Stool titanium dioxide is positively associated with stool alpha-1 antitrypsin and calprotectin in young healthy adults.

Titanium dioxide (TiO2/E171) is used widely in foods, primarily as a food additive. Animal models have shown that chronic TiO2 exposure may disturb homeostasis of the gastrointestinal tract by increasing gut permeability, inducing gut inflammation, and increasing the likelihood of microbial infection. Adults have a wide range of ingested TiO2,which span two to three orders of magnitude, with a small portion of individuals consuming near gram quantities of TiO2/day. However, research on the health effects of chronic ingestion of TiO2/E171 in humans is limited. We hypothesized that regularly ingested TiO2/E171 is associated with increased gut inflammation and gut permeability in healthy adults. We tested this hypothesis in a cross-sectional design by measuring clinically established stool markers of gut inflammation (calprotectin, lactoferrin) and gut permeability (alpha-1 antitrypsin; A1AT) in 35 healthy adults, and comparing these markers between relatively high and low TiO2 exposure groups. Participants were stratified by TiO2 stool content (high dry stool TiO2 content: 0.95-9.92 µg/mg, n = 20; low content: 0.01-0.04 µg/mg; n = 15). Differences in gut health markers were tested between high and low exposure groups by independent samples t-test or Mann-Whitney U test. Multivariable linear regression was used to assess the association between TiO2 in dry stool and measured stool alpha-1 antitrypsin (A1AT). Participants in the high stool TiO2 group had greater stool A1AT (42.7 ± 21.6 mg/dL; median: 38.3; range: 1.0-49.2 mg/dL), compared to the low TiO2 group (22.8 ± 13.6 mg/dL; median: 20.9; range: 8.7-93.0 mg/dL), P = 0.003. There was also greater stool calprotectin in the high TiO2 group (51.4 ± 48.6 µg/g; median 29.2 µg/g; range: 15.3-199.0 µg/g) than in the low group (47.5 ± 63.3 µg/g; median 18.8 µg/g; range: 1.6-198.1 µg/g), P = 0.04. No clear difference was observed for lactoferrin (high TiO2 group 1.6 ± 2.1 µg/g; median: 0.68 µg/g; range: 0.01-7.7 µg/g, low TiO2 group: 1.3 ± 2.6 µg/g; median: 0.2; range: 0.01-7.6 µg/g) (P = 0.15). A1AT concentration was positively associated with stool TiO2, after adjusting for confounders (ß ± SE: 19.6 ± 7.2; P = 0.01) R2 = 0.38). Community dwelling, healthy adults with the highest TiO2 stool content had higher stool A1AT and calprotectin, compared to those with the lowest TiO2 stool content. Ongoing research is needed to validate these observations in larger groups, and to determine the long-term effects of ingested TiO2 on human gut health, using these and additional health endpoints.

Evaluation of disposable protective garments against epoxy resin permeation and penetration from anti-corrosion coatings.

INTRODUCTION: Epoxy-based resin formulations are a frequent cause of allergic and irritant contact dermatitis in the construction and painting industries. Cases of epoxy resin contact dermatitis continue to persist across many sectors and are likely attributable to the growing use of epoxy products, including epoxy-based anti-corrosion coatings and inadequate skin protection. There are no published performance data against epoxy resins for garment materials and gloves to guide proper material selection in the workplace. OBJECTIVES: The objective of this study was to evaluate the resistance of 5 protective garment materials against permeation and penetration by bisphenol A diglycidyl ether and its higher oligomers found commonly in epoxy-based anti-corrosion coatings. METHODS: Five disposable garment materials were evaluated for resistance to bisphenol A diglycidyl ether monomers and oligomers during contact with epoxy-based anti-corrosion coatings, including latex gloves, nitrile gloves, Tyvek coveralls, polypropylene/polyethylene (PP/PE) coveralls, and a cotton T-shirt. A permeation test cell system was used to evaluate each garment material against an epoxy-based zinc-rich primer and an epoxy-based intermediate coating using a realistic application method. Glass fiber filters were used to collect permeating and penetrating epoxy resin during a 120-min test period. Bisphenol A diglycidyl ether quantification was performed with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Paint loading, coating thickness, and homogeneity were assessed on polytetrafluoroethylene filters sprayed in series in permeation test cells. RESULTS: Latex gloves provided the least resistance to permeation by BADGE in coating formulations, with a maximum cumulative permeation over the 2-h test interval of 21.7 ng cm-2 with the primer and 513.8 ng cm-2 with the intermediate coating product. Nitrile gloves were not permeated by either coating formulation. The Tyvek coveralls provided greater protection as compared to the PP/PE coveralls. The cotton T-shirt was penetrated by bisphenol A diglycidyl ether more frequently than any of the tested garment materials and resulted in a maximum cumulative penetration of 128 ng cm-2 with the primer and 28.0 ng cm-2 with the intermediate coating. CONCLUSION: Although all the garment materials evaluated during this study provided sufficient protection to prevent cumulative permeation in excess of the established acceptable permeation thresholds, the use of nitrile gloves and Tyvek coverall is highly recommended to minimize skin exposure to bisphenol A diglycidyl ether. We recommend cotton T-shirts to be used under Tyvek coveralls as a secondary layer of skin protection and for added comfort, but not as a primary protection layer.

Long-term wastewater-based surveillance and impacts of the COVID-19 pandemic on drug use trends in a U.S. Northeast rural town.

Herein we discuss the findings of a two-year wastewater-based drug use surveillance from September 2018 to August 2020 and present objective evidence on the impacts of the COVID-19 pandemic on drug use in a rural community. 24-h composite wastewater samples were collected twice each month from a university town in Northeastern United States and were analyzed for ten priority opioids and stimulants: morphine, codeine, hydrocodone, methadone, fentanyl cocaine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxy-N-ethylamphetamine (MDEA). All target drugs were detected at 100 % frequency in wastewater samples. On a mass basis, the average estimated per capita drug consumption were highest for cocaine, morphine, and amphetamine, and lowest for MDMA, MDEA, and hydrocodone. Furthermore, the estimated per capita consumption of fentanyl was higher than previous reports from rural and university settings in the U.S. Generally, drug consumption was higher during the spring semesters, with year-on-year semester increases also noted over the 2-y study period. Except for methadone and cocaine, the estimated average per capita consumption of drugs increased over the pandemic period, with the highest increase noted for MDMA (286 % increase compared to baseline, p = 0.016). Estimated average consumption of methadone and cocaine decreased slightly by 6 % and 7 %, respectively. These results demonstrate the utility and strength of wastewater-based approaches in capturing long-term and evolving trends in drug use within communities. Our study findings reflect the regionwide problem with opioid-related overdoses and increasing stimulant prescription rates. Our findings also provide objective data and insights for health policymakers on the effects of the pandemic period on community drug use in a rural U.S. town.

Biomarkers in long COVID-19: A systematic review.

Purpose: Long COVID, also known as post-acute sequelae of COVID-19, refers to the constellation of long-term symptoms experienced by people suffering persistent symptoms for one or more months after SARS-CoV-2 infection. Blood biomarkers can be altered in long COVID patients; however, biomarkers associated with long COVID symptoms and their roles in disease progression remain undetermined. This study aims to systematically evaluate blood biomarkers that may act as indicators or therapeutic targets for long COVID. Methods: A systematic literature review in PubMed, Embase, and CINAHL was performed on 18 August 2022. The search keywords long COVID-19 symptoms and biomarkers were used to filter out the eligible studies, which were then carefully evaluated. Results: Identified from 28 studies and representing six biological classifications, 113 biomarkers were significantly associated with long COVID: (1) Cytokine/Chemokine (38, 33.6%); (2) Biochemical markers (24, 21.2%); (3) Vascular markers (20, 17.7%); (4) Neurological markers (6, 5.3%); (5) Acute phase protein (5, 4.4%); and (6) Others (20, 17.7%). Compared with healthy control or recovered patients without long COVID symptoms, 79 biomarkers were increased, 29 were decreased, and 5 required further determination in the long COVID patients. Of these, up-regulated Interleukin 6, C-reactive protein, and tumor necrosis factor alpha might serve as the potential diagnostic biomarkers for long COVID. Moreover, long COVID patients with neurological symptoms exhibited higher levels of neurofilament light chain and glial fibrillary acidic protein whereas those with pulmonary symptoms exhibited a higher level of transforming growth factor beta. Conclusion: Long COVID patients present elevated inflammatory biomarkers after initial infection. Our study found significant associations between specific biomarkers and long COVID symptoms. Further investigations are warranted to identify a core set of blood biomarkers that can be used to diagnose and manage long COVID patients in clinical practice.

Assessment of personal inhalation and skin exposures to polymeric methylene diphenyl diisocyanate during polyurethane fabric coating.

Methylene diphenyl diisocyanate (MDI) monomers and polymeric MDI (pMDI) are aromatic isocyanates widely used in the production of polyurethanes. These isocyanates can cause occupational asthma, hypersensitivity pneumonitis, as well as contact dermatitis. Skin exposure likely contributes toward initial sensitization but is challenging to monitor and quantitate. In this work, we characterized workers' personal inhalation and skin exposures to pMDI in a polyurethane fabric coating factory for subsequent health effect studies. Full-shift personal and area air samples were collected from eleven workers in representative job areas daily for 1-2 weeks. Skin exposure to hands was evaluated concomitantly with a newly developed reagent-impregnated cotton glove dosimeter. Samples were analyzed for pMDI by liquid chromatography-tandem mass spectrometry. In personal airborne samples, the concentration of 4,4'-MDI isomer, expressed as total NCO, had a geometric mean (GM) and geometric standard deviation (GSD) of 5.1 and 3.3 ng NCO/m3, respectively (range: 0.5-1862 ng NCO/m3). Other MDI isomers were found at much lower concentrations. Analysis of 4,4'-MDI in the glove dosimeters exhibited much greater exposures (GM: 10 ng/cm2) and substantial variability (GSD: 20 ng NCO/cm2; range: 0-295 ng NCO/cm2). MDI inhalation exposure was well below occupational limits for MDI for all the job areas. However, MDI skin exposure to hands was substantial. These findings demonstrated the potential for substantial isocyanate skin exposure in work settings with very low airborne levels. This exposure characterization should inform future studies that aim to assess the health effects of work exposures to MDI and the effectiveness of protective measures.

Prognostic serum biomarkers in cancer patients with COVID-19: A systematic review.

PURPOSE: Cancer patients with COVID-19 likely express biomarker changes in circulation. However, the biomarkers used in SARS-CoV-2 infected cancer patients for COVID-19 severity and prognosis are largely unclear. Therefore, this systematic review aims to determine what biomarkers were measured in cancer patients with COVID-19 and their prognostic utility. METHODS: A systematic literature review in PubMed, Embase, and Scopus was performed on June 16th, 2021. The search keywords coronavirus, neoplasm, biomarkers, and disease progression were used to filter out 17 eligible studies, which were then carefully evaluated. RESULTS: A total of 4,168 patients, 16 types of cancer, and 60 biomarkers were included. Seven up-regulated markers, including CRP, d-dimer, ferritin, IL-2R, IL-6, LDH, and PCT, were identified in eligible studies. Albumin and hemoglobin were significantly down-regulated in cancer patients with COVID-19. Moreover, we observed that the SARS-CoV-2 infected cancer patients with lower CRP, ferritin, and LDH levels successfully survived from COVID-19 treatments. CONCLUSION: Several important clinical biomarkers, such as CRP, ferritin, and LDH, may serve as the prognostic markers to predict the outcomes following COVID-19 treatment and monitor the deterioration of COVID-19 in cancer patients.

On-Site Deployment of an Air-Liquid-Interphase Device to Assess Health Hazard Potency of Airborne Workplace Contaminants: The Case of 3-D Printers.

Biomonitoring of workers is an approach of evaluating workers' exposure to chemicals and particulate matter by measuring biomarkers of parent chemicals, their metabolites, and reaction products in workers' biospecimens. Prerequisites for biological monitoring in the workplace include permission to enter the workplace, approval of the study plan from the IRB (Institutional Review Board), and obtaining consent from workers. Because of the complex legal process involved in biomonitoring, few studies have been conducted so far on biomonitoring of workers' exposures to nanoparticles and other hazards from emerging materials and advanced nanotechnologies. We have developed a cell-based biomonitoring device that can evaluate acute cytotoxicity and various other effect biomakers, such as inflammation, at realistic workplace exposure. This device is based on air-liquid interphase (ALI) and can be used to evaluate cell toxicity and early effect biomarkers along adverse outcome pathways. Following exposure of A549 lung epithelial cells in ALI to workplace air for 1-2 h, the cells were processed to assess the induction of inflammatory and cell damage biomarkers. Initially, we estimated the deposition rate of nanoparticles in the transwell by exposing the cell-free ALI device to silver nanoparticle aerosols (AgNP 20-30 nm) for 2 h in the laboratory. Then A549 lung epithelial cells cultured on the transwell in the ALI device were exposed to AgNP nanoaerosols for 2 h and evaluated for cytotoxicity and induction of mRNAs of pro-inflammatory cytokines IL-1b, IL-6, and TNF-α. Then the cells in the ALI device were exposed to 3-D printer emissions at the workplace and evaluated for the same matched endpoints. The mRNA levels for IL-1b, IL-6, and TNF-α increased significantly at the end of 2-h exposure of A549 cells to the positive control AgNP aerosols. These mRNAs, as well as LDH and microprotein concentrations, increased even more after 24-h post-exposure incubation (p < 0.05). Cytotoxicity evaluation of 3-D printer emissions at 810 and 957 µg/m3, which was more than 80 times higher than the airborne total suspended particulate concentrations in the workplace air (9-12.5 µg/m3), suggested no significant acute cytotoxicity at the end of 2-h exposure to 3-D-printing emission, as well as at 24-h post-exposure incubation. Hyperspectral microscopic observation showed that 3-D printers emitted particles to be attached to A549 cells after 2-h exposure, and many particles were internalized by A549 cells after 24 h of post-exposure incubation. The mRNA expression of pro-inflammatory cytokine IL-1b and IL-6 increased significantly after 2-h exposure to 3-D printer emissions and after 24-h incubation (only IL-6). In contrast, the expression of TNF-α mRNA decreased significantly after 2 h of exposure to 3-D printers and decreased even more after 24-h post-exposure incubation. These results support the use of cell-based ALI devices for direct assessment of airborne hazards in the workplace, for probing toxicological properties of airborne contaminants using adverse molecular pathways, and for guiding study design for workplace biomonitoring. ALI devices can bridge conventional exposure assessment with cellular toxicity testing platforms for hazard and risk assessment.

Estimation of Titanium Dioxide Intake by Diet and Stool Assessment among US Healthy Adults.

BACKGROUND: Titanium dioxide (TiO2/E171) is used in foods primarily as a whitening agent. Little is known regarding TiO2 exposure in the United States. OBJECTIVES: To quantify stool TiO2 content among US adults and evaluate its association with estimated intake. METHODS: Adults participated in phase 1 [three 24-h dietary recalls (DRs) and stool TiO2 measured from 3 matched samples (n = 52)] and/or phase 2 [tailored FFQ and stool TiO2 measured from 3 samples over 3 mo (n = 61)]. TiO2 in foods was estimated from a database, and concentration in 49 additional foods and 339 stool samples were quantified using inductively coupled plasma mass spectrometry. Associations between dietary and stool TiO2 were assessed by log-linear multivariable regression. USDA food groups (n = 49, servings/d) were related to stool TiO2 by stepwise regression. RESULTS: TiO2 food content varied by brand. Mean TiO2 intake from three 24-h DRs [0.19 ± 0.31 mg/(kg body weight · d)] was lower than from the FFQ [0.30 ± 0.21 mg/(kg body weight · d)]. Dietary TiO2 was not predictive of stool TiO2, in phase 1 or phase 2, 10^(ß) per 10 times higher dietary TiO2: 1.138 [10^(95% CI): 0.635, 2.037, P = 0.66] and 0.628 [10^(95% CI): 0.206, 1.910, P = 0.41], respectively. Food groups related to stool TiO2 were 1) milk desserts, sauces, and gravies [10^(ß) per servings/d: 3.361; 10^(95% CI): 0.312, 36.163; P = 0.002] and 2) yeast breads [10^(ß): 1.430; 10^(95% CI): 0.709, 2.884; P = 0.002] in phase 1 and 1) cream and cream substitutes [10^(ß) = 10.925; 10^(95% CI): 1.952, 61.137; P = 0.01] and 2) milk and milk drinks [10^(ß) = 0.306; 10^(95% CI): 0.086, 1.092, P = 0.07] in phase 2. CONCLUSIONS: Intake of certain foods was associated with higher stool TiO2 content. There is a need for valid estimation of TiO2 intakes via the improvement of a dietary assessment method and a TiO2 food composition database. Future research should assess whether high stool TiO2 content is related to adverse health outcomes.

Elevated Urinary Biomarkers of Oxidative Damage in Photocopier Operators following Acute and Chronic Exposures.

Inhalation exposures to nanoparticles (NPs) from printers and photocopiers have been associated with upper airway and systemic inflammation, increased blood pressure, and cases of autoimmune and respiratory disorders. In this study we investigate oxidative stress induced by exposures to copier-emitted nanoparticles using a panel of urinary oxidative stress (OS) biomarkers representing DNA damage (8-hydroxydeoxyguanosine, 8-OHdG; 8-hydroxyguanosine, 8-OHG; 5-hydroxymethyl uracil 5-OHMeU), lipid peroxidation (8-isoprostane; 4-hydroxynonenal, HNE), and protein oxidation biomarkers (o-tyrosine, 3-chlorotyrosine, and 3-nitrotyrosine) under conditions of acute (single 6 h exposure, 9 volunteers, 110 urine samples) and chronic exposures (6 workers, 11 controls, 81 urine samples). Urinary biomarkers were quantified with liquid chromatography-tandem mass spectrometry after solid phase extraction sample cleanup. 8-OHdG, 8-OHG, 8-isoprostane, and HNE were significantly elevated in both the acute and chronic exposure study participants relative to the controls. In the acute exposure study, the geometric mean ratios post-/pre-exposure were 1.42, 1.10, 2.0, and 2.25, respectively. Urinary 8-OHG and HNE increased with time to at least 36 h post-exposure (post-/pre-exposure GM ratios increased to 3.94 and 2.33, respectively), suggesting slower generation and/or urinary excretion kinetics for these biomarkers. In chronically exposed operators, the GM ratios of urinary biomarkers relative to controls ranged from 1.52 to 2.94, depending on the biomarker. O-Tyrosine and 5-OHMeU biomarkers were not significantly different from the controls. 3-chlorotyrosine and 3-nitrotyrosine were not detected in the urine samples. We conclude that NPs from photocopiers induce systemic oxidative stress by damaging DNA, RNA, and lipids. Urinary levels of 8-OHdG, 8-OHG, HNE, and 8-isoprostane were orders of magnitude higher than in nanocomposite processing workers, comparable to nano titanium dioxide and fiberglass manufacturing workers, but much lower than in shipyard welding and carbon nanotube synthesis workers. Biomarkers 8-OHdG, 8-OHG, 8-isoprostane, and HNE appear to be more sensitive and robust urinary biomarkers for monitoring oxidative stress to NPs from photocopiers.

Biomarkers of oxidative stress in urine and plasma of operators at six Singapore printing centers and their association with several metrics of printer-emitted nanoparticle exposures.

Inhalation of nanoparticles emitted from toner-based printing equipment (TPE), such as laser printers and photocopiers, also known as PEPs, has been associated with systemic inflammation, hypertension, cardiovascular disease, respiratory disorders, and genotoxicity. Global serum metabolomics analysis in 19 healthy TPE operators found 52 dysregulated biomolecules involved in upregulation of inflammation, immune, and antioxidant responses and downregulation of cellular energetics and cell proliferation. Here, we build on the metabolomics study by investigating the association of a panel of nine urinary OS biomarkers reflecting DNA/RNA damage (8OHdG, 8OHG, and 5OHMeU), protein/amino acid oxidation (o-tyrosine, 3-chlorotyrosine, and 3-nitrotyrosine), and lipid oxidation (8-isoprostane, 4-hydroxy nonenal, and malondialdehyde [MDA]), as well as plasma total MDA and total protein carbonyl (TPC), with several nanoparticle exposure metrics in the same 19 healthy TPE operators. Plasma total MDA, urinary 5OHMeU, 3-chlorotyrosine, and 3-nitrotyrosine were positively, whereas o-tyrosine inversely and statistically significantly associated with PEPs exposure in multivariate models, after adjusting for age and urinary creatinine. Urinary 8OHdG, 8OHG, 5OHMeU, and total MDA in urine and plasma had group mean values higher than expected in healthy controls without PEPs exposure and comparable to those of workers experiencing low to moderate levels of oxidative stress (OS). The highest exposure group had OS biomarker values, most notably 8OHdG, 8OHG, and total MDA, that compared to workers exposed to welding fumes and titanium dioxide. Particle number concentration was the most sensitive and robust exposure metric. A combination of nanoparticle number concentration and OS potential of fresh aerosols is recommended for larger scale future studies.

Zinc Exposure Promotes Commensal-to-Pathogen Transition in Pseudomonas aeruginosa Leading to Mucosal Inflammation and Illness in Mice.

The opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa) is associated gastrointestinal (GI) inflammation and illness; however, factors motivating commensal-to-pathogen transition are unclear. Excessive zinc intake from supplements is common in humans. Due to the fact that zinc exposure enhances P. aeruginosa colonization in vitro, we hypothesized zinc exposure broadly activates virulence mechanisms, leading to inflammation and illness. P. aeruginosa was treated with excess zinc and growth, expression and secretion of key virulence factors, and biofilm production were determined. Effects on invasion, barrier function, and cytotoxicity were evaluated in Caco-2 cells co-cultured with P. aeruginosa pre-treated with zinc. Effects on colonization, mucosal pathology, inflammation, and illness were evaluated in mice infected with P. aeruginosa pre-treated with zinc. We found the expression and secretion of key virulence factors involved in quorum sensing (QS), motility (type IV pili, flagella), biosurfactants (rhamnolipids), toxins (exotoxin A), zinc homeostasis (CzcR), and biofilm production, were all significantly increased. Zinc exposure significantly increased P. aeruginosa invasion, permeability and cytotoxicity in Caco-2 cells, and enhanced colonization, inflammation, mucosal damage, and illness in mice. Excess zinc exposure has broad effects on key virulence mechanisms promoting commensal-to-pathogen transition of P. aeruginosa and illness in mice, suggesting excess zinc intake may have adverse effects on GI health in humans.

Urinary biomonitoring of occupational exposures to Bisphenol A Diglycidyl Ether (BADGE) - based epoxy resins among construction painters in metal structure coating.

Epoxy resin systems based on Bisphenol A Diglycidyl Ether (BADGE) monomer and its higher oligomers are important commercial formulations used widely in construction for protective coating of steel structures, such as bridges. The literature on occupational exposures and biomonitoring of BADGE-based epoxies among construction painters is remarkably limited. In this first occupational biomonitoring study of epoxies, 44 construction painters performing mid- and top-coating were recruited from 12 metal structure coating sites in New England. Cross-shift changes in the urinary levels of total BADGE and its three major hydrolysis derivatives - BADGE·2H2O, BADGE·H2O, BADGE·HCl·H2O - were assessed. Results for 81 urine samples collected from coating workers were compared with 28 urine samples of a reference group of 14 spray polyurethane foam (SPF) insulation workers. The highest concentrations of all biomarkers were found in the urine samples of mid-coat applicators. The major urinary biomarker of BADGE in this cohort of workers, BADGE·2H2O, was detected in 100% of urine samples. The post-shift BADGE·2H2O (specific gravity normalized data) in mid-coat applicators had a geometric mean (GM) of 1.46 ng/mL and a geometric standard deviation (GSD) of 3.6 (range, 0.2-18.7 ng/mL). The second most abundant biomarker in urine, BADGE·HCl·H2O, was measured in 84% of samples, and had a post-shift GM(GSD) of 0.17 (2.3) ng/mL (range, <0.025-0.59 ng/mL). BADGE·2H2O was 8.6 times more abundant than BADGE·HCl·H2O. BADGE·H2O was quantified only in 10% of the samples (range, 0.11-0.41 ng/mL). Free BADGE in post-shift urine, corrected for background, had GM (GSD) of 0.04 (2.5) ng/mL (range, <0.025-0.16 ng/mL). Urinary BADGE·2H2O were significantly higher (p = 0.01) in mid-coat applicators compared to top-coat and SPF workers. Post-shift urinary BADGE·2H2O in mid-coat applicators increased by ~2.9× (p = 0.02) and 1.36× in top-coat applicators (p = 0.18) compared to pre-shift values, but not in SPF workers (0.95×; p = 0.40). In conclusion, we demonstrate that (i) significant BADGE uptake occurs via inhalation and skin exposures during application of epoxy-containing paintings (mid-coat), suggesting the need for improvements in hygiene practices and personal protective measures; (ii) BADGE·2H2O is a robust and sensitive biomarker for biomonitoring of exposures to BADGE-based epoxies in occupational settings; and (iii) widespread occurrence of BADGE and BADGE·2H2O in the urine of all workers, including SPF workers, suggest common exposures from non-occupational sources, such as ingestion or do-it-yourself consumer applications of epoxy resins. In light of this observation, establishing a reliable biological monitoring guidance value (BMGV) for BADGE·2H2O will require more background biomonitoring and health effect data. An initial reference value for BADGE·2H2O of 0.5 ng/mL (SG-normalized) or 180 nmol/mol creatinine is being proposed as the threshold to discriminate occupational from non-occupational exposures based on the maximum values observed in the reference SPF group.

Characterization and Quantitation of Personal Exposures to Epoxy Paints in Construction Using a Combination of Novel Personal Samplers and Analytical Techniques: CIP-10MI, Liquid Chromatography-Tandem Mass Spectrometry and Ion Chromatography.

Epoxy resins are extremely versatile products that are widely used in construction for coatings, adhesives, primers, and sealers. Occupational exposures to epoxies cause allergic contact dermatitis, occupational asthma, hypersensitivity pneumonitis (epoxy-resin lung) and acute decline in lung function. Despite these health concerns, there is a striking paucity of quantitative exposure data to epoxy resins in construction. The lack of practical analytical methods and suitable personal samplers for monitoring of reactive two-component epoxide systems in real-world applications has been an unmet challenge for decades. Sampling and analysis methods for epoxies should be able to collect the paint aerosols efficiently, stop polymerization reactions at the time of sample collection, and subsequently provide detailed multispecies characterization of epoxides, as well as the total epoxide group (TEG) content of a sample, to properly document the chemical composition of exposures to epoxide paints. In this work, we present the development and application of two new complementary quantitative analytical methods-liquid chromatography-tandem mass spectrometry with online ultraviolet detection and ion chromatography (IC)-for multispecies characterization of raw products, as well as inhalation and skin exposures to epoxy formulations in real-world construction applications. A novel personal sampler, CIP-10MI, was used for personal sampling of airborne epoxies. We report for the first time the results of personal inhalation and potential skin exposures to individual monomers and oligomers of bisphenol A diglycidyl ether (BADGE), as well as TEG, during metal structure coatings in construction; compare analytical results of the two analytical methods; and provide recommendations for method selection in future field studies. High inhalation and potential skin exposures to epoxies point to the need for interventions to reduce exposures among painters in construction.

Chronic upper airway and systemic inflammation from copier emitted particles in healthy operators at six Singaporean workplaces.

Toner-based printing equipment (TPE), including laser printers and photocopiers, utilize several engineered nanomaterials (ENMs) to improve toner performance. Operation of TPE, which rarely employ any exposure controls, generates high exposures to nanoparticles that contain ENMs and complex organics. Epidemiological literature in copier operators documents respiratory effects, including nasal blockage, cough, excessive sputum, and breathing difficulties, cardiovascular effects, oxidative stress, and inflammation. However, epidemiological studies in humans with adequate exposure assessment and dose-response analysis are lacking. We present herein the analysis of the upper airway and systemic inflammation in plasma of 19 healthy copier operators at six Singapore workplaces. We employed a repeated panel design (four biomarker measurements over two weeks) combined with a multi-marker approach (14 inflammatory cytokines in plasma and nasal lavage (NL)), and comprehensive exposure assessment using four distinct exposure metrics. We investigated spatial and temporal patterns of markers of upper airway and systemic inflammation and their association with various exposure metrics. Several inflammatory markers, namely fractalkine, IL-1ß, and IL-1α in NL, and fractalkine, IL-1ß, TNF-α, and IFN-γ in plasma, were strongly and positively associated with at least one exposure metric, whereas GM-CSF was negatively associated. The inflammation score was also strongly associated with TPE nanoparticle exposures. Exposure to TPE emissions induced moderate upper airway inflammation and stronger systemic inflammation in these healthy operators, characterized by upregulation of at least IL-1ß, fractalkine, TNF-α and IFN-γ. Proinflammatory cytokines TNF-α, IFN-γ and IL-1ß play an important role in orchestrating inflammatory responses in various clinical conditions, including cardiovascular and autoimmune disease, and likely trigger activation of endothelial cells, leading to overexpression of fractalkine, a chemokine that is involved in and associated with multiple disorders, including atherosclerosis and vascular disease. Future larger-scale epidemiological studies in these workers and consumers exposed chronically to TPE nanoparticle emissions and proactive interventions to reduce or eliminate TPE exposures are recommended.

Assessment and Mitigation of Exposure of 3-D Printer Emissions.

This study monitored particulates, and volatile organic compounds (VOCs) emitted from 3-D printers using acrylonitrile-butadiene-styrene copolymer (ABS) filaments at a workplace to assess exposure before and after introducing exposure mitigation measures. Air samples were collected in the printing room and adjacent corridor, and real-time measurements of ultrafine and fine particle were also conducted. Extensive physicochemical characterizations of 3-D printer emissions were performed, including real-time (size distribution, number concentration) nanoparticle characterization, size-fractionated mass distribution and concentration, as well as chemical composition for metals by ICP-MS and VOCs by GC-FID, real-time VOC monitors, and proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF-MS). Air sampling showed low levels of total suspended particulates (TSP, 9-12.5/m3), minimal levels (1.93-4 ppm) of total volatile organic chemicals (TVOC), and formaldehyde (2.5-21.7 ppb). Various harmful gases, such as formaldehyde, acrolein, acetone, hexane, styrene, toluene, and trimethylamine, were detected at concentrations in the 1-100 ppb by PTR-TOF-MS when air sample was collected into the Tedlar bag from the front of the 3-D printer. Ultrafine particles having an average particle size (30 nm count median diameter and 71 nm mass median diameter) increased during the 3-D printing operation. They decreased to the background level after the 3-D printing operation, while fine particles continually increased after the termination of 3-D printing to the next day morning. The exposure to 3-D printer emissions was greatly reduced after isolating 3-D printers in the enclosed space. Particle number concentration measured by real-time particle counters (DMAS and OPC) were greatly reduced after isolating 3-D printers to the isolated place.

Exposures and urinary biomonitoring of aliphatic isocyanates in construction metal structure coating.

BACKGROUND: Isocyanates are highly reactive chemicals used widely in metal structure coating applications in construction. Isocyanates are potent respiratory and skin sensitizers and a leading cause of occupational asthma. At present, there is no cure for isocyanate asthma and no biomarkers of early disease. Exposure reduction is considered the most effective preventive strategy. To date, limited data are available on isocyanate exposures and work practices in construction trades using isocyanates, including metal structure coatings. OBJECTIVES: The primary objectives of this work were: i) to characterize isocyanate inhalation and dermal exposures among painters during metal structure coating tasks in construction; and ii) to assess the adequacy of existing work practices and exposure controls via urinary biomonitoring pre- and post-shift. METHODS: Exposures to aliphatic isocyanates based on 1,6-hexamethylene diisocyanate (1,6-HDI) and its higher oligomers (biuret, isocyanurate and uretdione) were measured among 30 workers performing painting of bridges and other metal structures in several construction sites in the Northeastern USA. Exposure assessment included simultaneous measurement of personal inhalation exposures (n = 20), dermal exposures (n = 22) and body burden via urinary biomonitoring pre- and post-shift (n = 53). Contextual information was collected about tasks, processes, materials, work practices, personal protective equipment (PPEs) and exposure controls, work histories, and environmental conditions. RESULTS: Breathing zone concentrations were the highest for biuret (median, 18.4 µg/m3), followed by 1,6-HDI monomer (median, 3.5 µg/m3), isocyanurate (median, 3.4 µg/m3) and uretdione (median, 1.7 µg/m3). The highest exposures, measured during painting inside an enclosed bridge on a hot summer day, were: 10,288 µg/m3 uretdione; 8,240 µg/m3 biuret; and 947 µg/m3 1,6-HDI. Twenty percent of samples were above the NIOSH ceiling exposure limit for 1,6- HDI (140 µg/m3) and 35% of samples were above the UK-HSE ceiling for total isocyanate group (70 µg NCO/m3). Isocyanate loading on the gloves was generally high, with a median of 129 µg biuret/pair and maximum of 60.8 mg biuret/pair. The most frequently used PPEs in the workplace were half-face organic vapor cartridge (OVC) respirators, disposable palmar dip-coated polymer gloves, and cotton coveralls. However, 32% of workers didn't wear any respirator, 47% wore standard clothing with short-sleeve shirts and 14% didn't wear any gloves while performing tasks involving isocyanates. Based on biomonitoring results, 58.4% of urine samples exceeded the biological monitoring guidance value (BMGV) of 1 µmol hexamethylene diamine (HDA)/mol creatinine. Post-shift geometric mean HDA normalized to specific gravity increased by 2.5-fold compared to pre-shift (GM, 4.7 vs. 1.9 ng/mL; p value, < 0.001), and only 1.4-fold when normalized to creatinine. CONCLUSIONS: Exposure and biomonitoring results, coupled with field observations, support the overall conclusions that (i) substantial inhalation and dermal exposures to aliphatic isocyanates occur during industrial coating applications in construction trades; that (ii) the current work practices and exposure controls are not adequately protective. High urinary creatinine values in the majority of workers, coupled with significant cross-shift increases and filed observations, point to the need for further investigations on possible combined effects of heat stress, dehydration, and nutritional deficiencies on kidney toxicity. Implementation of comprehensive exposure control programs and increased awareness are warranted in order to reduce isocyanate exposures and associated health risks among this cohort of construction workers.

Occupational Inhalation Exposures to Nanoparticles at Six Singapore Printing Centers.

Laser printers emit high levels of nanoparticles (PM0.1) during operation. Although it is well established that toners contain multiple engineered nanomaterials (ENMs), little is known about inhalation exposures to these nanoparticles and work practices in printing centers. In this report, we present a comprehensive inhalation exposure assessment of indoor microenvironments at six commercial printing centers in Singapore, the first such assessment outside of the United States, using real-time personal and stationary monitors, time-integrated instrumentation, and multiple analytical methods. Extensive presence of ENMs, including titanium dioxide, iron oxide, and silica, was detected in toners and in airborne particles collected from all six centers studied. We document high transient exposures to emitted nanoparticles (peaks of ∼500 000 particles/cm3, lung-deposited surface area of up to 220 µm2/cm3, and PM0.1 up to 16 µg/m3) with complex PM0.1 chemistry that included 40-60 wt % organic carbon, 10-15 wt % elemental carbon, and 14 wt % trace elements. We also record 271.6-474.9 pmol/mg of Environmental Protection Agency-priority polycyclic aromatic hydrocarbons. These findings highlight the potentially high occupational inhalation exposures to nanoparticles with complex compositions resulting from widespread usage of nano-enabled toners in the printing industry, as well as inadequate ENM-specific exposure control measures in these settings.

Pilot deep RNA sequencing of worker blood samples from Singapore printing industry for occupational risk assessment.

Several engineered nanomaterials (ENMs) are used in toner-based printing equipment (TPE) including laser printers and photocopiers to improve toner performance. High concentration of airborne nanoparticles due to TPE emissions has been documented in copy centers and chamber studies. Recent animal inhalation studies by our group suggested exposure to laser printer-emitted nanoparticles (PEPs) increased cardiovascular risk by impairing ventricular performance and inducing hypertension and arrhythmia, consistent with global transcriptomic and metabolomic profiling results. There has been no genome-wide transcriptomic analysis of workers exposed to TPE emissions to systematically assess the occupational exposure health risks. In this pilot study, deep RNA sequencing of blood samples of workers in two printing companies in Singapore was performed. The genome-scale analysis of the blood samples from TPE exposed workers revealed perturbed transcriptional activities related to inflammatory and immune responses, metabolism, cardiovascular impairment, neurological diseases, oxidative stress, physical morphogenesis/deformation, and cancer, when compared with the control peers (office workers). Many of these disease risks associated with particle inhalation exposures in such work environments were consistent with the observation from the PEPs rat inhalation studies. In particular, the cell adhesion molecules (CAMs) was a top significantly perturbed pathway in blood samples from exposed workers compared with the office workers in both companies. The protein expression of sICAM was verified in plasma of exposed workers, showing a positive correlation with daily average nanoparticle concentration in indoor air measured in these two companies. Larger scale genomic and molecular epidemiology studies in copier operators are warranted in order to assess potential risks from such particulate matter exposures.

Safer-by-design flame-sprayed silicon dioxide nanoparticles: the role of silanol content on ROS generation, surface activity and cytotoxicity.

BACKGROUND: Amorphous silica nanoparticles (SiO2 NPs) have been regarded as relatively benign nanomaterials, however, this widely held opinion has been questioned in recent years by several reports on in vitro and in vivo toxicity. Surface chemistry, more specifically the surface silanol content, has been identified as an important toxicity modulator for SiO2 NPs. Here, quantitative relationships between the silanol content on SiO2 NPs, free radical generation and toxicity have been identified, with the purpose of synthesizing safer-by-design fumed silica nanoparticles. RESULTS: Consistent and statistically significant trends were seen between the total silanol content, cell membrane damage, and cell viability, but not with intracellular reactive oxygen species (ROS), in the macrophages RAW264.7. SiO2 NPs with lower total silanol content exhibited larger adverse cellular effects. The SAEC epithelial cell line did not show any sign of toxicity by any of the nanoparticles. Free radical generation and surface reactivity of these nanoparticles were also influenced by the temperature of combustion and total silanol content. CONCLUSION: Surface silanol content plays an important role in cellular toxicity and surface reactivity, although it might not be the sole factor influencing fumed silica NP toxicity. It was demonstrated that synthesis conditions for SiO2 NPs influence the type and quantity of free radicals, oxidative stress, nanoparticle interaction with the biological milieu they come in contact with, and determine the specific mechanisms of toxicity. We demonstrate here that it is possible to produce much less toxic fumed silicas by modulating the synthesis conditions.

Is "nano safe to eat or not"? A review of the state-of-the art in soft engineered nanoparticle (sENP) formulation and delivery in foods.

With superior physicochemical properties, soft engineered nanoparticles (sENP) (protein, carbohydrate, lipids and other biomaterials) are widely used in foods. The preparation, functionalities, applications, transformations in gastrointestinal (GI) tract, and effects on gut microbiota of sENP directly incorporated for ingestion are reviewed herein. At the time of this review, there is no notable report of safety concerns of these nanomaterials found in the literature. Meanwhile, various beneficial effects have been demonstrated for the application of sENP. To address public perception and safety concerns of nanoscale materials in food, methodologies for evaluation of physiological effects of nanomaterials are reviewed. The combination of these complementary methods will be useful for the establishment of a comprehensive risk assessment system.