A prospective cohort study of presenteeism and poverty among Japanese workers during the COVID-19 pandemic.

OBJECTIVES: This study examined the association of presenteeism with experiences of poverty among Japanese workers during the COVID-19 pandemic. METHODS: A prospective cohort study of Japanese workers was conducted using an Internet monitoring survey. The baseline survey was conducted in December 2020, and a follow-up survey in December 2021. Of the 27 036 workers who participated, 18 560 (68.7%) completed the follow-up survey. The 11 081 who reported that they were not in financial difficulty in the baseline survey were included in the analysis. The degree of work functioning impairment was assessed at baseline using the Work Functioning Impairment Scale (WFun). Households' experience of not being able to pay for food and clothing was identified in the follow-up survey. The odds ratios (ORs) of presenteeism determined by WFun associated with poverty were estimated using a multilevel logistic model. The multivariate model included age, sex, marital status, job type, income, education, smoking, alcohol consumption, number of employees in the workplace, and the incidence rate of COVID-19 by prefecture at baseline. RESULTS: In the multivariate model, the odds ratio of experiencing food insecurity increased with high WFun score: compared with WFun scores of 13 or less, the OR was 1.87 (95% CI: 1.43-2.43, P < .001) for WFun scores of 14 or more and 3.26 (95% CI: 2.58-4.12, P < .001) for WFun scores of 21 or more. CONCLUSIONS: In addition to labor productivity, the adverse effects of presenteeism on social security-related concerns such as poverty require further attention.

Association between loneliness and psychological distress: A cross-sectional study among Japanese workers during the COVID-19 pandemic.

The purpose of this study was to examine the association between loneliness and psychological distress during the COVID-19 pandemic in Japan. We conducted a cross-sectional online study from 22 to 26 December 2020. A total of 27,036 participants, all employed at the time, were included in the analysis. Participants were asked if they felt loneliness in a single-item question. The Kessler 6 (K6) was used to assess psychological distress, defined as mild for K6 scores of 5 to 12 and severe for 13 or higher. The odds ratios (ORs) of psychological distress associated with loneliness were estimated using a multilevel logistic model nested in the prefecture of residence, with adjustment for age, sex, marital status, equivalent income, educational level, smoking, alcohol consumption, job type, number of workplace employees, and cumulative incidence rate of COVID-19 in the prefecture. Communication with friends, acquaintances, and family was strongly associated with psychological distress, so we adjusted for these factors and eating meals alone. Results showed a significant association between loneliness and psychological distress (OR = 36.62, 95% CI = 32.95-40.69). Lack of friends to talk to, lack of acquaintances to ask for help, and lack of people to communicate with through social networking sites were all strongly associated with psychological distress, as were family time and solitary eating. Even after adjusting for these factors, loneliness remained strongly associated with psychological distress (OR = 29.36, 95% CI = 26.44-32.98). The association between loneliness during the COVID-19 pandemic and psychological distress indicates the need for intervention.

Changes over time in pulmonary inflammatory response in rat lungs after intratracheal instillation of nickel oxide nanoparticles.

OBJECTIVE: Nickel oxide nanoparticles (NiONPs) are representative metal oxide NPs and are categorized as an insoluble nickel compound. Our previous studies suggested that NiONPs have more pulmonary toxicity than micron-sized NiO because they may dissolve slowly and produce many more Ni ions. We confirmed the hypothesis that the slow dissolution of NiONPs induces a change in inflammatory response over time. METHOD: We reanalyzed our previous data on intratracheally instilled NiONP to rats and focused on Ni retention in the lungs and the lung weight ratio for each rat to the mean of control rat lungs. We also measured the solubility of NiONPs and micron-sized NiO samples by means of an artificial lysosomal fluid (ALF, pH 4.5). RESULTS: The in vivo test of instilled NiONPs resulted in the biomarkers reaching their peak values at 1 week or 1 month, and not at 3 days, after instillation. We found that as the NiO mass in the lung increased, the lung weight ratios tended to increase. The relationships shifted to more toxic at 3 days to 1 month (P < .01). Compared to the dissolution of NiONPs in the ALF that took roughly 1 week, the dissolution of NiONPs in vivo was take about 1 month or more. CONCLUSION: When intratracheally instilled NiONPs dissolve slowly in the phagolysosomes of alveolar macrophages (AM), the resulting Ni ions cause the AM to transform into foamy cells at 1 month, and the inflammatory response persists even at 3 months after instillation.

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.

Continuous improvement of fitness-for-duty management programs for workers engaging in stabilizing and decommissioning work at the Fukushima Daiichi Nuclear Power Plant.

BACKGROUND: Numerous workers have participated in recovery efforts following the accident that occurred at the Tokyo Electric Power Company (TEPCO) Fukushima Daiichi Nuclear Power Plant after the Great East Japan Earthquake. These workers, belonging to various companies, have been engaged in various tasks since the accident. Given the hazards and stress involved in these tasks and the relatively long time required to transport sick or injured workers to medical institutions, it became necessary to quickly implement a more stringent management program for fitness for duty than in ordinary work environments. CASE: It took considerable time to introduce and improve a fitness-for-duty program because of several concerns. Various efforts were conducted, sometimes triggered by guidance from the Ministry of Health, Labour and Welfare (MHLW), but the implementation of the program was insufficient. In April 2016, a new program was initiated in which all primary contractors confirmed that their subcontractors had achieved five conditions for workers' fitness for duty on the basis of guidance from the MHLW and occupational health experts. TEPCO confirmed that all primary contractors had implemented the program successfully as of the end of November 2016. CONCLUSION: Following a disaster, even though the parties concerned understand the necessity of fitness-for-duty programs and that companies in high positions have responsibilities beyond their legal requirements, it is highly possible that they may hesitate to introduce such programs without guidance from the government. It is necessary to prepare a governmental framework and professional resources that introduce these stringent management programs quickly.

Analysis of pulmonary surfactant in rat lungs after inhalation of nanomaterials: Fullerenes, nickel oxide and multi-walled carbon nanotubes.

The health risks of inhalation exposure to engineered nanomaterials in the workplace are a major concern in recent years, and hazard assessments of these materials are being conducted. The pulmonary surfactant of lung alveoli is the first biological entity to have contact with airborne nanomaterials in inhaled air. In this study, we retrospectively evaluated the pulmonary surfactant components of rat lungs after a 4-week inhalation exposure to three different nanomaterials: fullerenes, nickel oxide (NiO) nanoparticles and multi-walled carbon nanotubes (MWCNT), with similar levels of average aerosol concentration (0.13-0.37 mg/m(3)). Bronchoalveolar lavage fluid (BALF) of the rat lungs stored after previous inhalation studies was analyzed, focusing on total protein and the surfactant components, such as phospholipids and surfactant-specific SP-D (surfactant protein D) and the BALF surface tension, which is affected by SP-B and SP-C. Compared with a control group, significant changes in the BALF surface tension and the concentrations of phospholipids, total protein and SP-D were observed in rats exposed to NiO nanoparticles, but not in those exposed to fullerenes. Surface tension and the levels of surfactant phospholipids and proteins were also significantly different in rats exposed to MWCNTs. The concentrations of phospholipids, total protein and SP-D and BALF surface tension were correlated significantly with the polymorphonuclear neutrophil counts in the BALF. These results suggest that pulmonary surfactant components can be used as measures of lung inflammation.

Intratracheal instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression.

The use of carbon nanotubes in the industry has grown; however, little is known about their toxicological mechanism of action. Single-wall carbon nanotube (SWCNT) suspensions were administered by single intratracheal instillation in rats. Persistence of alveolar macrophage-containing granuloma was observed around the sites of SWCNT aggregation at 90 days post-instillation in 0.2-mg- or 0.4-mg-injected doses per rat. Meanwhile, gene expression profiling revealed that a large number of genes involved in the inflammatory response were markedly upregulated until 90 days or 180 days post-instillation. Subsequently, gene expression patterns were dramatically altered at 365 days post-instillation, and the number of upregulated genes involved in the inflammatory response was reduced. These results suggested that alveolar macrophage-containing granuloma reflected a characteristic of the histopathological transition period from the acute-phase to the subchronic-phase of inflammation, as well as pulmonary acute phase response persistence up to 90 or 180 days after intratracheal instillation in this experimental setting. The expression levels of the genes Ctsk, Gcgr, Gpnmb, Lilrb4, Marco, Mreg, Mt3, Padi1, Slc26a4, Spp1, Tnfsf4 and Trem2 were persistently upregulated in a dose-dependent manner until 365 days post-instillation. In addition, the expression levels of Atp6v0d2, Lpo, Mmp7, Mmp12 and Rnase9 were significantly upregulated until 754 days post-instillation. We propose that these persistently upregulated genes in the chronic-phase response following the acute-phase response act as potential biomarkers in lung tissue after SWCNT instillation. This study provides further insight into the time-dependent changes in genomic expression associated with the pulmonary toxicity of SWCNTs.

Expression of cytokine-induced neutrophil chemoattractant in rat lungs following an intratracheal instillation of micron-sized nickel oxide nanoparticle agglomerates.

OBJECTIVE: In our previous study, we reported that the micron-sized nickel oxide nanoparticle agglomerates induced neutrophil infiltration and the gene expression of the cytokine-induced neutrophil chemoattractant (CINC)-2αß in a rat lung. In this study, we examined the expression of the CINCs family in the lung using the same rat model exposed to micron-sized nickel oxide nanoparticle agglomerates. METHODS: The count median diameter of nickel oxide nanoparticle agglomerates suspended in saline was 1.34 µm (primary diameter: 8.41 nm). Male Wistar rats received an intratracheal instillation of 1 mg (3.3 mg/kg) of nickel oxide nanoparticles and were dissected at 3 days, 1 week, 1 month, 3 months, and 6 months after the instillation. The negative control group received an instillation of saline. The concentration of CINC-1 in the lung and the bronchoalveolar lavage fluid (BALF), CINC-2αß in the BALF, and CINC-3 in the lung and the BALF was examined. RESULTS: The concentration of CINC-1 was elevated at 3 days, 3 months, and 6 months in the lung tissue and from 3 days to 6 months in the BALF. The concentration of CINC-2αß was elevated from 3 days to 3 months in the BALF. The concentration of CINC-3 was also elevated at 3 days, 1 week, 3 months, and 6 months in the lung tissue. Infiltration of neutrophil and alveolar macrophage was observed mainly in the alveoli during the observed time period. CONCLUSION: These results suggest that CINC-1 to -3 were totally involved in the lung injury caused by micron-sized nickel oxide nanoparticle agglomerates.

Relationship between smoking and a new index of arterial stiffness, the cardio-ankle vascular index, in male workers: a cross-sectional study.

BACKGROUND: Cigarette smoking is one of the major factors that increases arterial stiffness. The purpose of this study was to examine further the relationship between smoking status and arterial stiffness using a new index, the cardio-ankle vascular index (CAVI), in male Japanese workers. METHODS: This cross-sectional study included 4,729 male Japanese workers undergoing annual health checkups. CAVI was measured at the time of the annual health checkup between April 2007 and March 2008. The subjects were divided into three groups, smokers (n = 1,913), former smokers (n = 1,481) and non-smokers (n = 1,348) according to their responses to a questionnaire. We compared the CAVI in the three groups after adjusting for age. Multiple regression analysis was used to examine the association between CAVI and the number of cigarettes smoked per day in order to examine whether there was a dose-response relationship between smoking and CAVI. RESULTS: The mean CAVI for each group was 7.81 ± 0.02 for smokers, 7.70 ± 0.02 for former smokers and 7.64 ± 0.02 for non-smokers. A significant difference was observed between each group. According to the results of multiple regression analysis, the standardized ß of the number of cigarettes smoked per day was 0.09 (p < 0.01). This confirmed a positive association with CAVI. CONCLUSIONS: Our study demonstrated that there is a significant association between the number of cigarettes smoked per day and arterial stiffness, as measured by CAVI.

Pulmonary toxicity of well-dispersed multi-wall carbon nanotubes following inhalation and intratracheal instillation.

Multi-walled carbon nanotubes (MWCNTs), dispersed in suspensions consisting mainly of individual tubes, were used for intratracheal instillation and inhalation studies. Rats intratracheally received a dose of 0.2 mg, or 1 mg of MWCNTs and were sacrificed from 3 days to 6 months. MWCNTs induced a pulmonary inflammation, as evidenced by a transient neutrophil response in the low-dose groups, and presence of small granulomatous lesion and persistent neutrophil infiltration in the high-dose groups. In the inhalation study, rats were exposed to 0.37 mg/m(3) aerosols of well-dispersed MWCNTs (>70% of MWCNTs were individual fibers) for 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inhalation exposures delivered less amounts of MWCNTs into the lungs, and therefore less pulmonary inflammation responses was observed, as compared to intratracheal instillation. The results of our study show that well-dispersed MWCNT can produce pulmonary lesions, including inflammation.

Analysis of bronchoalveolar lavage fluid adhering to lung surfactant. Experiment on intratracheal instillation of nickel oxide with different diameters.

Nickel oxide with two different particle sizes, micron size (NiO) and submicron size (nNiOm), as well as crystalline silica as a positive control and titanium dioxide as a negative control, were intratracheally instilled in rats and the phospholipid concentration and the protein concentration and surface tension of bronchoalveolar lavage fluid (BALF), which are used in surfactant assessment, were measured to see if they could be effective biomarkers in toxicity assessment. The results showed that the NiO instilled group showed no significant difference compared to the control group throughout the observation period. In contrast, a significant difference was found in the nNiOm instilled group compared to the control group throughout the observation period. Moreover, a significant difference was found in the crystalline silica instilled group for each measurement compared to the control group while for the titanium dioxide group, almost no significant difference was found. These results indicate that submicronsized particles of nickel oxide with smaller median diameters potentially have a stronger biological effect than micron size particles. They also indicate that screening can be done by measuring the phospholipid concentration and the protein concentration and surface tension of BALF.

Pulmonary toxicity of well-dispersed single-wall carbon nanotubes after inhalation.

Single-wall carbon nanotubes (SWCNTs) were well-dispersed by ultrasonication to conduct an inhalation study. SWCNTs were generated using a pressurised nebuliser with liquid suspension of SWCNTs. Wistar rats were exposed to the well-dispersed SWCNT (diameter of bundle: 0.2 µm; length of bundle: 0.7 µm) for 4 weeks. The low and high mass concentrations of SWCNTs were 0.03 ± 0.003 and 0.13 ± 0.03 mg/m(3), respectively. The rats were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. There were no increases of total cell or neutrophil counts in the bronchoalveolar lavage fluid (BALF), or the concentration of cytokine-induced neutrophil chemoattractant in the lungs or BALF in both the high and low concentration-exposed groups. Pulmonary infiltration of neutrophils was not observed in either exposed group throughout the observation period. Well-dispersed SWCNT did not induce neutrophil inflammation in the lung under the conditions in the present study.

Pathological features of rat lung following inhalation and intratracheal instillation of C(60) fullerene.

We evaluated the pulmonary pathological features of rats that received a single intratracheal instillation and a 4-week inhalation of a fullerene. We used fullerene C(60) (nanom purple; Frontier Carbon Co. Ltd, Japan) in this study. Male Wistar rats received intratracheal dose of 0.1, 0.2, or 1 mg of C(60), and were sacrificed at 3 days, 1 week, 1 month, 3 months, 6 months, and 12 months. In the inhalation study, Wistar rats received C(60) or nickel oxide by whole-body inhalation for 6 h/day, 5 days/week, 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. During the observation period, no tumors or granulomas were observed in either study. Histopathological evaluation by the point counting method (PCM) showed that a high dose of C(60) (1 mg) instillation led to a significant increase of areas of inflammation in the early phase (until 1 week). In the inhalation study of the C(60)-exposed group, PCM evaluation showed significant changes in the C(60)-exposed group only at 3 days after exposure; after 1 month, no significant changes were observed. The present study demonstrated that the pulmonary inflammation pattern after exposure to well-characterized C(60) via both intratracheal and inhalation instillation was slight and transient. These results support our previous studies that showed C(60) has no significant adverse effects in intratracheal and inhalation instillation studies.

Expression of heme oxygenase-1 in the lungs of rats exposed to potassium octatitanate whiskers.

OBJECTIVES: 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 potassium octatitanate whiskers (PT1), which is one of the asbestos substitutes. METHODS: Male Wistar rats were administered 1 mg or 2 mg PT1 suspended in saline by a single intratracheal instillation and were sacrificed after recovery for 3 days, 1 wk, 1 mo, 3 mo or 6 mo. Gene expression of HO-1 protein and mRNA and immunostaining were investigated in rat lungs. RESULTS: HO-1 protein expression was increased from 3 days to 1 mo and at 6 mo in the 1 or 2 mg PT1-exposed groups, and the gene expression of HO-1 mRNA was also increased at 3 days and from 1 mo to 6 mo. HO-1-positive cells were mainly found in the alveolar macrophages and the bronchial epithelial cells in immunostaining. CONCLUSIONS: These findings suggest that HO-1 is involved in lung damage caused by PT1.

Pulmonary toxicity following an intratracheal instillation of nickel oxide nanoparticle agglomerates.

OBJECTIVE: We examined the pulmonary toxicity of nickel oxide nanoparticle agglomerates in the rat lung following an intratracheal instillation. METHODS: The weighted average surface primary diameter of nickel oxide nanoparticles was 8.41 nm, and the count median diameter of nickel oxide nanoparticle agglomerates suspended in saline was 1.34 µm. Male Wistar rats were exposed to 1 mg (3.3 mg/kg) of nickel oxide nanoparticles intratracheally. The control group received intratracheal instillation of saline. Rats were dissected 3 days, 1 wk, 1 mo, 3 mo, and 6 mo after the instillation. Cytokine-induced neutrophil chemoattractant (CINC)-2αß in the lung tissue was determined by quantitative measurement of protein by ELISA. RESULTS: The total cell count in bronchoalveolar lavage fluid (BALF) was increased persistently from 3 days to 6 mo. The neutrophil counts in BALF were also increased at 3 days, 1 wk, 3 mo, and 6 mo. In the lung tissue, infiltration of mainly neutrophils and alveolar macrophages was observed in alveoli from 3 days to 6 mo. The CINC-2αß concentration was elevated from 3 days to 6 mo in the lung tissue. CONCLUSIONS: These results showed that micron-sized nickel oxide nanoparticle agglomerates also induced a persistent inflammatory response.

Investigation of gene expression of MMP-2 and TIMP-2 mRNA in rat lung in inhaled nickel oxide and titanium dioxide nanoparticles.

In order to investigate whether or not dispersed nanoparticles have an effect of inflammation and fibrosis on animals, we developed a nanoparticle generation system and examined the gene expression of matrix metalloproteinase (MMP) and tissue inhibitor matrix proteinase (TIMP) in rat lung containing inhaled nickel oxide (NiO) or titanium dioxide (TiO(2)) nanoparticles. In both experiments, Wistar male rats were exposed to NiO or TiO(2) nanoparticles for 4 wk (6 h/day). The geometric mean diameters of NiO and TiO(2) in the chamber were 139 ± 12 nm and 51 ± 9 nm, respectively. The average concentration of the particle number of NiO and TiO(2) was 1.0E+05 /cm(3) and 2.8E+05 /cm(3), respectively. At 4 d, 1 and 3 months after the end of the inhalation, the rats exposed to these particles were sacrificed and the gene expressions of MMP-2, TIMP-2 and type I collagen were measured using RT-PCR. Pathological finding revealed that there was minimum inflammation with nickel oxide only at 4 d and no change with titanium oxide. However, there were no changes of the gene expression of MMP-2, TIMP-2, and type I collagen in either the NiO or TiO(2) exposure groups. In this study, inhalation of nickel oxide and titanium dioxide nanoparticles did not induce the gene expression of MMP-2 and TIMP-2 mRNA in rat lungs.

Expression of inflammation-related cytokines following intratracheal instillation of nickel oxide nanoparticles.

The objective of this study was to examine what kinds of cytokines are related to lung disorder by well-dispersed nanoparticles. The mass median diameter of nickel oxide in distilled water was 26 nm. Rats intratracheally received 0.2 mg of nickel oxide suspended in distilled water, and were sacrificed from three days to six months. The concentrations of 21 cytokines including inflammation, fibrosis and allergy-related ones were measured in the lung. Infiltration of alveolar macrophages was observed persistently in the nickel oxide-exposed group. Expression of macrophage inflammatory protein-1alpha showed a continued increase in lung tissue and broncho-alveolar lavage fluid (BALF) while interleukin-1alpha (IL-1alpha), IL-1beta in lung tissue and monocyte chemotactic protein-1 in BALF showed transient increases. Taken together, it was suggested that nano-agglomerates of nickel oxide nanoparticles have a persistent inflammatory effect, and the transient increase in cytokine expression and persistent increases in CC chemokine were involved in the persistent pulmonary inflammation.

[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.

Inflammogenic effect of well-characterized fullerenes in inhalation and intratracheal instillation studies.

BACKGROUND: We used fullerenes, whose dispersion at the nano-level was stabilized by grinding in nitrogen gas in an agitation mill, to conduct an intratracheal instillation study and an inhalation exposure study. Fullerenes were individually dispersed in distilled water including 0.1% Tween 80, and the diameter of the fullerenes was 33 nm. These suspensions were directly injected as a solution in the intratracheal instillation study. The reference material was nickel oxide in distilled water. Wistar male rats intratracheally received a dose of 0.1 mg, 0.2 mg, or 1 mg of fullerenes and were sacrificed after 3 days, 1 week, 1 month, 3 months, and 6 months. In the inhalation study, Wistar rats were exposed to fullerene agglomerates (diameter: 96 +/- 5 nm; 0.12 +/- 0.03 mg/m3; 6 hours/days for 5 days/week) for 4 weeks and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inflammatory responses and gene expression of cytokine-induced neutrophil chemoattractants (CINCs) were examined in rat lungs in both studies. RESULTS: In the intratracheal instillation study, both the 0.1 mg and 0.2 mg fullerene groups did not show a significant increase of the total cell and neutrophil count in BALF or in the expression of CINC-1,-2alphabeta and-3 in the lung, while the high-dose, 1 mg group only showed a transient significant increase of neutrophils and expression of CINC-1,-2alphabeta and -3. In the inhalation study, there were no increases of total cell and neutrophil count in BALF, CINC-1,-2alphabeta and-3 in the fullerene group. CONCLUSION: These data in intratracheal instillation and inhalation studies suggested that well-dispersed fullerenes do not have strong potential of neutrophil inflammation.