Outputs of dose–response assessments can be used as benchmarks that help to identify the need for risk management measures to reduce population health risks associated with exposure to chemicals. Various approaches can be used to facilitate the incorporation of chemical- or scenario-specific data into dose–response analyses, as a means of replacing or influencing default assumptions and extrapolations. The goal of the first part of this thesis was to examine the evolution of approaches to the incorporation of chemical- and scenario-specific data in dose–response assessments in regulatory settings, and identify contextual factors that serve as barriers and facilitators to the use of approaches. A main focus of the investigation was on physiological modelling, which is the most commonly-used category of approaches enabling extrapolations that depart from default assumptions. Evaluations of the dose–response applications of physiological modelling in the peer-reviewed scientific literature and in regulatory reports were conducted. Similarities between the scientific literature databases and regulatory reports were observed with respect to the evolution of physiological modelling in dose–response assessments, notably related to the timing, quantity, and annual frequency of publications. These similarities indicate that a factor in the low dose–response application of physiological modelling, relative to the overall production of physiological models, is an absence of data. However, variability in adoption of physiological modelling in regulatory dose–response assessments was observed among—and even within—organizations faced with the same data, indicating that other factors influence regulatory uptake of physiological modelling. Analysis of a survey indicated that factors acting as barriers or facilitators to regulatory risk assessors’ incorporation of increasingly data-informed approaches originated in both external and internal contexts. The external context was composed of the regulatory environment, domestic and international alignment, availability of external expertise, background of peer reviewers and stakeholders, availability and accessibility of software and tools, and chemical-dependent factors. The internal context was influenced by problem formulation, time and financial resources, organizational and management support, and training. A conceptual framework demonstrating how these factors impact a risk assessor’s ability to incorporate chemical- and scenario-specific data in dose–response analysis was developed, and subsequently used to provide recommendations on actions that could be taken to increase regulatory adoption of increasingly data-informed approaches. The second part of the thesis focused on the development of a knowledge translation tool designed to assist risk managers in the evaluation of dose–response analyses. The tool was focused on occupational exposure limits (OELs), and provides a guide to occupational hygienists in evaluating the relevance and reliability of individual OELs. When occupational hygienists are faced with multiple varying OELs for a chemical of interest, these evaluations can support the selection of the most appropriate OEL for a given situation. The usefulness of the tool was demonstrated for the selection of OELs for an OEL-rich compound (n-hexane), an OEL-poor compound (methamphetamine), and one additional compound (manganese). Such a tool can improve occupational hygienists’ understanding of the basis of OELs and the levels of protection afforded by each, which can contribute to more informed risk management decisions.

L'infection congénitale par le cytomégalovirus (CMV) est l'infection congénitale la plus courante, survenant chez 0,2 à 2,0 % des naissances vivantes. Elle représente la principale cause non génétique de surdité neurosensorielle chez les nourrissons. Cette infection entraîne des séquelles neurodéveloppementales permanentes telles que des problèmes de vision, un retard cognitif et, dans certains cas, elle peut même entraîner la mort. Avoir une meilleure compréhension des caractéristiques épidémiologiques de l'infection maternelle par le CMV peut contribuer à améliorer notre compréhension de la transmission de ce virus au fœtus et, par conséquent, à prévenir l'infection congénitale. Cette thèse vise à étudier les aspects épidémiologiques de l'infection maternelle par le CMV et de l'exposition professionnelle au CMV. Le premier objectif consiste à estimer la séroprévalence, l'incidence et les facteurs de risque de l'infection maternelle à CMV pendant la grossesse. Le deuxième objectif examine l'association entre l'infection maternelle à CMV et certaines complications de la grossesse, telles que la prééclampsie et l'accouchement prématuré. Le troisième objectif est une revue systématique et une méta-analyse visant à déterminer la prévalence, l'incidence de l'infection primaire, les risques relatifs et les facteurs de risque au sein de deux groupes exposés professionnellement au CMV, à savoir les travailleurs en service de garde et le personnel de santé. Les données de deux importantes cohortes au Québec, comprenant un total de 6048 participantes (Grossesse en santé et 3D), ainsi que leurs échantillons biologiques, ont été utilisées pour atteindre les objectifs 1 et 2. Dans le cadre de l'objectif 3, une recherche bibliographique a été réalisée en consultant six bases de données électroniques (PubMed [NLM], Ovid MEDLINE, Ovid All EBM Reviews, Ovid Embase, ISI Web of Science et EBSCO CINAHL Complete). Les résultats de l'objectif 1 (article 1), basés sur les données d'une des deux cohortes, révèlent une séroprévalence de 23,4 % (IC à 95 %, 22,1-24,7 %) chez les femmes enceintes, ainsi qu'une incidence d'infection primaire de 1,8 pour 100 années-personnes pendant la grossesse (IC à 95 %, 1,2-2,6). Les facteurs de risque associés à la séropositivité maternelle sont la multiparité (avoir un ou plusieurs enfants), une ethnie autre que caucasienne et un lieu de naissance autre que le Canada et les États-Unis. Les résultats de l'objectif 2 (article 2) ont révélé deux associations importantes : (1) une association entre la séropositivité maternelle au CMV et la prééclampsie, et (2) une association entre la séropositivité maternelle au CMV et l'accouchement prématuré. L'analyse de médiation, en prenant en compte la prééclampsie comme facteur médiateur de l'association entre l'infection maternelle au CMV et l'accouchement prématuré, a montré que la quasi-totalité (96,8 %) de l'effet total de la séropositivité maternelle au CMV agit directement sur l'accouchement prématuré, sans passer par la prééclampsie. La revue systématique et méta-analyse, qui correspond à l'objectif 3 (article 3), souligne l'importance de l'exposition professionnelle au CMV. Dans le groupe des travailleurs en service de garde, la séroprévalence du CMV et l'incidence de l'infection primaire pour 100 personnes-années sont élevées, atteignant respectivement 59,3 % (IC à 95 % : 49,8-68,6) et 7,4 (IC à 95 % : 3,9-11,8). De même, dans le groupe du personnel de santé, ces valeurs s'élèvent à 49,5 % (IC à 95 % : 40,3-58,7) et 3,1 (IC à 95 % : 1,3-5,6) respectivement. La séropositivité au CMV et l'infection primaire sont significativement plus fréquentes chez les travailleurs en service de garde par rapport aux groupes témoins sans exposition professionnelle, avec un RC (Rapport des cotes) de 1,6 (IC à 95 % : 1,2-2,3) et un RR (Rapport des Risques) de 3,4 (IC à 95 % : 1,3-8,8) respectivement. Cependant, aucune différence significative n'a été observée chez le personnel de santé (RC : 1,3 [IC à 95 % : 0,6-2,7] et RR : 0,9 [IC à 95 % : 0,6-1,2]). Dans les deux groupes, la séropositivité au CMV était associée à la multiparité, l'état civil, l'ethnicité et l'âge. En conclusion, cette étude démontre que la séroprévalence du CMV chez les femmes enceintes varie. La parité, l'ethnicité, le lieu de naissance et l'exposition professionnelle sont des facteurs à prendre en compte lors de l'élaboration de mesures préventives contre l'infection maternelle par le CMV. Les résultats de l'article 2 mettent en évidence que la séropositivité maternelle au CMV pourrait être un facteur de risque de prééclampsie et d'accouchement prématuré. Mots clés : cytomégalovirus, prévalence, incidence, séroconversion, grossesse, sérologie, prééclampsie, accouchement prématuré, exposition professionnelle, travailleur en service de garde, garderie, personnel de santé. / Cytomegalovirus infection is the most common congenital infection occurring in 0.2% to 2.0% of all live births. Congenital CMV infection is the most common non-genetic cause of sensorineural hearing loss. It results in permanent neurodevelopmental sequelae such as visual impairment, cognitive delay and in some cases, death. Knowing the epidemiological characteristics of maternal CMV infection could contribute to improve the understanding of the transmission of this virus to the fetus, and then, contribute to the prevention of congenital infection. The present thesis aims to study some epidemiological aspects of maternal CMV infection and occupational exposure to CMV. The first objective sought to estimate the seroprevalence, incidence, and risk factors of CMV infection during pregnancy. The second objective studied the association between maternal CMV infection and some adverse pregnancy outcomes, including preeclampsia and preterm delivery. The third objective was a systematic review and meta-analysis to determine the prevalence, incidence of primary infection, relative risks, and risk factors in the two groups occupationally exposed to CMV, namely childcare workers and healthcare workers. Data from two large Quebec cohorts with 6048 women (“Grossesse en santé” and “3D” cohorts), and their biobanks, were used to address objectives 1 and 2. For objective 3, a literature search was conducted in 6 electronic databases along with a meta-analysis (PubMed (NLM), Ovid MEDLINE, Ovid All EBM Reviews, Ovid Embase, ISI Web of Science, et EBSCO CINAHL complete). The results for objective 1 (article 1) on the data of one of the two cohorts show a seroprevalence of 23,4% among pregnant women (95% CI, 22.1–24.7%), an incidence of primary infection of 1,8 per 100 person-years during pregnancy (95% CI, 1.2–2.6). During the 5 years of the study, seroprevalence was stable and no seasonality was observed. Risk factors associated with maternal seropositivity were multiparity, i.e., having one or more children, non-Caucasian ethnicity, and place of birth other than Canada and the United States. The results for objective 2 (article 2) highlighted on the one hand the association between maternal CMV seropositivity and preterm birth, and on the other hand the association between maternal CMV seropositivity and preeclampsia. The mediation analysis considering preeclampsia as a mediating factor of the association between maternal CMV infection and preterm delivery showed that almost all the total effect of maternal CMV seropositivity i.e., 96,8%, acts directly on preterm delivery without passing through preeclampsia. The systematic review and meta-analysis (objective 3) noted the importance of occupational exposure to CMV. CMV seroprevalence and incidence of primary infection per 100 person-years remained high in the childcare worker group (59.3% [95% CI: 49.8-68.6] and 7.4 [95% CI: 3.9-11.8], respectively) and the healthcare worker group (49.5% [95% CI: 40.3-58.7] and 3.1 [95% CI: 1.3-5.6], respectively). CMV seropositivity and primary infection are significantly more prevalent among childcare workers compared to the comparison groups without occupational exposure. The Odds ratio (OR) for this difference is 1.6 (95% CI: 1.2-2.3), with a risk ratio (RR) of 3.4 (95% CI: 1.3-8.8). However, these differences are not observed in healthcare workers, where the OR is 1.3 (95% CI: 0.6-2.7) and the RR is 0.9 (95% CI: 0.6-1.2). In both groups, CMV seropositivity shows an association with factors such as multiparity, civil status, ethnicity, and age. In conclusion, this thesis shows that maternal CMV seroprevalence is variable. Parity, ethnicity, place of birth and occupational exposure would be the identified risk factors to consider when defining preventive measures for maternal CMV infection. The results of article 2 highlighted that maternal CMV seropositivity could be a risk factor for preeclampsia and preterm delivery. Keywords: cytomegalovirus, prevalence, incidence, seroconversion, pregnancy, serology, preeclampsia, preterm birth, occupational exposure, daycare worker, daycare center, healthcare workers.

Le captane est un fongicide utilisé pour prévenir l’apparition de champignons notamment dans la culture de petits fruits. Les travailleurs agricoles québécois cultivant les petits fruits sont susceptibles d’être exposés au captane dans leur milieu professionnel. La biosurveillance de l’exposition au captane couplée à la modélisation toxicocinétique permet une évaluation du risque de ces travailleurs agricoles. Ainsi, cette étude avait pour objectif de documenter la pertinence de l’utilisation des profils temporels de biomarqueurs d’exposition au captane dans l’urine pour évaluer l’exposition individuelle de travailleurs agricoles. À partir des profils d’excrétion urinaire de l’acide 2-thioxothiazolidine-4-carboxylique (TTCA), des informations auto-rapportées durant la période de suivi et d’un modèle toxicocinétique, les doses absorbées de captane pour chaque travailleur ont été estimées et les principales voies d’exposition ont été déterminées. Parmi les six travailleurs ayant appliqué du captane, le TTCA a été détecté dans leurs urines majoritairement après 20 heures post-exposition (moyenne de 30,0 ± 36,1 μmol/mol de créatinine entre 0 - 24 heures). La détection de TTCA semble donc être due à une exposition secondaire à l’application provenant de tâches telles que le nettoyage de l’équipement ou un travail dans les champs traités dans la journée suivant l’application. La simulation des profils temporels des travailleurs à l’aide de la modélisation toxicocinétique suggère une absorption majoritairement par voie orale du captane. Ceci serait compatible avec un comportement main-bouche suite à un contact avec des surfaces contaminées. Selon la modélisation des doses absorbées estimées de captane, la probabilité de dépassement de la dose journalière admissible (DJA) ou Acceptable daily intake (ADI en anglais) est inférieure à 1 (DJA fixée à 0,1 mg/kg pc/jour). L’utilisation de ce fongicide à court terme ne semble pas poser de risque appréciable pour la santé chez la majorité de ces travailleurs, sur la base de la comparaison avec la DJA (ADI). / Captan is a fungicide used to prevent the appearance of fungi especially in the cultivation of small fruit. Agricultural workers in Quebec who grow small fruit are likely to be occupationally exposed to captan. Biomonitoring of captan coupled with toxicokinetic modelling enables risk assessment of these field workers. The aim of this study was to document the relevance of using temporal profiles of biomarkers of exposure to captan in urine to assess the individual exposure of agricultural field workers. Using urinary excretion profiles for 2-thioxothiazolidine-4-carboxilic acid (TTCA), self-reported information during the follow-up period and a toxicokinetic model, the absorbed doses of captan for each worker were estimated. The main routes of exposure were also determined. Among the six agricultural field workers who applied captan, TTCA was detected in their urine mainly after 20 hours post-exposure (mean of 30.0 ± 36.1 μmol/mol creatinine between 0 and 24 hours). The detection of TTCA seems to be caused by secondary exposure to the application arising from tasks such as cleaning equipment or working in the treated fields on the day following application. Simulation of the temporal profiles of workers using toxicokinetic modelling suggests a predominantly oral absorption to captan. This would be compatible with hand-to-mouth behaviour following contact with contaminated surfaces. Based on modelling of estimated absorbed doses of captan, the probability of exceeding the acceptable daily intake (ADI) is less than 1 (ADI set at 0.1 mg/kg bw/day). Short-term use of this fungicide does not appear to pose any appreciable health risk for the majority of these workers based on comparison with the ADI.

BACKGROUND: Many women of reproductive age are employed in industries involving exposure to organic solvents. Animal toxicological studies and human case reports demonstrate that exposure to organic solvents can cause neuropsychological deficits in exposed offspring; however, there is limited data from prospective controlled human studies. OBJECTIVE: To compare neuropsychological functioning between children whose mothers were occupationally exposed to organic solvents during pregnancy with a non-exposed matched comparison group. METHODS: Participants were 48 women who had previously contacted the Motherisk Program in Toronto, Canada during pregnancy regarding occupational exposure to organic solvents and a matched comparison group of women with no known exposure to teratogens during pregnancy. Children (18 months to 8 years 11 months at time of study) were compared in areas of cognitive, language, motor, and behavioral functioning. RESULTS: Children whose mothers were exposed to organic solvents during pregnancy displayed a lower level of functioning when compared with their matched peers in areas of cognitive, language, motor, and behavioral domains. Although the scores on measures of behavioral functioning were not in the clinical range, the mothers of exposed children reported more challenging behavioral problems. In order to determine whether exposure predicted neuropsychological outcomes above and beyond maternal intellectual functioning, hierarchical regressions were run with maternal IQ and maternal education at Step 1and exposure status added at Step 2. In utero exposure to organic solvents predicted lower sores on global measures of Verbal IQ, receptive and expressive language scales above and beyond maternal intellectual functioning. Factors associated with higher levels of exposure (detecting odor, longer duration and total number of toxicity symptoms) was associated with poorer outcome on behavioral and motor functioning tests. CONCLUSION: Despite the fact that the exposed mothers experienced minimal symptoms of toxicity, detrimental effects were still evident in their offspring. Current safety standards for exposure were designed for adults and need to be reevaluated. Further studies addressing exposure to specific organic solvents, dose, and gestational timing of exposure are warranted.

BACKGROUND: Many women of reproductive age are employed in industries involving exposure to organic solvents. Animal toxicological studies and human case reports demonstrate that exposure to organic solvents can cause neuropsychological deficits in exposed offspring; however, there is limited data from prospective controlled human studies. OBJECTIVE: To compare neuropsychological functioning between children whose mothers were occupationally exposed to organic solvents during pregnancy with a non-exposed matched comparison group. METHODS: Participants were 48 women who had previously contacted the Motherisk Program in Toronto, Canada during pregnancy regarding occupational exposure to organic solvents and a matched comparison group of women with no known exposure to teratogens during pregnancy. Children (18 months to 8 years 11 months at time of study) were compared in areas of cognitive, language, motor, and behavioral functioning. RESULTS: Children whose mothers were exposed to organic solvents during pregnancy displayed a lower level of functioning when compared with their matched peers in areas of cognitive, language, motor, and behavioral domains. Although the scores on measures of behavioral functioning were not in the clinical range, the mothers of exposed children reported more challenging behavioral problems. In order to determine whether exposure predicted neuropsychological outcomes above and beyond maternal intellectual functioning, hierarchical regressions were run with maternal IQ and maternal education at Step 1and exposure status added at Step 2. In utero exposure to organic solvents predicted lower sores on global measures of Verbal IQ, receptive and expressive language scales above and beyond maternal intellectual functioning. Factors associated with higher levels of exposure (detecting odor, longer duration and total number of toxicity symptoms) was associated with poorer outcome on behavioral and motor functioning tests. CONCLUSION: Despite the fact that the exposed mothers experienced minimal symptoms of toxicity, detrimental effects were still evident in their offspring. Current safety standards for exposure were designed for adults and need to be reevaluated. Further studies addressing exposure to specific organic solvents, dose, and gestational timing of exposure are warranted.

Standard precautions are a set of guidelines that aim to protect health care workers from infections from blood, body fluids, secretions, excretions except sweat, non-intact skin, and mucous membranes while providing care to patients. However, compliance to the standard precautions is often low in low-income countries in spite of the greater risk of infection. This study examined the knowledge and practice of standard precautions among health care workers in public secondary health facilities in Abuja, the Federal Capital Territory of Nigeria. A quantitative descriptive survey was conducted with 83 doctors and 194 nurses using a structured questionnaire. Findings show suboptimal knowledge and practice of the standard precautions among the health care workers. Knowledge of post-exposure prophylaxis for HIV was low as well as hepatitis B immunization among the respondents. A lack or irregular supply of essential materials, such as personal protective equipment, was the main reason the respondents did not comply to the precautions. This report recommends the development and implementation of a comprehensive infection prevention and control program in health facilities in order to ensure compliance to the standard precautions by health care workers. / Public Health / M.A. (Public Health)

La banque de données IMIS (Integrated Management Information System) de l’agence américaine OSHA (Occupational Safety and Health Administration) contient l’ensemble des mesures de l’exposition effectuées par les inspecteurs d’OSHA chargés de vérifier la conformité aux valeurs limites d’exposition. Les résultats analytiques correspondant aux prélèvements effectués par les inspecteurs sont également disponibles dans la banque CEHD (Chemical Exposure Health Data). Ces deux banques représentent une source d’information potentielle majeure sur les conditions d’exposition aux substances chimiques en Amérique du Nord. Cependant, leur représentativité par rapport à la distribution réelle des niveaux d’exposition retrouvés dans les milieux de travail est largement inconnue. L’objectif de cette thèse est d’établir dans quelle mesure les données de contamination de l'air recueillies par l’agence fédérale américaine OSHA peuvent être utilisées pour l’estimation des expositions professionnelles en Amérique du Nord. Les analyses ont porté sur 511 047 et 588 818 mesures d’exposition contenues dans les banques IMIS et CEHD respectivement, pour la période 1979-2011. Premièrement, des modèles additifs généralisés ont été utilisés pour étudier l’association entre les variables reflétant les caractéristiques des établissements visités et des inspections et les niveaux d’exposition pour 77 agents chimiques (90% du contenu d’IMIS). Dans un second temps, une approche de régression de Poisson modifiée a été utilisée pour étudier les facteurs déterminants l’enregistrement ou non des échantillons de CEHD dans la banque IMIS en jumelant les deux banques pour 78 agents chimiques. Finalement, des modèles CART (Classification And Regression Tree) ont été développés permettant de prédire, parmi les résultats non détectés de la banque IMIS, lesquels correspondent à des mesures courte durée ou des moyennes pondérées sur 8 heures (VEMP-8h) en se basant sur les variables communes aux banques IMIS et CEHD. Dans la première analyse, les modèles statistiques ont montré que les niveaux d’exposition étaient plus susceptibles de dépasser la TLV (threshold limit value) pour les mesures effectuées sous un régime OSHA fédéral par rapport au régime OSHA d’État (rapport de cote (RC) de 1,22 à travers les agents). La probabilité de dépasser la TLV augmentait avec le nombre total des amendes reçues par un établissement, indépendamment de la nature des infractions (RC de 1,54 à travers les agents entre les catégories « élevée » et « aucune »). Elle était également plus élevée pour les visites de suivi que pour les visites planifiées (RC de 1,61). Dans la deuxième analyse, la comparaison des banques IMIS et CEHD a montré un taux d’enregistrement global de 38% des données CEHD dans IMIS. Les résultats non détectés (particulièrement ceux mesurés sur un panel d’agents – p. ex. panel de métaux) étaient moins susceptibles d’être enregistrés dans IMIS (risque relatif ~0,6). Finalement, les modèles CART ont prédit plus précisément le type de prélèvement (courte durée, VEMP-8h) pour les résultats non détectés dans IMIS que des méthodes simples d’attribution (p. ex. attribution du type le plus fréquent parmi les résultats détectés) pour les agents les plus pertinents (c.-à-d. ceux ayant une proportion substantielle de mesures ND, courte durée et VEMP-8h). Nos résultats ont montré la présence de plusieurs mécanismes de sélection dans le processus conduisant à l’enregistrement d’une mesure d’exposition dans IMIS, ce qui suggère l’existence de différences systématiques entre les niveaux rapportés dans les banques OSHA et les niveaux moyens d’exposition dans la population de travailleurs. La prise en compte des informations contextuelles aux mesures et l’emploi de méthodes prédictives peuvent aider à pallier partiellement ces biais et ainsi raffiner les portraits d’exposition établis à partir des données d’OSHA. / The Integrated Management Information System (IMIS) contains exposure measurements taken by the U.S. Occupational Safety and Health Administration (OSHA) inspectors to verify compliance with permissible exposure limits. Supplementary data containing analytical results of the field samples are available in the Chemical Exposure Health Database (CEHD). These databanks represent a major potential source of information on exposure conditions in North American workplaces. However, the degree to which they represent the actual distribution of the exposure levels found in the workplace is largely unknown.The objective of this thesis is to examine the extent to which exposure data collected by OSHA can be used for estimating occupational exposure in North America. Analyses focused on 511 047 and 588 818 exposure measurements in IMIS and CEHD respectively, for the period 1979-2011. First, generalized additive models were used to explore associations between exposure levels in IMIS and ancillary variables reflecting characteristics of establishments and inspections for 77 chemical agents (90% of IMIS content). Second, modified Poisson regression was used to identify determinants of recording or not of CEHD samples in IMIS by linking both databanks for 78 agents. Finally, Classification And Regression Tree (CART) models were applied to predict which non-detected (ND) results stored in IMIS are 8-hour time-weighted average (TWA) or short-term samples, based on common variables available in IMIS and CEHD databanks. In the first analysis, statistical modelling showed that measurements collected under federal OSHA plans were more likely to have a sample result exceed the TLV compared to measurements collected under state OSHA plans (odds ratio (OR) of 1,22 across agents). An increase in the total amount of penalty assessed to a company was associated with higher odds of having a sample result exceed the TLV (OR of 1,54 across agents for « high » vs. « none »). Follow-up inspections were more likely to have a sample result exceed the TLV compared to planned inspections (OR of 1,61 across agents). In the second analysis, linkage between CEHD and IMIS showed a 38% overall proportion of CEHD samples recorded into IMIS. Non-detects (especially ND records corresponding to analytical panels – e.g. panel of metals) were less likely to be recorded in IMIS (relative risk ~0,6). Finally, CART models predicted more accurately which IMIS ND results were TWA or short-term samples compared to simple methods of assignment (e.g. assignment of the most frequent category from detected values) for the most relevant agents (i.e. with high proportions of ND, short-term, and TWA results). Our findings showed the presence of several selection mechanisms in the process leading up to the recording of a sample in IMIS, which suggest systematic differences exist between OSHA measurements and actual occupational exposures in the general U.S. working population. These biases can be partially controlled by using ancillary information on exposure measurements together with predictive methods, thus helping to draw more accurate portraits of exposure levels from OSHA data.

Introduction : L’asthme professionnel (AP) est diagnostiqué au Québec avec le test de provocation bronchique spécifique (TPS). Le TPS consiste à exposer le patient à un agent causal suspecté en vue de provoquer une réaction asthmatique. Un TPS négatif est possible quand un agent causal a été omis de l’histoire professionnelle du patient. L’évaluation des expositions professionnelles par une expertise en hygiène en santé du travail est considérée comme une méthode précise, lorsque des données de mesure ne sont pas disponibles. Cependant, l'apport de cette méthode dans le diagnostic de l’AP n'a jamais été examiné dans un contexte clinique. Objectifs : Déterminer l'apport de l'évaluation des expositions professionnelles par une expertise en hygiène du travail dans l'investigation de l'AP. Comparer les expositions professionnelles détectées par un clinicien et par un hygiéniste chez 1) des sujets avec de l’AP prouvé par des TPS positifs, 2) chez des sujets avec des TPS négatifs. Méthodes : Une analyse des expositions potentielles par le clinicien a précédé la réalisation du TPS. Une évaluation des expositions professionnelles a été réalisée par un hygiéniste. L’hygiéniste n’avait pas connaissance du diagnostic du patient. Résultats : 120 sujets (TPS positifs : 67 négatifs :53) ont été enrôlés dans l’étude. L’hygiéniste a identifié l’agent causal dans la très grande majorité des TPS positifs. Dans 33 TPS négatifs, l’hygiéniste a détecté des agents sensibilisants non identifiés par le médecin. Conclusion : L’évaluation des expositions professionnelles par une expertise en hygiène du travail est une méthode pouvant compléter l'évaluation clinique pour la détection d’agents sensibilisants associés à l’AP. L’inclusion de cette approche dans l’évaluation clinique de l’AP aurait comme effet de réduire la survenance d’un diagnostic erroné. / Introduction: Occupational asthma (OA) is diagnosed in the province of Quebec with the specific inhalation challenge (SIC) test. The SIC test consists of exposing the patient to a suspected causal agent in order to induce an asthmatic reaction. When a causal agent has been omitted from the occupational history, the SIC test can be negative. An expert assessment of occupational exposures by an occupational hygienist is considered an accurate method when quantitative measurements are not available. However, its contribution has never been evaluated in the diagnosis of OA. Objective: Evaluate the contribution of an occupational exposure assessment by an expert industrial hygienist to the diagnosis of OA. Compare the occupational exposures detected by an occupational hygienist and a clinician in: 1) OA subjects with a positive SIC, 2) Subjects with a negative SIC. Methods: The clinician assessed the workplace exposures during a routine clinical evaluation preceding the performance of the SIC. An expert assessment of work histories was performed by an occupational hygienist blind to the diagnostic status of the patient. Results: 120 subjects (Positive SIC: 67 Negative SIC: 53) were enrolled in this study. The occupational hygienist detected the causal agent in almost all cases of OA. In 33 negative SIC, the occupational hygienist identified sensitizing agents which were not detected by the clinician. Conclusions: An expert assessment of occupational exposures by an occupational hygienist is a method which could complement the clinical assessment for the detection of sensitizing agents associated with OA. This method could be included in the clinical evaluation of OA in order to decrease the probability of misdiagnosis.

Objective: To determine if paternal preconception exposure to ionizing radiation through uranium mining increases the risk of congenital anomaly (CA) in offspring. Methods: A population-based matched case-control study was conducted. Cases were infants with CAs recorded in the Canadian Congenital Anomalies Surveillance System and born alive in Ontario 1979-86 (ICD-9 codes 740-759); controls were liveborn infants without CAs identified from Ontario birth certificates and individually matched to cases (case-control file {CCF}). Exposed fathers were identified through the linkage of the CCF to the Mining Master File or the National Dose Registry file, which include those who worked in Ontario uranium mines 1952-1986. For men who linked with a case or control child, radon, gamma and total gonadal doses were estimated for three preconception periods: entire, 3-months and 6-months. Odds ratios were estimated using conditional logistic regression. Results: Linkage of 28,991 uranium miners and 40,482 case-control pairs of fathers and offspring in the CCF identified 431 discordant pairs. There was no evidence of increased risk of a child having a CA if the father was ever a uranium miner before conception of the child (OR=0.89, 95% CI=0.74–1.08). Since gamma radiation (especially during the 6-month preconception period) is more biologically relevant to gonads than radon, further analyses were performed on 117 discordant pairs where data on gamma exposures were available. When ever/never miner, exposed to gamma (yes/no), and gamma dose-response variables were all in the model, there was no ever/never miner effect (OR=1.20, 95% CI=0.85–1.69, p-value=0.30), an inverse association for exposure to gamma (OR=0.42, 95% CI=0.25–0.71, p-value=0.001), but most importantly, there was no statistically significant dose-response relationship between gamma dose during the 6-month preconception period and all CAs (OR=1.15 per loge {mSv+0.01}, 95% CI=0.83–1.59, p-value=0.40). Similarly, no dose-response relationship was observed for exposure to gamma radiation in the 3-month preconception period, or for radon or total gonadal radiation in the 3- or 6-month preconception periods. Conclusion: There was no increased risk of a CA among liveborn children of Ontario uranium miners who were exposed to radon, gamma or total radiation during the 3- or 6-month periods before conception.

Objective: To determine if paternal preconception exposure to ionizing radiation through uranium mining increases the risk of congenital anomaly (CA) in offspring. Methods: A population-based matched case-control study was conducted. Cases were infants with CAs recorded in the Canadian Congenital Anomalies Surveillance System and born alive in Ontario 1979-86 (ICD-9 codes 740-759); controls were liveborn infants without CAs identified from Ontario birth certificates and individually matched to cases (case-control file {CCF}). Exposed fathers were identified through the linkage of the CCF to the Mining Master File or the National Dose Registry file, which include those who worked in Ontario uranium mines 1952-1986. For men who linked with a case or control child, radon, gamma and total gonadal doses were estimated for three preconception periods: entire, 3-months and 6-months. Odds ratios were estimated using conditional logistic regression. Results: Linkage of 28,991 uranium miners and 40,482 case-control pairs of fathers and offspring in the CCF identified 431 discordant pairs. There was no evidence of increased risk of a child having a CA if the father was ever a uranium miner before conception of the child (OR=0.89, 95% CI=0.74–1.08). Since gamma radiation (especially during the 6-month preconception period) is more biologically relevant to gonads than radon, further analyses were performed on 117 discordant pairs where data on gamma exposures were available. When ever/never miner, exposed to gamma (yes/no), and gamma dose-response variables were all in the model, there was no ever/never miner effect (OR=1.20, 95% CI=0.85–1.69, p-value=0.30), an inverse association for exposure to gamma (OR=0.42, 95% CI=0.25–0.71, p-value=0.001), but most importantly, there was no statistically significant dose-response relationship between gamma dose during the 6-month preconception period and all CAs (OR=1.15 per loge {mSv+0.01}, 95% CI=0.83–1.59, p-value=0.40). Similarly, no dose-response relationship was observed for exposure to gamma radiation in the 3-month preconception period, or for radon or total gonadal radiation in the 3- or 6-month preconception periods. Conclusion: There was no increased risk of a CA among liveborn children of Ontario uranium miners who were exposed to radon, gamma or total radiation during the 3- or 6-month periods before conception.