Objectives: Two- and 13-week inhalation toxicities of indium-tin oxide (ITO) and indium oxide (IO) were characterized for risk assessments of workers exposed to ITO. Methods: F344 rats of both sexes were exposed by inhalation to ITO or IO aerosol for 6 h/day, 5 day/wk for 2 wk at 0, 0.1, 1, 10 or 100 mg/m3 or 13 wk at 0, 0.1or 1 mg/m3. An aerosol generator and inhalation exposure system was constructed. Results: Blood and lung contents of indium were elevated in a dose-related manner in the ITO- and IO-exposed rats. ITO and IO particles were deposited in the lung, mediastinal lymph node and nasal-associated lymphoid tissue. Exposures to ITO and IO induced alveolar proteinosis, infiltrations of alveolar macrophages and inflammatory cells and alveolar epithelial hyperplasia in addition to increased lung weight. ITO affected the lung more severely than IO did. Fibrosis of alveolar wall developed and some of these lesions worsened at the end of the 26-week post-exposure period. Conclusions: Persistent pulmonary lesions including alveolar proteinosis and macrophage infiltration occurred after 2- and 13-week inhalation exposures of rats to ITO and IO. Fibrosis of alveolar wall developed later. These lesions occurred after ITO exposure at the same concentration as the current occupational exposure limit in the USA and at blood indium levels below the biological exposure index in Japan for indium.
Objectives: Nickel oxide (NiO) is an important industrial material, and it is also a harmful agent. The toxicity of NiO is size-related: nanoparticles are more toxic than fine-particles. The toxic mechanism induced by NiO nanoparticles remains unexplained, and the relationship between in vitro and in vivo NiO toxicity results is unclear. In the present study, we focused on the oxidative stress caused by NiO nanoparticles by examining and comparing in vitro and in vivo acute responses induced by NiO nanoparticles. Methods: Cellular responses induced by black NiO nanoparticles with a primary particle size of 20 nm, were examined in human lung carcinoma A549 cells. In vivo responses were examined by instillation of NiO nanoparticles into rat trachea. Bronchoalveolar lavage fluid (BALF) was collected after intratracheal instillation at different time points, and concentrations of lipid peroxide heme oxygenase-1 (HO-1), surfactant protein-D (SP-D) and lactate dehydrogenase (LDH) in BALF were measured. Results: The levels of intracellular reactive oxygen species and lipid peroxidation in A549 cells increased with increasing exposure to NiO nanoparticles, and increases in gene expressions of HO-1 and SP-D were observed in A549 cells. The lipid peroxide level in BALF significantly increased after 24 h instillation but decreased three days later. LDH leakage was also observed three days later. Conclusions: NiO nanoparticles induce oxidative stress-related lung injury. In vivo and in vitro oxidative stress was induced resulting in activation of antioxidant systems. Based on these responses, we conclude that the results of the in vivo and in vitro studies tend to correspond.
Objectives: To determine the capacity of human serum proteins to bind to titanium dioxide (TiO2) particles of different polymorphs and sizes. Methods: TiO2 particles were mixed with diluted human serum, purified human serum albumin (HSA) or purified human serum gamma-globulin (HGG) solutions. After incubation at 37°C for 1 h, the particles were sedimented by centrifugation, and proteins in the supernatant, as well as those bound to the particles, were analyzed. Results: The total protein concentration in the supernatant was lowered by TiO2, whereas the albumin/globulin ratio was elevated by the particles. Incubation with TiO2 also lowered the immunoglobulin, pre-albumin, beta2-microglobulin, ceruloplasmin and retinol-binding protein levels, but not ferritin levels, in the supernatant. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), proteins in the supernatant, especially HGG, were observed to decrease, while those released from the particles (after adding 1% SDS and heating) increased, depending on the dose of TiO2. Purified HGG and HSA were also bound to TiO2, although the former appeared to have a higher affinity. All the proteins tested showed the highest binding potency to the amorphous particles (<50 nm) and the lowest to the rutile particles (<5,000 nm), while binding to anatase particles was intermediate. The affinity to the larger anatase was higher than that to smaller anatase particles in most cases. Conclusions: Human serum proteins, including the two major components, HSA and HGG, are bound by TiO2 particles. The polymorph of the particles seems to be important for determining the binding capacity of the particles and it may affect distribution of the particles in the body.
Objectives: Benzene has been consistently associated with hematological disorders, including acute myeloid leukemia and aplastic anemia, but the mechanisms causing these disorders are still unclear. Various metabolites of benzene lead to toxicity through the production of reactive oxygen species (ROS), the inhibition of topoisomerase and DNA damage. However, benzene itself is considered to have no mutagenic or cytotoxic activity. In this study, we investigated the effects of benzene itself on a human myeloid cell line with or without benzene metabolizing enzyme inhibitors. Methods: A human myeloid cell line, HL-60, was exposed to benzene with or without cytochrome P450 2E1 or myeloperoxidase inhibitor. Cytotoxicity was evaluated in terms of global DNA methylation levels, induction of apoptosis, and ROS production. Results: Benzene did not change global DNA methylation levels. However, benzene itself increased the levels of apoptosis and ROS. This cytotoxicity did not change with the addition of benzene metabolizing enzyme inhibitors. Benzene itself increased the mRNA levels of oxidative stress-related genes and transcription factors of activator protein-1. Conclusions: Benzene did not influence global DNA methylation in HL-60 cells, but had cytotoxic effects and changed gene expression levels. To elucidate the mechanisms of benzene toxicity, benzene itself as well as benzene metabolites must be investigated.
Objectives: The number of workers with precarious employment has increased globally; however, few studies have used validated measures to investigate the relationship of job status to stress and mental health. Thus, we conducted a study to compare differential job stress experienced by permanent and fixed-term workers using an effort-reward imbalance (ERI) model questionnaire, and by evaluating depressive complaints and clinic utilization. Methods: Subjects were permanent or fixed-term male workers at a Japanese research institute (n=756). Baseline data on job stress and depressive complaints were collected in 2007. We followed up with the same population over a 1-year period to assess their utilization of the company clinic for mental health concerns. Results: The ERI ratio was higher among permanent workers than among fixed-term workers. More permanent workers presented with more than two depressive complaints, which is the standard used for the diagnosis of depression. ERI scores indicated that the effort component of permanent work was associated with distress, whereas distress in fixed-term work was related to job promotion and job insecurity. Moreover, over the one-year follow-up period, fixed-term workers visited the on-site clinic for mental concerns 4.04 times more often than permanent workers even after adjusting for age, lifestyle, ERI, and depressive complaints. Conclusions: These contrasting findings reflect the differential workloads and working conditions encountered by permanent and fixed-term workers. The occupational setting where employment status was intermingled, may have contributed to the high numbers of mental health-related issues experienced by workers with different employment status.
Objectives: The aim of this study was to investigate the genotoxic effects of indium trichloride (InCl3·4H2O; InCl3) using the in vivo bone marrow micronucleus test and the in vitro CHL/IU cell micronucleus test. Method: BALB/c mice were administered a single intraperitoneal (i.p.) injection of InCl 3 at a dose 0.625, 1.25, 2.5, 5, or 10 mg/kg b.w. The frequency of micronuclei, the ratio of polychromatic erythrocytes to normochromatic erythrocytes (P/N ratio) and body weight gain were determined 24 h after administration of the InCl3. In the in vitro micronucleus test, CHL/IU cells were treated continuously for 24, 48, or 72 h in the absence of S9mix (the continuous treatment method) and/or for 6 h with or without S9 mix followed by an 18, 42 or 66 h recovery time (the short time treatment method). The frequency of micronuclei was determined at the end of each culture period. Results: The frequency of micronuclei induced by InCl3 increased in the in vivo erythroblast-erythrocyte micronucleus test using BALB/c mice at doses of 2.5 and 5 mg/kg b.w. The P/N ratio, a marker of bone marrow toxicity, decreased significantly following the injection of InCl3. Body weight gain was also inhibited by InCl3. InCl3 induced micronuclei in the CHL/IU cell micronucleus test in both the continuous treatment method and the short time treatment method, both with and without S9mix. Conclusions: These results suggest that InCl3 has a genotoxic effect on mammalian cells both in vivo and in vitro.
Objectives: This study describes the exposure of coke plant workers to methoxyphenols. The relationship between exposure to methoxyphenols and urinary excretion of metabolites was examined. Methods: We determined concentrations of 2-methoxyphenol, 2-methoxy-4-methylphenol and 1-(4-hydroxy-3-methoxyphenyl)ethanone in the breathing-zone air and in the urine of workers, collected after the workshift. Urine metabolites were extracted after enzymatic hydrolysis by solid-phase extraction. Concentrations of methoxyphenols in air and urine were determined by gas chromatography with flame-ionization. Results: The time-weighted average concentrations (median) of methoxyphenols in the breathing zone air were as follows: 9.9 ng/m3, 15.4 ng/m3 and 92.5 ng/m3 for 2-methoxyphenol, 2-methoxy-4-methylphenol and 1-(4-hydroxy-3-methoxyphenyl)ethanone, respectively. The median values of urinary concentrations were as follows: 582.5, 190.1, 235.0 and 21.8 μmol/mol creatinine for 2-methoxyphenol, 2-methoxy-4 methylphenol, 1-(4-hydroxy-3-methoxyphenyl)ethanone and 2,6-dimethoxyphenol, respectively. A statistically significant correlation between the exposure level and the urinary level was found for 2-methoxyphenol (r=0.573, p<0.01). Conclusion: We found that the presence of 2-methoxyphenol in urine can be used as a biomarker for 2-methoxyphenol exposure. The analysis performed at the coke plant showed that the workers were exposed to relatively low concentrations of methoxyphenols.
Background: In Brazil, DDT was used to control malaria-transmitting mosquitoes from 1945 to 1997. Owing to concerns about the potential adverse health consequences of long-term exposures to DDT, workers of the National Foundation of Health (FNS) who had taken part in malaria control operations in the Amazon region were monitored for blood levels of DDT as well as for their health status between 1997 and 2001. Objectives: To evaluate blood levels of DDT/DDE and elimination half-life (t1/2) of pp'-DDE in malaria control personnel. Methods: Levels of DDT and pp'-DDE were measured in the blood serum of 119 public health workers (32-67 yr old, 117 males) from Pará state-Brazil. Serum levels of DDT/DDE were determined by gas chromatography with electron capture detection. Results: Blood serum levels of -Σ-DDT and pp'-DDE (mean ± SD) were as follows (μg/l): February 1997 (N=110), 231.5 ± 366.4 (156.9 ± 236.8 as pp'-DDE); February 1998 (N=116), 126.4 ± 86.6 (83.0 ± 54.6 as pp'-DDE); May 2001 (N=117), 50.4 ± 53.3 (39.4 ± 37.6 as pp'-DDE). The half-life (mean ± SD) of pp'-DDE was 29.5 ± 22.7 mo. Conclusions: Concentrations of Σ-DDT/ pp'-DDE in the blood serum of malaria control workers were much higher than levels found in the general population in Brazil and elsewhere. The half-life of pp'-DDE (29.5 mo) estimated for this group of occupationally exposed male adults was shorter than t1/2 values previously reported for environmentally exposed subjects.
Objectives: Since the existence of work-related stressors is inevitable in nurses' workplace, nurses usually use a variety of coping strategies which can be called cognitive, affective, and behavioral techniques. In this study, we aimed to explore the coping strategies employed by the Iranian clinical nurses in depth. Methods: This work was a qualitative study using Straus and Corbin's grounded theory approach focusing on the process of coping with job stress used by Iranian clinical nurses. Results: The results of the present qualitative study indicate that the core category was "on the route to coping" which contained six categories comprising work management, self-control, emotional, spiritual, cognitive, and interactional strategies. Conclusions: We conclude that in nursing it is inevitable that different kinds of strategies are used to cope with the many stressors. The conceptual model emerging from the data indicate that nurses are engaged in a dynamic process of struggling to cope with job stressors. In fact, they are "on the route to coping" with the job stressors. Considering the high level of stress in the nursing profession, the findings of this study have implications for both hospital managers and Iranian clinical nurses.
Objective: To compare occupational exposure to extremely-low-frequency magnetic field (ELF-MF) between dentists practicing in dental clinics and those employed in hospitals. Methods: Thirty-two dentists who worked at clinics (n=15) and 33 dentists employed at hospital dental departments (n=7) voluntarily provided their informed consent to participate in this measurement study. The study dentists were requested to wear an ELF-MF dosimeter for some 3 h at work to determine their personal exposure. Spot measurements taken at a number of locations in each dental office were used to indicate the work environment exposure level. Additionally, ELF-MF emitted from common dental equipment was also measured. All measurements were performed with EMDEX Lite meters. Results: The average environmental exposure to ELF-MF is higher in clinic dental offices than in hospital dental departments (0.55 vs. 0.15 μT, p=0.008). Personal dosimetry showed that on average, clinic dentists spent 35.71 and 19.39% of their time at exposures above 0.3 and 0.4 μT at work, respectively. The corresponding figures for hospital dentists were 19.61 and 13.92%. Additionally, ELF-MF was greater than 0.4 μT at 30 cm from all selected equipment, but the ELF-MF generally diminished as the distance from dental equipment increased. Uultraviolet air sterilization system produced 3 times as much ELF-MF as other dental equipment. Conclusions: This study suggests the possibility of over-exposure of dentists to power frequency ELF-MF. Additionally, certain dental equipment may produce ELF-MF levels greater than 0.4 μT in areas where dentists usually work when treating patients.
Aim: This paper presents the development process of the European framework for psychosocial risk management (PRIMA-EF). It also summarises and discusses key findings of research conducted through this policy-orientated research programme. Objectives: This paper presents an overview of the development process of PRIMA-EF. The background, methods and outcomes are described and discussed. The paper summarises the key findings of PRIMA-EF and concludes by a discussion of the merit of PRIMA-EF in the area of psychosocial risk management and its intended use. PRIMA-EF has been built on a review, critical assessment, reconciliation and harmonisation of existing European approaches for the management of psychosocial risks and the promotion of mental health at the workplace. The framework has been built from a theoretical analysis of the risk management process, identifying its key elements in logic and philosophy, strategy and procedures, areas and types of measurement, and from a subsequent analysis of European risk management approaches. It is meant to accommodate all existing psychosocial risk management approaches across Europe. It also provides a model and key indicators that relate to the psychosocial risk management process both at the enterprise and macro levels. Method: Experts, researchers, social partners, key European and international organisations and networks were involved throughout the development of PRIMA-EF. A number of methods were applied including literature, case study and policy reviews, interviews, surveys, focus groups and workshops. The scientific findings have been used to develop user-friendly tools for use at the enterprise and policy levels such as guidelines, indicators, guidance sheets, inventories and web-based tools. Conclusions: PRIMA-EF is intended as a framework for harmonizing practice and current methods in the area of psychosocial risk management. It can also be used as a guidance tool for the development of further methods both in Europe and internationally as it can provide a benchmark for validation of new methods. A number of priorities have been identified on the basis of PRIMA-EF for the future of psychosocial risk management and the promotion of mental health at workplace in Europe.
Objectives: During the last few decades, major global developments in the world of work include an international trend to shift production to developing countries, with wide variations in working conditions and exposure to traditional and emerging occupational risks, such as psychosocial risks. The latter have rarely been addressed or explored in developing and economically-emerging country contexts while we find an abundant body of research from industrialized countries. The research presented, which is part of a larger study, explored the perception of multi-disciplinary experts from different regions, as defined by the World Health Organization (WHO), of the nature of psychosocial hazards, and work-related stress, as well as their views on workplace priorities that require urgent attention. Methods: Semi-structured interviews were conducted with 29 experts from developing countries which were subjected to thematic analysis. A two-tiered Delphi survey was completed by 74 experts in the first round with 53 of these experts completing the survey in the second round. Results: Psychosocial hazards and work-related stress were mostly seen as interchangeable in terms of source and effect and all participants perceived them as concern to their workforce. Through the interviews and the Delphi surveys they allude to our contemporary understanding of psychosocial risks. Workplace risks of priority differed by region but primarily work-related stress, injury and accident prevention, and substance abuse and risk behaviors were reported to require urgent attention. Conclusions: The current lack of awareness and research in the area of psychosocial risks and work-related stress hampers action in developing countries. International experts should support the exchange of information and the development of interventions in workplaces in developing countries with a view to integrating these emerging risks into comprehensive occupational health and safety policy frameworks to make such approaches more effective.
Acknowledgements: The authors would like to thank Professor A.J.Bailer, Miami University and NIOSH, for reviewing this manuscript and helpful comments In addition, the authors would like to thank Dr. S.B.Koh and K.S. Kim for their comments and also all collegues for their contribution to health examinations. This study was supported by a faculty research grant of Yonsei University College of Medicine for 2005(6-2005-0122).