Publications by authors named "Dhimiter Bello"

73 Publications

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.

Ann Work Expo Health 2021 Mar 18. Epub 2021 Mar 18.

Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, 883 Broadway Street, Dugan Hall 108C, Lowell, MA 01854, USA.

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.
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http://dx.doi.org/10.1093/annweh/wxaa138DOI Listing
March 2021

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

NanoImpact 2020 Jul 13;19. Epub 2020 Aug 13.

Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.

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.
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http://dx.doi.org/10.1016/j.impact.2020.100248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840153PMC
July 2020

A nano-carrier platform for the targeted delivery of nature-inspired antimicrobials using Engineered Water Nanostructures for food safety applications.

Food Control 2019 Feb 29;96:365-374. Epub 2018 Sep 29.

Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.

Despite the progress in the area of food safety, foodborne diseases still represent a massive challenge to the public health systems worldwide, mainly due to the substantial inefficiencies across the farm-to-fork continuum. Here, we report the development of a nano-carrier platform, for the targeted and precise delivery of antimicrobials for the inactivation of microorganisms on surfaces using Engineered Water Nanostructures (EWNS). An aqueous suspension of an active ingredient (AI) was used to synthesize iEWNS, with the 'i' denoting the AI used in their synthesis, using a combined electrospray and ionization process. The iEWNS possess unique, active-ingredient-dependent physicochemical properties: i) they are engineered to have a tunable size in the nanoscale; ii) they have excessive electric surface charge, and iii) they contain both the reactive oxygen species (ROS) formed due to the ionization of deionized (DI) water, and the AI used in their synthesis. Their charge can be used in combination with an electric field to target them onto a surface of interest. In this approach, a number of nature-inspired antimicrobials, such as HO, lysozyme, citric acid, and their combination, were used to synthesize a variety of iEWNS-based nano-sanitizers. It was demonstrated through foodborne-pathogen-inactivation experiments that due to the targeted and precise delivery, and synergistic effects of AI and ROS incorporated in the iEWNS structure, a pico- to nanogram-level dose of the AI delivered to the surface using this nano-carrier platform is capable of achieving 5-log reductions in minutes of exposure time. This aerosol-based, yet 'dry' intervention approach using iEWNS nano-carrier platform offers advantages over current 'wet' techniques that are prevalent commercially, which require grams of the AI to achieve similar inactivation, leading to increased chemical risks and chemical waste byproducts. Such a targeted nano-carrier approach has the potential to revolutionize the delivery of antimicrobials for sterilization in the food industry.
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http://dx.doi.org/10.1016/j.foodcont.2018.09.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055713PMC
February 2019

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

Int J Hyg Environ Health 2020 05 28;226:113495. Epub 2020 Feb 28.

University of Massachusetts Lowell, Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, Lowell, MA, 01854, USA.

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/m), followed by 1,6-HDI monomer (median, 3.5 μg/m), isocyanurate (median, 3.4 μg/m) and uretdione (median, 1.7 μg/m). The highest exposures, measured during painting inside an enclosed bridge on a hot summer day, were: 10,288 μg/m uretdione; 8,240 μg/m biuret; and 947 μg/m 1,6-HDI. Twenty percent of samples were above the NIOSH ceiling exposure limit for 1,6- HDI (140 μg/m) and 35% of samples were above the UK-HSE ceiling for total isocyanate group (70 μg NCO/m). 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.
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http://dx.doi.org/10.1016/j.ijheh.2020.113495DOI Listing
May 2020

Occupational Inhalation Exposures to Nanoparticles at Six Singapore Printing Centers.

Environ Sci Technol 2020 02 5;54(4):2389-2400. Epub 2020 Feb 5.

School of Materials Science and Engineering , Nanyang Technological University , 50 Nanyang Avenue , 639798 , Singapore.

Laser printers emit high levels of nanoparticles (PM) 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/cm, lung-deposited surface area of up to 220 μm/cm, and PM up to 16 μg/m) with complex PM 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.
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http://dx.doi.org/10.1021/acs.est.9b06984DOI Listing
February 2020

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

Part Fibre Toxicol 2019 10 29;16(1):40. Epub 2019 Oct 29.

Center for Nanotechnology and Nanotoxicology, HSPH-NIEHS Nanosafety Center, Department of Environmental Health, Harvard T. H. Chan School of Public School, Harvard University, 665 Huntington, Boston, MA, 02115, USA.

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 SiO 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. SiO 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 SiO 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.
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http://dx.doi.org/10.1186/s12989-019-0325-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819463PMC
October 2019

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.

Adv Food Nutr Res 2019 23;88:299-335. Epub 2019 Apr 23.

U.S. Department of Agriculture, National Institute of Food and Agriculture, Washington DC, United States. Electronic address:

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.
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http://dx.doi.org/10.1016/bs.afnr.2019.03.004DOI Listing
December 2019

Comprehensive Assessment of Short-Lived ROS and HO in Laser Printer Emissions: Assessing the Relative Contribution of Metal Oxides and Organic Constituents.

Environ Sci Technol 2019 07 10;53(13):7574-7583. Epub 2019 Jun 10.

Department of Environmental Health and Harvard Center for Nanotechnology and Nanotoxicology , Harvard T. H. Chan School of Public Health , Boston , Massachusetts 02115 , United States.

Inhalation exposure to nanoparticles from toner-based laser printer and photocopier emissions (LPEs) induces airway inflammation and systemic oxidative stress, cytotoxicity, and genotoxicity (such as DNA damage). Recent evidence from human and in vitro studies suggests a strong role for oxidative stress caused by free radicals, such as reactive oxygen species (ROS), in the toxicity of laser printer emissions. However, the amount of ROS generated from laser printer nanoparticle emissions and the relative contribution of various fractions (vapors, organics, metals, and metal oxides) have not been investigated to-date. In this study, we aim to quantify short-lived ROS and HO laser printer emissions, as well as the relative contribution of various fractions of LPEs in ROS generation. An aerosol chamber with HEPA filtered air was used to generate LPE emissions from one representative printer. In separate experiments, size fractionated LPEs were collected on filters (particles) or impingers (particles and vapors). The nanoscale fraction of LPEs (PM) was further separated into the organic fraction and inorganic (transition metals/metal oxides) following a sequence of extraction with solvents and centrifugation. The short-lived ROS and HO generated from each fraction were quantified with an acellular Trolox-based liquid chromatography-electrospray-tandem mass spectrometry (LC-ESI-MS/MS) method recently developed in our lab. The particulate fraction of LPEs PM generated 2.68 times more total ROS (sum of short-lived ROS and HO) than the vapor fraction. In tested LPEs, transition metal oxides, which constituted 3% by mass, produced 69× and 202× times more short-lived ROS and HO, respectively, on a mass basis, than the organic fraction. Furthermore, fresh PM generated 282× and 32× times more short-lived ROS and HO, respectively, than aged and processed PM. We conclude that transition metal oxides, albeit a minor constituent of the LPE PM emissions, are the species responsible for the majority of acellular ROS in this printer. A larger range of printers should be tested in the future. Because transition metal oxides in toners originate primarily from engineering nanomaterials (ENMs) in printer toner powder, reformulation of toner powders to contain less of these ROS active metals is recommended.
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http://dx.doi.org/10.1021/acs.est.8b05677DOI Listing
July 2019

Assessment and control of exposures to polymeric methylene diphenyl diisocyanate (pMDI) in spray polyurethane foam applicators.

Int J Hyg Environ Health 2019 06 8;222(5):804-815. Epub 2019 May 8.

University of Massachusetts Lowell, Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, Lowell, MA, 01854, USA.

In this work we characterize personal inhalation and dermal exposures to diphenyl methane diisocyanate (MDI) and other species in polymeric MDI (pMDI) formulations during spray polyurethane foam (SPF) insulation at 14 sites in New England. We further assess the adequacy of current workplace practices and exposure controls via comparative urinary biomonitoring of the corresponding methylene diphenyl diamine (MDA) pre- and post-shift. MDI and pMDI are potent dermal and respiratory sensitizers and asthmagens, strong irritants of the skin, eyes, and the respiratory tract, and may cause skin burns. This study is the first comprehensive report to-date on the work practices, inhalation and dermal exposures to isocyanates and effectiveness of existing controls during SPF applications. Breathing zone exposures to 4,4' MDI (n = 31; 24 sprayers, 7 helpers) ranged from 0.9 to 123.0 μg/m3 and had a geometric mean (GM) of 13.8 μg/m3 and geometric standard deviation (GSD) of 4.8. Stationary near field area samples (n = 15) were higher than personal exposures: GM, 40.9 (GSD, 3.9) μg/m3, range 1.4-240.8 μg/m3. Sixteen percent of personal air samples and 35% of area samples exceeded the National Institute for Occupational Health and Safety's (NIOSH) full shift recommended exposure limit (REL) of 50 μg/m3, assuming zero exposure for the unsampled time. 4,4' MDI load on the glove dosimeters had a GM of 11.4 (GSD 2.9) μg/glove pair/min, suggesting high potential for dermal exposures. Urinary MDA had a GM of 0.7 (GSD, 3.0) μmol MDA/mol creatinine (range, nd-14.5 μmol MDA/mol creatinine). Twenty-five % of urine samples exceeded the Health and Safety Executive (HSE) biological monitoring guidance value (BMGV) of 1 μmol MDA/mol creatinine. We further report on field observations regarding current exposure controls, discuss implications of these findings and opportunities for improving work practices to prevent isocyanate exposures during SPF insulation.
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http://dx.doi.org/10.1016/j.ijheh.2019.04.014DOI Listing
June 2019

Evaluation of Disposable Protective Garments against Isocyanate Permeation and Penetration from Polyurethane Anticorrosion Coatings.

Ann Work Expo Health 2019 05;63(5):592-603

Department of Public Health, University of Massachusetts Lowell, One University Avenue, Lowell, MA, USA.

Background: Polyurethanes are a class of isocyanate-based organic coatings commonly used to control corrosion on high-value metallic structures. Despite their widespread use, dermal exposure to these isocyanate-containing coatings presents a significant occupational health risk to workers, including the development of allergic and irritant contact dermatitis and systemic sensitization. At present, little is known about the effectiveness of the protective garments commonly used to prevent dermal exposure to polyurethane coatings in construction trades.

Objectives: The primary objective of this study was to measure the permeation and penetration of isocyanates from polyurethane anticorrosion coatings though a selection of protective garments. In addition, a standardized spray procedure using a fixed-position spraying technique was evaluated as an option to minimize variability in coating application.

Methods: Five disposable garment materials were evaluated for resistance to isocyanates during this study: latex gloves (0.076 mm), nitrile gloves (0.078 mm), Tyvek coveralls (0.105 mm), polypropylene/polyethylene (PP/PE) coveralls (0.116 mm), and a cotton t-shirt (0.382 mm). A permeation test cell system was used to evaluate each garment material against two products: a polyurethane zinc-rich primer based on 4,4'-methylene diphenyl diisocyanate and an aliphatic finish coating based on prepolymers of 1,6-hexamethylene diisocyanate. Glass fiber filters pretreated with 1-(9-anthracenylmethyl)piperazine were used to collect penetrating isocyanates during the 120-min test period, which were analyzed by liquid chromatography-tandem mass spectrometry. Polytetrafluoroethylene loading filters were sprayed in series with permeation test cells and analyzed gravimetrically to assess the homogeneity of coating application.

Results: The latex gloves demonstrated the highest rate of isocyanate permeation of all evaluated garments during testing with both coatings (primer: 27.38 ng cm-2 min-1; finish coating: 7.39 ng cm-2 min-1). Nitrile gloves were much more resistant than latex gloves (primer: 1.89 ng cm-2 min-1; finish coating: 1.26 ng cm-2 min-1) and were not permeated by the finish coating until after 15 min. The PP/PE coverall provided the most consistent resistance to both coatings (primer: 0.08 ng cm-2 min-1; finish coating: 1.27 ng cm-2 min-1), whereas the Tyvek coverall was readily permeated by the primer (primer: 3.47 ng cm-2 min-1; finish coating: 0.87 ng cm-2 min-1). The cotton t-shirt was rapidly permeated by the primer during the first 5 min of exposure (primer: 146.65 ng cm-2 min-1; finish coating: 4.64 ng cm-2 min-1). In addition, the fixed-position spraying technique used during this study demonstrated a significant reduction in loading variability within each batch of test cells when compared to manual spray application.

Conclusion: Nitrile gloves demonstrated superior resistance to both isocyanate-containing coatings in comparison to latex gloves. Although both coverall materials were resistant to permeating isocyanate within the established thresholds, the PP/PE coverall provided more consistent resistance to both coatings. Owing to the cotton t-shirt's high rate of penetration with both coatings, it is recommended only as a secondary barrier. Study results showed that the use of fixed-position spray techniques provided consistent and reproducible results within each batch of test cells. Additional test design modifications are necessary to further reduce variability between batches and ensure more consistent coating thickness.
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http://dx.doi.org/10.1093/annweh/wxz032DOI Listing
May 2019

Dilysine-Methylene Diphenyl Diisocyanate (MDI), a Urine Biomarker of MDI Exposure?

Chem Res Toxicol 2019 04 18;32(4):557-565. Epub 2019 Feb 18.

Department of Public Health , University of Massachusetts , Lowell , Massachusetts 01854 , United States.

Biomonitoring of methylene diphenyl diisocyanate (MDI) in urine may be useful in industrial hygiene and exposure surveillance approaches toward disease (occupational asthma) prevention and in understanding pathways by which the internalized chemical is excreted. We explored possible urine biomarkers of MDI exposure in mice after respiratory tract exposure to MDI, as glutathione (GSH) reaction products (MDI-GSH), and after skin exposure to MDI dissolved in acetone. LC-MS analyses of urine identified a unique m/ z 543.29 [M + H] ion from MDI-exposed mice but not from controls. The m/ z 543.29 [M + H] ion was detectable within 24 h of a single MDI skin exposure and following multiple respiratory tract exposures to MDI-GSH reaction products. The m/ z 543.29 [M + H] ion possessed properties of dilysine-MDI, including (a) an isotope distribution pattern for a molecule with the chemical formula CHNO, (b) the expected collision-induced dissociation (CID) fragmentation pattern upon MS/MS, and (c) a retention time in reversed-phase LC-MS identical to that of synthetic dilysine-MDI. Further MDI-specific Western blot studies suggested albumin (which contains multiple dilysine sites susceptible to MDI carbamylation) as a possible source for dilysine-MDI and the presence of MDI-conjugated albumin in urine up to 6 days after respiratory tract exposure. Two additional [M + H] ions ( m/ z 558.17 and 863.23) were found exclusively in urine of mice exposed to MDI-GSH via the respiratory tract and possessed characteristics of previously described cyclized MDI-GSH and oxidized glutathione (GSSG)-MDI conjugates, respectively. Together the data identify urinary biomarkers of MDI exposure in mice and possible guidance for future translational investigation.
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http://dx.doi.org/10.1021/acs.chemrestox.8b00262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465083PMC
April 2019

Deep Airway Inflammation and Respiratory Disorders in Nanocomposite Workers.

Nanomaterials (Basel) 2018 Sep 16;8(9). Epub 2018 Sep 16.

UMass, Lowell, Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, Lowell, MA 01854, USA.

Thousands of researchers and workers worldwide are employed in nanocomposites manufacturing, yet little is known about their respiratory health. Aerosol exposures were characterized using real time and integrated instruments. Aerosol mass concentration ranged from 0.120 mg/m³ to 1.840 mg/m³ during nanocomposite machining processes; median particle number concentration ranged from 4.8 × 10⁴ to 5.4 × 10⁵ particles/cm³. The proportion of nanoparticles varied by process from 40 to 95%. Twenty employees, working in nanocomposite materials research were examined pre-shift and post-shift using spirometry and fractional exhaled nitric oxide (FeNO) in parallel with 21 controls. Pro-inflammatory leukotrienes (LT) type B4, C4, D4, and E4; tumor necrosis factor (TNF); interleukins; and anti-inflammatory lipoxins (LXA4 and LXB4) were analyzed in their exhaled breath condensate (EBC). Chronic bronchitis was present in 20% of researchers, but not in controls. A significant decrease in forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) was found in researchers post-shift ( ˂ 0.05). Post-shift EBC samples were higher for TNF ( ˂ 0.001), LTB4 ( ˂ 0.001), and LTE4 ( ˂ 0.01) compared with controls. Nanocomposites production was associated with LTB4 ( ˂ 0.001), LTE4 ( ˂ 0.05), and TNF ( ˂ 0.001), in addition to pre-shift LTD4 and LXB4 (both ˂ 0.05). Spirometry documented minor, but significant, post-shift lung impairment. TNF and LTB4 were the most robust markers of biological effects. Proper ventilation and respiratory protection are required during nanocomposites processing.
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http://dx.doi.org/10.3390/nano8090731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164906PMC
September 2018

Synergistic effects of engineered nanoparticles and organics released from laser printers using nano-enabled toners: potential health implications from exposures to the emitted organic aerosol.

Environ Sci Nano 2017 Nov 30;4(11):2144-2156. Epub 2017 Aug 30.

Department of Environmental Health, Center for Nanotechnology and Nanotoxicology, T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

Recent studies have shown that engineered nanoparticles (ENPs) are incorporated into toner powder used in printing equipment and released during their use. Thus, understanding the functional and structural composition and potential synergistic effects of this complex aerosol and released gaseous co-pollutants is critical in assessing their potential toxicological implications and risks. In this study, toner powder and PEPs were thoroughly examined for functional and molecular composition of the organic fraction and the concentration profile of 16 Environmental Protection Agency (EPA)-priority polycyclic aromatic hydrocarbons (PAH) using state of the art analytical methods. Results show significant differences in abundance of non-exchangeable organic hydrogen of toner powder and PEPs, with a stronger aromatic spectral signature in PEPs. Changes in structural composition of PEPs are indicative of radical additions and free-radical polymerization favored by catalytic reactions, resulting in formation of functionalized organic species. Particularly, accumulation of aromatic carbons with strong styrene-like molecular signatures on PEPs is associated with formation of semivolatile heavier aromatic species (., PAHs). Further, the transformation of low molecular weight PAHs in the toner powder to high molecular weight PAHs in PEPs was documented and quantified. This may be a result of synergistic effects from catalytic metal/metal oxide ENPs incorporated into the toner and the presence/release of semi-volatile organic species (SVOCs). The presence of known carcinogenic PAHs on PEPs raises public health concerns and warrants further toxicological assessment.
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http://dx.doi.org/10.1039/C7EN00573CDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121699PMC
November 2017

Markers of Oxidative Stress in the Exhaled Breath Condensate of Workers Handling Nanocomposites.

Nanomaterials (Basel) 2018 Aug 10;8(8). Epub 2018 Aug 10.

Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, Lowell, MA 01854, USA.

Researchers in nanocomposite processing may inhale a variety of chemical agents, including nanoparticles. This study investigated airway oxidative stress status in the exhaled breath condensate (EBC). Nineteen employees (42.4 ± 11.4 y/o), working in nanocomposites research for 18.0 ± 10.3 years were examined pre-shift and post-shift on a random workday, together with nineteen controls (45.5 ± 11.7 y/o). Panels of oxidative stress biomarkers derived from lipids, nucleic acids, and proteins were analyzed in the EBC. Aerosol exposures were monitored during three major nanoparticle generation operations: smelting and welding (workshop 1) and nanocomposite machining (workshop 2) using a suite of real-time and integrated instruments. Mass concentrations during these operations were 0.120, 1.840, and 0.804 mg/m³, respectively. Median particle number concentrations were 4.8 × 10⁴, 1.3 × 10⁵, and 5.4 × 10⁵ particles/cm³, respectively. Nanoparticles accounted for 95, 40, and 61%, respectively, with prevailing Fe and Mn. All markers of nucleic acid and protein oxidation, malondialdehyde, and aldehydes C₆⁻C were elevated, already in the pre-shift samples relative to controls in both workshops. Significant post-shift elevations were documented in lipid oxidation markers. Significant associations were found between working in nanocomposite synthesis and EBC biomarkers. More research is needed to understand the contribution of nanoparticles from nanocomposite processing in inducing oxidative stress, relative to other co-exposures generated during welding, smelting, and secondary oxidation processes, in these workshops.
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http://dx.doi.org/10.3390/nano8080611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116291PMC
August 2018

Dissolution Behavior and Biodurability of Ingested Engineered Nanomaterials in the Gastrointestinal Environment.

ACS Nano 2018 08 23;12(8):8115-8128. Epub 2018 Jul 23.

Department of Environmental Health and the Harvard Center for Nanotechnology and Nanotoxicology, Harvard T. H. Chan School of Public Health , Harvard University , Boston , Massachusetts 02115 , United States.

Engineered nanomaterials (ENM) are extensively used as food additives in numerous food products, and at present, little is known about the fate of ingested ENM (iENM) in the gastrointestinal (GI) environment. Here, we investigated the dissolution behavior, biodurability, and persistence of four major iENM (TiO, SiO, ZnO, and two FeO) in individual simulated GI fluids (saliva, gastric, and intestinal) and a physiologically relevant digestion cascade (saliva → gastric → intestinal) in the fasted state over physiologically relevant time frames. TiO was found to be the most biodurable and persistent iENM in simulated GI fluids with a maximum of only 0.42% (4 μM Ti ion release) dissolution in cascade digestion, followed by iron oxides, of which the rod-like morphology was more biodurable and persistent (0.7% maximum dissolution, 8.7 μM Fe) than the acicular one (2.27% maximum dissolution, 16.7 μM Fe) in the cascade digestion, respectively. SiO and ZnO were less biodurable than FeO, with 65.5% (416 μM Si) and 100% (1718.1 μM Zn) dissolution in the gastric phase, respectively. In the intestinal phase, however, Si ions reprecipitated, possibly due to sudden pH changes, while ZnO remained completely dissolved. These observations were also confirmed using high-resolution particle size and concentration, and electron microscopy, time-dependent analysis. In terms of decreasing biodurability and persistence in the simulated GI environment, the tested nanomaterials can be ranked as follows: TiO ≫ rod-like FeO > acicular FeO ≫ SiO > ZnO, which is in agreement with limited animal biokinetics data. Chronic uptake of these iENM as particles or ions by the GI tract, especially in the presence of a food matrix and authentic digestive media, and associated implications for human health warrants further investigation.
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http://dx.doi.org/10.1021/acsnano.8b02978DOI Listing
August 2018

Ingested engineered nanomaterials: state of science in nanotoxicity testing and future research needs.

Part Fibre Toxicol 2018 07 3;15(1):29. Epub 2018 Jul 3.

Biomedical Engineering & Biotechnology Program, University of Massachusetts Lowell, Lowell, MA, 01854, USA.

Background: Engineered nanomaterials (ENM) are used extensively in food products to fulfill a number of roles, including enhancement of color and texture, for nutritional fortification, enhanced bioavailability, improved barrier properties of packaging, and enhanced food preservation. Safety assessment of ingested engineered nanomaterials (iENM) has gained interest in the nanotoxicology community in recent years. A variety of test systems and approaches have been used for such evaluations, with in vitro monoculture cell models being the most common test systems, owing to their low cost and ease-of-use. The goal of this review is to systematically assess the current state of science in toxicological testing of iENM, with particular emphasis on model test systems, their physiological relevance, methodological strengths and challenges, realistic doses (ranges and rates), and then to identify future research needs and priorities based on these assessments.

Methods: Extensive searches were conducted in Google Scholar, PubMed and Web of Science to identify peer-reviewed literature on safety assessment of iENM over the last decade, using keywords such as "nanoparticle", "food", "toxicity", and combinations thereof. Relevant literature was assessed based on a set of criteria that included the relevance of nanomaterials tested; ENM physicochemical and morphological characterization; dispersion and dosimetry in an in vitro system; dose ranges employed, the rationale and dose realism; dissolution behavior of iENM; endpoints tested, and the main findings of each study. Observations were entered into an excel spreadsheet, transferred to Origin, from where summary statistics were calculated to assess patterns, trends, and research gaps.

Results: A total of 650 peer-reviewed publications were identified from 2007 to 2017, of which 39 were deemed relevant. Only 21% of the studies used food grade nanomaterials for testing; adequate physicochemical and morphological characterization was performed in 53% of the studies. All in vitro studies lacked dosimetry and 60% of them did not provide a rationale for the doses tested and their relevance. Only 12% of the studies attempted to consider the dissolution kinetics of nanomaterials. Moreover, only 1 study attempted to prepare and characterize standardized nanoparticle dispersions.

Conclusion: We identified 5 clusters of factors deemed relevant to nanotoxicology of food-grade iENM: (i) using food-grade nanomaterials for toxicity testing; (ii) performing comprehensive physicochemical and morphological characterization of iENM in the dry state, (iii) establishing standard NP dispersions and their characterization in cell culture medium, (iv) employing realistic dose ranges and standardized in vitro dosimetry models, and (v) investigating dissolution kinetics and biotransformation behavior of iENM in synthetic media representative of the gastrointestinal (GI) tract fluids, including analyses in a fasted state and in the presence of a food matrix. We discussed how these factors, when not considered thoughtfully, could influence the results and generalizability of in vitro and in vivo testing. We conclude with a set of recommendations to guide future iENM toxicity studies and to develop/adopt more relevant in vitro model systems representative of in vivo animal and human iENM exposure scenarios.
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http://dx.doi.org/10.1186/s12989-018-0265-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029122PMC
July 2018

Testing of Disposable Protective Garments Against Isocyanate Permeation From Spray Polyurethane Foam Insulation.

Ann Work Expo Health 2018 07;62(6):754-764

Department of Public Health, University of Massachusetts Lowell, One University Avenue, Lowell, MA, USA.

Background: Diisocyanates (isocyanates), including methylene diphenyl diisocyanate (MDI), are the primary reactive components of spray polyurethane foam (SPF) insulation. They are potent immune sensitizers and a leading cause of occupational asthma. Skin exposure to isocyanates may lead to both irritant and allergic contact dermatitis and possibly contribute to systemic sensitization. More than sufficient evidence exists to justify the use of protective garments to minimize skin contact with aerosolized and raw isocyanate containing materials during SPF applications. Studies evaluating the permeation of protective garments following exposure to SPF insulation do not currently exist.

Objectives: To conduct permeation testing under controlled conditions to assess the effectiveness of common protective gloves and coveralls during SPF applications using realistic SPF product formulations.

Methods: Five common disposable garment materials [disposable latex gloves (0.07 mm thickness), nitrile gloves (0.07 mm), vinyl gloves (0.07 mm), polypropylene coveralls (0.13 mm) and Tyvek coveralls (0.13 mm)] were selected for testing. These materials were cut into small pieces and assembled into a permeation test cell system and coated with a two-part slow-rise spray polyurethane foam insulation. Glass fiber filters (GFF) pretreated with 1-(9-anthracenylmethyl)piperazine) (MAP) were used underneath the garment to collect permeating isocyanates. GFF filters were collected at predetermined test intervals between 0.75 and 20.00 min and subsequently analyzed using liquid chromatography-tandem mass spectrometry. For each garment material, we assessed (i) the cumulative concentration of total isocyanate, including phenyl isocyanate and three MDI isomers, that effectively permeated the material over the test time; (ii) estimated breakthrough detection time, average permeation rate, and standardized breakthrough time; from which (iii) recommendations were developed for the use of similar protective garments following contamination by two-component spray polyurethane foam systems and the limitations of such protective garments were identified.

Results: Each type of protective garment material demonstrated an average permeation rate well below the ASTM method F-739 standardized breakthrough rate threshold of 100.0 ng/cm2 min-1. Disposable latex gloves displayed the greatest total isocyanate permeation rate (4.11 ng/cm2 min-1), followed by the vinyl and nitrile gloves, respectively. The Tyvek coverall demonstrated a greater average rate of isocyanate permeation than the polypropylene coveralls. Typical isocyanate loading was in the range of 900 to 15,000 ng MDI/cm2.

Conclusion: Permeation test data collected during this study indicated that each type of protective garment evaluated, provided a considerable level of protection (i.e. 10-110-fold reduction from the level of direct exposure) against the isocyanate component of the SPF insulation mixture. Nitrile gloves and polypropylene coveralls demonstrated the lowest rate of permeation and the lowest cumulative permeation of total isocyanate for each garment type.
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http://dx.doi.org/10.1093/annweh/wxy030DOI Listing
July 2018

Exposure to organophosphate flame retardants in spray polyurethane foam applicators: Role of dermal exposure.

Environ Int 2018 04 6;113:55-65. Epub 2018 Feb 6.

University of Massachusetts Lowell, Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, Lowell, MA 01854, United States. Electronic address:

Background: Spray polyurethane foam (SPF) is a highly effective thermal insulation material that has seen considerable market growth in the past decade. Organophosphate flame retardants (PFRs) are added to SPF formulations to meet fire code requirements. A common flame retardant used in SPF formulations is tris 1-chloro 2-propyl phosphate (TCIPP), a suspected endocrine disruptor. Exposure monitoring efforts during SPF applications have focused primarily on the isocyanate component, a potent respiratory and dermal sensitizer. However, to our knowledge, there is no monitoring data for TCIPP.

Objective: To characterize occupational exposures to TCIPP and other flame retardants during SPF insulation.

Methods: Workers at four SPF insulation sites and one foam removal site (total n = 14) were recruited as part of this pilot study. Personal inhalation exposure to TCIPP was monitored with a CIP-10MI inhalable sampler and potential dermal exposure was assessed through the use of a glove dosimeter. Biomarkers of TCIPP and three other PFRs were measured in urine collected from workers pre-and post-shift. Linear mixed effect models were used to analyze associations of urinary biomarkers with inhalation and dermal exposures and paired t-tests were used to examine the difference on the means of urinary biomarkers pre-and post-shift. Chemical analysis of all species was performed with liquid chromatography-electrospray ionization tandem mass spectrometry.

Results: Geometric mean (GM) concentrations of TCIPP in personal air monitors and glove dosimeters collected from SPF applicators, 294.7 μg/m and 18.8 mg/pair respectively. Overall, GM concentrations of the two TCIPP urinary biomarkers BCIPP and BCIPHIPP and (6.2 and 88.8 μg/mL) were 26-35 times higher than reported in the general population. Post-shift levels of TCIPP biomarkers were higher than pre-shift even though workers at insulation sites wore supplied air respirators, gloves and coveralls. The urinary biomarkers for the other PFRs were not elevated post shift. Concentrations of TCIPP on glove dosimeters were positively associated with post-shift urinary TCIPP biomarkers (p < 0.05) whereas concentrations in personal air samples were not.

Conclusions: High levels of urinary biomarkers for TCIPP among SPF applicators, including post-shift, points to absorption of TCIPP during the work shift, in spite of the use of best industry exposure control practices. Dermal exposure appears to be an important, if not the primary exposure pathway for TCIPP, although inhalation or incidental ingestion of foam particles post-SPF application cannot be ruled out in this pilot study.
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http://dx.doi.org/10.1016/j.envint.2018.01.020DOI Listing
April 2018

An integrated electrolysis - electrospray - ionization antimicrobial platform using Engineered Water Nanostructures (EWNS) for food safety applications.

Food Control 2018 Mar 29;85:151-160. Epub 2017 Sep 29.

Center for Nanotechnology and Nanotoxicology, Harvard School of Public Health, Harvard University, Boston, MA 02115, USA.

Engineered water nanostructures (EWNS) synthesized utilizing electrospray and ionization of water, have been, recently, shown to be an effective, green, antimicrobial platform for surface and air disinfection, where reactive oxygen species (ROS), generated and encapsulated within the particles during synthesis, were found to be the main inactivation mechanism. Herein, the antimicrobial potency of the EWNS was further enhanced by integrating electrolysis, electrospray and ionization of de-ionized water in the EWNS synthesis process. Detailed physicochemical characterization of these enhanced EWNS (eEWNS) was performed using state-of-the-art analytical methods and has shown that, while both size and charge remain similar to the EWNS (mean diameter of 13 nm and charge of 13 electrons), they possess a three times higher ROS content. The increase of the ROS content as a result of the addition of the electrolysis step before electrospray and ionization led to an increased antimicrobial ability as verified by inactivation studies using stainless steel coupons. It was shown that a 45-minute exposure to eEWNS resulted in a 4-log reduction as opposed to a 1.9-log reduction when exposed to EWNS. In addition, the eEWNS were assessed for their potency to inactivate natural microbiota (total viable and yeast and mold counts), as well as, inoculated on the surface of fresh organic blackberries. The results showed a 97% (1.5-log) inactivation of the total viable count, a 99% (2-log) reduction in the yeast and mold count and a 2.5-log reduction of the inoculated after 45 minutes of exposure, without any visual changes to the fruit. This enhanced antimicrobial activity further underpins the EWNS platform as an effective, dry and chemical free approach suitable for a variety of food safety applications and could be ideal for delicate fresh produce that cannot withstand the classical, wet disinfection treatments.
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http://dx.doi.org/10.1016/j.foodcont.2017.09.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764107PMC
March 2018

Assessment of reactive oxygen species generated by electronic cigarettes using acellular and cellular approaches.

J Hazard Mater 2018 Feb 29;344:549-557. Epub 2017 Oct 29.

Department of Environmental Health, Center for Nanotechnology and Nanotoxicology, Harvard School of Public Health, Boston, MA 02115, USA. Electronic address:

Electronic cigarettes (e-cigs) have fast increased in popularity but the physico-chemical properties and toxicity of the generated emission remain unclear. Reactive oxygen species (ROS) are likely present in e-cig emission and can play an important role in e-cig toxicity. However, e-cig ROS generation is poorly documented. Here, we generated e-cig exposures using a recently developed versatile exposure platform and performed systematic ROS characterization on e-cig emissions using complementary acellular and cellular techniques: 1) a novel acellular Trolox-based mass spectrometry method for total ROS and hydrogen peroxide (HO) detection, 2) electron spin resonance (ESR) for hydroxyl radical detection in an acellular and cellular systems and 3) in vitro ROS detection in small airway epithelial cells (SAEC) using the dihydroethidium (DHE) assay. Findings confirm ROS generation in cellular and acellular systems and is highly dependent on the e-cig brand, flavor, puffing pattern and voltage. Trolox method detected a total of 1.2-8.9nmol HO/puff; HO accounted for 12-68% of total ROS. SAEC cells exposed to e-cig emissions generated up to eight times more ROS compared to control. The dependency of e-cig emission profile on e-cig features and operational parameters should be taken into consideration in toxicological studies.
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http://dx.doi.org/10.1016/j.jhazmat.2017.10.057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848214PMC
February 2018

Nanoparticle exposures from nano-enabled toner-based printing equipment and human health: state of science and future research needs.

Crit Rev Toxicol 2017 Sep 19;47(8):678-704. Epub 2017 May 19.

a Department of Environmental Health, Harvard T.H. Chan School of Public Health , Center for Nanotechnology and Nanotoxicology , Boston , MA , USA.

Toner formulations used by laser printers (LP) and photocopiers (PC), collectively called "toner-based printing equipment" (TPE), are nano-enabled products (NEP) because they contain several engineered nanomaterials (ENM) that improve toner performance. It has been shown that during consumer use (printing), these ENM are released in the air, together with other semi-volatile organic nanoparticles, and newly formed gaseous co-pollutants such as volatile organic compounds (VOC). The aim of this review is to detail and analyze physico-chemical and morphological (PCM), as well as the toxicological properties of particulate matter (PM) emissions from TPE. The review covers evolution of science since the early 2000, when this printing technology first became a subject of public interest, as well as the lagging regulatory framework around it. Important studies that have significantly changed our understanding of these exposures are also highlighted. The review continues with a critical appraisal of the most up-to-date cellular, animal and human toxicological evidence on the potential adverse human health effects of PM emitted from TPE. We highlight several limitations of existing studies, including (i) use of high and often unrealistic doses in vitro or in vivo; (ii) unrealistically high-dose rates in intratracheal instillation studies; (iii) improper use of toners as surrogate for emitted nanoparticles; (iv) lack of or inadequate PCM characterization of exposures; and (v) lack of dosimetry considerations in in vitro studies. Presently, there is compelling evidence that the PM from TPE are biologically active and capable of inducing oxidative stress in vitro and in vivo, respiratory tract inflammation in vivo (in rats) and in humans, several endpoints of cellular injury in monocultures and co-cultures, including moderate epigenetic modifications in vitro. In humans, limited epidemiological studies report typically 2-3 times higher prevalence of chronic cough, wheezing, nasal blockage, excessive sputum production, breathing difficulties, and shortness of breath, in copier operators relative to controls. Such symptoms can be exacerbated during chronic exposures, and in individuals susceptible to inhaled pollutants. Thus respiratory, immunological, cardiovascular, and other disorders may be developed following such exposures; however, further toxicological and larger scale molecular epidemiological studies must be done to fully understand the mechanism of action of these TPE emitted nanoparticles. Major research gaps have also been identified. Among them, a methodical risk assessment based on "real world" exposures rather than on the toner particles alone needs to be performed to provide the much-needed data to establish regulatory guidelines protective of individuals exposed to TPE emissions at both the occupational and consumer level. Industry-wide molecular epidemiology as well as mechanistic animal and human studies are also urgently needed.
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http://dx.doi.org/10.1080/10408444.2017.1318354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857386PMC
September 2017

Biokinetics of engineered nano-TiO in rats administered by different exposure routes: implications for human health.

Nanotoxicology 2017 05 19;11(4):431-433. Epub 2017 May 19.

b Toxicology and Risk Assessment , The Chemours Company , Wilmington , DE , USA.

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http://dx.doi.org/10.1080/17435390.2017.1330436DOI Listing
May 2017

Haemolytic activity of soil from areas of varying podoconiosis endemicity in Ethiopia.

PLoS One 2017 11;12(5):e0177219. Epub 2017 May 11.

Wellcome Trust Centre for Global Health Research, Brighton and Sussex Medical School, University of Sussex, Brighton, East Sussex United Kingdom.

Background: Podoconiosis, non-filarial elephantiasis, is a non-infectious disease found in tropical regions such as Ethiopia, localized in highland areas with volcanic soils cultivated by barefoot subsistence farmers. It is thought that soil particles can pass through the soles of the feet and taken up by the lymphatic system, leading to the characteristic chronic oedema of the lower legs that becomes disfiguring and disabling over time.

Methods: The close association of the disease with volcanic soils led us to investigate the characteristics of soil samples in an endemic area in Ethiopia to identify the potential causal constituents. We used the in vitro haemolysis assay and compared haemolytic activity (HA) with soil samples collected in a non-endemic region of the same area in Ethiopia. We included soil samples that had been previously characterized, in addition we present other data describing the characteristics of the soil and include pure phase mineral standards as comparisons.

Results: The bulk chemical composition of the soils were statistically significantly different between the podoconiosis-endemic and non-endemic areas, with the exception of CaO and Cr. Likewise, the soil mineralogy was statistically significant for iron oxide, feldspars, mica and chlorite. Smectite and kaolinite clays were widely present and elicited a strong HA, as did quartz, in comparison to other mineral phases tested, although no strong difference was found in HA between soils from the two areas. The relationship was further investigated with principle component analysis (PCA), which showed that a combination of an increase in Y, Zr and Al2O3, and a concurrent increase Fe2O3, TiO2, MnO and Ba in the soils increased HA.

Conclusion: The mineralogy and chemistry of the soils influenced the HA, although the interplay between the components is complex. Further research should consider the variable biopersistance, hygroscopicity and hardness of the minerals and further characterize the nano-scale particles.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177219PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426718PMC
September 2017

Indoor Air Quality in Photocopy Centers, Nanoparticle Exposures at Photocopy Workstations, and the Need for Exposure Controls.

Ann Work Expo Health 2017 01;61(1):110-122

Department of Work Environment, University of Massachusetts Lowell, One University Avenue, Lowell, MA 01854, USA.

Background: Photocopiers emit large amounts of nanoparticles (NP) and are a significant source of indoor air pollution. These emissions induce airway inflammation, irritation, and systemic oxidative stress in humans, lung injury and inflammation in animals, and cytotoxicity and epigenetic modifications in vitro. However, little is known regarding NP exposures at the workstation in the photocopy work environment, or the extent and use of emission controls.

Objective: To survey the photocopy work environment with regards to emissions controls and to evaluate IAQ with emphasis on NP exposure at the operator's workstation.

Methods: Work process, physical characteristics of the centers, and use of controls were recorded. Particle total number concentration (TNC), temperature, carbon dioxide, carbon monoxide, and percent relative humidity were measured during a random workday.

Results: Geometric mean (GM) TNC at workstations ranged between 1900 and 23000 particles cm-3, GSD 1.2-2.8, and maximum of 217000 particles cm-3. Fresh air ventilation was found to be less than American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) guidelines in 7 of 15 centers. Only one center used any type of emissions control. Elevated TNC at workstations was significantly correlated with number of copies (r = 0.72). While indoor/outdoor TNC ratios might be expected to be ≤1.0, the ratio here was >1.0 in 40% of centers visited, supporting the finding that copier emissions are a significant source of indoor air pollution. Number of copies per day was the most significant contributor to TNC.

Conclusion: High NP concentrations at workstations were common and specific emission controls almost nonexistent. While 46% of copy centers had insufficient ventilation, high exposures were documented even for cases when ASHRAE ventilation guidelines per person were met or exceeded. We present various options to address IAQ in photocopy environment, including new clean photocopy technologies, engineering controls, and a comprehensive awareness campaign to improve the environmental health and safety, design, and operational conditions of these workplaces.
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http://dx.doi.org/10.1093/annweh/wxw016DOI Listing
January 2017

Markers of lipid oxidative damage in the exhaled breath condensate of nano TiO production workers.

Nanotoxicology 2017 02 9;11(1):52-63. Epub 2016 Dec 9.

h UMass Lowell, Department of Public Health , College of Health Sciences , Lowell, MA , USA.

Nanoscale titanium dioxide (nanoTiO) is a commercially important nanomaterial. Animal studies have documented lung injury and inflammation, oxidative stress, cytotoxicity and genotoxicity. Yet, human health data are scarce and quantitative risk assessments and biomonitoring of exposure are lacking. NanoTiO is classified by IARC as a group 2B, possible human carcinogen. In our earlier studies we documented an increase in markers of inflammation, as well as DNA and protein oxidative damage, in exhaled breath condensate (EBC) of workers exposed nanoTiO. This study focuses on biomarkers of lipid oxidation. Several established lipid oxidative markers (malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, 8-isoProstaglandin F2α and aldehydes C-C) were studied in EBC and urine of 34 workers and 45 comparable controls. The median particle number concentration in the production line ranged from 1.98 × 10 to 2.32 × 10 particles/cm with ∼80% of the particles <100 nm in diameter. Mass concentration varied between 0.40 and 0.65 mg/m. All 11 markers of lipid oxidation were elevated in production workers relative to the controls (p < 0.001). A significant dose-dependent association was found between exposure to TiO and markers of lipid oxidation in the EBC. These markers were not elevated in the urine samples. Lipid oxidation in the EBC of workers exposed to (nano)TiO complements our earlier findings on DNA and protein damage. These results are consistent with the oxidative stress hypothesis and suggest lung injury at the molecular level. Further studies should focus on clinical markers of potential disease progression. EBC has reemerged as a sensitive technique for noninvasive monitoring of workers exposed to engineered nanoparticles.
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http://dx.doi.org/10.1080/17435390.2016.1262921DOI Listing
February 2017

Residual Isocyanates in Medical Devices and Products: A Qualitative and Quantitative Assessment.

Environ Health Insights 2016 13;10:175-190. Epub 2016 Oct 13.

Department of Environmental and Occupational Health Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA.

We conducted a pilot qualitative and quantitative assessment of residual isocyanates and their potential initial exposures in neonates, as little is known about their contact effect. After a neonatal intensive care unit (NICU) stockroom inventory, polyurethane (PU) and PU foam (PUF) devices and products were qualitatively evaluated for residual isocyanates using Surface SWYPE™. Those containing isocyanates were quantitatively tested for methylene diphenyl diisocyanate (MDI) species, using UPLC-UV-MS/MS method. Ten of 37 products and devices tested, indicated both free and bound residual surface isocyanates; PU/PUF pieces contained aromatic isocyanates; one product contained aliphatic isocyanates. Overall, quantified mean MDI concentrations were low (4,4'-MDI = 0.52 to 140.1 pg/mg) and (2,4'-MDI = 0.01 to 4.48 pg/mg). The 4,4'-MDI species had the highest measured concentration (280 pg/mg). Commonly used medical devices/products contain low, but measurable concentrations of residual isocyanates. Quantifying other isocyanate species and neonatal skin exposure to isocyanates from these devices and products requires further investigation.
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http://dx.doi.org/10.4137/EHI.S39149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067089PMC
October 2016

Markers of lipid oxidative damage among office workers exposed intermittently to air pollutants including nanoTiO2 particles.

Rev Environ Health 2017 Mar;32(1-2):193-200

Nanoscale titanium dioxide (nanoTiO2) is a commercially important nanomaterial used in numerous applications. Experimental studies with nanotitania have documented lung injury and inflammation, oxidative stress, and genotoxicity. Production workers in TiO2 manufacturing with a high proportion of nanoparticles and a mixture of other air pollutants, such as gases and organic aerosols, had increased markers of oxidative stress, including DNA and protein damage, as well as lipid peroxidation in their exhaled breath condensate (EBC) compared to unexposed controls. Office workers were observed to get intermittent exposures to nanoTiO2 during their process monitoring. The aim of this study was to investigate the impact of such short-term exposures on the markers of health effects in office workers relative to production workers from the same factory. Twenty-two office employees were examined. They were occupationally exposed to (nano)TiO2 aerosol during their daily visits of the production area for an average of 14±9 min/day. Median particle number concentration in office workers while in the production area was 2.32×104/cm3. About 80% of the particles were <100 nm in diameter. A panel of biomarkers of lipid oxidation, specifically malondialdehyde (MDA), 4-hydroxy-trans-hexenal (HHE), 4-hydroxy-trans-nonenal (HNE), 8-isoprostaglandin F2α (8-isoprostane), and aldehydes C6-C12, were studied in the EBC and urine of office workers and 14 unexposed controls. Nine markers of lipid oxidation were elevated in the EBC of office employees relative to controls (p<0.05); only 8-isoprostane and C11 were not increased. Significant association was found in the multivariate analysis between their employment in the TiO2 production plant and EBC markers of lipid oxidation. No association was seen with age, lifestyle factors, or environmental air contamination. The EBC markers in office employees reached about 50% of the levels measured in production workers, and the difference between production workers and office employees was highly significant (p<0.001). None of these biomarkers were elevated in urine. The approach presented here seems to be very sensitive and useful for non-invasive monitoring of employees exposed to air pollutants, including gases, organic aerosols, and nanoTiO2, and may prove useful for routine biomonitoring purposes. Among them, aldehydes C6, C8, C9, and C10 appear to be the most sensitive markers of lipid oxidation in similar occupational cohorts. One major challenge with sensitive biomonitoring techniques, however, is their non-specificity and difficulty in interpreting the meaning of their physiological values in the context of chronic disease development and damage-repair kinetics.
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http://dx.doi.org/10.1515/reveh-2016-0030DOI Listing
March 2017

Development of an Interception Glove Sampler for Skin Exposures to Aromatic Isocyanates.

Ann Occup Hyg 2016 Nov 30;60(9):1092-1103. Epub 2016 Sep 30.

2.Yale Occupational and Environmental Medicine Program, Yale School of Medicine, 135 College Street, New Haven, CT 06510, USA.

Objectives: Skin is an important exposure route for isocyanate chemicals and contributes to systemic sensitization. Methods for assessing skin exposure are currently limited and generally rely upon removal (e.g. tape-strip) techniques prone to underestimation. The aim of this study is to (i) develop and field test an interception-based hand exposure sampler to monitor potential skin exposure to isocyanates in the workplace, (ii) to develop an analytical method based on ultra-high-performance liquid chromatography-UV absorbance-tandem mass spectrometry (UHPLC-UV-MS/MS) for analyzing glove samples; and (iii) compare it with tape-stripping skin sampling method.

Methods: Laboratory investigations assessed different glove materials/fabrics, methods for impregnating with 1-(9-anthracenylmethyl)piperazine (MAP) derivatizing agent, methylene diphenyl diisocyanate (MDI) uptake and recovery, and durability. Following use, gloves were dissected into sections corresponding to different spatial regions (finger, palm) and analyzed using a newly developed UHPLC-UV-MS/MS method capable of differentiating and quantitating different MDI isomers with high sensitivity. Performance of the glove sampler was further assessed in a pilot field study using six workers.

Results: A MAP-impregnated thin cotton glove sampler and UHPLC-UV-MS/MS analytical method for detecting MDI were successfully developed in laboratory studies. In subsequent field studies, a total of 384 samples from 14 glove pairs identified full-shift exposures ranged from 0.01 to 306 µg of 4,4'-MDI/worker for each hand. Surface area adjusted MDI values measured with the glove sampler (0.13-572ng MDI cm) were considerably higher (~400-fold) than values obtained with tape stripping.

Conclusion: A glove sampler and a novel UHPLC-UV-MS/MS analytical method were developed to quantitatively measure MDI skin exposure. The novel interception technique overcomes inherent limitations of removal techniques for measuring isocyanate skin exposure and may be useful in exposure surveillance and future research on isocyanate's health risks.
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http://dx.doi.org/10.1093/annhyg/mew052DOI Listing
November 2016

Occupational dermal exposure to nanoparticles and nano-enabled products: Part I-Factors affecting skin absorption.

Int J Hyg Environ Health 2016 08 27;219(6):536-44. Epub 2016 May 27.

TNO, Department Risk Analysis for Products in Development, Zeist, The Netherlands; University of the Witwatersrand, Faculty of Health Sciences, School of Public Health, Johannesburg, South Africa.

The paper reviews and critically assesses the evidence on the relevance of various skin uptake pathways for engineered nanoparticles, nano-objects, their agglomerates and aggregates (NOAA). It focuses especially in occupational settings, in the context of nanotoxicology, risk assessment, occupational medicine, medical/epidemiological surveillance efforts, and the development of relevant exposure assessment strategies. Skin uptake of nanoparticles is presented in the context of local and systemic health effects, especially contact dermatitis, skin barrier integrity, physico-chemical properties of NOAA, and predisposing risk factors, such as stratum corneum disruption due to occupational co-exposure to chemicals, and the presence of occupational skin diseases. Attention should be given to: (1) Metal NOAA, since the potential release of ions may induce local skin effects (e.g. irritation and contact dermatitis) and absorption of toxic or sensitizing metals; (2) NOAA with metal catalytic residue, since potential release of ions may also induce local skin effects and absorption of toxic metals; (3) rigid NOAA smaller than 45nm that can penetrate and permeate the skin; (4) non rigid or flexible NOAA, where due to their flexibility liposomes and micelles can penetrate and permeate the intact skin; (5) impaired skin condition of exposed workers. Furthermore, we outline possible situations where health surveillance could be appropriate where there is NOAA occupational skin exposures, e.g. when working with nanoparticles made of sensitizer metals, NOAA containing sensitizer impurities, and/or in occupations with a high prevalence of disrupted skin barrier integrity. The paper furthermore recommends a stepwise approach to evaluate risk related to NOAA to be applied in occupational exposure and risk assessment, and discusses implications related to health surveillance, labelling, and risk communication.
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http://dx.doi.org/10.1016/j.ijheh.2016.05.009DOI Listing
August 2016

Occupational dermal exposure to nanoparticles and nano-enabled products: Part 2, exploration of exposure processes and methods of assessment.

Int J Hyg Environ Health 2016 08 22;219(6):503-12. Epub 2016 May 22.

Institute of Occupational Medicine, Edinburgh, UK; Heriot Watt University, Edinburgh, UK.

Over the past decade, the primary focus of nanotoxicology and nanoenvironmental health and safety efforts has been largely on inhalation exposure to engineered nanomaterials, at the production stage, and much less on considering risks along the life cycle of nano-enabled products. Dermal exposure to nanomaterials and its health impact has been studied to a much lesser extent, and mostly in the context of intentional exposure to nano-enabled products such as in nanomedicine, cosmetics and personal care products. How concerning is dermal exposure to such nanoparticles in the context of occupational exposures? When and how should we measure it? In the first of a series of two papers (Larese Filon et al., 2016), we focused our attention on identifying conditions or situations, i.e. a combination of nanoparticle physico-chemical properties, skin barrier integrity, and occupations with high prevalence of skin disease, which deserve further investigation. This second paper focuses on the broad question of dermal exposure assessment to nanoparticles and attempts to give an overview of the mechanisms of occupational dermal exposure to nanoparticles and nano-enabled products and explores feasibility and adequacy of various methods of quantifying dermal exposure to NOAA. We provide here a conceptual framework for screening, prioritization, and assessment of dermal exposure to NOAA in occupational settings, and integrate it into a proposed framework for risk assessment.
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http://dx.doi.org/10.1016/j.ijheh.2016.05.003DOI Listing
August 2016