Health Effects of Toner Exposure Among Japanese Toner-Handling Workers: A 10-Year Prospective Cohort Study.

The main objective of this study was to evaluate the risk of the respiratory diseases, i.e. pneumoconiosis, lung fibrosis, granulomatous pneumonitis, lung cancer and bronchial asthma, which have been reported as related to toner exposure. The second main objective was to clarify the association between toner exposure and parameters related with toner-handling worker's health. We conducted a 10-year prospective cohort study from 2004 to 2013 in 296 Japanese toner-handling workers. The evaluation of toner exposure and medical health check were performed once a year. There was no obvious evidence of occurrence of lung diseases. We also investigated several health parameters to recognize the change of respiratory health before onset of pneumoconiosis, lung fibrosis, lung cancer and bronchial asthma. However there were some sporadic statistically significant findings, to bring all health parameters, we did not find obvious evidence that toner exposure would cause adverse health effects as a whole. We concluded that the possibility that toner exposure would cause adverse health effects was quite low.

The respiratory effects of toner exposure according to long-term occupational toner handling history: A longitudinal analysis, 2004-2013.

OBJECTIVES: This report shows the relationship between toner exposure and respiratory effects for individuals with a longterm occupational toner-handling history, from 2004 to 2013. MATERIAL AND METHODS: Authors studied 752 Japanese male workers in toner handling workshops. A total of 673 men who participated in an annual monitoring survey were analyzed in this study. The following monitoring was performed in the same season each year: personal exposure measurements, biological markers, respiratory function tests, a chest X-ray, chronic respiratory symptoms and incidences of respiratory diseases. To evaluate the toner exposure effect, the exposure categories suitable for each evaluation index were established. RESULTS: For those with an occupational toner-handling history, the mean occupational toner-handling period was 14.36 years (standard deviation = 6.62); one participant had 35 years of exposure, which was the longest and one participant had 1 year of exposure which was the shortest. There were no statistically significant differences in the rate of change of respiratory function tests. An ANOVA conducted on blood and urine test results showed that statistically significantly differences were observed for a few items but all the values were very low and within the standard range. CONCLUSIONS: Authors conducted a 10-year ongoing study, but no obvious negative influences on health were attributed to toner exposure. In a work environment where adequate administrative controls are in place, personal toner exposure levels may be expected to be low, with no adverse effects on human health. Int J Occup Med Environ Health 2018;31(6):809-822.

Cancer Risks of Hexavalent Chromium in the Respiratory Tract.

Hexavalent chromium (Cr(VI)) compounds are recognized as carcinogens in the respiratory tract, giving rise to cancers of the lung, nose and nasal sinuses, especially in certain occupational environments. Inhalation exposure of Cr(VI)-containing particles, dusts and fumes commonly occurs in chromium-related occupational environments, such as chromium production, plating, welding of chromium-containing metals and alloys, electroplating, chromium-containing pigments and paints. Epidemiological surveys of chromium compounds have shown strong associations between exposure to Cr(VI) and mortality due to lung cancer, as well as positive associations with cancers of the nose and nasal cavity. Nasal symptoms, such as nasal irritation, ulceration and perforation of the nasal septum, nasal turbinate engorgement and hypertrophy, are important signs for the early diagnosis of lung cancer and cancers of the nose and nasal cavity in those with an occupational history of Cr(VI) exposure. Cr(VI) exposure in the workplace remains a serious problem as a cause of lung cancer and cancers of nose and nasal cavity, especially in relatively small enterprises that use chromium compounds. Appropriate protection for workers should be considered in occupations that involve exposure to chromium compounds.

Assessment of Pulmonary Toxicity Induced by Inhaled Toner with External Additives.

We investigated the harmful effects of exposure to a toner with external additives by a long-term inhalation study using rats, examining pulmonary inflammation, oxidative stress, and histopathological changes in the lung. Wistar rats were exposed to a well-dispersed toner (mean of MMAD: 2.1 µm) at three mass concentrations of 1, 4, and 16 mg/m3 for 22.5 months, and the rats were sacrificed after 6 months, 12 months, and 22.5 months of exposure. The low and medium concentrations did not induce statistically significant pulmonary inflammation, but the high concentration did, and, in addition, a histopathological examination showed fibrosis in the lung. Although lung tumor was observed in one sample of high exposure for 22.5 months, the cause was not statistically significant. On the other hand, a persistent increase in 8-OHdG was observed in the high exposure group, indicating that DNA damage by oxidative stress with persistent inflammation leads to the formation of tumorigenesis. The results of our studies show that toners with external additives lead to pulmonary inflammation, oxidative stress, and fibrosis only at lung burdens beyond overload. These data suggest that toners with external additives may have low toxicity in the lung.

Extremophilic polysaccharide nanoparticles for cancer nanotherapy and evaluation of antioxidant properties.

Polysaccharides that show finest bioactivities and physicochemical properties are always promising for bionanoscience applications. Mauran is such a macromolecule extracted from halophilic bacterium, Halomonas maura for biotechnology and nanoscience applications. Antioxidant properties of MR/CH nanoparticles were studied using biochemical assays to prove the versatility of these test nanoparticles for biomedical applications. Here, we demonstrate the prospects of extremophilic polysaccharide, mauran based nanoparticles for scavenging reactive oxygen species in both in vitro and ex vivo conditions. 5-fluorouracil loaded MR/CH nanoparticles were tested for anticancer proliferation and compared their therapeutic efficiency using breast adenocarcinoma and glioma cells. Fluorescently labeled nanoparticles were employed to show the cellular uptake of these nanocarriers using confocal microscopic imaging and flow cytometry.

[Continuing investigation of effect of toner and its by-product on human health and occupational health management of toner].

OBJECTIVE: As there are reports that ultrafine particles are generated by thermal printer toner, and that mucosal irritation symptoms were observed in users. When printers were operated, we have been examining the effects of not only toner but its by-products on human health. METHODS: We conducted a review of epidemiological and animal data on toner and its by-products such as ultrafine particles and volatile organic compounds (VOC). This was the second survey and it confirmed the results of the first survey. RESULTS: We reviewed the data, and summarized the results as follows. 1) Four cross-sectional studies reported no definite harmful effects of toner. 2) Ultrafine particles were generated in greater numbers at higher fuser heating and higher toner coverages. Ultrafine particles were also observed at lower rates in idle mode. 3) High-sensitive c-reactive protein in serum and heart rate variability (HRV) were useful biomarkers of not only exposure to ultrafine particles but disorder of cardiovascular disease, 8-hydroxydeoxyguanosine in urine is a biomarker of acute lung injury by welder fume, and VEGF and CA15-3 are highly sensitive and specific biomarkers of pulmonary fibrosis. 4) Physico-chemical properties of ultrafine particles were examined, and specific parameters related to pulmonary responses were not observed. CONCLUSIONS: Taken together, we found that there are some biomarkers which are related to not only exposure and but disorders induced by ultrafine particles, and that the generation of ultrafine particles with the operation of printers was associated with other factors than the fixing process. Until now there has been insufficient data for estimation of the hazards of toner and its by-products. However, continuing examinations are useful for complementing and correcting the information and data on toners and for revising the measures of occupational health. We will continue these examinations of toner and its by-products in the future.

Relationships between diabetes and medical and dental care costs: findings from a worksite cohort study in Japan.

The purpose of this study was to evaluate the relationships between diabetes and medical and dental care costs from a 5-yr prospective observation of Japanese workers. The data were derived from health and dental examinations and health insurance claims of 4,086 workers aged 40-54 yr. At baseline, the subjects were assigned to four categories: known diabetes; undiagnosed diabetes; impaired fasting glucose (IFG); and non-diabetic. The differences in health care costs among the non-diabetics, IFG and undiagnosed diabetes groups were not seen at baseline, but the costs incurred by the subjects with undiagnosed diabetes substantially increased thereafter. Over 5 yr of the study period, compared with the non-diabetic group, subjects with known diabetes incurred 3.9- and 2.9-fold higher annual inpatient and outpatient costs, respectively, while subjects in the undiagnosed diabetes group incurred 3.0- and 1.6-fold higher costs, respectively. There were no significant associations between annual dental care costs and diabetic status. The excess costs of medical care among subjects with diabetes were attributable to diabetes itself, heart disease and cerebrovascular disease, but not cancer. Among middle-aged workers, diabetics incurred significantly greater medical care costs than non-diabetics, whereas IFG was not associated with higher costs.

National use of asbestos in relation to economic development.

BACKGROUND: National disparities in asbestos use will likely lead to an unequal burden of asbestos diseases. OBJECTIVES: As economic status may be linked to asbestos use, we assessed, globally, the relationship between indicators of national economic development and asbestos use. METHODS: For the 135 countries that have ever used asbestos, per capita asbestos use (kilograms per capita per year) was compared with per capita gross domestic product (GDP) in 1990 Geary-Khamis dollars (GKD) for the period 1920-2003. Countries were grouped into three income levels (high, middle, and low) that were adapted from the 2003 World Bank categories. RESULTS: The historical pattern of asbestos use followed the environmental Kuznets curve in which use by high-income countries peaked when incomes attained 10,000-15,000 GKD and essentially ceased at income levels over 20,000 GKD. Currently, middle- and low-income countries are increasing their use of asbestos, closely following the paths once traced by higher income countries. CONCLUSIONS: Developing countries have the opportunity to eliminate asbestos use sooner than high-income countries and thus reduce the future burden of asbestos diseases.

[Treatment of asbestos-containing waste products to prevent harm to the lungs ].

The amount of industrial wastes with asbestos such as dismantled construction materials has increased. We have reviewed the effect of asbestos-containing products subjected to harmless treatment on the lungs. Usually, the harmless treatment of asbestos is confirmed by the disappearance of fibrous materials and crystal structures by electron microscopy and X-ray diffraction. However, it is very important to perform animal studies and in vitro studies in order to examine the effect of the treated asbestos-containing products on the lungs. From previous treatments of asbestos using acids or high temperature, almost treated materials tended to show decreased toxicity in vitro and in vivo studies. There are some reports of the adverse effects of the treatment. If new harmless treatments of asbestos are developed, it is necessary to perform animal studies and in vitro studies of asbestos-containing products using new harmless treatments.

[New investigation of the effect of toner and its by-products on human health and occupational health management of toner].

We need a new investigation of the effect of not only toner but also of its by-products on human health, because of the generation of fine particles and the release of volatile organic compounds (VOC) in the process of photocopy. Therefore, we gathered epidemiological and animal data on toner and its by-products, and examined the occupational health management of toner. We examined the effect of carbonblack as the main component of toner, and titanium dioxide and amorphous silica as surface-adhesive nanomaterials, and VOC on human health, and reviewed them. We summarize the results as follows. 1) High sensitive c-reactive protein in serum, 8-hydroxydeoxyguanosine in urine, and heart rate variability (HRV) are useful for biological monitoring of exposure to toner and its by-products. 2) Particle number concentrations have been often measured by scanning mobility particle sizer (SMPS) compared with other apparatus, although this is not measurement gold standard. Taken together, we have examined whole occupational health management of toner and its by-products.

Recent mortality from pleural mesothelioma, historical patterns of asbestos use, and adoption of bans: a global assessment.

BACKGROUND: In response to the health risks posed by asbestos exposure, some countries have imposed strict regulations and adopted bans, whereas other countries have intervened less and continue to use varying quantities of asbestos. OBJECTIVES: This study was designed to assess, on a global scale, national experiences of recent mortality from pleural mesothelioma, historical trends in asbestos use, adoption of bans, and their possible interrelationships. METHODS: For 31 countries with available data, we analyzed recent pleural mesothelioma (International Classification of Diseases, 10th Revision) mortality rates (MRs) using age-adjusted period MRs (deaths/million/year) from 1996 to 2005. We calculated annual percent changes (APCs) in age-adjusted MRs to characterize trends during the period. We characterized historical patterns of asbestos use by per capita asbestos use (kilograms per capita/year) and the status of national bans. RESULTS: Period MRs increased with statistical significance in five countries, with marginal significance in two countries, and were equivocal in 24 countries (five countries in Northern and Western Europe recorded negative APC values). Countries adopting asbestos bans reduced use rates about twice as fast as those not adopting bans. Turning points in use preceded bans. Change in asbestos use during 1970-1985 was a significant predictor of APC in mortality for pleural mesothelioma, with an adjusted R(2) value of 0.47 (p < 0.0001). CONCLUSIONS: The observed disparities in global mesothelioma trends likely relate to country-to-country disparities in asbestos use trends.

Differential expression of EC-SOD, Mn-SOD and CuZn-SOD in rat lung exposed to crystalline silica.

Superoxide dismutases (SODs) are antioxidant enzymes that catalyze the dismutation of superoxide into hydrogen peroxide. There are 3 kinds of isozymes: extracellular superoxide dismutase (EC-SOD), manganese-containing superoxide dismutase (Mn-SOD) and copper- and zinc-containing superoxide dismutase (CuZn-SOD). To examine the expression of SOD isozymes in lungs injured by crystalline silica, we intratracheally instilled male Wistar rats with 2 mg (8 mg/kg) of crystalline silica and investigated the mRNA, protein level and distribution of SOD isozymes in the rat lungs using RT-PCR, western blot analysis and immunostaining, respectively at from 3 d to 180 d of recovery following the exposure. EC-SOD mRNA levels significantly increased from 3 d to 90 d and the EC-SOD protein level was significantly higher after 90 and 180 d recovery in the crystalline silica exposed groups than in the control groups. Mn-SOD increased in silica treated rat lungs at both mRNA and protein levels, peaking at 30 d post-exposure. CuZn-SOD mRNA levels were decreased at 3, 7 and 30 d, and CuZn-SOD protein levels were also significantly lower than the control group at 90 and 180 d recovery. There was prominent EC-SOD immunostaining mainly in the plasma and alveolar macrophages and strong Mn-SOD staining in alveolar macrophages and interstitial cells of the proximal and distal portions of the alveolar duct following crystalline silica exposure. There was less CuZn-SOD staining in epithelial cells at terminal bronchioles in the crystalline silica-exposed group. These findings suggest that these SOD isozymes may be related to lung injury induced by crystalline silica.

[Relationship between lifestyle and subjective symptoms in a food products company].

Although the relationship between lifestyle and subjective symptoms has been reported in the general population, relatively few studies have looked at the link between these two in workplace. To investigate the relationship between lifestyle and subjective symptoms, a cross-sectional study was carried out using data from 4,540 workers aged 20-69 years old in a food products company. The subjective symptoms with a prevalence of more than 10% in either males or females were selected as dependent variables: fatigue, dropsical swelling of hands or feet, stiff neck or shoulders, backpain, deterioration of eye sight, dizziness, diarrhea and constipation. We used a multiple logistic regression model to calculate the odds ratio(OR) and 95% confidence interval(CI) for each subjective symptom according to lifestyle: regular physical activity, proper sleeping, nine hours or less of work, having breakfast, having a nutritionally balanced diet, no smoking and moderate drinking of alcohol. We adjusted for age and type of occupation by gender. The findings confirmed the relationship between smoking and alcohol drinking and subjective symptoms in both genders. In addition, proper sleeping was likely to prevent musculoskeletal symptoms in females.

Ecological association between asbestos-related diseases and historical asbestos consumption: an international analysis.

BACKGROUND: The potential for a global epidemic of asbestos-related diseases is a growing concern. Our aim was to assess the ecological association between national death rates from diseases associated with asbestos and historical consumption of asbestos. METHODS: We calculated, for all countries with data, yearly age-adjusted mortality rates by sex (deaths per million population per year) for each disease associated with asbestos (pleural, peritoneal, and all mesothelioma, and asbestosis) in 2000-04 and mean per head asbestos consumption (kg per person per year) in 1960-69. We regressed death rates for the specified diseases against historical asbestos consumption, weighted by the size of sex-specific national populations. FINDINGS: Historical asbestos consumption was a significant predictor of death for all mesothelioma in both sexes (adjusted R2=0.74, p<0.0001, 2.4-fold [95% CI 2.0-2.9] mortality increase was predicted per unit consumption increase for men; 0.58, p<0.0001, and 1.6-fold [1.4-1.9] mortality increase was predicted for women); for pleural mesothelioma in men (0.29, p=0.0015, 1.8-fold [1.3-2.5]); for peritoneal mesothelioma in both sexes (0.54, p<0.0001, 2.2-fold [1.6-2.9] for men, 0.35, p=0.0008, and 1.4-fold for women [1.2-1.6]); and for asbestosis in men (0.79, p<0.0001, 2.7-fold [2.2-3.4]). Linear regression lines consistently had intercepts near zero. INTERPRETATION: Within the constraints of an ecological study, clear and plausible associations were shown between deaths from the studied diseases and historical asbestos consumption, especially for all mesothelioma in both sexes and asbestosis in men. Our data strongly support the recommendation that all countries should move towards eliminating use of asbestos.

Change of heme oxygenase-1 expression in lung injury induced by chrysotile asbestos in vivo and in vitro.

Oxidative stress is thought to be the pathogenesis of pulmonary fibrosis induced by asbestos, and heme oxygenase-1 (HO-1) protects lung tissue against oxidative stress. We hypothesized that HO-1 is also associated with oxidative lung injury caused by exposure to chrysotile asbestos. This study was conducted to investigate the HO-1 expression of lungs in lung injury by chrysotile asbestos in vivo and in vitro. Male Wistar rats were administered 1 mg or 2 mg chrysotile suspended in saline by a single intratracheal instillation and were sacrificed at 3 days, 1 wk, 1 mo, 3 mo, and 6 mo of recovery time. The expression of HO-1 was observed by Western blot analysis, reverse-transcription polymerase chain reaction, and immunostaining. Protein levels of HO-1 increased at from 3 days to 6 mo following intratracheal instillation of 1 or 2 mg chrysotile. The mRNA levels of HO-1 increased at 3 mo and 6 mo following intratracheal instillation of 1 or 2 mg chrysotile. HO-1-positive cells were mainly found in the alveolar macrophages during immunostaining. We then examined HO-1 protein expression in human alveolar epithelial cells (A549). A549 cells were incubated with chrysotile at concentrations of 0, 12.5, 25, 50, and 100 microg/ml over 24 h. Increased expression of HO-1 protein was found following exposure to 25 or 50 microg/ml of chrysotile. Increased expression of HO-1 was also found at 6, 12, 24, and 48 h after exposure to 50 microg/ml of chrysotile with a peak at 24 h. These findings suggest that HO-1 is related to lung injury arising from exposure to chrysotile asbestos in vivo and in vitro.

Association of psychological well-being with oral conditions in Japanese workers.

Although the effect of disorders on psychological well-being is well-known, there are few studies focusing on oral conditions at the worksite. The present study examined the association between psychological well-being and oral conditions of Japanese workers. A cross-sectional study was performed using data from 1381 Japanese civil service officers aged 20-59 yr old. Psychological well-being was measured with the 12-item version of the General Health Questionnaire (GHQ-12) in a comprehensive health questionnaire, while measures for oral condition included self-rated oral health, oral symptoms and clinical indicators: dental caries, periodontal status and number of missing teeth. The mean GHQ scores according to the levels of each oral condition were estimated by analysis of variance, separately for males and females. Higher scores corresponded to poorer psychological well-being. Age, gender, smoking and type of occupation were adjusted in a multivariate analysis. Psychological well-being was not associated significantly with dental caries, periodontal status or number of missing teeth. The adjusted means of the GHQ scores for ;conscious of appearance of mouth' were significantly different among the categories for both genders (male: p<0.001, female: p=0.018). For five of six oral symptoms, the adjusted means of GHQ scores were lowest for those respondents who rated their oral symptoms as ;never or hardly ever.' Our results did not show that psychological well-being was associated with oral conditions measured by clinical indicators. However, an association was found between some oral symptoms and psychological well-being. Absence of oral symptoms seems to be related to better psychological well-being.

The development and regulation of occupational exposure limits in Japan.

The Ministry of Health, Labor and Welfare, on an administrative basis, establishes and supervises the Administrative Concentration Level, which can be viewed as an Occupational Exposure Limit (OEL) legally binding employers to maintain a good working environment. The Japan Society for Occupational Health, on a scientific basis, establishes the Recommended OELs, which can be viewed as a reference value for preventing adverse health effects on individual workers. In the case of carcinogens, Reference Values are recommended instead of OELs, corresponding to lifetime excessive risk of 10(-3) and 10(-4). The former is based on monitoring of the ambient working environment (area monitoring) while the latter is based on the monitoring of the individual worker. The two OELs influence each other in the course of establishment.

Negative effect of long-term inhalation of toner on formation of 8-hydroxydeoxyguanosine in DNA in the lungs of rats in vivo.

We assessed the effects of long-term inhalation of toner on the pathological changes and formation of 8-hydroxydeoxyguanosine (8-OH-Gua) in DNA in a rat model. Female Wistar rats (10 wk old) were divided evenly into a high concentration exposure group (H: 15.2 mg/m(3)), a low concentration exposure group (L: 5.5 mg/m(3)), and a control group. The mass median aerodynamic diameter of the toner was 4.5 microm. The rats were sacrificed at the termination of a 1-yr or 2-yr inhalation period. Pathological examination was performed on the left lung, and the level of 8-OH-Gua in DNA from the right lung was measured using a high-performance liquid chromatography (HPLC) column. The pathological findings showed that lung cancer was not observed in any of the exposed or control groups, though pleural thickening and small foci of collagen were observed in toner-exposed rat lungs. Inhalation of the toner for 1 and even 2 yr did not induce the formation of 8-OH-Gua in DNA in rat lungs. These data suggest that long-term inhalation of toner may not induce lung tumors.

Expression of heme oxygenase-1 in the lungs of rats exposed to crocidolite asbestos.

Oxidative stress is thought to be the pathogenesis of pulmonary fibrosis induced by asbestos, and heme oxygenase-1 (HO-1) protects lung tissue against oxidative stress. We hypothesized that HO-1 is associated with oxidative lung injury caused by exposure to asbestos. This study was conducted to investigate the time course of HO-1 expression of lungs exposed to crocidolite asbestos in vivo. Male Wistar rats were administered 1 mg or 2 mg crocidolite asbestos suspended in saline by a single intratracheal instillation and were sacrificed at 3 d, 1 wk, 1 mo, 3 mo, and 6 mo of recovery time. The expression of HO-1 was observed by Western blot analysis and immunostaining. Protein levels of HO-1 increased at from 3 d to 6 mo following intratracheal instillation of 2 mg crocidolite asbestos. The levels of HO-1 increased at 1 wk and 1 mo following intratracheal instillation of 1 mg crocidolite asbestos. Many HO-1-positive cells were found, particularly in the alveolar macrophages, during immunostaining. These findings suggest that HO-1 may be related to lung disorder induced by dust and therefore can act as a biomarker of lung injury due to dust exposure.

Effect of long-term inhalation of toner on extracellular matrix in the lungs of rats in vivo.

We assessed the effects of long-term inhalation of toner on the pathological changes and gene expression with the synthesis and degradation of collagenous extracellular matrix in a rat model. Female Wistar rats (10 wk old) were divided evenly into a high concentration exposure group (H: 15.2 mg/m3), a low concentration exposure group (L: 5.5 mg/m3), and a control group. The mass median aerodynamic diameter of toner was 4.5 microm. The rats were sacrificed at the termination of a 1-yr or 2-yr inhalation period. Pathological examination was performed from the left lung, and transcriptional levels of mRNA extracted from the right lung were assessed by semiquantitative reverse-transcription polymerase chain polymerase (RT-PCR). The pathological findings showed mild pulmonary fibrosis in 20% (L, 1 yr), 40% (H, 1 yr), 56% (L, 2 yr) and 62% (H, 2 yr), while lung cancer was not observed in any of the exposed groups. In the 1-yr high-concentration group, gene expression of matrix metalloproteinase-2 (MMP-2) and type I collagen mRNA in the rat lungs increased, while tissue inhibitors of metalloproteinase-2 (TIMP-2) decreased. The 2-yr high-concentration group increased in message level of type I collagen and TIMP-2 but not that of MMP-2. These data suggested that results of gene expression of MMP, TIMP, and collagen in the 2-yr exposure may lead to accumulation of collagen compared to the 1-yr exposure, and that the imbalance of the expression of MMPs, TIMPs, and extracellular matrix might be associated with pulmonary fibrosis induced by toner.