Industrial Health
Online ISSN : 1880-8026
Print ISSN : 0019-8366
ISSN-L : 0019-8366
Volume 35 , Issue 3
Showing 1-18 articles out of 18 articles from the selected issue
  • Haruhiko Sakurai
    1997 Volume 35 Issue 3 Pages 299-300
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
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  • Takashi KANEKO, Pei-Yu WANG, Akio SATO
    1997 Volume 35 Issue 3 Pages 301-324
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    The epidemiological studies performed thus far have presented only limited evidence for the carcinogenicity of trichloroethylene (TRI) to humans. However, these studies had drawbacks such as insufficient size of cohort, short observation period, and inadequate TRI exposure assessment; therefore, no concrete conclusion has been reached concerning TRI carcinogenicity to humans. Despite the limited epidemiological evidence as to the carcinogenicity of TRI, the International Agency for Research on Cancer (IARC) has changed the carcinogenicity classification of TRI from Group 3 (not classifiable as to carcinogenicity to humans) to Group 2A (probably carcinogenic to humans). In regard to the new classification by the IARC, the committee for occupational exposure limits of the Japan Society for Occupational Health has made a proposal that it is too early to classify the carcinogenicity of TRI as Group 2A and that it is proper to promote exposure control with the carcinogenicity being classified as 2B for the moment. There are species differences in TRI carcinogenicity, particularly between rats and mice. Although experimental studies have found no evidence that TRI induces liver cancer in rats, there is ample evidence that TRI promotes the development of liver cancer in mice, particularly in B6C3F1 mice. The carcinogenicity of TRI in this strain of mice may be based on an epigenetic mechanism rather on a genotoxic mechanism and the liver cancer may be induced only after TRI has been inhaled for a long period of time at concentrations high enough to cause cytotoxicity. Conversely, with no reports showing TRI-induced renal tumors in mice, the possibility has been suggested that this chemical induces such tumors in male rats. The species differences are mainly accounted for by differences in the metabolism of TRI between rats and mice. From a general survey of the literature, it can be concluded that TRI itself is not mutagenic. However, the conjugation of TRI with glutathione (GSH), a minor pathway of TRI metabolism, results in mutagenic metabolites in the kidney of rats. The acute toxicity of TRI is neurotoxicity based on its anesthetic action. An exposure to extremely high levels of TRI may cause the liver and kidney disorders. Repeated exposures to high levels of TRI may result in neuro-, hepato-, and/or nephrotoxicity. The main symptoms appearing after chronic exposure at low levels are neurological changes represented by subjective symptoms relating to central and autonomic nervous systems, or by a lowered conduction velocity of the nerves or a prolonged latency of the nerve responses. For the present, it is reasonable to use the neurological findings for establishing the reference values of TRI for both work and general environments. A value of 25ppm (135mg/m3) is proposed as a reference value for work environments, and 25-50ppb (135-270μg/m3) for the general environment (1/1, 000 of the value for work environment).
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  • Hitoshi NAKAISHI, Mari YAMAMOTO, Masaaki ISHIDA, Isamu SOMEYA, Yuuichi ...
    1997 Volume 35 Issue 3 Pages 325-329
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    [Purpose] Pinguecula and pterygium are speculated to be associated with corneal and conjunctival microtrauma from exposure to sunlight and/or dust. Occupational motorcycle driving is suspected to be associated with such exposure, so we investigated the prevalence of pingueculae and pterygia in motorcycle policemen. [Method] Slit lamp finding obtained by periodic eye checkup for policemen (783 motorcycle policemen and 207 control indoor workers) together with questionnaire were used for analyses. All pingueculae and pterygia were diagnosed under the definite criteria. [Results] The overall prevalence of pingueculae was 590/1, 566 eyes (37.7%) among motorcycle policemen against 127/414 eyes (30.6%) among the indoor workers (p<0.01). Besides, with increasing age, the prevalence of pingueculae in the motorcycle policemen clearly exceeded those among the indoor controls. The prevalence of pterygia were very small to be analysed. [Conclusion] Our results exhibited a significant relationship between occupational motorcycle driving and the prevalence of pingueculae. Thus it is strongly suggested that they should wear eye protection equipments (goggles, face shield and so on) to prevent from developing these lesions.
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  • Maria Beatriz G. VILLANUEVA, Hiroshi JONAI, Midori SOTOYAMA, Naomi HIS ...
    1997 Volume 35 Issue 3 Pages 330-336
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    The effects of the VDT screen height on working posture and electromyographic (EMG) activities of the neck and shoulder muscles were determined in 10 healthy subjects. The subjects performed a mouse-driven interactive task at the screen height settings of 80, 100 and 120cm. Changes in body positions were measured by video image and frame analysis. Surface EMG recordings were done on the neck extensor muscle and the descending part of the trapezius muscle, both on the right side. The results of the postural analysis showed that at higher screen height settings, the neck became significantly more erect. The subjects also assumed a more backward-leaning trunk position at higher screen heights. The EMG activities of the neck and shoulder muscles were related to the neck angle and trunk inclination, respectively. A more flexed neck produced significantly higher neck extensor muscle activities. A backward-leaning trunk was also noted to decrease trapezius muscle activity in some subjects.
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  • Masatoshi TANAKA, Kazutoshi NAKAMURA, Kisaburo SATO, Kazuko TANAKA
    1997 Volume 35 Issue 3 Pages 337-342
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    We physically examined of forest workers in the northern part of Fukushima District, Japan. The main purpose of this study was to survey the state of finger functions, especially the differences between the functions of right and left fingers of forest workers. This physical examination was conducted in winter. The items of the physical examination were hand grip strength, finger skin temperature, vibration sensation threshold, nail pressure test of the finger. Subjects were classified into A and B groups on the base of the results of the physical examination. A group is normal or slight disorder, and B group is disorder or illness. Hand grip strength was measured five times at five-second intervals. The decrease ratio of the left hand grip strength was greater than that of the right hand grip strength. Although there were significant differences among each finger of A and B groups, there were no big differences in the skin temperatures of the fingers in each group. Vibration sensation threshold was measured for II, III and IV fingers. The vibration sensation threshold of the index finger was the most sensitive and that of IV finger was the least sensitive. The vibration sensation threshold of the right fingers was more sensitive than that of the left fingers. The reaction times of the nail pressure test of the right fingers were generally faster than those of the left fingers. Forestry workers in Japan become elderly. There are big differences among the physical reactions or strengths of elderly people. Standard values for the measuring items for ageing are needed.
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  • Setsuo MAEDA, Miyuki MORIOKA, Yoshiharu YONEKAWA, Kazuo KANADA, Yukio ...
    1997 Volume 35 Issue 3 Pages 343-352
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    A vibrotactile threshold measurement system that enables the thresholds at the fingertips to be determined more rapidly and precisely has been developed. This system was studied to assess the impact of various factors on the obtained values. An experiment using two different types of equipment was also conducted to assess the repeatability of measurement. One system was similar to that required by International Standard (System A), and the other system was of the currently used in Japan (System B). The subjects were nine males and one female, measurements were taken on three different days. This paper compares the structure of the equipment used internationally (ISO/CD13091) and the equipment typically used in Japan and the measurements of vibrotactile thresholds taken at a 125Hz frequency using Systems A and B. The measurement method and conditions adopted were almost the same as those outlined in the ISO draft. The results of this experiment showed that there were some differences between the two systems. The vibrotactile thresholds measured using System B showed higher values than did those measured using System A. The results also indicated that equipment that satisfies ISO standards provides sufficient repeatability for use as a diagnostic aid. Also, this paper is shown the vibrotactile measurement equipment conditions must be considered when using vibrotactile threshold measurement equipment in Japan.
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  • Seishiro HIRANO
    1997 Volume 35 Issue 3 Pages 353-358
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    This report shows the quantitative time-course profiles of transpulmonary migration of polymorphonuclear leukocytes (PMN) and the adhesive interaction of alveolar macrophages to the alveolar surface in response to intratracheally (i.t.) instilled endotoxin. Groups of mice received i.t. instillation of lipopolysaccharide (LPS), and free cells in the bronchoalveolar lavage (BAL) fluid were counted. PMN remaining in the lung tissue after the BAL procedure were also enumerated following enzymatic tissue digestion. Recovery of macrophages from the alveolar space by BAL was significantly decreased at 0.5 and 2h post i.t. instillation and returned to the control value after 5h, suggesting that alveolar macrophages became adhesive to the alveolar wall in response to LPS. Neither BAL nor lung tissue-associated PMN were increased until 0.5h post i.t. instillation of LPS. The lung tissue-associated PMN peaked at 2h, while the number of BAL PMN peaked at 5h post instillation. Furthermore, although the number of BAL PMN remained at the maximum value even at 24h post i.t. instillation of LPS, the lung tissue-associated PMN returned to the control level at this point. These results suggest that (1) the adhesive interaction of alveolar macrophages to the alveolar surface increased rapidly (<0.5h), (2) accumulation of PMN in the lung occurred later than the adhesion of alveolar macrophages (0.5 to 2h) and (3) transpulmonary infiltration of PMN was completed within 24h following i.t. instillation of LPS.
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  • Hajime DRANO, Sadao GOTOH, Akira SHIRAHATA, Ken HIGASHI, Yuji KARASAKI
    1997 Volume 35 Issue 3 Pages 359-366
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    The potential influences of crocidolite asbestos fibers and man made mineral fibers (potassium titanate whisker and magnesium sulfate whisker) on a procoagulant system of human umbilical vein endothelial cells (HUVECs) were investigated by measuring the activity and antigen level of thrombomodulin (TM) on the cell surface. Statistically significant increases in both the TM activity and TM antigen level were observed on HUVECs treated with crocidolite asbestos fibers for 48h and 72h compared to untreated cells at low concentrations of the fibers which showed no sign of a cytotoxic effect on the cells. An extensive increase in both the TM activity and TM antigen level was also observed on HUVECs treated with potassium titanate whisker or magnesium sulfate whisker for 48h and 72h. A statistical analysis revealed that these fibers had almost the same effects on the increases in both TM activity and the TM antigen level of HUVECs treated with the fibers for 48h and 72h, but a treatment of magnesium sulfate whisker at more than 1.25μg/ml for 24h was slightly more effective in increasing TM activity on HUVECs compared to other fibers (p<0.05). The [3H]leucine incorporation in HUVECs increased when the cells were treated with crocidolite asbestos or man-made mineral fibers (MMMFs), indicating that the increases in TM activity and the TM antigen level on HUVECs directly exposed to those fibers may not reflect the sole induction of anticoagulant activities, but the general cell damage induced by the fibers.
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  • Ana BOGADI-ŠARE, Vlatka BRUMEN, Rajka TURK, Višnja KARAC ...
    1997 Volume 35 Issue 3 Pages 367-373
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    The aim of the study was to establish a correlation between biomarkers of exposure and cytogenetic test results in workers occupationally exposed to benzene and toluene, with special reference to confounding factors influencing the outcome of the cytogenetic test. The incidence of structural chromosome aberrations and sister chromatid exchanges was studied in the peripheral blood lymphocytes cell genome of 49 female shoe-makers, mean age 38 years, mean length of occupational exposure 17 years and in a group of 27 well-matched controls. Workers were exposed to concentrations of benzene up to 15ppm and of toluene up to 50ppm. The presence of benzene and toluene in the workers' blood samples, and the presence of phenol in pre-and post-shift urine were considered proof of occupational exposure. Chromosomal aberration analysis revealed a significant increase in dicentric incidence in the exposed group compared to the controls (P=0.004). However, significant correlation between cytogenetic test results and the exposure biomarkers was not established. On the contrary, correlation between the cytogenetic test results and data on confounding factors (e.g. age and alcohol consumption), was marked. The major point raised by this study is the influence of confounding factors on the cytogenetic test outcome. This imposes the need for caution in the interpretation of cytogenetic test results, and ultimately in the estimation of individual genotoxicity risk related to low level benzene exposure.
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  • Tsutomu YOSHIDA, Syogo SHIMA, Kaoru NAGAOKA, Hiroshige TANIWAKI, Akihi ...
    1997 Volume 35 Issue 3 Pages 374-379
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    The relationship between airborne concentration of beryllium in the working environment and workers' beryllium lymphocyte transformation test (Be-LTT) values was examined based on data obtained from a four-year survey (1992-1995) conducted at beryllium-copper alloy manufacturing factories. This study showed that the T cells of workers continuously exposed to beryllium of more than 0.01μg/m3 could be activated and that the cell-mediated immune response of workers could be promoted. On the other hand, the Be-LTT of workers exposed to beryllium levels of less than 0.01μg/m3 was shown to be unaffected by beryllium. These findings suggest that beryllium sensitization is not manifested when level of beryllium in working environment are less than 0.01μg/m3. Therefore, in such cases workers do not develop Chronic beryllium disease (CBD). We concluded that the Be-LTT can be applied as a medical indicator to detect the development of CBD.
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  • Young LIM, Sun-Hyung KIM, Young-Jin CHO, Kyoung-Ah KIM, Min-Wha OH, Kw ...
    1997 Volume 35 Issue 3 Pages 380-387
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    Silica is a well-known occupational fibrogenic agent and its primary target cell is alveolar macrophage. Particle-stimulated macrophages are believed to release various mediator which can regulate the inflammation as well as pulmonary fibrosis. Even though oxygen radicals play the major role among these mediators, the mechanisms concerning the stimulation of alveolar macrophages are not clear yet. The present study was carried out to investigate the signal transduction pathway on oxygen radical generation in silica-stimulated alveolar macrophages. Silica induced oxygen radical generation in a dose-response pattern. Extracellular calcium depletion, calcium channel blockers, and calcium release blocker decreased the effect of silica on oxygen radical generation. Silica increased intracellular calcium through the influx of calcium through the calcium channel and the calcium release from the intracellular calcium store. To know the role of protein kinase C (PKC), phospholipase C (PLC), and protein tyrosine kinase (PTK) in silica-induced oxygen radical generation, we pretreated alveolar macrophages with inhibitors of these enzymes. Inhibitors of PKC (sphingosine and staurosporine), PLC (neomycin and U-73122), and PTK (genistein and erbstatin) suppressed the silica-induced oxygen radical generation. Silica increased the PLC activity at the concentration of 5mg/ml. The inhibitors of PTK and PLC suppressed the action of silica on the PLC activity. From these results, we suggest that silica induces oxygen radical generation through PTK, PLC, and PKC in alveolar macrophages.
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  • Kazuhiro SATO, Yukinori KUSAKA, Qunwei ZHANG, Benyi LI, Kenichiro OKAD ...
    1997 Volume 35 Issue 3 Pages 388-393
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    Epidemiological Studies have reported that the formation of renal stones is often observed in workers exposed to cadmium (Cd). Citrate is known to be a protective factor against renal stone formation. We previously reported that direct exposure to high-level cadmium impaired the citrate uptake by the brush border membrane vesicles (BBMV), which may mean that the formation of renal stones from exposure to Cd could be prevented. In the present study, to clarify the mechanism of Cd-induced renal stone formation, the characteristics of BBMV-induced citrate uptake were determined in Cd-intoxicated rats. Cd intoxication was induced by daily subcutaneous injections of CdCl2 at a dose of 2mg Cd/kg body wt per day for 17 to 20 days. The BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by the Millipore rapid membrane filtration technique. The citrate uptake per mg protein was not significantly different between the two groups. The volume of BBMV was significantly reduced (50%) in Cd-intoxicated rats compared with that of control rats. Percentages of the equilibrium value were also significantly inhibited in Cd-intoxicated rats.
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  • Shohei KIRA, Yusaku NOGAMI, Kazuhisa TAKETA, Masana OGATA
    1997 Volume 35 Issue 3 Pages 394-398
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    Oil mists at an automobile factory were measured size-selectively. Furthermore, subjective symptoms were surveyed through the distribution of a questionnaire. The measured levels of respirable-size, 2-10 micrometer oil mists at 3 selected workshops ranged 0.04-0.09mg/m3 for the lower exposed group (17 men), 0.10-0.18mg/m3 for the higher exposed group (16 men) to water-insoluble oil, and 0.08-0.29mg/m3 for the higher exposed group (19 men) to water-soluble oil. The higher the level of exposure to respirable-size particulates, the more workers complained of dissatisfaction with air quality. As to the subjective symptoms, the “yes” rate for “irritated nose” and “sneezing” showed significant differences among the unexposed, lower exposed, and higher exposed groups. Workers using water-soluble oil complained of “uncomfortable smell” more than those who used water-insoluble oil. The results of this study suggested that it is necessary to measure the levels of oil mists size-selectively.
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  • Shinji KUMAGAI, Ichiro MATSUNAGA
    1997 Volume 35 Issue 3 Pages 399-403
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    o-Dichlorobenzene (o-DCB) is used as an organic solvent, as a chemical intermediate, and as a heat transfer medium. In humans, o-DCB is metabolized to 2, 3- and 3, 4-dichlorophenols, and 3, 4- and 4, 5-dichlorocatechols, and these metabolites are eliminated via the kidneys. In this study, we tried to determine the concentrations of urinary 2, 3- and 3, 4-dichlorophenols using a gas chromatograph (GC). When control urine specimens were spiked at concentrations of 10, 20 and 40mg/l, the mean recovery rates of 2, 3- and 3, 4-dichlorophenols were 98.3 to 101.9% (CV=4.0 to 4.8%) and 100.6 to 105.4% (CV=2.5 to 7.0%), respectively. Next, urine samples collected from ten male workers exposed to o-DCB were analyzed. The concentrations of urinary 2, 3- and 3, 4-dichlorophenols determined by the GC method closely agreed with those by the HPLC method, which we had developed in a previous study, and these metabolite concentrations were linearly correlated to the 8-h TWA values of o-DCB in the range of 0.1 to 2.3ppm. Consequently, the GC method can be used for biological monitoring of o-DCB, though it is necessary that the linear relation is confirmed in a higher range of exposure.
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  • Sang-Hoon BYEON, Se-Min OH, Woo-Sik KIM, Chang-Ha LEE
    1997 Volume 35 Issue 3 Pages 404-414
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    Using an activated carbon felt (ACF, KF-1600), the applicability of an ACF passive sampler in monitoring organic vapors was evaluated. The evaluated results of the ACF passive sampler were compared with those of a 3M (Model 3500) passive sampler. At low-humidity condition (8±3% RH), the sampling rates of the ACF passive sampler for volatile organic vapors were within the range of±25% from the results of a charcoal tube, which was the reference method recommended by NIOSH. However, at high humidity condition (90±5% RH), even though the sampling rates for toluene, MIBK, and PCE were within the range of ±25%, the sampling rates of the ACF sampler for n-hexane and MEK decreased steeply with time after being high at the beginning of the exposure time. Under this condition, the sampling rate of the 3M passive sampler for MEK was also high at the beginning of the exposure time. In case of the ACF passive sampler, the sampling rates of the relatively strong adsorbates such as toluene, MIBK, and PCE were much less affected by humidity than those of n-hexane and MEK which were weak adsorbates.
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  • Norihiko KOHYAMA, Isamu TANAKA, Masayuki TOMITA, Mitsuhiro KUDO, Yasus ...
    1997 Volume 35 Issue 3 Pages 415-432
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    Standard reference samples of fibrous minerals to be used for in vitro and in vivo (injection) biological experiments were prepared. Ten samples were selected from among the fibrous minerals currently used in industry: man-made mineral fibers (MMMF); glass wool (GW1), rock wool (RW1), micro glass fiber (MG1), refractory ceramic fibers (RF1, RF2), and mullite fibers (RF3), whiskers; potassium titanate (PT1), silicon carbide (SC1) and rutile (TiO2) (TO1), and a natural fibrous mineral; wollastonite (WO1). The MMMF samples were prepared by using the size-selective press method. The whisker samples and WO1 were all commercial products. The prepared samples were examined by X-ray diffraction and X-ray fluorescence analyses, and no impurities were identified in any of the samples at a level of 1%, although WO1 was found to have about 5% calcite and a trace amountof quartz (<1%). The fiber sizes were measured by TEM. The geometric-mean length (μm), width (μm) and SD (in parenthesis) are: GW1 20.0 (2.58), 0.88 (3.10); RW1 16.5 (2.51), 1.80 (2.32); MG1 3.0 (2.22), 0.24 (2.35); RF1 12.0 (2.36), 0.77 (2.53); RF2 11.0 (1.96), 1.10 (2.00); RF3 11.0 (1.75), 2.40 (1.37); PT1 6.0 (2.04), 0.35 (1.51); SC1 6.40 (2.45), 0.30 (1.58); TO1 2.1(2.00), 0.14 (1.53); WO1 10.5 (2.03), 1.00 (1.72). We concluded that these prepared fiber samples can be safely used for biological experiments. Sample sets containing about one gram of each sample known as JFM standard reference samples are provided by the Japan Fibrous Material Research Association (JFMRA).
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  • Fumio SERITA
    1997 Volume 35 Issue 3 Pages 433-439
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    A new efficient cell was developed to generate a large quantity of aerosol using an ultrasonic nebulizer. The currently used conventional pail-type cell cannot generate such a large quantity of aerosol because a large portion of the mist is lost by agglomeration and subsequent liquefaction onto the cell wall and liquid surface. The newly developed cell is a chimney-type cell characterized by the attachment of a vertical cylinder at its center and a partition to separate the cell into upper and lower compartments, each of which is supplied with a carrier air flow. The mist emanating from the fluid surface is carried upward through the vertical cylinder by a laminar primary airflow. Thesecondary airflow served to sheath the primary airflow containing the mist and to prevent the impact and adhesion of the mist on the surrounding wall. The nebulizing rate of TiO2 suspension was found to be three times higher with the chimney-type than with the pail-type. No differences were found between the two types in terms of particle diameters, particle size distribution, and the electron microscopic images of the aerosol. It was concluded that a commercially available ultrasonic nebulizer equipped with the chimney-type cell allowed generation of a large quantity of aerosol for use in inhalation animal experiments.
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  • Yoko SHIMIZU, Shigenori MAKINO, Tsutomu TAKATA
    1997 Volume 35 Issue 3 Pages 441-450
    Published: 1997
    Released: March 29, 2007
    JOURNALS FREE ACCESS
    In this paper we will report the results of nation-wide surveys on employee health conducted and published by the Ministry of Labour in 1982, 1987, and 1992. The subjects were approximately 20, 000 employees in 1982, approximately 15, 000 in 1987, and approximately 16, 000 in 1992, from throughout Japan. Using the results of the surveys, we will show trends in the status of employee work-related stress, as well as trends in means of relaxation over the past decade. The percentage of employees with work-related stress among all subjects gradually increased as follows: 50.6% in 1982, 55.0% in 1987, and 57.3% in 1992. The percentage of employees with work-related stress increased remarkably from 1982 through 1992 among the following groups: the 50-59 age group in males; employees in the electricity, gas, heat and water-supply industries; those in the real estate industry; administrative and managerial workers; employees of large establishments with more than 5, 000 employees; and employees performing shift work involving no night duty. The problem of “human relationships in the workplace” was associated with the increasing stress levels among 50-59-year-old males, 40-49-year-old females, employees of large establishments with more than 5, 000 employees, those in the real estate industry, and service workers. In terms of means of relaxing to relieve fatigue and stress, employees tended to engage in active pursuits such as “eating out and shopping” and “driving and traveling” over the past decade. In 1992, on the other hand, 22.0% of males and 5.9% of females selected “smoking” as a means of relaxation. This shows the need for stress management in the workplace in order to prevent health problems related to smoking.
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