Particulate air pollution from different sources and mortality in 7.5 million adults - The Dutch Environmental Longitudinal Study (DUELS).

BACKGROUND: Long-term exposure to particulate air pollution has been associated with mortality in urban cohort studies. Few studies have investigated the association between emission contributions from different particle sources and mortality in large-scale population registries, including non-urban populations. OBJECTIVES: The aim of the study was to evaluate the associations between long-term exposure to particulate air pollution from different source categories and non-accidental mortality in the Netherlands based on existing national databases. METHODS: We used existing Dutch national databases on mortality, individual characteristics, residence history, neighbourhood characteristics and modelled air pollution concentrations from different sources and air pollution components: particulate matter PM10, primary particulate matter PM10 (PPM10), particulate matter PM2.5, primary particulate matter PM2.5 (PPM2.5), elemental carbon (EC), nitrogen dioxide (NO2) and secondary inorganic aerosol (SIA) in PM10 (SIA10) or in PM2.5 (SIA2.5). We established a cohort of 7.5 million individuals 30 years or older. We followed the cohort for eight years (2008-2015). We applied Cox proportional hazard regression models adjusting for potential individual and area-specific confounders. RESULTS: We found statistically significant associations between total and primary particulate matter (PM10 and PM2.5), elemental carbon and mortality. Adjustment for nitrogen dioxide did not change the associations. Secondary inorganic aerosol showed less consistent associations. All primary PM sources were associated with mortality, except agricultural emissions and, depending on the statistical model, industrial PM emissions. CONCLUSIONS: We could not identify one or more specific source categories of particulate air pollution as main determinants of the mortality effects found in this and in a previous study. This suggests that present policy measures should be focussed on the wider spectrum of air pollution sources instead of on specific sources.

The use of the DR CALUX bioassay and indicator polychlorinated biphenyls for screening of elevated levels of dioxins and dioxin-like polychlorinated biphenyls in eel.

The DR CALUX bioassay is a very suitable screening method for dioxins and dioxin-like-PCBs in feed and food. This was, e. g. demonstrated in a survey in the Netherlands to control the dioxin levels in eel. The DR CALUX assay, but also indicator polychlorinated biphenyls (PCB) were evaluated as a screening method. Based on the limit for polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/F) [at that time 8 pg toxic equivalents (TEQ)/g eel], and the relation between PCDD/F and dioxin-like-PCB, a decision limit of 30 pg TEQ/g eel was used for screening of 153 field samples. Suspected samples (21) and part of the higher contaminated negative samples (35) were analyzed by GC/MS for dioxins, non-ortho, mono-ortho and indicator PCB, revealing 13 samples exceeding the action limit of 30 pg TEQ/g eel. Only one sample slightly exceeded the dioxin level of 8 pg TEQ/g eel. The relatively low sensitivity for mono-ortho PCB was overcome by the use of reference samples, as shown by the correlation of 0.93 between GC/MS and CALUX determined total TEQ levels. The present data show that the DR CALUX assay can be used for screening of total TEQ levels in eel. The use for dioxins only requires a safe, and therefore relatively low, decision limit. The indicator PCB also showed a good correlation with total TEQ levels, mainly due to the large contribution of the mono-ortho PCB at higher concentrations. The relation with dioxins was very poor and as such indicator PCB seem less suitable than the DR CALUX assay for screening for dioxins only. The present study clearly shows that part of the wild eel samples contains high total TEQ levels and will exceed the future European Union limit of 12 pg TEQ/g eel for dioxins and dioxin-like PCB. Especially at high TEQ levels, dioxin-like PCB contribute most to the total TEQ. In practice, wild eel presents only a minor part of the eel consumed.

Stable isotope tagging of epitopes: a highly selective strategy for the identification of major histocompatibility complex class I-associated peptides induced upon viral infection.

Identification of peptides presented in major histocompatibility complex (MHC) class I molecules after viral infection is of strategic importance for vaccine development. Until recently, mass spectrometric identification of virus-induced peptides was based on comparative analysis of peptide pools isolated from uninfected and virus-infected cells. Here we report on a powerful strategy aiming at the rapid, unambiguous identification of naturally processed MHC class I-associated peptides, which are induced by viral infection. The methodology, stable isotope tagging of epitopes (SITE), is based on metabolic labeling of endogenously synthesized proteins during infection. This is accomplished by culturing virus-infected cells with stable isotope-labeled amino acids that are expected to be anchor residues (i.e. residues of the peptide that have amino acid side chains that bind into pockets lining the peptide-binding groove of the MHC class I molecule) for the human leukocyte antigen allele of interest. Subsequently these cells are mixed with an equal number of non-infected cells, which are cultured in normal medium. Finally peptides are acid-eluted from immunoprecipitated MHC molecules and subjected to two-dimensional nanoscale LC-MS analysis. Virus-induced peptides are identified through computer-assisted detection of characteristic, binomially distributed ratios of labeled and unlabeled molecules. Using this approach we identified novel measles virus and respiratory syncytial virus epitopes as well as infection-induced self-peptides in several cell types, showing that SITE is a unique and versatile method for unequivocal identification of disease-related MHC class I epitopes.

A systematic approach for optimisation of supercritical-fluid extraction of polycyclic aromatic hydrocarbons from earthworms.

A systematic approach using a mathematical model as an alternative to time-consuming empirical optimisation of a supercritical-fluid extraction (SFE) procedure is presented. The model was applied to the extraction of 15 polycyclic aromatic hydrocarbons (PAH). The selected fat-containing matrix is the earthworm used in ecotoxicological absorption studies. Settings for optimal recovery were established for the important parameters (temperature, pressure, amount of trapping sorbent, flow, and dynamic extraction time) using a D-optimal experimental design (including quadratic terms and interactions). The recoveries were modelled using a two sigmoid-model with parameters for each of the individual PAH. The main objective was to optimise the conditions for 15 PAH congeners by maximisation of the lowest recovery. The results show that for some parameters, e.g. the amount of sorbent material, optimal conditions are identical for all PAH. For other parameters, e.g. extraction time, the optimum is PAH dependent. The advantage of this optimisation procedure is that, within three days of analysis (73 experiments), optimised extraction conditions for the extraction of the set of 15 PAH were found but also optimum conditions for specific subsets can be extracted from the collected data for specific subsets.

Survey of the occurrence of residues of methyl tertiary butyl ether (MTBE) in Dutch drinking water sources and drinking water.

An indicative survey has been carried out in The Netherlands investigating the presence of methyl tertiary butyl ether (MTBE) in drinking water and the corresponding sources. In total, 71 different sites used for the preparation of drinking water in The Netherlands were sampled in two successive seasons in 2001 involving the analysis of 156 samples. (ground water (n = 88), surface water (n = 17), bank filtrate water (n = 6) and drinking water (n = 45)). To combine high sample throughput with high selectivity and sensitivity, off-line purge and trap for sampling and gas chromatography mass spectrometry equipped with an automated thermal desorption sampler (TDS-GC-MS) was selected as the preferred analytical methodology. The developed procedure enabled the analysis of at least 40 samples per day and provided a limit of quantification of 2 ng l(-1). In the first period 63 samples of raw water were analyzed. Concentrations ranged between < 10 ng l(-1) and 420 ng l(-1) with a median concentration below 10 ng l(-1). The second period was focused at the re-sampling of positive locations (MTBE > 10 ng l(-1)) and a few additional drinking water utilities of which both the raw and drinking water of the utilities were analyzed. The median concentration of MTBE in the selected set of drinking water samples was 20 ng l(-1) (n = 45). At one location MTBE was found at a level of 2900 ng l(-1) caused by point source contamination of the ground water (11 900 ng l(-1)). Special attention has been paid to the quality of the results by analyzing all samples in duplicate and the analysis of control samples during each series of analyses.