Infant and Adult Inhalation Exposure to Resuspended Biological Particulate Matter.

Human-induced resuspension of floor dust is a dynamic process that can serve as a major indoor source of biological particulate matter (bioPM). Inhalation exposure to the microbial and allergenic content of indoor dust is associated with adverse and protective health effects. This study evaluates infant and adult inhalation exposures and respiratory tract deposited dose rates of resuspended bioPM from carpets. Chamber experiments were conducted with a robotic crawling infant and an adult performing a walking sequence. Breathing zone (BZ) size distributions of resuspended fluorescent biological aerosol particles (FBAPs), a bioPM proxy, were monitored in real-time. FBAP exposures were highly transient during periods of locomotion. Both crawling and walking delivered a significant number of resuspended FBAPs to the BZ, with concentrations ranging from 0.5 to 2 cm-3 (mass range: ∼50 to 600 µg/m3). Infants and adults are primarily exposed to a unimodal FBAP size distribution between 2 and 6 µm, with infants receiving greater exposures to super-10 µm FBAPs. In just 1 min of crawling or walking, 103-104 resuspended FBAPs can deposit in the respiratory tract, with an infant receiving much of their respiratory tract deposited dose in their lower airways. Per kg body mass, an infant will receive a nearly four times greater respiratory tract deposited dose of resuspended FBAPs compared to an adult.

Characterization of particle exposure in ferrochromium and stainless steel production.

This study describes workers' exposure to fine and ultrafine particles in the production chain of ferrochromium and stainless steel during sintering, ferrochromium smelting, stainless steel melting, and hot and cold rolling operations. Workers' personal exposure to inhalable dust was assessed using IOM sampler with a cellulose acetate filter (AAWP, diameter 25 mm; Millipore, Bedford, MA). Filter sampling methods were used to measure particle mass concentrations in fixed locations. Particle number concentrations and size distributions were examined using an SMPS+C sequential mobile particle sizer and counter (series 5.400, Grimm Aerosol Technik, Ainring, Germany), and a hand-held condensation particle counter (CPC, model 3007, TSI Incorporated, MN). The structure and elemental composition of particles were analyzed using TEM-EDXA (TEM: JEM-1220, JEOL, Tokyo, Japan; EDXA: Noran System Six, Thermo Fisher Scientific Inc., Madison,WI). Workers' personal exposure to inhalable dust averaged 1.87, 1.40, 2.34, 0.30, and 0.17 mg m(-3) in sintering plant, ferrochromium smelter, stainless steel melting shop, hot rolling mill, and the cold rolling mill, respectively. Particle number concentrations measured using SMPS+C varied from 58 × 10(3) to 662 × 10(3) cm(-3) in the production areas, whereas concentrations measured using SMPS+C and CPC3007 in control rooms ranged from 24 × 10(3) to 243 × 10(3) cm(-3) and 5.1 × 10(3) to 97 × 10(3) cm(-3), respectively. The elemental composition and the structure of particles in different production phases varied. In the cold-rolling mill non-process particles were abundant. In other sites, chromium and iron originating from ore and recycled steel scrap were the most common elements in the particles studied. Particle mass concentrations were at the same level as that reported earlier. However, particle number measurements showed a high amount of ultrafine particles, especially in sintering, alloy smelting and melting, and tapping operations. Particle number concentration and size distribution measurements provide important information regarding exposure to ultrafine particles, which cannot be seen in particle mass measurements.

Genotoxicity of inhaled nanosized TiO(2) in mice.

In vitro studies have suggested that nanosized titanium dioxide (TiO(2)) is genotoxic. The significance of these findings with respect to in vivo effects is unclear, as few in vivo studies on TiO(2) genotoxicity exist. Recently, nanosized TiO(2) administered in drinking water was reported to increase, e.g., micronuclei (MN) in peripheral blood polychromatic erythrocytes (PCEs) and DNA damage in leukocytes. Induction of micronuclei in mouse PCEs was earlier also described for pigment-grade TiO(2) administered intraperitoneally. The apparent systemic genotoxic effects have been suggested to reflect secondary genotoxicity of TiO(2) due to inflammation. However, a recent study suggested that induction of DNA damage in mouse bronchoalveolar lavage (BAL) cells after intratracheal instillation of nanosized or fine TiO(2) is independent of inflammation. We examined here, if inhalation of freshly generated nanosized TiO(2) (74% anatase, 26% brookite; 5 days, 4 h/day) at 0.8, 7.2, and (the highest concentration allowing stable aerosol production) 28.5 mg/m(3) could induce genotoxic effects in C57BL/6J mice locally in the lungs or systematically in peripheral PCEs. DNA damage was assessed by the comet assay in lung epithelial alveolar type II and Clara cells sampled immediately following the exposure. MN were analyzed by acridine orange staining in blood PCEs collected 48 h after the last exposure. A dose-dependent deposition of Ti in lung tissue was seen. Although the highest exposure level produced a clear increase in neutrophils in BAL fluid, indicating an inflammatory effect, no significant effect on the level of DNA damage in lung epithelial cells or micronuclei in PCEs was observed, suggesting no genotoxic effects by the 5-day inhalation exposure to nanosized TiO(2) anatase. Our inhalation exposure resulted in much lower systemic TiO(2) doses than the previous oral and intraperitoneal treatments, and lung epithelial cells probably received considerably less TiO(2) than BAL cells in the earlier intratracheal study.

Respiratory symptoms and conditions related to occupational exposures in machine shops.

OBJECTIVES: Since there are few data on the effects of metalworking in populations representing a variety of metal companies or on dose-response relationships concerning metalworking, this study investigated the relationship between occupational exposures in machine shops and the occurrence of upper and lower respiratory symptoms, asthma, and chronic bronchitis. METHODS: A cross-sectional study of 726 male machine workers and 84 male office workers from 64 companies was conducted in southern Finland. All of the participants filled out a questionnaire, and aerosol measurements were performed in 57 companies. RESULTS: Exposure to metalworking fluids (MWF) showed a greater risk [odds ratio (OR)>or=2) for upper-airway symptoms, cough, breathlessness, and current asthma than exposures in office work did. Exposure to aerosol levels above the median (>or=0.17 mg/m3 in the general workshop air) was related to an increased risk (OR>or=2) of nasal and throat symptoms, cough, wheezing, breathlessness, chronic bronchitis, and current asthma. Machine workers with a job history of >or=15 years experienced increased throat symptoms, cough, and chronic bronchitis. CONCLUSIONS: This large study representing machine shops in southern Finland showed that machine workers experience increased nasal and throat symptoms, cough, wheezing, breathlessness, and asthma even in environments with exposure levels below the current occupational exposure limit for oil mists. The study suggests that improving machine shop environments could benefit the health of this workforce. It also suggests that it is time to consider reducing the current Finnish occupational exposure limit for oil mist or introducing the use of other health-relevant indicators of exposure.

Optimized dispersion of nanoparticles for biological in vitro and in vivo studies.

BACKGROUND: The aim of this study was to establish and validate a practical method to disperse nanoparticles in physiological solutions for biological in vitro and in vivo studies. RESULTS: TiO2 (rutile) dispersions were prepared in distilled water, PBS, or RPMI 1640 cell culture medium. Different ultrasound energies, various dispersion stabilizers (human, bovine, and mouse serum albumin, Tween 80, and mouse serum), various concentrations of stabilizers, and different sequences of preparation steps were applied. The size distribution of dispersed nanoparticles was analyzed by dynamic light scattering and zeta potential was measured using phase analysis light scattering. Nanoparticle size was also verified by transmission electron microscopy. A specific ultrasound energy of 4.2 x 105 kJ/m3 was sufficient to disaggregate TiO2 (rutile) nanoparticles, whereas higher energy input did not further improve size reduction. The optimal sequence was first to sonicate the nanoparticles in water, then to add dispersion stabilizers, and finally to add buffered salt solution to the dispersion. The formation of coarse TiO2 (rutile) agglomerates in PBS or RPMI was prevented by addition of 1.5 mg/ml of human, bovine or mouse serum albumin, or mouse serum. The required concentration of albumin to stabilize the nanoparticle dispersion depended on the concentration of the nanoparticles in the dispersion. TiO2 (rutile) particle dispersions at a concentration lower than 0.2 mg/ml could be stabilized by the addition of 1.5 mg/ml albumin. TiO2 (rutile) particle dispersions prepared by this method were stable for up to at least 1 week. This method was suitable for preparing dispersions without coarse agglomerates (average diameter < 290 nm) from nanosized TiO2 (rutile), ZnO, Ag, SiOx, SWNT, MWNT, and diesel SRM2975 particulate matter. CONCLUSION: The optimized dispersion method presented here appears to be effective and practicable for preparing dispersions of nanoparticles in physiological solutions without creating coarse agglomerates.

Respiratory exposure to components of water-miscible metalworking fluids.

Water-miscible metalworking fluids (MWFs) are capable of causing respiratory symptoms and diseases. Recently, much emphasis has been put on developing new methods for assessing respiratory exposure to MWF emulsions. The air concentrations of ingredients and contaminants of MWF and inhalable dust were measured in 10 metal workshops in southern Finland. Oil mist was determined by infra red spectroscopy analysis after tetrachloroethylene extraction from the filter. Aldehydes were collected on Sep-Pak chemosorbents and analysed by liquid chromatography. Volatile organic compounds (VOCs) were collected on Tenax adsorbents and analysed by gas chromatography with mass spectrometric detection after thermal desorption. Endotoxins were collected on glass fibre filter and analysed by enzyme-based spectrophotometry, and viable microbes were collected on polycarbonate filter and cultured. Inhalable dust was collected on cellulose acetate filter and quantified gravimetrically. Associations between the different exposures were calculated with Spearman's correlations. The mean concentration of oil mist was 0.14 (range <0.010-0.60) mg m(-3). The mean total concentration of aldehydes was 0.095 (0.026-0.38) mg m(-3), with formaldehyde as the main aldehyde. The average total concentration of VOC was 1.9 (0.34-4.5) mg m(-3) consisting mainly of high-boiling aliphatic hydrocarbons. Several potential sensitizing chemicals such as terpenes were found in small quantities. The concentration of microbial contaminants was low. All the measured air concentrations were below the Finnish occupational exposure limits. The exposure in machine shops was quantitatively dominated by volatile compounds. Additional measurements of MWF components such as aldehydes, alkanolamines and VOCs are needed to get more information on the chemical composition of workshops' air. New air cleaning methods should be introduced, as oil mist separators are insufficient to clean the air of small molecular impurities.

Use of nasal provocation test in the diagnostics of occupational rhinitis.

OBJECTIVES: The purpose of the study was to evaluate the usefulness and clinical value of the nasal provocation test (NPT) with various allergens and non-IgE-mediated irritants in the diagnostics assessing occupational rhinitis. METHODS: A large number nasal provocation data from patients with suspected occupational rhinitis was evaluated retrospectively. The results of nasal provocation tests with different agents, as well as the correlation of nasal scoring to weighed mucus secretion, were analyzed. RESULTS: Altogether 507 NPTs were done in three years in 165 persons. In total, 39% of the allergen provocations (125/318) were positive. The most common positive reactions were against flours, animal epithelia, storage mites and various plants. Wood dusts, mainly through non-IgE-mediated reactions, gave 50% positive results. Positive NPTs to moulds were observed mainly in sensitized patients. Altogether, 10% of the control provocations were positive. The weighting of mucus secretion added sensitivity of NPT. CONCLUSIONS: The NPT is an essential standard tool in the diagnostics of allergic occupational rhinitis; however it needs to be evaluated in the context of the medical and work history and knowledge of sensitization. Although expensive and laborious, NPT is safe and easy for the patient. We still need reliable diagnostic tools for non-allergic work-related rhinitis.

Systemic inflammatory responses following welding inhalation challenge test.

AIM: The aim of this study was to investigate inflammatory and respiratory responses to welding fume exposure in patients with suspected occupational asthma. METHODS: Sixteen patients referred to the Finnish Institute of Occupational Health underwent mild steel (MS) and stainless steel (SS) welding challenge tests, due to suspicion of OA. Platelet count, leucocytes and their differential count, hemoglobin, sensitive CRP, lipids, glucose and fibrinogen were analyzed in addition to interleukin (IL)-1ß, IL-6, IL-8, TNF-α, endothelin-1, and E-selectin in plasma samples. Peak expiratory flow (PEF), forced expiratory volume in 1 min (FEV1) and exhaled nitric oxide (NO) measurements were performed before and after the challenge test. Personal particle exposure was assessed using IOM and a mini sampler. Particle size distribution was measured by an Electric Low Pressure Impactor (ELPI). RESULTS: The number of leukocytes, neutrophils, and platelets increased significantly, and the hemoglobin level and number of erythrocytes decreased significantly after both the MS and SS exposure tests. Five of the patients were diagnosed with OA, and their maximum fall in FEV1 values was 0.70 l (±0.32) 4 h after SS exposure. MS welding generated an average inhalable particle mass concentration of 31.6, and SS welding of 40.2 mg/m3. The mean particle concentration measured inside the welding face shields by the mini sampler was 30.2 mg/m3 and 41.7 mg/m3, respectively. CONCLUSIONS: Exposure to MS and SS welding fume resulted in a mild systemic inflammatory response. The particle concentration from the breathing zones correlated with the measurements inside the welding face shields.

Inflammatory response to acute exposure to welding fumes during the working day.

OBJECTIVES: To investigate cardiorespiratory and inflammatory responses in male workers following exposure to welding fumes and airborne particles in actual workplace conditions. MATERIALS AND METHODS: We measured blood leukocytes and their differential counts, platelet count, hemoglobin, sensitive C-reactive protein, fibrinogen, E-selectin, IL-(interleukin)1ß, IL-6, IL-8, tumor necrosis factor alpha (TNF-α) and endothelin-1 in blood samples of twenty workers before and after their working day. We also studied peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and exhaled nitric oxide (NO). We assessed heart rate variability (HRV) by obtaining 24-hour ambulatory electrocardiograms. RESULTS: The total blood leukocytes and neutrophils increased after the work shift, whereas IL-1ß and E-selectin decreased significantly. There were no statistically significant changes in exhaled NO, FEV1, PEF or HRV. CONCLUSION: Occupational exposure to welding fumes and particles caused a slight, acute inflammatory effect estimated based on the increased values of leukocytes and neutrophils in blood and a decrease in the interleukin 1ß and E-selectin values, but no changes in the pulmonary function (exhaled NO, FEV1, PEF) or HRV during the working day were observed.

Exposure to CeO(2) nanoparticles during flame spray process.

The use of nanotechnology in different fields is increasing rapidly. Engineered nanoparticles (ENPs) may have adverse effect on human health, but little is known about the exposure levels of ENPs at occupational settings. In this study, exposure levels of cerium oxide (CeO(2)) ENPs were measured during enclosed flame spray process used for coating and surface modification of materials. Particle number concentration, mass concentration, and morphology and composition of the ENPs were studied. The average particle number concentration varied from 4.7·10(3) to 2.1·10(5) 1/cm(3) inside the enclosure, and from 4.6·10(3) to 1.4·10(4) 1/cm(3) outside the enclosure. The average mass concentrations inside and outside the enclosure were 320 and 66 µg/m(3), respectively. A batch-type process caused significant variation in the concentrations, especially inside the enclosure. CeO(2) ENPs were mainly chainlike aggregates, consisting of spherical 20-40 nm primary particles having crystalline structure. In conclusion, enclosure of the process with efficient ventilation seemed to be an effective means to reduce the exposure to CeO(2) ENPs as expected.

Risk assessment of engineered nanomaterials and nanotechnologies--a review.

With the increasing utilization of engineered nanomaterials (ENM), the potential exposure of workers to ENM is likely to increase significantly. Very little is known though, of the risks posed by ENM to human health, in particular concerning those characteristics that are technologically attractive: small size, high surface to mass ratio, and surface reactivity. ENM risk assessment is hampered by a lack of exposure as well as toxicity data specific to the multitude of ENM being developed. An economical approach to this problem urgently calls for intelligent testing strategies to capture essential features of ENM, thereby allowing over-arching ENM risk assessment. The data gaps of ENM risk assessment include (1) ENM aerosol standards and agreement on ENM key metrics; (2) dependable exposure scenarios, affordable monitoring technologies, exposure data and models; and (3) biomedical data on ENM translocation and toxicity, and associated testing strategies (which must be linked to the exposure scenarios). The special features of ENM do not, however, create a need to amend the current overall approach to the risk assessment of chemicals.

Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice.

The importance of nanotechnologies and engineered nanoparticles has grown rapidly. It is therefore crucial to acquire up-to-date knowledge of the possible harmful health effects of these materials. Since a multitude of different types of nanosized titanium dioxide (TiO(2)) particles are used in industry, we explored their inflammatory potential using mouse and cell models. BALB/c mice were exposed by inhalation for 2 h, 2 h on 4 consecutive days, or 2 h on 4 consecutive days for 4 weeks to several commercial TiO(2) nanoparticles, SiO(2) nanoparticles, and to nanosized TiO(2) generated in a gas-to-particle conversion process at 10 mg/m(3). In addition, effects of in vitro exposure of human macrophages and fibroblasts (MRC-9) to the different particles were assessed. SiO(2)-coated rutile TiO(2) nanoparticles (cnTiO(2)) was the only sample tested that elicited clear-cut pulmonary neutrophilia. Uncoated rutile and anatase as well as nanosized SiO(2) did not induce significant inflammation. Pulmonary neutrophilia was accompanied by increased expression of tumor necrosis factor-alpha (TNF-alpha) and neutrophil-attracting chemokine CXCL1 in the lung tissue. TiO(2) particles accumulated almost exclusively in the alveolar macrophages. In vitro exposure of murine and human macrophages to cnTiO(2) elicited significant induction of TNF-alpha and neutrophil-attracting chemokines. Stimulation of human fibroblasts with cnTiO(2)-activated macrophage supernatant induced high expression of neutrophil-attracting chemokines, CXCL1 and CXCL8. Interestingly, the level of lung inflammation could not be explained by the surface area of the particles, their primary or agglomerate particle size, or radical formation capacity but is rather explained by the surface coating. Our findings emphasize that it is vitally important to take into account in the risk assessment that alterations of nanoparticles, e.g., by surface coating, may drastically change their toxicological potential.

Inhalation challenge test in the diagnosis of occupational rhinitis.

BACKGROUND: Evaluations of rhinitis reactions in inhalation challenges (ICs) are sparse compared with research on nasal challenges. This study evaluates the outcome of IC tests in assessing occupational rhinitis (OR). It presents the largest rhinologic IC data in the literature, analyzing the exposure method of various agents causing OR and their relation to asthma. METHODS: Challenge tests performed on 829 individuals with suspected cases of OR were reviewed. Results from both exposures with occupational agents (n = 1229) and placebo (n = 838) were evaluated. RESULTS: A total of 10% of the occupational ICs (n = 123) were positive, suggesting OR, and 13% (n = 161) showed asthmatic reaction in the same challenge. In control challenges 2% showed rhinitis and 6% showed asthma symptoms. The most common agents tested were molds (160 tests), flours, and animal fodders (115 tests) and formaldehyde (122 tests). Obeche wood dust and latex produced positive nasal reactions the most frequently, followed by acid anhydrides. CONCLUSION: Although IC is a resource-intensive methodology, the evaluation of nasal symptoms and signs together with bronchial reactions saves time and expense compared with the organization of multiple individual challenges. We encourage the simultaneous evaluation of both nasal and bronchial reactions in IC tests.

Determination of occupational exposure to alkanolamines in metal-working fluids.

Overall exposure to alkanolamines in metal-working fluids (MWFs) in machine shops was studied by determining alkanolamines in air samples and in rinse-off samples from the hands of machinists. Methods for collecting airborne alkanolamines and alkanolamines absorbed to the skin of the hands were developed and tested. The exposure measurements were carried out in nine machine shops. After a 2 h working period the dominant hand of 37 machinists was rinsed with 200 ml of 20% isopropanol for 1 min in a plastic bag. Personal air samples were also collected during the 2 h working period onto acid-treated glass fibre filters. The filter samples were desorbed with methanol and analysed by liquid chromatography with mass spectrometric detection (LC-MS). The rinse-off samples were also analysed for alkanolamines by LC-MS. The median air concentration of monoethanolamine (EA) was 57 microg m-3, diethanolamine (DEA) 64 microg m-3 and triethanolamine (TEA) 6 microg m-3. The workers' overall exposure to alkanolamines was estimated by calculating the amount in inhaled air and the amount on the skin. The median amount of EA on the skin of the dominant hand was 9-43 times the median amount in inhaled air during 2 h exposure. The corresponding ratio for DEA was 100 and for TEA 170. According to this study the exposure to alkanolamines occurs mainly through the skin. EA was the only alkanolamine with a noticeable inhalation uptake compared to the skin uptake. Total exposure to MWFs may be reduced by reducing skin exposure. The hand rinsing method can be used to assess the efficiency of protective gloves.

Occupational dermatitis and allergic respiratory diseases in Finnish metalworking machinists.

AIM: To investigate the incidences and trends of occupational skin diseases (OSDs) and allergic respiratory diseases (ARDs) in machinists working in the fabrication of metal products. METHODS: Data from the Finnish Register of Occupational Diseases during 1992-2001 were analysed. Incidence rates for skin and respiratory diseases of machinists were calculated and compared to the total working population. The patients investigated at the Finnish Institute of Occupational Health in the same period were described in detail. RESULTS: A total of 279 dermatoses and 34 ARDs were reported. Skin diseases accounted for 27% of all occupational diseases. The incidences of the skin and respiratory diseases were 1.6 and 0.2 cases per 1000 person-years, respectively. This represents a 3-fold risk for getting an OSD compared to the total working population. The number of allergic contact dermatitis (ACD) increased 3-fold during the study period. The most common causes of ACD were metalworking fluids (MWFs) and their ingredients such as formaldehyde, ethanolamines and colophony. Eighty-five per cent of ARDs were asthmas. The commonest causes of asthma were metal dusts and fumes, epoxy resins and hardeners and MWFs and their components. CONCLUSIONS: Contact dermatitis is a common occupational health problem in metalworking machinists, whereas occupational respiratory disease is rare. Only a few specific chemicals in the metalworking have thus far been identified as respiratory allergens. Specific skin tests and inhalation challenge tests with MWFs and their ingredients are recommended if an OSD or a respiratory disease is suspected.

Anosmia in association with occupational use of a waterproof coating chemical.

A case of acute permanent anosmia is described in a renovation worker during exposure to a waterproof coating chemical. The chemical consisted of several substances of which four (acetone, acrylates, butyl acetate and carbon disulfide) has been previously reported to induce hyposmia or anosmia in workers. Other aetiologies were clinically excluded but a large arachnoidea cyst in the frontal part of the left temporobasal fossa with possible compression of the left entorhinal cortex. The toxic aetiology of anosmia is supported by the acute onset and the temporal relationship with occupational exposure. The silent cyst as the cause of anosmia is improbable, but it may have had some contributory role. Our case illustrates both the challenges when clinically examining patients with work-related olfactory impairment and the importance of multi-disciplinary approach to such patients.