Distribution of 2,2',5,5'-Tetrachlorobiphenyl (PCB52) Metabolites in Adolescent Rats after Acute Nose-Only Inhalation Exposure.

Inhalation of PCB-contaminated air is increasingly recognized as a route for PCB exposure. Because limited information about the disposition of PCBs following inhalation exposure is available, this study investigated the disposition of 2,2',5,5'-tetrachlorobiphenyl (PCB52) and its metabolites in rats following acute, nose-only inhalation of PCB52. Male and female Sprague-Dawley rats (50-58 days of age, 210 ± 27 g; n = 6) were exposed for 4 h by inhalation to approximately 14 or 23 µg/kg body weight of PCB52 using a nose-only exposure system. Sham animals (n = 6) were exposed to filtered lab air. Based on gas chromatography-tandem mass spectrometry (GC-MS/MS), PCB52 was present in adipose, brain, intestinal content, lung, liver, and serum. 2,2',5,5'-Tetrachlorobiphenyl-4-ol (4-OH-PCB52) and one unknown monohydroxylated metabolite were detected in these compartments except for the brain. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis identified several metabolites, including sulfated, methoxylated, and dechlorinated PCB52 metabolites. These metabolites were primarily found in the liver (7 metabolites), lung (9 metabolites), and serum (9 metabolites) due to the short exposure time. These results demonstrate for the first time that complex mixtures of sulfated, methoxylated, and dechlorinated PCB52 metabolites are formed in adolescent rats following PCB52 inhalation, laying the groundwork for future animal studies of the adverse effects of inhaled PCB52.

Long-term cancer and overall mortality associated with drinking water nitrate in the United States.

OBJECTIVES: Nitrate is a probable carcinogen regulated in drinking water by the US Environmental Protection Agency (EPA) to a maximum contaminant level (MCL) of 10 mg/L nitrate-nitrogen (NO3-N; equivalent to 44.3 mg/L NO3). We aimed to determine the association of US drinking water nitrate levels with overall as well as cardiovascular, cancer, and other cause mortality. STUDY DESIGN: This study used a population-based retrospective cohort design. METHODS: We analyzed data from 2029 participants of the 2005-2006 National Health and Nutrition Examination Survey followed for mortality until 2019 for a median of 13.9 years. We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) for mortality associated with drinking water nitrate, adjusting for covariates that included socio-economic factors and pack-years of cigarette smoking. RESULTS: Drinking water nitrate was detected in 50.8 % of the samples, had a median concentration of 0.77 mg/L NO3, and was above US EPA MCL in 0.4 % of participants. In adjusted analysis, drinking water nitrate detection was associated with 73 % higher cancer mortality (HR: 1.73, 95% CI: 1.19-2.51), whereas a 10-fold increase in drinking water nitrate levels was associated with 69 % higher cancer mortality (HR: 1.69, 95% CI: 1.24-2.31) and 21 % higher overall mortality (HR: 1.21, 95% CI: 1.00-1.46). Drinking water nitrate below EPA MCL was still associated with higher cancer mortality (HR: 1.61, 95% CI: 1.07-2.43 per 10-fold increase and HR: 1.61, 95% CI: 1.08-2.42 for detection). CONCLUSIONS: Levels of drinking water nitrate may be an overlooked contributor to cancer mortality in the United States.

Use of a polymeric implant system to assess the neurotoxicity of subacute exposure to 2,2',5,5'-tetrachlorobiphenyl-4-ol, a human metabolite of PCB 52, in male adolescent rats.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that ubiquitously exist in the environment. PCB exposure has been linked to cancer and multi-system toxicity, including endocrine disruption, immune inhibition, and reproductive and neurotoxicity. 2,2',5,5'-Tetrachlorobiphenyl (PCB 52) is one of the most frequently detected congeners in the environment and human blood. The hydroxylated metabolites of PCB 52 may also be neurotoxic, especially for children whose brains are still developing. However, it is challenging to discern the contribution of these metabolites to PCB neurotoxicity because the metabolism of PCB is species-dependent. In this study, we evaluated the subacute neurotoxicity of a human-relevant metabolite, 2,2',5,5'-tetrachlorobiphenyl-4-ol (4-52), on male adolescent Sprague Dawley rats, via a novel polymeric implant drug delivery system grafted subcutaneously, at total loading concentrations ranging from 0%, 1%, 5%, and 10% of the implant (w/w) for 28 days. Y-maze, hole board test, open field test, and elevated plus maze were performed on exposure days 24-28 to assess their locomotor activity, and exploratory and anxiety-like behavior. 4-52 and other possible hydroxylated metabolites in serum and vital tissues were quantified using gas chromatography with tandem mass spectrometry (GC-MS/MS). Our results demonstrate the sustained release of 4-52 from the polymeric implants into the systemic circulation in serum and tissues. Dihydroxylated and dechlorinated metabolites were detected in serum and tissues, depending on the dose and tissue type. No statistically significant changes were observed in the neurobehavioral tasks across all exposure groups. The results demonstrate that subcutaneous polymeric implants provide a straightforward method to expose rats to phenolic PCB metabolites to study neurotoxic outcomes, e.g., in memory, anxiety, and exploratory behaviors.

Identification of PCB congeners and their thresholds associated with diabetes using decision tree analysis.

Few studies have investigated the potential combined effects of multiple PCB congeners on diabetes. To address this gap, we used data from 1244 adults in the National Health and Nutrition Examination Survey (NHANES) 2003-2004. We used (1) classification trees to identify serum PCB congeners and their thresholds associated with diabetes; and (2) logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of diabetes with combined PCB congeners. Of the 40 PCB congeners examined, PCB 126 has the strongest association with diabetes. The adjusted OR of diabetes comparing PCB 126 > 0.025 to ≤ 0.025 ng/g was 2.14 (95% CI 1.30-3.53). In the subpopulation with PCB 126 > 0.025 ng/g, a lower PCB 101 concentration was associated with an increased risk of diabetes (comparing PCB 101 < 0.72 to ≥ 0.72 ng/g, OR 3.3, 95% CI 1.27-8.55). In the subpopulation with PCB 126 > 0.025 & PCB 101 < 0.72 ng/g, a higher PCB 49 concentration was associated with an increased risk of diabetes (comparing PCB 49 > 0.65 to ≤ 0.65 ng/g, OR 2.79, 95% CI 1.06-7.35). This nationally representative study provided new insights into the combined associations of PCBs with diabetes.

Immunomodulatory Effects of Subacute Inhalation Exposure to Copper Oxide Nanoparticles in House Dust Mite-Induced Asthma.

It has been shown that inhalation exposure to copper oxide nanoparticles (CuO NPs) results in pulmonary inflammation. However, immunomodulatory consequences after CuO NP inhalation exposure have been less explored. We tested the effect of CuO NP aerosols on immune responses in healthy, house dust mite (HDM) asthmatic, or allergen immunotherapy (AIT)-treated asthmatic mice (BALB/c, females). The AIT consisted of a vaccine comprising HDM allergens and CpG-loaded nanoparticles (CpG NPs). AIT treatment involved mice being immunized (via subcutaneous (sc) injection; 2 doses) while concomitantly being exposed to CuO NP aerosols (over a 2 week period), starting on the day of the first vaccination. Mice were then sensitized twice by sc injection and subsequently challenged with HDM extract 10 times by intranasal instillation. The asthmatic model followed the same timeline except that no immunizations were administered. All mice were necropsied 24 h after the end of the HDM challenge. CuO NP-exposed healthy mice showed a significant decrease in TH1 and TH2 cells, and an elevation in T-bet+ Treg cells, even 40 days after the last exposure to CuO NPs. Similarly, the CuO NP-exposed HDM asthma model demonstrated decreased TH2 responses and increased T-bet+ Treg cells. Conversely, CuO NP inhalation exposure to AIT-treated asthmatic mice resulted in an increase in TH2 cells. In conclusion, immunomodulatory effects of inhalation exposure to CuO NPs are dependent on immune conditions prior to exposure.

Identification of PCB Congeners and their Thresholds associated with Diabetes using Decision Tree Analysis.

Few studies have investigated the potential combined effects of multiple PCB congeners on diabetes. To address this gap, we used data from 1244 adults in the National Health and Nutrition Examination Survey (NHANES) 2003-2004. We used 1) classification trees to identify serum PCB congeners and their thresholds associated with diabetes; and 2) logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of diabetes with combined PCB congeners. Of the 40 PCB congeners examined, PCB 126 has the strongest association with diabetes. The adjusted OR of diabetes comparing PCB 126 > 0.025 to ≤ 0.025 ng/g was 2.14 (95% CI 1.30-3.53). In the subpopulation with PCB 126 > 0.025 ng/g, a lower PCB 101 concentration was associated with an increased risk of diabetes (comparing PCB 101 < 0.72 to ≥ 0.72 ng/g, OR = 3.3, 95% CI: 1.27-8.55). In the subpopulation with PCB 126 > 0.025&PCB 101 < 0.72 ng/g, a higher PCB 49 concentration was associated with an increased risk of diabetes (comparing PCB 49 > 0.65 to ≤ 0.65 ng/g, OR = 2.79, 95% CI: 1.06-7.35). This nationally representative study provided new insights into the combined associations of PCBs with diabetes.

An algorithm for quantitatively estimating occupational endotoxin exposure in the biomarkers of exposure and effect in agriculture study: II. Application to the study population.

BACKGROUND: We developed an algorithm to quantitatively estimate endotoxin exposure for farmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) Study. METHODS: The algorithm combined task intensity estimates derived from published data with questionnaire responses on activity duration to estimate task-specific cumulative endotoxin exposures for 13 tasks during four time windows, ranging from "past 12 months" to "yesterday/today." We applied the algorithm to 1681 participants in Iowa and North Carolina. We examined correlations in endotoxin metrics within- and between-task. We also compared these metrics to prior day full-shift inhalable endotoxin concentrations from 32 farmers. RESULTS: The highest median task-specific cumulative exposures were observed for swine confinement, poultry confinement, and grind feed. Inter-quartile ranges showed substantial between-subject variability for most tasks. Time window-specific metrics of the same task were moderately-highly correlated. Between-task correlation was variable, with moderately-high correlations observed for similar tasks (e.g., between animal-related tasks). Prior day endotoxin concentration increased with the total metric and with task metrics for swine confinement, clean other animal facilities, and clean grain bins. SIGNIFICANCE: This study provides insight into the variability and sources of endotoxin exposure among farmers in the BEEA study and summarizes exposure estimates for future investigations in this population.

An algorithm for quantitatively estimating occupational endotoxin exposure in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study: I. Development of task-specific exposure levels from published data.

BACKGROUND/OBJECTIVE: Farmers conduct numerous tasks with potential for endotoxin exposure. As a first step to characterize endotoxin exposure for farmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) Study, we used published data to estimate task-specific endotoxin concentrations. METHODS: We extracted published data on task-specific, personal, inhalable endotoxin concentrations for agricultural tasks queried in the study questionnaire. The data, usually abstracted as summary measures, were evaluated using meta-regression models that weighted each geometric mean (GM, natural-log transformed) by the inverse of its within-study variance to obtain task-specific predicted GMs. RESULTS: We extracted 90 endotoxin summary statistics from 26 studies for 9 animal-related tasks, 30 summary statistics from 6 studies for 3 crop-related tasks, and 10 summary statistics from 5 studies for 4 stored grain-related tasks. Work in poultry and swine confinement facilities, grinding feed, veterinarian services, and cleaning grain bins had predicted GMs > 1000 EU/m3 . In contrast, harvesting or hauling grain and other crop-related tasks had predicted GMs below 100 EU/m3 . SIGNIFICANCE: These task-specific endotoxin GMs demonstrated exposure variability across common agricultural tasks. These estimates will be used in conjunction with questionnaire responses on task duration to quantitatively estimate endotoxin exposure for study participants, described in a companion paper.

Innovative compounds to reduce ß-D-glucans, endotoxin, and allergens newly discovered on smartphones.

Background: Eight-four percent of people own smartphones and view them 14 billion times daily, making them potential vectors for environmental hazards such as allergens, ß-D-glucans (BDGs), and endotoxin. Whether these toxins are prevalent and the effectiveness of cleaning solutions targeting these agents on smartphones have not been studied. Objective: We sought to determine (1) whether phones are reservoirs of allergen, endotoxin, and BDGs and (2) if present, whether their levels can be effectively reduced by using specific cleaning methods. Methods: Electrostatic wipes used to wipe the phones of 15 volunteers were tested to determine their allergen, BDG, and endotoxin levels. Cleaning interventions were done on simulated phone models; 70% isopropyl alcohol, 0.184% benzyl and ethyl benzyl ammonium chloride (Clorox nonbleach [The Chlorox Company, Oakland, Calif]), 0.12% chlorhexidine, 0.05% cetylpyridinium, 3% benzyl benzoate, and 3% tannic acid wipes were used and compared with wipes with no solution (the control). Results: The smartphones showed high and variable levels of BDG and endotoxin. Cat and dog allergens were found mostly on the smartphones of pet owners. The combination of chlorhexidine and cetylpyridinium significantly reduced BDG levels (mean 269 ng/wipe vs 1930 ng/wipe for the control [P < .05]) and endotoxin, (mean 349 vs 1320 endotoxin units/wipe for the control [P < .05]). The combination of benzyl benzoate and tannic acid significantly reduced the levels of cat and dog allergens (dog, mean level of 14 ng/wipe versus 407 ng/wipe for the control [P < .001]; cat, mean level of 55 ng/wipe versus 1550 ng/wipe for the control [P < .001]). The combination mixture solutions had the greatest reductions compared with the control. Conclusions: There are elevated levels of BDG, allergens, and endotoxin on smartphones. The combination of chlorhexidine and cetylpyridinium was the most effective in reducing BDG and endotoxin levels, and the combination of benzyl benzoate and tannic acid was most effective in reducing cat and dog allergen levels on smartphones.

Imaging-based assessment of lung function in a population cooking indoors with biomass fuel: a pilot study.

Biomass fuels (wood) are commonly used indoors in underventilated environments for cooking in the developing world, but the impact on lung physiology is poorly understood. Quantitative computed tomography (qCT) can provide sensitive metrics to compare the lungs of women cooking with wood vs. liquified petroleum gas (LPG). We prospectively assessed (qCT and spirometry) 23 primary female cooks (18 biomass, 5 LPG) with no history of cardiopulmonary disease in Thanjavur, India. CT was obtained at coached total lung capacity (TLC) and residual volume (RV). qCT assessment included texture-derived ground glass opacity [GGO: Adaptive Multiple Feature Method (AMFM)], air-trapping (expiratory voxels ≤ -856HU) and image registration-based assessment [Disease Probability Measure (DPM)] of emphysema, functional small airways disease (%AirTrapDPM), and regional lung mechanics. In addition, within-kitchen exposure assessments included particulate matter <2.5 µm(PM2.5), black carbon, ß-(1, 3)-d-glucan (surrogate for fungi), and endotoxin. Air-trapping went undetected at RV via the threshold-based measure (voxels ≤ -856HU), possibly due to density shifts in the presence of inflammation. However, DPM, utilizing image-matching, demonstrated significant air-trapping in biomass vs. LPG cooks (P = 0.049). A subset of biomass cooks (6/18), identified using k-means clustering, had markedly altered DPM-metrics: greater air-trapping (P < 0.001), lower TLC-RV volume change (P < 0.001), a lower mean anisotropic deformation index (ADI; P < 0.001), and elevated % GGO (P < 0.02). Across all subjects, a texture measure of bronchovascular bundles was correlated to the log-transformed ß-(1, 3)-d-glucan concentration (P = 0.026, R = 0.46), and black carbon (P = 0.04, R = 0.44). This pilot study identified environmental links with qCT-based lung pathologies and a cluster of biomass cooks (33%) with significant small airways disease.NEW & NOTEWORTHY Quantitative computed tomography has identified a cluster of women (33%) cooking with biomass fuels (wood) with image-based markers of functional small airways disease and associated alterations in regional lung mechanics. Texture and image registration-based metrics of lung function may allow for early detection of potential inflammatory processes that may arise in response to inhaled biomass smoke, and help identify phenotypes of chronic lung disease prevalent in nonsmoking women in the developing world.

Blood Concentrations of Volatile Organic Compounds Among US Workers From Various Trades.

OBJECTIVE: This study aimed to examine blood benzene, toluene, ethylbenzene, o-xylene, and m-/p-xylene (BTEX) concentrations and their trends contrasting construction workers with workers in other occupations from 1999 to 2014 in the United States. Methods: Using data from the National Health and Nutrition Examination Survey, quantile regressions were performed to investigate associations between occupation and blood BTEX concentrations. Results: We found that high-risk and construction occupations were associated with increased blood concentrations of toluene, o-xylene, and m-/p-xylene at the 50-90th percentiles (P 50-90 ), and ethylbenzene at P 70-90 . Moreover, although blood concentrations of ethylbenzene, o-xylene, and m-/p-xylene trended down among all US workers, no decreasing trend was observed for benzene and toluene among construction workers. Conclusions: Future studies are warranted to address questions about specific tasks to better assess VOC exposure from various trades.

Implementing machine learning methods with complex survey data: Lessons learned on the impacts of accounting sampling weights in gradient boosting.

Despite the prominent use of complex survey data and the growing popularity of machine learning methods in epidemiologic research, few machine learning software implementations offer options for handling complex samples. A major challenge impeding the broader incorporation of machine learning into epidemiologic research is incomplete guidance for analyzing complex survey data, including the importance of sampling weights for valid prediction in target populations. Using data from 15, 820 participants in the 1988-1994 National Health and Nutrition Examination Survey cohort, we determined whether ignoring weights in gradient boosting models of all-cause mortality affected prediction, as measured by the F1 score and corresponding 95% confidence intervals. In simulations, we additionally assessed the impact of sample size, weight variability, predictor strength, and model dimensionality. In the National Health and Nutrition Examination Survey data, unweighted model performance was inflated compared to the weighted model (F1 score 81.9% [95% confidence interval: 81.2%, 82.7%] vs 77.4% [95% confidence interval: 76.1%, 78.6%]). However, the error was mitigated if the F1 score was subsequently recalculated with observed outcomes from the weighted dataset (F1: 77.0%; 95% confidence interval: 75.7%, 78.4%). In simulations, this finding held in the largest sample size (N = 10,000) under all analytic conditions assessed. For sample sizes <5,000, sampling weights had little impact in simulations that more closely resembled a simple random sample (low weight variability) or in models with strong predictors, but findings were inconsistent under other analytic scenarios. Failing to account for sampling weights in gradient boosting models may limit generalizability for data from complex surveys, dependent on sample size and other analytic properties. In the absence of software for configuring weighted algorithms, post-hoc re-calculations of unweighted model performance using weighted observed outcomes may more accurately reflect model prediction in target populations than ignoring weights entirely.

Multilevel Risk Factors for Sleep-Disordered Breathing-Related Symptom Burden in an Urban Pediatric Community-Based Sample.

BACKGROUND: Pediatric sleep-disordered breathing (SDB) disproportionately affects children with low socioeconomic status (SES). The multilevel risk factors that drive these associations are not well understood. RESEARCH QUESTION: What are the associations between SDB risk factors, including individual health conditions (obesity, asthma, and allergies), household SES (maternal education), indoor exposures (environmental tobacco smoke [ETS] and pests), and neighborhood characteristics (neighborhood disadvantage), and pediatric SDB symptoms? STUDY DESIGN AND METHODS: Cross-sectional analyses were performed on 303 children (aged 6-12 years) enrolled in the Environmental Assessment of Sleep Youth study from 2018 to 2022. Exposures were determined by caregiver reports, assays of measured settled dust from the child's bedroom, and neighborhood-level Census data (deriving the Childhood Opportunity Index to characterize neighborhood disadvantage). The primary outcome was the SDB-related symptom burden assessed by the OSA-18 questionnaire total score. Using linear regression models, we calculated associations between exposures and SDB-related symptom burden, adjusting for sociodemographic factors, then health conditions, indoor environment, and neighborhood factors. RESULTS: The sample included 303 children (39% Hispanic, Latino, Latina, or Spanish origin; 30% Black or African American; 22% White; and 11% other). Increasing OSA-18 total scores were associated with low household SES after adjustment for demographic factors, and with asthma, allergies, ETS, pests (mouse, cockroach, and rodents), and an indoor environmental index (sum of the presence of pests and ETS; 0-2) after adjusting for sociodemographic factors. Even after further adjusting for asthma, allergies, and neighborhood disadvantage, ETS and pest exposure were associated with OSA-18 (ETS: ß = 12.80; 95% CI, 7.07-18.53, also adjusted for pest; pest exposure: ß = 3.69; 95% CI, 0.44-6.94, also adjusted for ETS). INTERPRETATION: In addition to associations with ETS, a novel association was observed for indoor pest exposure and SDB symptom burden. Strategies to reduce household exposure to ETS and indoor allergens should be tested as approaches for reducing sleep health disparities.

Characterization of sub-pollen particles in size-resolved atmospheric aerosol using chemical tracers.

Pollen grains may contain allergens that exacerbate allergic respiratory diseases like asthma and rhinitis. In the presence of water, pollen grains (10-100 µm) can rupture to produce sub-pollen particles (SPP) with diameters <2.5 µm, which in comparison to intact pollen grains, have longer atmospheric lifetimes and greater penetration to the lower lung. The current study examines SPP, fungal spores, and bacteria in size-resolved atmospheric particulate matter (PM) using chemical and biological tracers. During springtime tree pollen season in Iowa City, Iowa, fine particle (PM2.5) concentrations of fructose (a pollen chemical tracer) increased on rainy sampling periods, especially during severe thunderstorms, and peaked when a tornado struck nearby. Submicron fluorescent particles, measured by single-particle fluorescence spectroscopy, were also enhanced during rain events, particularly thunderstorms in agreement with the chemical tracer measurements. PM2.5 sucrose (a pollen chemical tracer) concentrations were higher in early spring when nighttime temperatures were closer to freezing, while fructose concentrations were higher in late spring with warmer temperatures, consistent with chemical tracers being sensitive to seasonal temperature influences. The first co-located measurements of fructose and Bet v 1 (birch pollen allergen), indicated that SPP ranged in diameter from <0.25 to 2.5 µm during rainy sampling periods and that allergens and carbohydrates exhibited distinct size distributions. Meanwhile, mannitol (a fungal spore tracer) peaked on warm, dry days following rain and was primarily in supermicron particles (>1.0 µm), which is consistent with intact fungal spore diameters (1-30 µm). Bacterial endotoxins in PM also increased during extreme weather events, primarily in supermicron particles. While the concentrations of fructose, mannitol, and endotoxin all increased in PM2.5 µm during thunderstorms, the greatest relative increase in concentration was observed for fructose. Together, these observations suggest that SPP containing starch granules and allergens (Bet v 1) were released during rainy sampling periods. This study advances the use of chemical tracers to track SPP and other bioaerosols in the atmosphere, by providing new insight to their size distribution and response to extreme weather conditions.

Cerium Oxide Enhances the Toxicity of Zinc Oxide Nanoparticles in Human Lung Epithelial Cell Cultures.

Recently, many approaches have been developed to improve the performance of nanomaterials. Combining more than one nanomaterial is one such approach that achieves superior results. However, during the fabrication of nanomaterials or formulation of end products, materials can be released into the ambient air and be inhaled by workers. The adverse health outcomes of inhaling such compounds are unknown. In this study, we examined such effects in combining two of the most utilized nanomaterials in several industrial sectors: zinc oxide (ZnO) and cerium oxide (CeO2). These materials can be found together in sunscreens, polyvinyl alcohol (PVA) films, and construction products. The aim of this study was to assess the adverse biological outcomes of CeO2-ZnO nano-mixtures in human lung epithelial cells. A549 human lung epithelial cells were treated with increasing concentrations of ZnO or CeO2 NPs alone, or as a mixture of both, under submerged conditions for 24 h. After treatment, cell viability, reactive oxygen species (ROS) formation, cell membrane integrity, and cytokine production were examined. ZnO NPs showed a dose-dependent trend for all endpoints. CeO2 NPs did not exhibit any toxic effect in any individual concentrations. When higher doses of ZnO were combined with increasing doses of CeO2, loss of cell viability and an elevation in cell membrane leakage were observed. Interleukin 8 (IL-8) and ROS generation were higher when ZnO NPs were combined with CeO2 NPs, compared to cells that were treated with ZnO alone. The release of monocyte chemoattractant protein-1 (MCP-1) was reduced in the cells that were treated with higher doses of ZnO and CeO2. Thus, the presence of CeO2 enhanced the toxicity of ZnO in A549 cells at non-toxic levels of CeO2. This suggests an additive toxicity of these two nanomaterials.

Occurrence and spatial distribution of individual polychlorinated biphenyl congeners in residential soils from East Chicago, southwest Lake Michigan.

We report individual polychlorinated biphenyl congeners and the sum of all congeners (ΣPCB) in residential soils of East Chicago, Indiana. ΣPCB in soils ranged from 20 to 1700 ng/g dry weight (DW), with a geometric mean of 120 ng/g DW. These values are significantly higher than other locations, but similar or lower to locations nearby well-known PCB contamination sites. No PCB spatial distribution pattern was observed. PCB concentrations increase with total organic carbon in the soils and proximity to Indiana Harbor and Ship Canal (IHSC), where sediments are contaminated with PCBs. Most samples are similar in their PCB distribution and Aroclor 1254 yielded the highest similarity to all the samples. A fifth of the samples highly resemble other PCB profiles such as EPA background and Cedar Rapids Iowa soils, and volatilization from Lake Michigan, whereas volatilization from IHSC could not explain the PCBs found in soils. IHSC was expected to be the main source of PCBs in the nearby soils. It is possible that soils are impacted by variety of known and unknown sources, including volatilization from Lake Michigan, resulting in a regional PCB signal. Although PCB concentrations are higher than other locations, samples were below the current US EPA non-cancer residential soil level remediation goal for dioxin TEQ.

Time course of pulmonary inflammation and trace element biodistribution during and after sub-acute inhalation exposure to copper oxide nanoparticles in a murine model.

BACKGROUND: It has been shown that copper oxide nanoparticles (CuO NPs) induce pulmonary toxicity after acute or sub-acute inhalation exposures. However, little is known about the biodistribution and elimination kinetics of inhaled CuO NPs from the respiratory tract. The purposes of this study were to observe the kinetics of pulmonary inflammation during and after CuO NP sub-acute inhalation exposure and to investigate copper (Cu) biodistribution and clearance rate from the exposure site and homeostasis of selected trace elements in secondary organs of BALB/c mice. RESULTS: Sub-acute inhalation exposure to CuO NPs led to pulmonary inflammation represented by increases in lactate dehydrogenase, total cell counts, neutrophils, macrophages, inflammatory cytokines, iron levels in bronchoalveolar lavage (BAL) fluid, and lung weight changes. Dosimetry analysis in lung tissues and BAL fluid showed Cu concentration increased steadily during exposure and gradually declined after exposure. Cu elimination from the lung showed first-order kinetics with a half-life of 6.5 days. Total Cu levels were significantly increased in whole blood and heart indicating that inhaled Cu could be translocated into the bloodstream and heart tissue, and potentially have adverse effects on the kidneys and spleen as there were significant changes in the weights of these organs; increase in the kidneys and decrease in the spleen. Furthermore, concentrations of selenium in kidneys and iron in spleen were decreased, pointing to disruption of trace element homeostasis. CONCLUSIONS: Sub-acute inhalation exposure of CuO NPs induced pulmonary inflammation, which was correlated to Cu concentrations in the lungs and started to resolve once exposure ended. Dosimetry analysis showed that Cu in the lungs was translocated into the bloodstream and heart tissue. Secondary organs affected by CuO NPs exposure were kidneys and spleen as they showed the disruption of trace element homeostasis and organ weight changes.

Serum antioxidant vitamins and respiratory morbidity and mortality: a pooled analysis.

BACKGROUND: Oxidative stress plays a key role in the pathogenesis of respiratory diseases; however, studies on antioxidant vitamins and respiratory outcomes have been conflicting. We evaluated whether lower serum levels of vitamins A, C, D, and E are associated with respiratory morbidity and mortality in the U.S. adult population. METHODS: We conducted a pooled analysis of data from the 1988-1994 and 1999-2006 National Health and Nutrition Examination Survey (participants aged ≥ 20 years). We estimated covariate-adjusted odds ratios (aOR) per interquartile decrease in each serum vitamin level to quantify associations with respiratory morbidity, and covariate-adjusted hazard ratios (aHR) to quantify associations with respiratory mortality assessed prospectively through 2015. Vitamin supplementation and smoking were evaluated as potential effect modifiers. RESULTS: Lower serum vitamin C increased the odds of wheeze among all participants (overall aOR: 1.08, 95% CI: 1.01-1.16). Among smokers, lower serum α-tocopherol vitamin E increased the odds of wheeze (aOR: 1.11, 95% CI: 1.04-1.19) and chronic bronchitis/emphysema (aOR: 1.13, 95% CI: 1.03-1.24). Conversely, lower serum γ-tocopherol vitamin E was associated with lower odds of wheeze and chronic bronchitis/emphysema (overall aORs: 0.85, 95% CI: 0.79-0.92 and 0.85, 95% CI: 0.76-0.95, respectively). Lower serum vitamin C was associated with increased chronic lower respiratory disease (CLRD) mortality in all participants (overall aHR: 1.27, 95% CI: 1.07-1.51), whereas lower serum 25-hydroxyvitamin D (25-OHD) tended to increase mortality from CLRD and influenza/pneumonia among smokers (aHR range: 1.33-1.75). Mortality from influenza/ pneumonia increased with decreasing serum vitamin A levels in all participants (overall aHR: 1.21, 95% CI: 0.99-1.48). In pooled analysis, vitamin C deficiency and 25-OHD insufficiency were associated with mortality from influenza/pneumonia, increasing mortality risk up to twofold. CONCLUSIONS: Our analysis of nationally representative data on over 34,000 participants showed that lower serum levels of vitamins A, C, D, and α-tocopherol vitamin E are associated with increased respiratory morbidity and/or mortality in U.S. adults. The results underscore the importance of antioxidant vitamins in respiratory health.

A Task-Specific Algorithm to Estimate Occupational (1→3)-ß-D-glucan Exposure for Farmers in the Biomarkers of Exposure and Effect in Agriculture Study.

OBJECTIVES: Farmers may be exposed to glucans (a cell component of molds) through a variety of tasks. The magnitude of exposure depends on each farmer's activities and their duration. We developed a task-specific algorithm to estimate glucan exposure that combines measurements of (1→3)-ß-D-glucan with questionnaire responses from farmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study. METHODS: To develop the algorithm, we first derived task-based geometric means (GMs) of glucan exposure for farming tasks using inhalable personal air sampling data from a prior air monitoring study in a subset of 32 BEEA farmers. Next, these task-specific GMs were multiplied by subject-reported activity frequencies for three time windows (the past 30 days, past 7 days, and past 1 day) to obtain subject-, task-, and time window-specific glucan scores. These were summed together to obtain a total glucan score for each subject and time window. We examined the within- and between-task correlation in glucan scores for different time frames. Additionally, we assessed the algorithm for the 'past 1 day' time window using full-shift concentrations from the 32 farmers who participated in air monitoring the day prior to an interview using multilevel statistical models to compare the measured glucan concentration with algorithm glucan scores. RESULTS: We focused on the five highest exposed tasks: poultry confinement (300 ng/m3), swine confinement (300 ng/m3), clean grain bins (200 ng/m3), grind feed (100 ng/m3), and stored seed or grain (50 ng/m3); the remaining tasks were <50 ng/m3 and had similar concentrations to each other. Overall, 67% of the participants reported at least one of these tasks. The most prevalent task was stored seed or grain (64%). The highest median glucan scores were observed for poultry confinement and swine confinement; these tasks were reported by 2% and 8% of the participants, respectively. The correlation between scores for the same task but different time windows was high for swine confinement and poultry confinement, but low for clean grain bins. Task-specific scores had low correlation with other tasks. Prior day glucan concentration was associated with the total glucan 'past 1 day' score and with swine confinement and clean grain bin task scores. CONCLUSIONS: This study provides insight into the variability and key sources of glucan exposure in a US farming population. It also provides a framework for better glucan exposure assessment in epidemiologic studies and is a crucial starting point for evaluating health risks associated with glucans in future epidemiologic evaluations of this population.

PCB Sulfates in Serum from Mothers and Children in Urban and Rural U.S. Communities.

Serum samples from 24 subjects (6 mother-daughter and 6 mother-son dyads) in a rural community (Columbus Junction, Iowa) and 24 subjects (6 mother-daughter and 6 mother-son dyads) in an urban community (East Chicago, Indiana) were analyzed for 74 sulfated metabolites of polychlorinated biphenyls (PCBs). We detected significantly higher mean concentrations of total assessed PCB sulfates in the urban group (110-8900 ng/g fresh weight of serum, mean = 3400 ng/g, standard error = 300) than in the rural cohort (530-6700 ng/g fresh weight of serum, mean = 1800 ng/g, standard error = 500). Eight PCB sulfate congeners (4-PCB 2 sulfate, 4'-PCB 2 sulfate, 2'-PCB 3 sulfate, 4'-PCB 3 sulfate, 4-PCB 11 sulfate, 4'-PCB 18 sulfate, 4'-PCB 25 sulfate, and 4-PCB 52 sulfate) contributed over 90% of the total assessed PCB sulfates in most individuals. The serum samples were enriched in PCB sulfates with fewer than 5 chlorine atoms, and this congener distribution differed from those of PCBs and hydroxylated PCBs in previous studies in the same communities. Regression analysis indicated several significant congener-specific correlations in mother-child dyads, and these relationships differed by location and by mother-daughter or mother-son dyads. This is the first study reporting a broad range of PCB sulfates in populations from urban and rural areas.