Polycyclic aromatic hydrocarbons in residential dust: sources of variability.

BackgroundThere is interest in using residential dust to estimate human exposure to environmental contaminants.ObjectivesWe aimed to characterize the sources of variability for polycyclic aromatic hydrocarbons (PAHs) in residential dust and provide guidance for investigators who plan to use residential dust to assess exposure to PAHs.MethodsWe collected repeat dust samples from 293 households in the Northern California Childhood Leukemia Study during two sampling rounds (from 2001 through 2007 and during 2010) using household vacuum cleaners, and measured 12 PAHs using gas chromatography-mass spectrometry. We used a random- and a mixed-effects model for each PAH to apportion observed variance into four components and to identify sources of variability.ResultsMedian concentrations for individual PAHs ranged from 10 to 190 ng/g of dust. For each PAH, total variance was apportioned into regional variability (1-9%), intraregional between-household variability (24-48%), within-household variability over time (41-57%), and within-sample analytical variability (2-33%). Regional differences in PAH dust levels were associated with estimated ambient air concentrations of PAH. Intraregional differences between households were associated with the residential construction date and the smoking habits of residents. For some PAHs, a decreasing time trend explained a modest fraction of the within-household variability; however, most of the within-household variability was unaccounted for by our mixed-effects models. Within-household differences between sampling rounds were largest when the interval between dust sample collections was at least 6 years in duration.ConclusionsOur findings indicate that it may be feasible to use residential dust for retrospective assessment of PAH exposures in studies of health effects

Untargeted lipidomic features associated with colorectal cancer in a prospective cohort.

BackgroundEpidemiologists are beginning to employ metabolomics and lipidomics with archived blood from incident cases and controls to discover causes of cancer. Although several such studies have focused on colorectal cancer (CRC), they all followed targeted or semi-targeted designs that limited their ability to find discriminating molecules and pathways related to the causes of CRC.MethodsUsing an untargeted design, we measured lipophilic metabolites in prediagnostic serum from 66 CRC patients and 66 matched controls from the European Prospective Investigation into Cancer and Nutrition (Turin, Italy). Samples were analyzed by liquid chromatography-high-resolution mass spectrometry (LC-MS), resulting in 8690 features for statistical analysis.ResultsRather than the usual multiple-hypothesis-testing approach, we based variable selection on an ensemble of regression methods, which found nine features to be associated with case-control status. We then regressed each selected feature on time-to-diagnosis to determine whether the feature was likely to be either a potentially causal biomarker or a reactive product of disease progression (reverse causality).ConclusionsOf the nine selected LC-MS features, four appear to be involved in CRC etiology and merit further investigation in prospective studies of CRC. Four other features appear to be related to progression of the disease (reverse causality), and may represent biomarkers of value for early detection of CRC

Dermal Exposure to Jet Fuel JP-8 Significantly Contributes to the Production of Urinary Naphthols in Fuel-Cell Maintenance Workers

Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been recognized as a major source of chemical exposure, both inhalation and dermal, for fuel-cell maintenance workers. We investigated the contributions of dermal and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel-cell maintenance workers using naphthalene as a surrogate for JP-8 exposure. Dermal, breathing zone, and exhaled breath measurements of naphthalene were obtained using tape-strip sampling, passive monitoring, and glass bulbs, respectively. Levels of urinary 1- and 2-naphthols were determined in urine samples and used as biomarkers of JP-8 exposure. Multiple linear regression analyses were conducted to investigate the relative contributions of dermal and inhalation exposure to JP-8, and demographic and work-related covariates, to the levels of urinary naphthols. Our results show that both inhalation exposure and smoking significantly contributed to urinary 1-naphthol levels. The contribution of dermal exposure was significantly associated with levels of urinary 2-naphthol but not with urinary 1-naphthol among fuel-cell maintenance workers who wore supplied-air respirators. We conclude that dermal exposure to JP-8 significantly contributes to the systemic dose and affects the levels of urinary naphthalene metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic studies are warranted in order to gain additional knowledge on naphthalene metabolism in the skin and the contribution to systemic exposure

Health and environmental consequences of the world trade center disaster.

The attack on the World Trade Center (WTC) created an acute environmental disaster of enormous magnitude. This study characterizes the environmental exposures resulting from destruction of the WTC and assesses their effects on health. Methods include ambient air sampling; analyses of outdoor and indoor settled dust; high-altitude imaging and modeling of the atmospheric plume; inhalation studies of WTC dust in mice; and clinical examinations, community surveys, and prospective epidemiologic studies of exposed populations. WTC dust was found to consist predominantly (95%) of coarse particles and contained pulverized cement, glass fibers, asbestos, lead, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated furans and dioxins. Airborne particulate levels were highest immediately after the attack and declined thereafter. Particulate levels decreased sharply with distance from the WTC. Dust pH was highly alkaline (pH 9.0-11.0). Mice exposed to WTC dust showed only moderate pulmonary inflammation but marked bronchial hyperreactivity. Evaluation of 10,116 firefighters showed exposure-related increases in cough and bronchial hyperreactivity. Evaluation of 183 cleanup workers showed new-onset cough (33%), wheeze (18%), and phlegm production (24%). Increased frequency of new-onset cough, wheeze, and shortness of breath were also observed in community residents. Follow-up of 182 pregnant women who were either inside or near the WTC on 11 September showed a 2-fold increase in small-for-gestational-age (SGA) infants. In summary, environmental exposures after the WTC disaster were associated with significant adverse effects on health. The high alkalinity of WTC dust produced bronchial hyperreactivity, persistent cough, and increased risk of asthma. Plausible causes of the observed increase in SGA infants include maternal exposures to PAH and particulates. Future risk of mesothelioma may be increased, particularly among workers and volunteers exposed occupationally to asbestos. Continuing follow-up of all exposed populations is required to document the long-term consequences of the disaster

Enrichment of cysteinyl adducts of human serum albumin

We report a method to enrich cysteinyl adducts of human serum albumin (HSA)2, representing biomarkers of exposure to systemic electrophiles. Because the major site of HSA adduction is the single free sulfhydryl group at Cys34, we used thiol-affinity resins to remove mercaptalbumin (i.e., unadducted HSA) from the cysteinyl adducts. Electrospray ionization mass spectrometry was used to detect mercaptalbumin and HSA-Cys34 modifications before and after enrichment of HSA. Differences in adduct content were detected across samples of freshly-isolated, archived, and commercial HSA. Cysteinylated and glycosylated adducts were present in all samples with abundances decreasing in the order: commercial HSA > archived HSA > fresh HSA. After enrichment of HSA, mercaptalbumin was no longer observed in mass spectra. The ratio of HSA adducts post-/pre-enrichment, quantified via the Bradford assay and gel electrophoresis, was 0.029 mg adducts/mg HSA in fresh HSA and 0.323 mg adducts/mg HSA in archived HSA. The apparent elevation of adduct levels in archived samples could be due to differences in specimen preparation and storage, rather than to differences in circulating HSA adducts. We conclude that thiol-affinity resins can efficiently remove mercaptalbumin from HSA samples prior to characterization and quantitation of protein adducts of reactive systemic electrophiles

Albumin Adducts of Electrophilic Benzene Metabolites in Benzene-Exposed and Control Workers

BACKGROUND: Metabolism of benzene produces reactive electrophiles, including benzene oxide (BO), 1,4-benzoquinone (1,4-BQ), and 1,2-benzoquinone (1,2-BQ), that are capable of reacting with blood proteins to produce adducts. OBJECTIVES: The main purpose of this study was to characterize relationships between levels of albumin adducts of these electrophiles in blood and the corresponding benzene exposures in benzene-exposed and control workers, after adjusting for important covariates. Because second blood samples were obtained from a subset of exposed workers, we also desired to estimate within-person and between-person variance components for the three adducts. METHODS: We measured albumin adducts and benzene exposures in 250 benzene-exposed workers (exposure range, 0.26–54.5 ppm) and 140 control workers (exposure range < 0.01–0.53 ppm) from Tianjin, China. Separate multiple linear regression models were fitted to the logged adduct levels for workers exposed to benzene < 1 ppm and ≥ 1 ppm. Mixed-effects models were used to estimate within-person and between-person variance components of adduct levels. RESULTS: We observed nonlinear (hockey-stick shaped) exposure–adduct relationships in log-scale, with inflection points between about 0.5 and 5 ppm. These inflection points represent air concentrations at which benzene contributed marginally to background adducts derived from smoking and from dietary and endogenous sources. Adduct levels were significantly affected by the blood-collection medium (serum or plasma containing either heparin or EDTA), smoking, age, and body mass index. When model predictions of adduct levels were plotted versus benzene exposure ≥ 1 ppm, we observed marked downward concavity, particularly for adducts of the benzoquinones. The between-person variance component of adduct levels increased in the order 1,2-BQ < 1,4-BQ < BO, whereas the within-person variance components of the three adducts followed the reverse order. CONCLUSIONS: Although albumin adducts of BO and the benzoquinones reflect exposures to benzene ≥ 1 ppm, they would not be useful biomarkers of exposure at ambient levels of benzene, which tend to be < 0.01 ppm, or in those working populations where exposures are consistently < 1 ppm. The concavity of exposure–adduct relationships is consistent with saturable metabolism of benzene at air concentrations > 1 ppm. The surprisingly large effect of the blood-collection medium on adduct levels, particularly those of the benzoquinones, should be further investigated