (specific response, produced by anaphylactic immunoglobulins). Animais exposed to HQ or HQ/PHE presented reduced n,3umbers of PMN and MN cells in the bronchoalveolar lavage fluid (BALF) and lesser myeloperoxidase (MPO) activity in the pulmonary tissue. The reduced influx of leukocytes is not dependent oh alterations on the numbers of circulating leukocytes either adhesion molecules expressions on leukocytes (L-selectin or β2 integrin) and on lung microvascular endothelium (ICAM-1, V CAM-1 or PECAM-1) responsible for leukocyte-endothelial interactions. On the other hand, rats exposed to ali schedules of exposures presented reduced numbers of leukocytes in the BALF and lesser MPO activity in the pulmonary tissue after an antigenic stimulus. As shown to inflammation induced by LPS, no alterations on circulating leukocyte numbers and adhesion molecules expressions were detected. However, the impaired leukocyte migration to the inflamed lung may be dependent, at last in part, on reduced levels of circulating anaphylactic antibodies, as detected by passive cutaneous anaphylaxis test, and by consequent reduced ability of mast cell desgranulation, evidenced by in vitro trachea contraction. Together, our data show that HQ and PHE exposure differently affect the specific and non-specific ínflammatory reactions.

Notre avons étudié le rôle de la profession et des expositions professionnelles aux solvants pétroliers et chlorés dans deux études épidémiologiques sur les facteurs de risque professionnels des cancers du sein chez l'homme et chez la femme. A l’inverse du cancer du sein féminin (50000 nouveaux cas par an en France), le cancer du sein chez l’homme est un cancer rare (<500 cas par an). Il constitue cependant un modèle intéressant pour l’étude des expositions professionnelles qui sont généralement plus élevées chez l’homme que chez la femme. Chez les hommes, nos résultats suggèrent un risque de cancer augmenté chez les mécaniciens de véhicules à moteur et un rôle cancérogène des solvants tels que le benzène et le trichloréthylène. Chez les femmes, malgré des risques élevés mais non significatifs dans plusieurs professions, aucune association avec les expositions aux solvants n’était mise en évidence pour les faibles niveaux d’exposition observés. / We have investigated the role of the occupation and of occupational exposures to petroleum and chlorinated solvents using the data of two epidemiological studies on occupational risk factors of breast cancers in men and in women. Unlike female breast cancer (50,000 new cases per year inFrance), cancer of male breast cancer is a rare disease (<500 cases per year). It should be seen as an interesting model for studying the effects of occupational exposures in the disease as these exposure are generally much higher in men than in women. For men, our results suggest that the risk of cancer is increased among motor vehicle mechanics and support the hypothesis of a carcinogenic effect of solvents such as benzene and trichloroethylene in disease occurrence. In women, several occupations were at increased risk of breast cancer, but results were generally not statistically significant. No association of female breast cancer incidence with exposure to solvents was observed.