Quantitative Exposure Estimates Research Articles

Opportunities and challenges in using NIH’s Dietary Supplement Label Database for research on non-nutrient ingredients: Use case for ingredients in honeybee products

BackgroundNon-nutrient bioactive ingredients of foods such as bee products are often of interest in preclinical and clinical research to explore their possible beneficial effects. The National Institute of Health’s Dietary Supplement Label Database (DSLD) contains over 165,000 labels of dietary supplements marketed in the United States of America (US), including declarations on labels for many ingredients such as those in honeybee products which have been used in foods and traditional medicines for centuries worldwide and are now also appearing in dietary supplements. MethodsThis article presents a use case for honeybee products that describes and tests the utility of the DSLD and other databases available in the US as research tools for identifying and quantifying the prevalence of such ingredients. It focuses on the limitations to the information on product composition in these databases and describes how to code the ingredients using the LanguaL™ and FoodEx2 classification and description systems and the strengths and limitations of information on honeybee product ingredients, including propolis, bee pollen, royal jelly, beeswax. Results and conclusionsCodes for the ingredients are provided for identifying their presence in LanguaL™ and FoodEx2 classification and description systems used in Europe and elsewhere. The prevalence of dietary supplement products containing these ingredients in DSLD and on the US market is low compared to some other products and ingredients. Unfortunately label declarations in DSLD do not provide quantitative information and so the data can be used only to screen for their presence, but cannot be used for quantitative exposure estimates by researchers and regulators.

Diesel Exhaust Exposure and Cause-Specific Mortality in the Diesel Exhaust in Miners Study II (DEMS II) Cohort.

With the exception of lung cancer, the health effects associated with diesel exhaust for other cancers and nonmalignant health outcomes are not well understood. We extended the mortality follow-up of the Diesel Exhaust in Miners Study, a cohort study of 12,315 workers, by 18 y (ending 31 December 2015), more than doubling the number of observed deaths to , to evaluate associations between mortality and diesel exhaust exposure. Quantitative estimates of historical exposure to respirable elemental carbon (REC), a surrogate for diesel exhaust, were created for all jobs, by year and facility, using measurements collected from each mine, as well as historical measurements. Standardized mortality ratios (SMRs) and hazard ratios (HRs) were estimated for the entire cohort and by worker location (surface, underground). We observed an excess of death for cancers of the lung, trachea, and bronchus (; ; 95% CI: 1.13, 1.37). Among workers who ever worked underground, where the majority of diesel exposure occurred, excess deaths were evident for lung, trachea, and bronchus cancers (; ; 95% CI: 1.11, 1.42). Several nonmalignant diseases were associated with excess mortality among workers ever-employed underground, including ischemic heart disease (; 95% CI: 1.00, 1.16), cerebrovascular disease (; 95% CI: 1.04, 1.43), and nonmalignant diseases of the respiratory system (; 95% CI: 1.01, 1.26). Continuous 15-y lagged cumulative REC exposure was associated with increased lung cancer risk (; 95% CI: 1.24, 3.03), but the risk declined at the highest exposures (; 95% CI: 0.74, 2.26). We also observed a significant trend in non-Hodgkin lymphoma (NHL) risk with increasing 20-y lagged cumulative REC (; 95% CI: 1.00, 9.79; ). Increased risks of lung cancer mortality observed in the original study were sustained. Observed associations between diesel exposure and risk of death from NHL and the excesses in deaths for diseases of the respiratory and cardiovascular system, including ischemic heart disease and cerebrovascular disease, warrant further study and provide evidence of the potential widespread public health impact of diesel exposure. https://doi.org/10.1289/EHP12840.

Development of a quantitative North and Central European job exposure matrix for wood dust.

Wood dust is an established carcinogen also linked to several non malignant respiratory disorders. A major limitation in research on wood dust and its health effects is the lack of (historical) quantitative estimates of occupational exposure for use in general population-based case-control or cohort studies. The present study aimed to develop a multinational quantitative Job Exposure Matrix (JEM) for wood dust exposure using exposure data from several Northern and Central European countries. For this, an occupational exposure database containing 12653 personal wood dust measurements collected between 1978 and 2007 in Denmark, Finland, France, The Netherlands, Norway, and the United Kingdom (UK) was established. Measurement data were adjusted for differences in inhalable dust sampling efficiency resulting from the use of different dust samplers and analysed using linear mixed effect regression with job codes (ISCO-88) and country treated as random effects. Fixed effects were the year of measurement, the expert assessment of exposure intensity (no, low, and high exposure) for every ISCO-88 job code from an existing wood dust JEM and sampling duration. The results of the models suggest that wood dust exposure has declined annually by approximately 8%. Substantial differences in exposure levels between countries were observed with the highest levels in the United Kingdom and the lowest in Denmark and Norway, albeit with similar job rankings across countries. The jobs with the highest predicted exposure are floor layers and tile setters, wood-products machine operators, and building construction labourers with geometric mean levels for the year 1997 between 1.7 and 1.9 mg/m3. The predicted exposure estimates by the model are compared with the results of wood dust measurement data reported in the literature. The model predicted estimates for full-shift exposures were used to develop a time-dependent quantitative JEM for exposure to wood dust that can be used to estimate exposure for participants of general population studies in Northern European countries on the health effects from occupational exposure to wood dust.

Pleural mesothelioma risk by industry and occupation: results from the Multicentre Italian Study on the Etiology of Mesothelioma (MISEM)

BackgroundThe Italian mesothelioma registry (ReNaM) estimates mesothelioma incidence and addresses its etiology by assessing cases’ exposures but cannot provide relative risk estimates.Objectivesi) To estimate pleural mesothelioma relative risk by industry and occupation and by ReNaM categories of asbestos exposure; and ii) to provide quantitative estimates of the exposure–response relationship.MethodsA population-based mesothelioma case–control study was conducted in 2012–2014 in five Italian regions. Cases and age and gender frequency-matched controls were interviewed using a standard ReNaM questionnaire. Experts coded work histories according to international standard classifications of industries/occupations and assigned asbestos exposure according to ReNaM categories. Job codes were further linked to SYN-JEM, a quantitative job-exposure matrix. Cumulative exposure (CE, f/mL-years) was computed by summing individual exposures over lifetime work history. Unconditional logistic regression analyses adjusted by gender, centre and age were fitted to calculate odds ratios (OR) and 95% confidence intervals (CI).ResultsAmong men we observed increased risks of mesothelioma in many industries and associated occupations, including: asbestos-cement (OR = 3.43), manufacture of railroad equipment (OR = 8.07), shipbuilding and repairing (OR = 2.34), iron and steel mills (OR = 2.15), and construction (OR = 1.94). ORs by ReNaM exposure categories were as follows: definite/probable occupational exposure (OR = 15.8, men; OR = 8.80, women), possible occupational (OR = 2.82, men; OR = 3.70, women), sharing home with an exposed worker (OR = 2.55, men; OR = 10.3, women), residential (OR = 2.14, men; OR = 3.24, women). Based on SYN-JEM, mesothelioma risk increased by almost 30% per f/mL-year (OR = 1.28, CI 1.16–1.42).ConclusionsOut study involved five regions with historically different types and levels of industrial development, encompassing one third of the Italian population and half of Italian mesothelioma cases. As expected, we found increased pleural mesothelioma risk in the asbestos industry and in trades with large consumption of asbestos materials. Clear associations were found using both qualitative (ReNaM classifications) and quantitative estimates (using SYN-JEM) of past asbestos exposure, with clear evidence of an exposure–response relationship.

Asbestos Exposure in Patients with Malignant Pleural Mesothelioma included in the PRIMATE Study, Lombardy, Italy.

The PRIMATE study is an Italian translational research project, which aims to identify personalized biomarkers associated with clinical characteristics of malignant pleural mesothelioma (MPM). For this purpose, characteristics of MPM patients with different degrees of asbestos exposure will be compared to identify somatic mutations, germline polymorphism, and blood inflammatory biomarkers. In this framework, we assessed exposure to asbestos for 562 cases of MPM extracted from the Lombardy region Mesothelioma Registry (RML), for which a complete interview based on a standardized national questionnaire and histopathological specimens were available. Exposure assessment was performed: (1) through experts' evaluation (considered as the gold standard for the purpose of this study), according to the guidelines of the Italian National Mesothelioma Registry (ReNaM) and (2) using a job-exposure matrix (SYN-JEM) to obtain qualitative (ever/never) and quantitative estimates of occupational asbestos exposure (cumulative exposure expressed in fibers per mL (f/mL)). The performance of SYN-JEM was evaluated against the experts' evaluation. According to experts' evaluation, occupational asbestos exposure was recognized in 73.6% of men and 23.6% of women; furthermore, 29 men (7.8%) and 70 women (36.9%) had non-occupational exposure to asbestos. When applying SYN-JEM, 225 men (60.5%) and 25 women (13.2%) were classified as occupationally exposed, with a median cumulative exposure higher for men (1.7 f/mL-years) than for women (1.2 f/mL-years). The concordance between the two methods (Cohen’s kappa) for occupational exposure assessment was 0.46 overall (0.41 in men, and 0.07 in women). Sensitivity was higher in men (0.73) than in women (0.18), while specificity was higher in women (0.88) than in men (0.74). Overall, both methods can be used to reconstruct past occupational exposure to asbestos, each with its own advantages and limitations.

Lifetime exposure to disinfection by-products and risk of cancer at six anatomic sites in Iowa, USA

Background: Disinfection by-products (DBPs) are suspected risk factors for multiple cancers. In our population-based case-control study in Iowa, we previously found moderate risks of bladder, brain, and rectal (but not colon, kidney, or pancreatic) cancers with duration of use of chlorinated surface water, known to have elevated DBP levels. We reanalyzed these data using quantitative estimates of lifetime DBP exposure. Methods: We identified 1,225 bladder, 586 colon, 566 rectal, 311 brain, 334 kidney, and 302 pancreatic cancer cases and 2,106 controls (1986-1989). We developed historical annual estimates of total trihalomethanes (TTHM) and the sum of five haloacetic acids (HAA5) levels for Iowa public water supplies. Using residential water source histories for each participant, we computed lifetime average exposure (µg/L) and exposure years above the U.S. maximum contaminant levels (MCL) for TTHM (>80 µg/L) and HAA5 (>60 µg/L); private well users were assumed to have no DBP exposure. We estimated odds ratios (ORs) and 95% confidence intervals (CI) for exposure quantiles from logistic regression models adjusted for potential confounders.Results: Rectal cancer risk was associated with lifetime average TTHM exposure above the 93.5th percentile (≥51.7 µg/L; OR=1.56, 95%CI=1.0-2.6; p-trend=0.02) and with 25+ years of exposure to levels above the MCL (OR=1.65, 95%CI=1.0-2.7; p-trend=0.05) but not with shorter duration; results were similar for men and women. Lifetime average TTHM exposure was not significantly associated with other cancers. 25+ years of exposure ≥80 µg/L TTHM was associated with increased odds of colon (OR=1.96, 95%CI=1.1-3.5), bladder (OR=1.38, 95% CI=1.0-2.0), and brain (OR=2.59, 95%CI=1.0-6.4) cancer among men, but not women or for shorter duration of exposure at this level. We observed sporadic positive associations with HAA5 exposures across cancer sites.Conclusions: Our findings contribute new quantitative evidence of associations between high levels of TTHM and rectal, colon, bladder, and brain cancers.

Quantitative and semiquantitative estimates of mold exposure in infancy and childhood respiratory health.

Previous epidemiologic studies of dampness and mold relied on metrics that did not fully assess exposure-response relationships. Our objective was to examine quantitative metrics of dampness and mold during infancy and respiratory health outcomes during childhood. In-home visits were conducted before age 1 for children in the Cincinnati Childhood Allergy and Air Pollution Study. Respiratory outcomes included age 3 wheeze and age 7 asthma and wheeze. The associations between home exposure and respiratory outcomes were evaluated for 779 children using logistic regression adjusting for household income, neighborhood socioeconomic status, and the presence of pests. Children residing in homes with ≥0.29 m2 of moisture damage were significantly more likely to have wheezing at age 3 and persistent wheeze through age 7 (adjusted odds ratio [aOR] = 2.2; 95% confidence interval [CI] = 1.0, 4.3 and aOR = 3.2; CI = 1.3, 7.5, respectively). Additionally, homes having ≥0.19 m2 of mold damage were associated with wheezing at age 3 and early transient wheeze assessed at age 7 (aOR = 2.9; CI = 1.3, 6.4 and aOR = 3.5; CI = 1.5, 8.2, respectively). Mold damage <0.19 m2 and moisture damage <0.29 m2 were not associated with health outcomes. Mold and moisture damage were also not associated with asthma. Our data indicate that only the highest categories analyzed for mold (≥0.19 m2) and moisture damage (≥0.29 m2) in homes at age 1 were significantly associated with wheeze at ages 3 and 7; however, data below these levels were too sparse to assess the shape of the relationship or explore potential health-relevant thresholds.

A quantitative risk assessment model for Staphylococcus aureus and Salmonella associated with consumption of informally marketed milk products in Tigray, Ethiopia

AbstractThe aim of this work was to collect relevant input data for integration into Monte‐Carlo simulation using 10,000 iterations to obtain quantitative estimates of exposure and associated risk to Staphylococcus aureus and Salmonella. Higher prevalence rates of S. aureus (54.9 vs. 28.3%) and Salmonella (12.9 vs. 11.1%) were observed for raw milk distributed via collection milk collection centers (MCC) compared to those via dairy farms (DF). Prevalence found for S. aureus in traditionally fermented milk averaged only 3.7%. Although the 90% CI estimated probabilities of exposures to S. aureus due to DF and MCC raw milk consumption at levels higher than the D‐R value found were 10.6 and 23.5%, respectively, exposures to Salmonella were within the pathogen's tolerable limit. While annual likely of risk of illness by S. aureus due to DF and MCC raw milk consumptions resulted in up to 24.2 and 48.3% estimated illnesses, respectively, traditionally fermented milk consumption was found very much less risky; and resulted only 2.5% estimated illnesses per‐serving‐per‐year. The corresponding values for Salmonella per‐serving‐per‐year estimated illnesses via raw milk sales are, respectively, 5.72 and 11.41% compared to 1.8 and 4.02% when they come in boiled forms.

Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile.

We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.

Development of Quantitative Estimates of Wood Dust Exposure in a Canadian General Population Job-Exposure Matrix Based on Past Expert Assessments.

The CANJEM general population job-exposure matrix summarizes expert evaluations of 31 673 jobs from four population-based case-control studies of cancer conducted in Montreal, Canada. Intensity in each CANJEM cell is represented as relative distributions of the ordinal (low, medium, high) ratings of jobs assigned by the experts. We aimed to apply quantitative concentrations to CANJEM cells using Canadian historical measurements from the Canadian Workplace Exposure Database (CWED), taking exposure to wood dust as an example. We selected 5170 personal and area wood dust measurements from 31 occupations (2011 Canadian National Occupational Classification) with a non-zero exposure probability in CANJEM between 1930 and 2005. The measurements were taken between 1981 and 2003 (median 1989). A Bayesian hierarchical model was applied to the wood dust concentrations with occupations as random effects, and sampling duration, year, sample type (area or personal), province, and the relative proportion of jobs exposed at medium and high intensity in CANJEM cells as fixed effects. The estimated geometric mean (GM) concentrations for a CANJEM cell with all jobs exposed at medium or high intensity were respectively 1.3 and 2.4 times higher relative to a cell with all jobs at low intensity. An overall trend of -3%/year in exposure was observed. Applying the model estimates to all 198 cells in CANJEM with some exposure assigned by the experts, the predicted 8-hour, personal wood dust GM concentrations by occupation for 1989 ranged from 0.48 to 1.96 mg m-3. The model provided estimates of wood dust concentrations for any CANJEM cell with exposure, applicable for quantitative risk assessment at the population level. This framework can be implemented for other agents represented in both CANJEM and CWED.

Characterizing exposure to household air pollution within the Prospective Urban Rural Epidemiology (PURE) study

BackgroundHousehold air pollution (HAP) from combustion of solid fuels is an important contributor to disease burden in low- and middle-income countries (LIC, and MIC). However, current HAP disease burden estimates are based on integrated exposure response curves that are not currently informed by quantitative HAP studies in LIC and MIC. While there is adequate evidence supporting causal relationships between HAP and respiratory disease, large cohort studies specifically examining relationships between quantitative measures of HAP exposure with cardiovascular disease are lacking. ObjectiveWe aim to improve upon exposure proxies based on fuel type, and to reduce exposure misclassification by quantitatively measuring exposure across varying cooking fuel types and conditions in diverse geographies and socioeconomic settings. We leverage technology advancements to estimate household and personal PM2.5 (particles below 2.5 μm in aerodynamic diameter) exposure within the large (N~250,000) multi-country (N~26) Prospective Urban and Rural Epidemiological (PURE) cohort study. Here, we detail the study protocol and the innovative methodologies being used to characterize HAP exposures, and their application in epidemiologic analyses. Methods/designThis study characterizes HAP PM2.5 exposures for participants in rural communities in ten PURE countries with >10% solid fuel use at baseline (Bangladesh, Brazil, Chile, China, Colombia, India, Pakistan, South Africa, Tanzania, and Zimbabwe). PM2.5 monitoring includes 48-h cooking area measurements in 4500 households and simultaneous personal monitoring of male and female pairs from 20% of the selected households. Repeat measurements occur in 20% of households to assess impacts of seasonality. Monitoring began in 2017, and will continue through 2019. The Ultrasonic Personal Aerosol Sampler (UPAS), a novel, robust, and inexpensive filter based monitor that is programmable through a dedicated mobile phone application is used for sampling. Pilot study field evaluation of cooking area measurements indicated high correlation between the UPAS and reference Harvard Impactors (r = 0.91; 95% CI: 0.84, 0.95; slope = 0.95). To facilitate tracking and to minimize contamination and analytical error, the samplers utilize barcoded filters and filter cartridges that are weighed pre- and post-sampling using a fully automated weighing system. Pump flow and pressure measurements, temperature and RH, GPS coordinates and semi-quantitative continuous particle mass concentrations based on filter differential pressure are uploaded to a central server automatically whenever the mobile phone is connected to the internet, with sampled data automatically screened for quality control parameters. A short survey is administered during the 48-h monitoring period. Post-weighed filters are further analyzed to estimate black carbon concentrations through a semi-automated, rapid, cost-effective image analysis approach. The measured PM2.5 data will then be combined with PURE survey information on household characteristics and behaviours collected at baseline and during follow-up to develop quantitative HAP models for PM2.5 exposures for all rural PURE participants (~50,000) and across different cooking fuel types within the 10 index countries. Both the measured (in the subset) and the modelled exposures will be used in separate longitudinal epidemiologic analyses to assess associations with cardiopulmonary mortality, and disease incidence. DiscussionThe collected data and resulting characterization of cooking area and personal PM2.5 exposures in multiple rural communities from 10 countries will better inform exposure assessment as well as future epidemiologic analyses assessing the relationships between quantitative estimates of chronic HAP exposure with adult mortality and incident cardiovascular and respiratory disease. This will provide refined and more accurate exposure estimates in global CVD related exposure-response analyses.

Mortality Among Hardmetal Production Workers: Occupational Exposures.

To generate quantitative exposure estimates for use in retrospective occupational cohort mortality studies of the hardmetal industry. Job-exposure matrices (JEMs) were constructed for cobalt, tungsten, and nickel over the time period 1952 to 2014. The JEMs consisted of job class categories, based on job titles and processes performed, and exposure estimates calculated from available company industrial hygiene measurements. Exposure intervals of one-half order magnitude were established for all three agents. Eight job classes had significantly decreasing time trends for cobalt exposure; no significant time trends were detected for tungsten or nickel exposures. The levels of exposures determined for this study were similar to or lower than those previously reported for the hardmetal industry during the 1952 to 2014 study period.

The Validity and Applicability of Using a Generic Exposure Assessment Model for Occupational Exposure to Nano-Objects and Their Aggregates and Agglomerates.

Control banding can be used as a first-tier assessment to control worker exposure to nano-objects and their aggregates and agglomerates (NOAA). In a second tier, more advanced modelling approaches are needed to produce quantitative exposure estimates. As currently no general quantitative nano-specific exposure models are available, this study evaluated the validity and applicability of using a generic exposure assessment model (the Advanced REACH Tool-ART) for occupational exposure to NOAA. The predictive capability of ART for occupational exposure to NOAA was tested by calculating the relative bias and correlations (Pearson) between the model estimates and measured concentrations using a dataset of 102 NOAA exposure measurements collected during experimental and workplace exposure studies. Moderate to (very) strong correlations between the ART estimates and measured concentrations were found. Estimates correlated better to measured concentration levels of dust (r = 0.76, P < 0.01) than liquid aerosols (r = 0.51, P = 0.19). However, ART overestimated the measured NOAA concentrations for both the experimental and field measurements (factor 2-127). Overestimation was highest at low concentrations and decreased with increasing concentration. Correlations seemed to be better when looking at the nanomaterials individually compared to combined scenarios, indicating that nanomaterial-specific characteristics are not well captured within the mechanistic model of the ART. Although ART in its current state is not capable to estimate occupational exposure to NOAA, the strong correlations for the individual nanomaterials indicate that the ART (and potentially other generic exposure models) have the potential to be extended or adapted for exposure to NOAA. In the future, studies investigating the potential to estimate exposure to NOAA should incorporate more explicitly nanomaterial-specific characteristics in their models.

Exposure-response estimate for lung cancer and asbestosis in a predominantly chrysotile-exposed Chinese factory cohort.

Cumulative fiber exposures, predominantly chrysotile, were estimated in a Chinese asbestos worker cohort and exposure-response relationships with lung cancer mortality and cumulative incidence of asbestosis were determined. Individual time-dependent cumulative exposures were estimated for 577 asbestos workers, followed prospectively for 37 years. Occupational history and smoking data were obtained from company records and personal interviews; vital status and causes of death were ascertained from death registries and hospital records. Hazard ratios were generated for disease outcomes, with adjustments for smoking and age. Median cumulative fiber exposure for the cohort was 132.6 fiber-years/ml (IQR 89.3-548.4). Exposure-response relationships were demonstrated for both disease outcomes, with nearly sixfold and threefold increased risks seen at the highest exposure level for lung cancer deaths and asbestosis, respectively. Evidence using quantitative exposure estimates was provided for increased risks of lung cancer mortality and development of asbestosis in a predominantly chrysotile-exposed cohort.

Antibiotics and Antibiotic Resistance in Agroecosystems: State of the Science.

We propose a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of natural ecosystems, and agricultural productivity. Available evidence for each causal link is briefly summarized, and key knowledge gaps are highlighted. A lack of quantitative estimates of human exposure to environmental bacteria, in general, and antibiotic-resistant bacteria, specifically, is a significant data gap hindering the assessment of effects on human health. The contribution of horizontal gene transfer to resistance in the environment and conditions that might foster the horizontal transfer of antibiotic resistance genes into human pathogens also need further research. Existing research has focused heavily on human health effects, with relatively little known about the effects of antibiotics and antibiotic resistance on natural and agricultural ecosystems. The proposed causal model is used to elucidate gaps in knowledge that must be addressed by the research community and may provide a useful starting point for the design and analysis of future research efforts.

Meta-Analysis of Cardiac Mortality in Three Cohorts of Carbon Black Production Workers.

Epidemiological studies have demonstrated associations between airborne environmental particle exposure and cardiac disease and mortality; however, few have examined such effects from poorly soluble particles of low toxicity such as manufactured carbon black (CB) particles in the work place. We combined standardised mortality ratio (SMR) and Cox proportional hazards results from cohort studies of US, UK and German CB production workers. Under a common protocol, we analysed mortality from all causes, heart disease (HD), ischemic heart disease (IHD) and acute myocardial infarction (AMI). Fixed and random effects (RE) meta-regression models were fit for employment duration, and for overall cumulative and lugged quantitative CB exposure estimates. Full cohort meta-SMRs (RE) were 1.01 (95% confidence interval (CI) 0.79–1.29) for HD; 1.02 (95% CI 0.80–1.30) for IHD, and 1.08 (95% CI 0.74–1.59) for AMI mortality. For all three outcomes, meta-SMRs were heterogeneous, increased with time since first and time since last exposure, and peaked after 25–29 or 10–14 years, respectively. Meta-Cox coefficients showed no association with lugged duration of exposure. A small but imprecise increased AMI mortality risk was suggested for cumulative exposure (RE-hazards ratio (HR) = 1.10 per 100 mg/m3-years; 95% CI 0.92–1.31), but not for lugged exposures. Our results do not demonstrate that airborne CB exposure increases all-cause or cardiac disease mortality.

Esophagus cancer and occupational exposure to asbestos: results from a meta-analysis of epidemiology studies.

The relationship between occupational asbestos exposure and esophagus cancer (EC) is not fully understood. We performed a meta-analysis to quantitatively assess the association. We systematically searched databases of PubMed, EMBASE, and Web of Science for studies with quantitative estimates of asbestos exposure and EC mortality. Pooled standardized mortality ratios (SMRs) and their corresponding 95% confidence intervals (CIs) were calculated. Twenty cohort studies on EC and asbestos exposure were included in this meta-analysis. Overall, occupational exposure to asbestos was associated with an excess risk of EC (SMR = 1.24, 95% CI: 1.13-1.38, P < 0.001), with little evidence of heterogeneity among studies (I(2) = 0.0%, P = 0.682). Being male, exposure to chrysotile or mixed asbestos, working at textile industry, long study follow-up (≥20 years), Asia, Europe and America cohorts with larger cohort size (>500), and high-exposure group all contribute to significantly higher SMR. Publication bias was not detected (Egger's test P-value = 0.374). This meta-analysis suggested that occupational asbestos exposure might be associated with an increased risk of EC in male. High-exposure level of asbestos could contribute to significantly higher risk of EC mortality.

Transfer of oxytetracycline from swine manure to three different aquatic plants: Implications for human exposure

Little is known regarding the potential for pharmaceuticals including antibiotics to be accumulated in edible aquatic plants and enter the human food chain. This work investigates the transfer of a widely used veterinary antibiotic, oxytetracycline (OTC), from swine manure to aquatic plants by firstly characterizing desorption from swine manure to water and fitting data to both nonlinear and linear isotherms. Bioconcentration of OTC from water was then quantified with aquatic plants of contrasting morphology and growth habit viz. watermeal (Wolffia globosa Hartog and Plas), cabomba (Cabomba caroliniana A. Gray) and water spinach (Ipomoea aquatica Forsk.). Watermeal and water spinach are widely consumed in Southeast Asia. The OTC desorption and bioconcentration data were used to provide the first quantitative estimates of human exposure to OTC from a manure-water-aquatic plant route. Results show that under certain conditions (plants growing for 15d in undiluted swine manure effluent (2% w/v solids) and an initial OTC swine manure concentration of 43mgkg−1 (dry weight)), this pathway could provide a significant fraction (>48%) of the acceptable daily intake (ADI) for OTC. While effluent dilution, lower OTC manure concentrations and not all plant material consumed being contaminated would be expected to diminish the proportion of the ADI accumulated, uptake from aquatic plants should not be ignored when determining human exposure to antibiotics such as OTC.

An expert-based job exposure matrix for large scale epidemiologic studies of primary hip and knee osteoarthritis: the Lower Body JEM.

BackgroundWhen conducting large scale epidemiologic studies, it is a challenge to obtain quantitative exposure estimates, which do not rely on self-report where estimates may be influenced by symptoms and knowledge of disease status. In this study we developed a job exposure matrix (JEM) for use in population studies of the work-relatedness of hip and knee osteoarthritis.MethodsBased on all 2227 occupational titles in the Danish version of the International Standard Classification of Occupations (D-ISCO 88), we constructed 121 job groups comprising occupational titles with expected homogeneous exposure patterns in addition to a minimally exposed job group, which was not included in the JEM. The job groups were allocated the mean value of five experts’ ratings of daily duration (hours/day) of standing/walking, kneeling/squatting, and whole-body vibration as well as total load lifted (kg/day), and frequency of lifting loads weighing ≥20 kg (times/day). Weighted kappa statistics were used to evaluate inter-rater agreement on rankings of the job groups for four of these exposures (whole-body vibration could not be evaluated due to few exposed job groups). Two external experts checked the face validity of the rankings of the mean values.ResultsA JEM was constructed and English ISCO codes were provided where possible. The experts’ ratings showed fair to moderate agreement with respect to rankings of the job groups (mean weighted kappa values between 0.36 and 0.49). The external experts agreed on 586 of the 605 rankings.ConclusionThe Lower Body JEM based on experts’ ratings was established. Experts agreed on rankings of the job groups, and rankings based on mean values were in accordance with the opinion of external experts.

0333 The contribution of occupational studies to the identification of carcinogens in the IARC Monographs and how to further improve it

ObjectivesTo discuss the important role of occupational studies in identifying carcinogens and suggest how it could be still greater.MethodThe contribution of occupational studies to the IARC monographs is reviewed.ResultsOccupational epidemiology...