Prenatal exposure to common plasticizers: a longitudinal study on phthalates, brain volumetric measures, and IQ in youth.

Exposure to phthalates, used as plasticizers and solvents in consumer products, is ubiquitous. Despite growing concerns regarding their neurotoxicity, brain differences associated with gestational exposure to phthalates are understudied. We included 775 mother-child pairs from Generation R, a population-based pediatric neuroimaging study with prenatal recruitment, who had data on maternal gestational phthalate levels and T1-weighted magnetic resonance imaging in children at age 10 years. Maternal urinary concentrations of phthalate metabolites were measured at early, mid-, and late pregnancy. Child IQ was assessed at age 14 years. We investigated the extent to which prenatal exposure to phthalates is associated with brain volumetric measures and whether brain structural measures mediate the association of prenatal phthalate exposure with IQ. We found that higher maternal concentrations of monoethyl phthalate (mEP, averaged across pregnancy) were associated with smaller total gray matter volumes in offspring at age 10 years (ß per log10 increase in creatinine adjusted mEP = -10.7, 95%CI: -18.12, -3.28). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (ß for mediated path =-0.31, 95%CI: -0.62, 0.01, p = 0.05, proportion mediated = 18%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. Our findings suggest the global impact of prenatal phthalate exposure on brain volumetric measures that extends into adolescence and underlies less optimal cognitive development.

Characterization of the internal working-life exposome using minimally and non-invasive sampling methods - a narrative review.

During recent years, we are moving away from the 'one exposure, one disease'-approach in occupational settings and towards a more comprehensive approach, taking into account the totality of exposures during a life course by using an exposome approach. Taking an exposome approach however is accompanied by many challenges, one of which, for example, relates to the collection of biological samples. Methods used for sample collection in occupational exposome studies should ideally be minimally invasive, while at the same time sensitive, and enable meaningful repeated sampling in a large population and over a longer time period. This might be hampered in specific situations e.g., people working in remote areas, during pandemics or with flexible work hours. In these situations, using self-sampling techniques might offer a solution. Therefore, our aim was to identify existing self-sampling techniques and to evaluate the applicability of these techniques in an occupational exposome context by conducting a literature review. We here present an overview of current self-sampling methodologies used to characterize the internal exposome. In addition, the use of different biological matrices was evaluated and subdivided based on their level of invasiveness and applicability in an occupational exposome context. In conclusion, this review and the overview of self-sampling techniques presented herein can serve as a guide in the design of future (occupational) exposome studies while circumventing sample collection challenges associated with exposome studies.

Fetal Growth Trajectories Among Small for Gestational Age Babies and Child Neurodevelopment.

BACKGROUND: Being born small for gestational age (SGA, <10th percentile) is a risk factor for worse neurodevelopmental outcomes. However, this group is a heterogeneous mix of healthy and growth-restricted babies, and not all will experience poor outcomes. We sought to determine whether fetal growth trajectories can distinguish who will have the worst neurodevelopmental outcomes in childhood among babies born SGA. METHODS: The present analysis was conducted in Generation R, a population-based cohort in Rotterdam, the Netherlands (N = 5,487). Using group-based trajectory modeling, we identified fetal growth trajectories for weight among babies born SGA. These were based on standard deviation scores of ultrasound measures from mid-pregnancy and late pregnancy in combination with birth weight. We compared child nonverbal intelligence quotient (IQ) and attention deficit hyperactivity disorder (ADHD) symptoms at age 6 between SGA babies within each growth trajectory to babies born non-SGA. RESULTS: Among SGA individuals (n = 656), we identified three distinct fetal growth trajectories for weight. Children who were consistently small from mid-pregnancy (n = 64) had the lowest IQ (7 points lower compared to non-SGA babies, 95% confidence interval [CI] = -11.0, -3.5) and slightly more ADHD symptoms. Children from the trajectory that started larger but were smaller at birth showed no differences in outcomes compared to children born non-SGA. CONCLUSIONS: Among SGA children, those who were smaller beginning in mid-pregnancy exhibited the worst neurodevelopmental outcomes at age 6. Fetal growth trajectories may help identify SGA babies who go on to have poor neurodevelopmental outcomes.

Prenatal Exposure to Nonpersistent Chemical Mixtures and Offspring IQ and Emotional and Behavioral Problems.

Prenatal exposure to nonpersistent chemicals such as phthalates, bisphenols, and organophosphate (OP) pesticides is ubiquitous and occurs in mixtures. So far, epidemiological studies investigating neurodevelopmental consequences of these exposures have mainly been restricted to single-pollutant models. Thus, we studied the association between prenatal exposure to nonpersistent chemical mixtures and child IQ and emotional and behavioral problems. Data came from 782 mother-child pairs. Eleven phthalate, one bisphenol, and five OP pesticide urinary exposure biomarkers were measured three times during pregnancy and averaged. Nonverbal IQ, internalizing and attention problems, aggressive behavior, and autistic traits were assessed at child age 6 years. We used quantile g-computation to estimate the change in each outcome per quartile increase in all chemicals within the mixture. Higher exposure to the mixture was associated with lower nonverbal IQ (-4.0 points (95%CI = -7.0, -1.0), -5.5 points (95%CI = -10.2, -0.9), and -4.6 points (95%CI = -10.8, 1.5) for the second, third, and fourth quartile, respectively, compared to the first quartile). These results were mainly driven by the phthalate mixture. No association was observed with emotional and behavioral problems. Prenatal exposure to nonpersistent chemical mixtures was associated with lower nonverbal IQ in children. Exposure to chemical mixtures during gestation is universal and may impact neurodevelopment.

Neighbourhood and path-based greenspace in three European countries: associations with objective physical activity.

BACKGROUND: Greenspace has been associated with health benefits in many contexts. An important pathway may be through outdoor physical activity. We use a novel approach to examine the link between greenspace microenvironments and outdoor physical activity levels in the HEALS study conducted in Edinburgh (UK), the Netherlands, and Athens and Thessaloniki (Greece). METHODS: Using physical activity tracker recordings, 118 HEALS participants with young children were classified with regard to daily minutes of moderate to vigorous physical activity (MVPA); 60 were classified with regard to the metabolic equivalent task (MET)-minutes for each of the 1014 active trips they made. Greenspace indicators were generated for Normalised Difference Vegetation Index (NDVI), tree cover density (TCD), and green land use (GLU). We employed linear mixed-effects models to analyse (1) daily MVPA in relation to greenspace within 300 m and 1000 m of residential addresses and (2) trip MET-minutes in relation to average greenspace within a 50 m buffer of walking/cycling routes. Models were adjusted for activity, walkability, bluespace, age, sex, car ownership, dog ownership, season, weekday/weekend day, and local meteorology. RESULTS: There was no clear association between MVPA-minutes and any residential greenspace measure. For example, in fully adjusted models, a 10 percentage point increase in NDVI within 300 m of home was associated with a daily increase of 1.14 (95% CI - 0.41 to 2.70) minutes of MVPA. However, we did find evidence to indicate greenspace markers were positively linked to intensity and duration of activity: in fully adjusted models, 10 percentage point increases in trip NDVI, TCD, and GLU were associated with increases of 10.4 (95% CI: 4.43 to 16.4), 10.6 (95% CI: 4.96 to 16.3), and 3.36 (95% CI: 0.00 to 6.72) MET-minutes, respectively. The magnitude of associations with greenspace tended to be greater for cycling. CONCLUSIONS: More strenuous or longer walking and cycling trips occurred in environments with more greenspace, but levels of residential greenspace did not have a clear link with outdoor MVPA. To build on our research, we suggest future work examine larger, more diverse populations and investigate the influence of greenspace for trip purpose and route preference.

Prenatal exposure to organophosphate pesticides and brain morphology and white matter microstructure in preadolescents.

BACKGROUND: Prenatal exposure to organophosphate (OP) pesticides associate with impaired neurodevelopment in humans and animal models. However, much uncertainty exists about the brain structural alterations underlying these associations. The objective of this study was to determine whether maternal OP pesticide metabolite concentrations in urine repeatedly measured during gestation are associated with brain morphology and white matter microstructure in 518 preadolescents aged 9-12 years. METHOD: Data came from 518 mother-child pairs participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands. Maternal urine concentrations were determined for 6 dialkylphosphates (DAPs) including 3 dimethyl (DM) and 3 diethyl (DE) alkyl phosphate metabolites, collected at early, mid, and late pregnancy. At child's age 9-12 years, magnetic resonance imaging was performed to obtain T1-weighted images for brain volumes and surface-based cortical thickness and cortical surface area, and diffusion tensor imaging was used to measure white matter microstructure through fractional anisotropy (FA) and mean diffusivity (MD). Linear regression models were fit for the averaged prenatal exposure across pregnancy. RESULTS: DM and DE metabolite concentrations were not associated with brain volumes, cortical thickness, and cortical surface area. However, a 10-fold increase in averaged DM metabolite concentrations across pregnancy was associated with lower FA (B = -1.00, 95%CI = -1.80, -0.20) and higher MD (B = 0.13, 95%CI = 0.04, 0.21). Similar associations were observed for DE concentrations. CONCLUSIONS: This study provides the first evidence that OP pesticides may alter normal white matter microstructure in children, which could have consequences for normal neurodevelopment. No associations were observed with structural brain morphology, including brain volumes, cortical thickness, and cortical surface area.

Urban greenspace and the indoor environment: Pathways to health via indoor particulate matter, noise, and road noise annoyance.

BACKGROUND/AIM: The exposome includes urban greenspace, which may affect health via a complex set of pathways, including reducing exposure to particulate matter (PM) and noise. We assessed these pathways using indoor exposure monitoring data from the HEALS study in four European urban areas (Edinburgh, UK; Utrecht, Netherlands; Athens and Thessaloniki, Greece). METHODS: We quantified three metrics of residential greenspace at 50 m and 100 m buffers: Normalised Difference Vegetation Index (NDVI), annual tree cover density, and surrounding green land use. NDVI values were generated for both summer and the season during which the monitoring took place. Indoor PM2.5 and noise levels were measured by Dylos and Netatmo sensors, respectively, and subjective noise annoyance was collected by questionnaire on an 11-point scale. We used random-effects generalised least squares regression models to assess associations between greenspace and indoor PM2.5 and noise, and an ordinal logistic regression to model the relationship between greenspace and road noise annoyance. RESULTS: We identified a significant inverse relationship between summer NDVI and indoor PM2.5 (-1.27 µg/m3 per 0.1 unit increase [95% CI -2.38 to -0.15]) using a 100 m residential buffer. Reduced (i.e., <1.0) odds ratios (OR) of road noise annoyance were associated with increasing summer (OR = 0.55 [0.31 to 0.98]) and season-specific (OR = 0.55 [0.32 to 0.94]) NDVI levels, and tree cover density (OR = 0.54 [0.31 to 0.93] per 10 percentage point increase), also at a 100 m buffer. In contrast to these findings, we did not identify any significant associations between greenspace and indoor noise in fully adjusted models. CONCLUSIONS: We identified reduced indoor levels of PM2.5 and noise annoyance, but not overall noise, with increasing outdoor levels of certain greenspace indicators. To corroborate our findings, future research should examine the effect of enhanced temporal resolution of greenspace metrics during different seasons, characterise the configuration and composition of green areas, and explore mechanisms through mediation modelling.

Comparison of methods for converting Dylos particle number concentrations to PM2.5 mass concentrations.

The aim of this study was to (a) develop a method for converting particle number concentrations (PNC) obtained by Dylos to PM2.5 mass concentrations, (b) compare this conversion with similar methods available in the literature, and (c) compare Dylos PM2.5 obtained using all available conversion methods with gravimetric samples. Data were collected in multiple residences in three European countries using the Dylos and an Aerodynamic Particle Sizer (APS, TSI) in the Netherlands or an optical particle counter (OPC, GRIMM) in Greece. Two statistical fitted curves were developed based on Dylos PNC and either an APS or an OPC particle mass concentrations (PMC). In addition, at the homes of 16 volunteers (UK and Netherlands), Dylos measurements were collected along with gravimetric samples. The Dylos PNC were transformed to PMC using all the fitted curves obtained during this study (and three found in the literature) and were compared with gravimetric samples. The method developed in the present study using an OPC showed the highest correlation (Pearson (R) = 0.63, Concordance (ρc ) = 0.61) with gravimetric data. The other methods resulted in an underestimation of PMC compared to gravimetric measurements (R = 0.65-0.55, ρc  = 0.51-0.24). In conclusion, estimation of PM2.5 concentrations using the Dylos is acceptable for indicative purposes.

Cardiovascular effects among workers exposed to multiwalled carbon nanotubes.

OBJECTIVES: The increase in production of multiwalled carbon nanotubes (MWCNTs) has led to growing concerns about health risks. In this study, we assessed the association between occupational exposure to MWCNTs and cardiovascular biomarkers. METHODS: A cross-sectional study was performed among 22 workers of a company commercially producing MWCNTs (subdivided into lab personnel with low or high exposure and operators), and a gender and age-matched unexposed population (n=42). Exposure to MWCNTs and 12 cardiovascular markers were measured in participants' blood (phase I). In a subpopulation of 13 exposed workers and six unexposed workers, these measures were repeated after 5 months (phase II). We analysed associations between MWCNT exposure and biomarkers of cardiovascular risk, adjusted for age, body mass index, sex and smoking. RESULTS: We observed an upward trend in the concentration of endothelial damage marker intercellular adhesion molecule-1 (ICAM-1), with increasing exposure to MWCNTs in both phases. The operator category showed significantly elevated ICAM-1 geometric mean ratios (GMRs) compared with the controls (phase I: GMR=1.40, P=1.30E-3; phase II: GMR=1.37, P=0.03). The trends were significant both across worker categories (phase I: P=1.50E-3; phase II: P=0.01) and across measured GM MWCNT concentrations (phase I: P=3.00E-3; phase II: P=0.01). No consistent significant associations were found for the other cardiovascular markers. CONCLUSION: The associations between MWCNT exposure and ICAM-1 indicate endothelial activation and an increased inflammatory state in workers with MWCNT exposure.

Occupational Exposure to Multi-Walled Carbon Nanotubes During Commercial Production Synthesis and Handling.

The world-wide production of carbon nanotubes (CNTs) has increased substantially in the last decade, leading to occupational exposures. There is a paucity of exposure data of workers involved in the commercial production of CNTs. The goals of this study were to assess personal exposure to multi-walled carbon nanotubes (MWCNTs) during the synthesis and handling of MWCNTs in a commercial production facility and to link these exposure levels to specific activities. Personal full-shift filter-based samples were collected, during commercial production and handling of MWCNTs, R&D activities, and office work. The concentrations of MWCNT were evaluated on the basis of EC concentrations. Associations were studied between observed MWCNT exposure levels and location and activities. SEM analyses showed MWCNTs, present as agglomerates ranging between 200 nm and 100 µm. Exposure levels of MWCNTs observed in the production area during the full scale synthesis of MWCNTs (N = 23) were comparable to levels observed during further handling of MWCNTs (N = 19): (GM (95% lower confidence limit-95% upper confidence limit)) 41 µg m(-3) (20-88) versus 43 µg m(-3) (22-86), respectively. In the R&D area (N = 11) and the office (N = 5), exposure levels of MWCNTs were significantly (P < 0.05) lower: 5 µg m(-3) (2-11) and 7 µg m(-3) (2-28), respectively. Bagging, maintenance of the reactor, and powder conditioning were associated with higher exposure levels in the production area, whereas increased exposure levels in the R&D area were related to handling of MWCNTs powder.

Combining Decision Rules from Classification Tree Models and Expert Assessment to Estimate Occupational Exposure to Diesel Exhaust for a Case-Control Study.

OBJECTIVES: To efficiently and reproducibly assess occupational diesel exhaust exposure in a Spanish case-control study, we examined the utility of applying decision rules that had been extracted from expert estimates and questionnaire response patterns using classification tree (CT) models from a similar US study. METHODS: First, previously extracted CT decision rules were used to obtain initial ordinal (0-3) estimates of the probability, intensity, and frequency of occupational exposure to diesel exhaust for the 10 182 jobs reported in a Spanish case-control study of bladder cancer. Second, two experts reviewed the CT estimates for 350 jobs randomly selected from strata based on each CT rule's agreement with the expert ratings in the original study [agreement rate, from 0 (no agreement) to 1 (perfect agreement)]. Their agreement with each other and with the CT estimates was calculated using weighted kappa (κ w) and guided our choice of jobs for subsequent expert review. Third, an expert review comprised all jobs with lower confidence (low-to-moderate agreement rates or discordant assignments, n = 931) and a subset of jobs with a moderate to high CT probability rating and with moderately high agreement rates (n = 511). Logistic regression was used to examine the likelihood that an expert provided a different estimate than the CT estimate based on the CT rule agreement rates, the CT ordinal rating, and the availability of a module with diesel-related questions. RESULTS: Agreement between estimates made by two experts and between estimates made by each of the experts and the CT estimates was very high for jobs with estimates that were determined by rules with high CT agreement rates (κ w: 0.81-0.90). For jobs with estimates based on rules with lower agreement rates, moderate agreement was observed between the two experts (κ w: 0.42-0.67) and poor-to-moderate agreement was observed between the experts and the CT estimates (κ w: 0.09-0.57). In total, the expert review of 1442 jobs changed 156 probability estimates, 128 intensity estimates, and 614 frequency estimates. The expert was more likely to provide a different estimate when the CT rule agreement rate was <0.8, when the CT ordinal ratings were low to moderate, or when a module with diesel questions was available. CONCLUSIONS: Our reliability assessment provided important insight into where to prioritize additional expert review; as a result, only 14% of the jobs underwent expert review, substantially reducing the exposure assessment burden. Overall, we found that we could efficiently, reproducibly, and reliably apply CT decision rules from one study to assess exposure in another study.

Effectiveness of a Multidimensional Randomized Control Intervention to Reduce Quartz Exposure Among Construction Workers.

There is little evidence with respect to the effectiveness of intervention programs that focus on the reduction of occupational quartz exposure in the construction industry. This article evaluates the effectiveness of a multidimensional intervention which was aimed at reducing occupational quartz exposure among construction workers by increasing the use of technical control measures. Eight companies participating in the cluster randomized controlled trial were randomly allocated to the intervention (four companies) or control condition (four companies). The multidimensional intervention included engineering, organizational, and behavioural elements at both organizational and individual level. Full-shift personal quartz exposure measurements and detailed observations were conducted before and after the intervention among bricklayers, carpenters, concrete drillers, demolishers, and tuck pointers (n = 282). About 59% of these workers measured at baseline were reassessed during follow-up. Bayesian hierarchical models were used to evaluate the intervention effect on exposure levels. Concrete drillers in the intervention group used technical control measures, particularly water suppression, for a significantly greater proportion of the time spent on abrasive tasks during follow-up compared to baseline (93 versus 62%; P < 0.05). A similar effect, although not statistically significant, was observed among demolishers. A substantial overall reduction in quartz exposure (73 versus 40% in the intervention and control group respectively; P < 0.001) was observed for concrete drillers, demolishers, and tuck pointers. The decrease in exposure in the intervention group compared to controls was significantly larger for demolishers and tuck pointers, but not for concrete drillers. The observed effect could at least partly be explained by the introduced interventions; the statistically significant increased use of control measures among concrete drillers explains the observed effect to some extent in this job category only. Sensitivity analyses indicated that the observed decrease in exposure may also partly be attributable to changes in work location and abrasiveness of the tasks performed. Despite the difficulties in assessing the exact magnitude of the intervention, this study showed that the structured intervention approach at least partly contributed to a substantial reduction in quartz exposure among high exposed construction workers.

Using hierarchical cluster models to systematically identify groups of jobs with similar occupational questionnaire response patterns to assist rule-based expert exposure assessment in population-based studies.

OBJECTIVES: Rule-based expert exposure assessment based on questionnaire response patterns in population-based studies improves the transparency of the decisions. The number of unique response patterns, however, can be nearly equal to the number of jobs. An expert may reduce the number of patterns that need assessment using expert opinion, but each expert may identify different patterns of responses that identify an exposure scenario. Here, hierarchical clustering methods are proposed as a systematic data reduction step to reproducibly identify similar questionnaire response patterns prior to obtaining expert estimates. As a proof-of-concept, we used hierarchical clustering methods to identify groups of jobs (clusters) with similar responses to diesel exhaust-related questions and then evaluated whether the jobs within a cluster had similar (previously assessed) estimates of occupational diesel exhaust exposure. METHODS: Using the New England Bladder Cancer Study as a case study, we applied hierarchical cluster models to the diesel-related variables extracted from the occupational history and job- and industry-specific questionnaires (modules). Cluster models were separately developed for two subsets: (i) 5395 jobs with ≥1 variable extracted from the occupational history indicating a potential diesel exposure scenario, but without a module with diesel-related questions; and (ii) 5929 jobs with both occupational history and module responses to diesel-relevant questions. For each subset, we varied the numbers of clusters extracted from the cluster tree developed for each model from 100 to 1000 groups of jobs. Using previously made estimates of the probability (ordinal), intensity (µg m(-3) respirable elemental carbon), and frequency (hours per week) of occupational exposure to diesel exhaust, we examined the similarity of the exposure estimates for jobs within the same cluster in two ways. First, the clusters' homogeneity (defined as >75% with the same estimate) was examined compared to a dichotomized probability estimate (<5 versus ≥5%; <50 versus ≥50%). Second, for the ordinal probability metric and continuous intensity and frequency metrics, we calculated the intraclass correlation coefficients (ICCs) between each job's estimate and the mean estimate for all jobs within the cluster. RESULTS: Within-cluster homogeneity increased when more clusters were used. For example, ≥80% of the clusters were homogeneous when 500 clusters were used. Similarly, ICCs were generally above 0.7 when ≥200 clusters were used, indicating minimal within-cluster variability. The most within-cluster variability was observed for the frequency metric (ICCs from 0.4 to 0.8). We estimated that using an expert to assign exposure at the cluster-level assignment and then to review each job in non-homogeneous clusters would require ~2000 decisions per expert, in contrast to evaluating 4255 unique questionnaire patterns or 14983 individual jobs. CONCLUSIONS: This proof-of-concept shows that using cluster models as a data reduction step to identify jobs with similar response patterns prior to obtaining expert ratings has the potential to aid rule-based assessment by systematically reducing the number of exposure decisions needed. While promising, additional research is needed to quantify the actual reduction in exposure decisions and the resulting homogeneity of exposure estimates within clusters for an exposure assessment effort that obtains cluster-level expert assessments as part of the assessment process.

Night work and breast cancer risk in a general population prospective cohort study in The Netherlands.

Experimental studies in animals indicate that disruption of the circadian rhythm is carcinogenic, and night work has been suggested to be a probable breast cancer cause in humans. Findings among humans, however are inconsistent, often gathered with retrospective study designs, and only based on specific populations, such as nurses. We used data on night work collected in the Dutch Labor Force Surveys of 1996 until 2009, and individually linked these with National registers on hospital admission. Among 285,723 women without breast cancer at baseline, 2,531 had a hospital admission for breast cancer during an average of 7 years of follow up in the registers. Occasional and regular night work were not associated with the risk of hospital admission for breast cancer (adjusted hazard ratios 1.04; 95 % confidence interval 0.85-1.27, and 0.87; 0.72-1.05, respectively). Working more hours per week, or more years in a job entailing night work did not show increased breast cancer risks. Hazard ratios neither differed between nurses and women with other occupations. Our results show no association of night work with incident breast cancer, and suggest that night work generally does not increase the risk of breast cancer among women in the Dutch working population.

Exhaled nitric oxide in spray painters exposed to isocyanates: effect modification by atopy and smoking.

BACKGROUND: Isocyanate asthma is one of the most frequently identified forms of occupational asthma in industrialised countries. The underlying mechanisms have not been clarified. There is only limited information about the relationship between exhaled nitric oxide (eNO) and occupational exposure to isocyanates and asthma. OBJECTIVES: To investigate the association between isocyanate exposure and eNO levels in isocyanate-exposed workers and to elucidate whether eNO acts as a marker of airway inflammation controlling for smoking and atopy in an industry-wide survey. METHODS: Information on estimated personal isocyanate exposure, measured eNO levels, health effects and sensitisation were analysed in 229 workers from a cross-sectional study. Univariate and multiple regression analyses were used to explore the exposure-response relationships between isocyanate exposure and eNO, stratified by smoking and atopy. RESULTS: A marginally significant exposure-response relationship was found between isocyanate exposure and eNO in atopic, non-smokers (p=0.054). eNO was significantly associated with atopy and smoking, bronchial hyper-responsiveness (BHR), work-related conjunctivitis and rhinitis after adjustment for age, gender, atopy and smoking (p<0.05). A borderline significant association was found between eNO and asthma-like symptoms after adjustment for age, gender, atopy and current smoking (p=0.055). In a small group of isocyanate-exposed workers with positive serum-specific immunoglobulin E (IgE) antibodies to hexamethylene diisocyanate (HDI), elevated eNO levels were clearly exposure related. eNO was associated with the positive specific IgG antibodies to HDI in non-atopic, non-smokers (p=0.03). CONCLUSIONS: Increased eNO levels may indicate increased airway inflammation in atopic, non-smokers exposed to isocyanates especially at higher levels of isocyanate exposure.

Quartz and respirable dust in the Dutch construction industry: a baseline exposure assessment as part of a multidimensional intervention approach.

Quartz exposure can cause several respiratory health effects. Although quartz exposure has been described in several observational workplace studies, well-designed intervention studies that investigate the effect of control strategies are lacking. This article describes a baseline exposure study that is part of a multidimensional intervention program aiming to reduce quartz exposure among construction workers. In this study, personal respirable dust and quartz exposure was assessed among 116 construction workers (bricklayers, carpenters, concrete drillers, demolishers, and tuck pointers). Possible determinants of exposure, like job, tasks, and work practices, use of control measures, and organizational and psychosocial factors, were explored using exposure models for respirable dust and quartz separately. Stratified analyses by job title were performed to evaluate the effect of control measures on exposure and to explore the association between control measures and psychosocial factors. Overall, 62% of all measurements exceeded the Dutch occupational exposure limit for quartz and 11% for respirable dust. Concrete drillers and tuck pointers had the highest exposures for quartz and respirable dust (0.20 and 3.43mg m(-3), respectively). Significant predictors of elevated quartz exposure were abrasive tasks and type of material worked on. Surprisingly, in a univariate model, an increased knowledge level was associated with an increase in exposure. Although control measures were used infrequently, if used they resulted in approximately 40% reduction in quartz exposure among concrete drillers and tuck pointers. Only among concrete drillers, the use of control measures was associated with a higher score for social influence (factor 1.6); knowledge showed an inverse association with use of control measures for concrete drillers, demolishers, and tuck pointers. In conclusion, the detailed information on determinants of exposure, use of control measures, and constraints to use these control measures can be used for the determination and systematic prioritization of intervention measures used to design and implement our intervention strategy. This study underlines the need for multidisciplinary workplace exposure control strategies although larger study populations are necessary to determine a possible causal association between organizational and psychosocial factors and psychosocial factors and control measures.

'Relieved Working' study: systematic development and design of an intervention to decrease occupational quartz exposure at construction worksites.

BACKGROUND: Occupational quartz exposure continues to be a serious hazard in the construction industry. Until now, evidence-based interventions aimed at reducing quartz exposure are scarce. The aim of this study was to systematically develop an intervention and to describe the study to evaluate its effectiveness. METHODS/DESIGN: The intervention was developed according to the principles of the Intervention Mapping protocol, meaning that evidence from the literature was combined with information collected from stakeholders (e.g., construction workers, managers and researchers). The intervention aimed to integrate technical, behavioural and organizational factors. The intervention consists of two plenary meetings for all employers within the company, and individual visits at construction worksites, including specific intervention materials. Additionally, a demonstration session regarding control measures was organized for all managers. The effectiveness of the intervention will be evaluated in a cluster randomized controlled trial among eight construction companies, with measurements at baseline and follow-up. Outcome measures are personal respirable dust and quartz exposure by means of exposure assessment, and behavioural and organizational determinants which will be assessed by means of questionnaires. Additionally, a process evaluation will shed light on whether the intervention (does not) works, and, if so, the reasons for this. DISCUSSION: Applying Intervention Mapping in the development of an intervention to reduce occupational quartz exposure was useful, as different stakeholders provided input for the intervention as well as the implementation strategy. Therefore, the feasibility of the intervention has been enhanced, as it appeals to construction workers and managers and will not unduly interfere with the ongoing construction work. TRIAL REGISTRATION NUMBER: NTR4586 (May 7th 2014).

Narrative review of occupational exposures and noncommunicable diseases.

OBJECTIVE: Within the scope of the Exposome Project for Health and Occupational Research on applying the exposome concept to working life health, we aimed to provide a broad overview of the status of knowledge on occupational exposures and associated health effects across multiple noncommunicable diseases (NCDs) to help inform research priorities. METHODS: We conducted a narrative review of occupational risk factors that can be considered to have "consistent evidence for an association," or where there is "limited/inadequate evidence for an association" for 6 NCD groups: nonmalignant respiratory diseases; neurodegenerative diseases; cardiovascular/metabolic diseases; mental disorders; musculoskeletal diseases; and cancer. The assessment was done in expert sessions, primarily based on systematic reviews, supplemented with narrative reviews, reports, and original studies. Subsequently, knowledge gaps were identified, e.g. based on missing information on exposure-response relationships, gender differences, critical time-windows, interactions, and inadequate study quality. RESULTS: We identified over 200 occupational exposures with consistent or limited/inadequate evidence for associations with one or more of 60+ NCDs. Various exposures were identified as possible risk factors for multiple outcomes. Examples are diesel engine exhaust and cadmium, with consistent evidence for lung cancer, but limited/inadequate evidence for other cancer sites, respiratory, neurodegenerative, and cardiovascular diseases. Other examples are physically heavy work, shift work, and decision latitude/job control. For associations with limited/inadequate evidence, new studies are needed to confirm the association. For risk factors with consistent evidence, improvements in study design, exposure assessment, and case definition could lead to a better understanding of the association and help inform health-based threshold levels. CONCLUSIONS: By providing an overview of knowledge gaps in the associations between occupational exposures and their health effects, our narrative review will help setting priorities in occupational health research. Future epidemiological studies should prioritize to include large sample sizes, assess exposures prior to disease onset, and quantify exposures. Potential sources of biases and confounding need to be identified and accounted for in both original studies and systematic reviews.

Inside the black box: starting to uncover the underlying decision rules used in a one-by-one expert assessment of occupational exposure in case-control studies.

OBJECTIVES: Evaluating occupational exposures in population-based case-control studies often requires exposure assessors to review each study participant's reported occupational information job-by-job to derive exposure estimates. Although such assessments likely have underlying decision rules, they usually lack transparency, are time consuming and have uncertain reliability and validity. We aimed to identify the underlying rules to enable documentation, review and future use of these expert-based exposure decisions. METHODS: Classification and regression trees (CART, predictions from a single tree) and random forests (predictions from many trees) were used to identify the underlying rules from the questionnaire responses, and an expert's exposure assignments for occupational diesel exhaust exposure for several metrics: binary exposure probability and ordinal exposure probability, intensity and frequency. Data were split into training (n=10 488 jobs), testing (n=2247) and validation (n=2248) datasets. RESULTS: The CART and random forest models' predictions agreed with 92-94% of the expert's binary probability assignments. For ordinal probability, intensity and frequency metrics, the two models extracted decision rules more successfully for unexposed and highly exposed jobs (86-90% and 57-85%, respectively) than for low or medium exposed jobs (7-71%). CONCLUSIONS: CART and random forest models extracted decision rules and accurately predicted an expert's exposure decisions for the majority of jobs, and identified questionnaire response patterns that would require further expert review if the rules were applied to other jobs in the same or different study. This approach makes the exposure assessment process in case-control studies more transparent, and creates a mechanism to efficiently replicate exposure decisions in future studies.