Particle toxicology and health - where are we?

BACKGROUND: Particles and fibres affect human health as a function of their properties such as chemical composition, size and shape but also depending on complex interactions in an organism that occur at various levels between particle uptake and target organ responses. While particulate pollution is one of the leading contributors to the global burden of disease, particles are also increasingly used for medical purposes. Over the past decades we have gained considerable experience in how particle properties and particle-bio interactions are linked to human health. This insight is useful for improved risk management in the case of unwanted health effects but also for developing novel medical therapies. The concepts that help us better understand particles' and fibres' risks include the fate of particles in the body; exposure, dosimetry and dose-metrics and the 5 Bs: bioavailability, biopersistence, bioprocessing, biomodification and bioclearance of (nano)particles. This includes the role of the biomolecule corona, immunity and systemic responses, non-specific effects in the lungs and other body parts, particle effects and the developing body, and the link from the natural environment to human health. The importance of these different concepts for the human health risk depends not only on the properties of the particles and fibres, but is also strongly influenced by production, use and disposal scenarios. CONCLUSIONS: Lessons learned from the past can prove helpful for the future of the field, notably for understanding novel particles and fibres and for defining appropriate risk management and governance approaches.

Correction to: Particle toxicology and health - where are we?

After the publication of this article [1] it was hihglighted that the number of deaths related to natural disasters was incorrectly reported in the second paragraph of the Hazards from Natural particulates and the evolution of the biosphere section. This correction article shows the correct and incorrect statement. This correction does not change the idea presented in the article that from an evolutionary view point, natural disasters account only for a small fraction of the people on the planet. The original article has been updated.

Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient-based study.

Exposure to asbestos results in serious risk of developing lung and mesothelial diseases. Currently, there are no biomarkers that can be used to diagnose asbestos exposure. The purpose of the present study was to determine whether the levels or detection rate of chemokine (C-C motif) ligand 3 (CCL3) in the serum are elevated in persons exposed to asbestos. The primary study group consisted of 76 healthy subjects not exposed to asbestos and 172 healthy subjects possibly exposed to asbestos. The secondary study group consisted of 535 subjects possibly exposed to asbestos and diagnosed with pleural plaque (412), benign hydrothorax (10), asbestosis (86), lung cancer (17), and malignant mesothelioma (10). All study subjects who were possibly exposed to asbestos had a certificate of asbestos exposure issued by the Japanese Ministry of Health, Labour and Welfare. For the primary study group, levels of serum CCL3 did not differ between the two groups. However, the detection rate of CCL3 in the serum of healthy subjects possibly exposed to asbestos (30.2%) was significantly higher (P < 0.001) than for the control group (6.6%). The pleural plaque, benign hydrothorax, asbestosis, and lung cancer groups had serum CCL3 levels and detection rates similar to that of healthy subjects possibly exposed to asbestos. The CCL3 chemokine was detected in the serum of 9 of the 10 patients diagnosed with malignant mesothelioma. Three of the patients with malignant mesothelioma had exceptionally high CCL3 levels. Malignant mesothelioma cells from four biopsy cases and an autopsy case were positive for CCL3, possibly identifying the source of the CCL3 in the three malignant mesothelioma patients with exceptionally high serum CCL3 levels. In conclusion, a significantly higher percentage of healthy persons possibly exposed to asbestos had detectable levels of serum CCL3 compared to healthy unexposed control subjects.

Trends in asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma.

OBJECTIVES: We aimed to elucidate changes in asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma over time. METHODS: Lung tissues were obtained from 46 patients with mesothelioma who died or underwent surgery between 1971 and 2005. All of the patients had a history of occupational asbestos exposure. We classified patients into four groups according to the period during which their lung tissue was obtained. Asbestos and non-asbestos fibre concentrations were determined by transmission electron microscopy with energy-dispersive X-ray analysis using a low-temperature ashing procedure. RESULTS: From the 1970s to the 2000s, we observed a decrease in the geometric mean of total asbestos concentration (67.4-1.05 million fibres per gram dry lung), chrysotile concentration (25.0-0.66 million fibres per gram dry lung), amphibole asbestos concentration (21.3-0.76 million fibres per gram dry lung), and non-asbestos fibre concentration (326-19.3 million fibres per gram dry lung). The mean duration of asbestos exposure decreased from 33.7 to 17.6 years, and the mean duration since the last exposure increased from 0.3 to 21.5 years. The percentage of longer fibres to total fibres tended to increase over time, whereas the mean fibre length did not differ significantly. CONCLUSIONS: The present study suggested that asbestos and non-asbestos fibre concentrations in the lung tissues of Japanese patients with mesothelioma who have occupational histories of asbestos exposure may have decreased from the 1970s to the 2000s.

Asbestos in organochlorine insecticide powder sprinkled between pages of antiquarian books in a library in Japan.

Librarians at a university had planned to check the collection prior to the library renovations that began in 2015. They had previous knowledge of the presence of a light greyish-white powder with an unpleasant odour (hereinafter referred to as 'powder') sprinkled between the pages of antiquarian books in the library archive. The purpose of this study was to identify this powder with the help of experts from both inside and outside the university. The powder was qualitatively analysed using gas chromatography with mass spectrometry after hexane extraction. The powder was examined under a polarised light microscope and a field-emission scanning electron microscope equipped with an energy-dispersive X-ray spectrometer. Benzene hexachloride (BHC) was detected in the powder. Talc was the most abundant particle in the powder. The powder also contained 0.52 wt% asbestos, which belonged to the tremolite-actinolite series. No other types of asbestos were detected. The powder was presumed to be a bulking agent for BHC, and its major constituent was talc. This is the first report on asbestos-containing insecticides.

Comparison of lung asbestos fiber content in cancer subjects with healthy individuals with no known history of occupational asbestos exposure in Korea.

To evaluate the effects of environmental asbestos exposure on the inducement of lung cancer, pulmonary asbestos and non-asbestos fiber content was determined in 36 normal Korean subjects and 38 lung cancer subjects with no known occupational history of asbestos exposure. Pulmonary asbestos fiber content was measured by transmission electron microscopy (TEM) with energy-dispersive x-ray analysis after applying a low-temperature ashing procedure. Chrysotile fibers were the major fiber type found in the lungs of the Korean subjects. The asbestos fiber concentrations found in the lungs of normal males (25) and females (11) were 0.26 x 10(6) fibers/g of dry lung tissue and 0.16 x 10(6) fibers/g of dry lung tissue, respectively. The asbestos concentrations found in the lungs of cancer subjects were 0.16 x 10(6) fibers/g of dry lung tissue for 32 males and 0.44 x 10(6) fibers/g of dry lung tissue for 6 females. No statistical difference was found in pulmonary asbestos content between the normal and lung cancer subjects, whereas a statistical difference was noted between normal and lung cancer subjects with respect to lung non-asbestos content, indicating a potential role for non-asbestos fibers being associated with lung cancer.

Transfer of occupational health problems from a developed to a developing country: lessons from the Japan-South Korea experience.

Many corporations move their manufacturing facilities or technologies from developed to developing countries. Stringent regulations have made it costly for industries to operate in developed, industrialized countries. In addition, labor costs are high in these countries, and there is increasing awareness among the general public of the health risks associated with industry. The relocation of hazardous industries to developing countries is driven by economic considerations: high unemployment, a cheaper labor force, lack of regulation, and poor enforcement of any existing regulations make certain countries attractive to business. The transfer of certain industries from Japan to Korea has also brought both documented occupational diseases and a new occupational disease caused by chemicals without established toxicities. Typical examples of documented occupational diseases are carbon disulfide poisoning in the rayon manufacturing industry, bladder cancer in the benzidine industry, and mesothelioma in the asbestos industry. A new occupational disease due to a chemical without established toxicities is 2-bromopropane poisoning. These examples suggest that counter-measures are needed to prevent the transfer of occupational health problems from a developed to a developing country. Corporate social responsibility should be emphasized, close inter-governmental collaboration is necessary and cooperation among non-governmental organizations is helpful.

Musculoskeletal pain and night-shift naps in nursing home care workers.

BACKGROUND: Care workers in nursing homes are at high risk of developing musculoskeletal disorders (MSDs). Many care workers work in shifts, which may compromise both the quality of care they give and their working life. Taking a nap during night shifts has been proposed to ameliorate shift work-related problems, but its relationship with MSDs is not clear. AIMS: To explore how MSD pain differs according to frequency of night-shift naps. METHODS: A questionnaire study was conducted on 111 care workers at three nursing homes. Of 98 respondents, data from 66 shift workers (54 women) were analysed. Data on self-rated pain in multiple sites (neck, shoulder, arm, leg and low back), naps during night shifts and relevant variables were collected. Participants were categorized into three groups on the basis of frequency of night-shift naps taken during the previous month: non-nappers, <50% nappers and >or =50% nappers. RESULTS: Pain at all sites, with the exception of low back pain, differed significantly among the three groups. Pain scores were lowest at the arm and leg for the > or =50% nappers. Neck and shoulder pain was lower for the > or =50% nappers and the non-nappers compared to the <50% nappers. CONCLUSIONS: Reduced pain in the arm and leg was associated with taking a nap at least once every two night shifts among the nursing home care workers. No association was found between low back pain and night-shift naps in this sample.

Work schedule differences in sleep problems of nursing home caregivers.

Nursing home caregivers (n=775; 604 women; mean age 33.6 years) were studied to examine how work schedules affect their sleep. The shift group (n=536) worked under a rotating two-shift system (n=365), a rotating three-shift system (n=66), or other types of shifts (n=78). The non-shift group included 222 caregivers. Participants completed a questionnaire about working conditions, sleep problems, health, lifestyle, and demographic factors. The two-shift caregivers reported the highest levels of difficulty initiating sleep (DIS, 37.6%), insomnia symptoms (43.0%), and poor quality of sleep (24.9%) among the groups. Adjusted odds ratios for these problems were significantly greater for the two-shift caregivers than for non-shift counterparts: DIS (odds ratio 2.86, 95% confidence interval 1.57-5.20), insomnia symptoms (2.33, 1.36-4.02), and poor sleep quality (2.15, 1.09-4.22). Our data suggest that working under a rotating two-shift system, which has a longer night shift, is associated with an elevated risk of sleep problems for nursing home caregivers.

Heat Strain and Hydration of Japanese Construction Workers during Work in Summer.

Objectives: The aim was to ascertain hydration and heat strain of construction workers in Japan during the summer who are at the highest risk of heat-related disorders. Methods: The subjects were 23 construction workers, whose average age was 41, average weight was 69 kg, and average height was 170 cm. We measured thermal working conditions with a wet bulb globe temperature (WBGT) measurement instrument affixed to the helmet of each worker, at fixed points outdoors in the sun and indoors. Heat strain was evaluated for water intake, urine specific gravity (Usg), urine temperature (UT), heart rate (HR), and body weight during work. Results: The average WBGT measured on the worker helmets over 3 consecutive days was 28.0 ± 0.7, 27.6 ± 0.8, and 27.6 ± 1.1°C. The average water intake was 2.6 l during a work shift. The average Usg, UT, and % HR reserve were the highest in the first half of afternoon work. Seventy-eight percent of the subjects exceeded at least one of the ACGIH TLV physiological guidelines for heat strain in terms of HR and weight loss or a clinically dehydrated level of Usg. Conclusions: Heat strain was the highest in the first half of afternoon work. The number of dehydrated workers increased during this shift because of insufficient water intake. Adequate hydration is required to decrease the risk of heat-related disorders among construction workers in the summer.

Overtime, job stressors, sleep/rest, and fatigue of Japanese workers in a company.

To ascertain the usefulness of a 21-item checklist that assesses accumulated fatigue due to overwork, we examined (1) the associations between overtime work, job stressors, or the quantity of sleep/rest and subjective symptoms of fatigue, and (2) whether sleeping hours and monthly days off are associated with the accumulated fatigue parameter using the checklist. Questionnaire surveys were administered twice to Japanese workers at a plant of a manufacturing company. Among the 390 registered workers, 383 workers (284 males and 99 females) in the first survey and 350 workers (260 males and 90 females) in the second survey responded. The subjective symptoms score significantly increased according to the order of grade of overtime work, other job stressors, and sleep/rest subscales in both sexes by ANOVA. The subjective symptoms grade was significantly associated with the other job stressors grade and sleep/rest grade, but not with overtime work. The accumulated fatigue parameter was negatively correlated with daily sleeping hours (significant Spearman's correlation coefficient (r(s)) =-0.318 and -0.340 in the 1st and 2nd surveys) and with monthly days off (r(s)=-0.250 and -0.151) among all of the subjects. It may be possible to assess overwork by the accumulated fatigue parameter.

[Usage survey of care equipment in care service facilities for the elderly].

Musculoskeletal disorders(MSD)have been increasing recently among care workers. Since providing care workers with appropriate equipment is effective for preventing MSD, we conducted a questionnaire survey in two nursing homes and a healthcare facility for the elderly to clarify equipment usage, problems and points for improvement. A total of 81 care workers(average age 32.2 yr; 63 females, 18 males)participated in the survey. The average number of residents and the average resident's care level were 70.0 and 3.6, respectively. Wheelchair and height adjustable beds were fully available and always used in all facilities. Portable lifts, ceiling lifts and transfer boards were, however, few in all 3 facilities and the proportion of use was 14.8%, 16.0%, and 23.5%, respectively. Participants reported that it is time consuming to move residents from place to place with lifts and there is a danger of dropping a resident. Although approximately 90% of care workers had received education and training on care techniques, the workload on the low back was found to be great. Therefore, we thought that care workers must consistently use care equipment. To achieve such increased usage, we must improve the usability of the equipment.

Asbestos exposures during reprocessing of automobile brakes and clutches.

Asbestos exposures of workers in three small factories reprocessing automobile brakes and clutches in Japan were investigated. Airborne asbestos was collected on a membrane filter using an air sampler. From 1982 to 1989, asbestos counting was performed on 295 samples (198 personal and 97 stationary), using phase contrast microscopy. Only chrysotile asbestos was detected. Workers who reprocessed automobile brakes and clutches were exposed to asbestos concentrations of 0.025-76.4 fibers/cm3. Geometric mean asbestos concentrations during attaching linings to brake shoes and attaching facings to clutch disks were 0.859 fibers/cm3 and 0.780 fibers/cm3, respectively. Concentrations during stripping worn brake linings and clutch facings were 0.484 fibers/cm3 and 0.382 fibers/cm3, respectively. Machine grinding and leveling of new brake-lining surfaces represent potential sources of heavy asbestos exposures, unless enclosures and local ventilation are efficient.

Arm pain and daytime sleepiness among nursing home employees.

We investigated the relationship between musculoskeletal disorders and sleep problems among 98 employees (79 women) at three nursing homes. Self-reported data were collected regarding pain in the neck, shoulders, arms, legs, and low back, sleep disturbances, daytime sleepiness (Epworth Sleepiness Scale), and the level of workload on the hands, legs, and low back by type of care. Pain in the arms was significantly associated with less difficulty initiating sleep, fewer symptoms of insomnia, and a higher level of daytime sleepiness. After adjusting for age and gender, only the association between arm pain and daytime sleepiness remained significant (Odds Ratio 6.70, 95% Confidence Interval 1.40-31.97). Participants with both arm pain and daytime sleepiness showed significantly greater levels of workload in some kinds of care in a systemic manner than counterparts without either complaint. These findings suggest that arm pain is associated with elevated sleep propensity/fatigue in nursing home work.

The association among ferruginous body, uncoated fibers, asbestos and non-asbestos fibers in lung tissue in terms of length.

To demonstrate the correlations between the concentrations of ferruginous body as well as uncoated fiber both of which can be observed with phase-contrast microscope and the concentration of various inorganic fibers including asbestos which requires the observation with TEM or SEM, we measured those indices among Japanese and Korean cases. Though the concentration of ferruginous body in lung tissue is an important index of asbestos exposure, uncoated fibers observed with phase-contrast microscope might be another index especially in such cases with relatively low exposure due to their history of living in a general environment. However, to establish the reliability of uncoated fibers as an index of asbestos exposure, analysis with more cases and from various backgrounds must be carried out.

Pulmonary asbestos and non-asbestos fiber concentrations in autopsied inhabitants in Pohang, Korea.

To establish reference values for pulmonary asbestos and non-asbestos fiber concentrations in rural Korean residents, and their comparison with those of urban Korean residents and the Japanese, autopsied lung samples from 22 subjects (20 males and 2 females), in Pohang, without known occupational asbestos exposure histories, were analyzed for asbestos and non-asbestos fibers, using transmission electron microscope equipped with an energy dispersive X-ray analyzer. Chrysotile was the major fiber type found in the lungs of the subjects. The residents in Pohang had significantly lower asbestos and non-asbestos fiber concentrations than the Korean urban residents. The Koreans had significantly lower asbestos and non-asbestos fiber concentrations than the Japanese.

Airborne asbestos and non-asbestos fiber concentrations in non-occupational environments in Korea.

Both airborne asbestos and non-asbestos fiber concentrations were evaluated in Korean non-occupational environments. The airborne fiber concentrations were analyzed in 96 air samples, from 48 different points, by transmission electron microscopy, with energy-dispersive X-ray analysis. The geometric means of the airborne asbestos and non-asbestos fiber concentrations were 0.62 and 67.86, and 0.30 and 17.47 fibers/liter in urban and rural areas, respectively. There were significant differences in both the airborne asbestos and non-asbestos fiber concentrations between the urban and rural areas (p<0.05). The geometric means of airborne asbestos and non-asbestos fiber concentrations were 0.67 and 37.93, and 0.27 and 30.67 fibers/liter at the points less than 10 m and more than 30 m away from highways, respectively. The airborne asbestos concentrations were significantly higher at the points less than 10 m away than at the points more than 30 m away from highways (p<0.01).

Thorium-232 exposure during tungsten inert gas arc welding and electrode sharpening.

To assess the exposure of welders to thorium-232 (232Th) during tungsten inert gas arc (TIG) welding, airborne concentrations of 232Th in the breathing zone of the welder and background levels were measured. The radioactive concentrations were 1.11 x 10(-2) Bq/m3 during TIG welding of aluminum (TIG/Al), 1.78 x 10(-4) Bq/m3 during TIG welding of stainless steel (TIG/SS), and 1.93 x 10(-1) Bq/m3 during electrode sharpening, with 5.82 x 10(-5) Bq/m3 background concentration. Although the annual intake of 232Th estimated using these values did not exceed the annual limit intake (ALI, 1.6 x 10(2) Bq), we recommend reducing 232Th exposure by substituting thoriated electrodes with a thorium-free electrodes, setting up local ventilation systems, and by using respiratory protective equipment. It is also necessary to inform workers that thoriated tungsten electrodes contain radioactive material.

[Stevens-Johnson syndrome accompanied by acute hepatitis in workers exposed to trichloroethylene or tetrachloroethylene].

Since the late 1980s, there has been an increasing tendency in the number of case reports on Stevens-Johnson syndrome accompanied by acute hepatitis in workers exposed to trichloroethylene from Asian countries. Recently, mass outbreaks of it have been disclosed in the Philippines and China. Besides trichloroethylene, although the number is small, a similar health disorder has also occurred in workers using tetrachloroethylene. Since the above-mentioned facts are not yet well recognized in the occupational health community, this review is aimed at making clear (1) the clinical features of the health disorder, (2) details of patients' jobs, working environments, and exposure to hazardous chemicals, and (3) the relationship between exposure to trichloroethylene or tetrachloroethylene and the health disorder. Based on a critical review of articles, the following were pointed out. First, it is important to carefully observe the health status of workers exposed to trichloroethylene or tetrachloroethylene and to take countermeasures to reduce exposure. Secondly, circumstantial evidence suggests a cause-effect relationship between the two chemicals and the health disorder; but at the present time it is impossible to rule out the participation of unelucidated factors promoting the occurrence of the health disorder or the existence of a hidden genuine causative substance. Therefore further investigation to trace such a case is needed. Thirdly, the mechanism of the health disorder and the reason why there seems to be a large inter-individual difference in sensitivity to the causative agent should be clarified.

Formation of the nitrative DNA lesion 8-nitroguanine is associated with asbestos contents in human lung tissues: a pilot study.

OBJECTIVES: Asbestos causes lung cancer and malignant mesothelioma, and chronic inflammation is considered to participate in carcinogenesis. However, biomarkers to evaluate its carcinogenic risk have not been established. Reactive oxygen/nitrogen species are generated in biological systems under inflammatory conditions and may contribute to carcinogenesis by causing DNA damage. In this study, we examined the relationship between the formation of 8-nitroguanine (8-nitroG), a mutagenic DNA lesion formed during inflammation, and asbestos contents in human lung tissues. METHODS: We obtained non-tumor lung tissues from patients with (n=15) and without mesothelioma (n=21). The expression of 8-nitroG and related molecules was examined by immunohistochemistry, and their staining intensities were semiquantitatively evaluated. Asbestos contents in lung tissues were analyzed by analytical transmission electron microscopy. RESULTS: In subjects without mesothelioma, staining intensities of 8-nitroG and apurinic/apyrimidinic endonuclease 1 (APE1) were significantly correlated with total asbestos and amphibole contents (p<0.05), but not with chrysotile content. In mesothelioma patients, their staining intensities were not correlated with asbestos contents. The double immunofluorescence technique revealed that APE1 was expressed in 8-nitroG-positive cells, suggesting that abasic sites were formed possibly due to the removal of 8-nitroG. The staining intensities of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative DNA lesion, and its repair enzyme 8-oxoguanine DNA-glycosylase were correlated with age (p<0.05), but not with asbestos contents in subjects without mesothelioma. CONCLUSIONS: This is the first study to demonstrate that 8-nitroG formation is associated with asbestos contents in human lung tissues. This finding raises a possibility that 8-nitroG serves as a biomarker that can be used to evaluate asbestos exposure and carcinogenic risk.