研究者詳細 - 武林　亨

論文 - 武林　亨

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代替フロンによる急性肝炎─2,2-ジクロロ-1,1,1-トリフルオロエタン（HCFC-123）の事例─

大前和幸，武林亨

医学のあゆみ 191 （ 2 ） 172-173 1999年10月

研究論文（学術雑誌）, 共著

Occupational exposure limits based on biological monitoring : the Japan Society for Occupational Health

Omae Kazuyuki, Takebayashi Toru, Sakurai Haruhiko

International Archieves of Occupational and Environmental Health 72 （ 4 ） 271-273 1999年07月

研究論文（学術雑誌）, 共著

Stabilometry in epidemiological use - Measurement bias by different instructions -

Nishiwaki Yuji, Imai Azusa, Takebayashi Toru, Nishiwaki Noriko, Omae Kazuyuki

Journal of Occupational Health 41 （ 2 ） 129 - 130 1999年04月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Animal models of asthma and chronic bronchitis

Drazen J. M., Takebayashi T., Long N. C., De Sanctis G. T., Shore S. A.

Clinical and Experimental Allergy, Supplement 29 （ 2 ） 37 - 47 1999年

研究論文（学術雑誌）, 共著, ISSN 0960-2178

Human asthma is characterized by three critical phenotypic traits: intermittent reversible airway obstruction, airway hyperresponsiveness and airway inflammation. In animal models of asthma, airway hyperresponsiveness is an important feature. This trait is characterized by an exaggerated bronchoconstrictor response that would have little physiological consequence in an otherwise unaffected or normal individual. In this article we explore two distinct facets of airway responsiveness. The first is the genetic basis for variations in airway responsiveness that occur in mice in the absence of any specific environmental manipulation. We demonstrate that standard genetic approaches can be successfully applied to the identification of regions of the mouse genome linked to the expression of airway hyperresponsiveness. The second topic addressed in this review is the change in airway responsiveness induced in rats by repeated exposure to sulphur dioxide gas. With daily exposure to high concentrations of sulphur dioxide gas, there is chronic injury and repair of epithelial cells. Over time, rats develop mucous hypersecretion, airway inflammation, increased airway resistance and airway hyperresponsiveness. This model has provided useful information on the mechanisms underlying the pathophysiological events that typify the chronic bronchitis in humans.

Meso-2,3-dimercaptosuccinic acid（DMSA）およびその誘導体の鉛中毒治療効果

大前和幸，武林亨

産業医学ジャーナル 22 （ 6 ） 77-80 1999年

研究論文（学術雑誌）, 共著

2,2-ジクロロ-1,1,1-トリフルオロエタン (HCFC-123) による健康影響

大前和幸，武林亨

産業医学ジャーナル 21 （ 6 ） 90-91 1998年11月

研究論文（学術雑誌）, 共著

Toxicity of silicon compounds in semiconductor industries

Nakashima Hiroshi, Omae Kazuyuki, Takebayashi Toru, Ishizuka Chizuru, Uemura Takamoto

Journal of Occupational Health 40 （ 4 ） 270 - 275 1998年10月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

The toxicities of silane (SiH₄), tetraethoxysilane (Si(OC₂H₅)₄, TEOS) and dichlorosilane (SiH₂Cl₂, DCS) were reviewed in order to compare the toxicological properties of silicon compounds used in the semiconductor industry. Silane and TEOS showed similar toxicities, characterized by nephrotoxicity. Mice subjected to silane (2500, 5000 and 10000 ppm) or TEOS (1000 ppm) acute exposure developed acute tubular necrosis. Tubulo- interstitial nephritis was seen in mice which were subjected to an acute inhalation study and survived 2 wk of the observation period or those subjected to subacute inhalation studies of TEOS (100 and 200 ppm for 2 or 4 wk). Silane and TEOS, however, differed in the concentration at which they showed signs of toxicity. This may be due to their solubility in water and other metabolic factors, but their metabolic pathways have not yet been elucidated. TEOS injured nasal mucosa (1000 ppm for 2 h or more and 50, 100 and 200 ppm for 2 or 4 wk). It was observed at a lower concentration than nephrotoxicity in the 50 and 100 ppm subacute inhalation study. On the other hand, silane caused nasal mucosal lesions only at 5000 or 10000 ppm for acute inhalation, and those of subacute inhalation were mild (1000 ppm for 2 or 4 wk). DCS showed another type of adverse effect. It was an irritant and/or a corrosive agent to the respiratory tract in the acute (64 ppm for 1,2, 4 or 8 h) and subacute (32 ppm for 2 or 4 wk) inhalation study. The fate of DCS in air was also studied and it was shown to form small particles including silicon and chlorine (CI) atoms. CI seems to play an important role in the toxicity of DCS.

Toxicity of silicon compounds in semiconductor industries

Nakashima Hiroshi, Omae Kazuyuki, Takebayashi Toru, Ishizuka Chizuru, Uemura Takamoto

Journal of Occupational Health 40 （ 4 ） 270-275 1998年10月

研究論文（学術雑誌）, 共著

Exposure to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) and acute liver dysfunction

Takebayashi Toru, Kabe Isamu, Endo Yu'ichi, Tanaka Shigeru, Miyauchi Hiroyuki, Nozi Kazuko, Imamiya Shun Ichiro, Takahashi Ken, Omae Kazuyuki

Journal of Occupational Health 40 （ 4 ） 334 - 338 1998年10月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Acute liver dysfunction has been reported among workers repeatedly exposed to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123), a substitute for trichlorofluoromethane. Causality between occupational exposure to HCFC-123 and liver dysfunction was examined. Levels of exposure to HCFC-123 were estimated retrospectively by reproducing working conditions and by a job record survey. Health surveillance, including liver function and subjective symptoms, was done when two workers first complained of ill health. The mean HCFC-123 concentration in air was more than 200 ppm with a peak concentration of about 1,000 ppm in a processing area where HCFC-123 was used. HCFC-123 of 18-24 ppm was detected in the adjunct areas where HCFC-123 vapor was not generated. Workers (n=14) were then classified into high (n=5) and low (n=9) exposure groups according to the estimated exposure level, which was confirmed by determination of urinary trifluoroacetic acid. Mean serum AST and ALT levels were 236 IU// and 476 IU// among the high-exposed workers, and exceeded 500 IU// in three workers. Various types of symptoms involving the central nervous system and digestive organs, and irritation of the mucous membrane, were also experienced. The degree and prevalence of these health effects were higher in the high exposure group, which indicates the exposure- effect and exposure-response relationships. The consistency and temporality of the relationship between HCFC-123 exposure and the observed health effects were also confirmed. We conclude that repeated exposure to high concentrations of HCFC-123 for no more than five weeks causes acute severe liver dysfunction with various symptoms in humans. Biological plausibility must be clarified to confirm the causality.

Environmental and biological monitoring of 2,2-dichloro-1,1,1- trifluoroethane (HCFC-123)

Tanaka Shigeru, Kabe Isamu, Takebayashi Toru, Endo Yu'ichi, Miyauchi Hiroyuki, Nozi Kazuko, Takahashi Ken, Seki Yukio, Omae Kazuyuki

Journal of Occupational Health 40 （ 4 ） 348 - 349 1998年10月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Role of tachykinins in airway responses to ozone in rats

Takebayashi Toru, Abraham Joseph, Murthy G. G Krishna, Lilly Craig, Rodger Ian, Shore Stephanie A.

Journal of Applied Physiology 85 （ 2 ） 442 - 450 1998年08月

研究論文（学術雑誌）, 共著, ISSN 8750-7587

Previous studies that used neonatal capsaicin (Cap) treatment to ablate C fibers indicate that C fibers act to inhibit lung damage and airway hyperresponsiveness after ozone (O₃) exposure in rats. The purpose of this study was to determine 1) the role of tachykinins in these protective effects and 2) whether differences in minute ventilation (V̇E) during O₃ exposure might account for the effect of Cap. In the first study, male Sprague-Dawley rats were exposed to 1 part/million O₃ or air for 3 h. Four hours later, a bronchoalveolar lavage (BAL) was performed or airway responsiveness was measured. Rats were treated with CP-99994 and SR-48968, selective neurokinin- 1-and -2-receptor antagonists, respectively, or with vehicle (Veh). O₃ caused an increase in the number of neutrophils recovered from BAL fluid in both the Veh-treated and tachykinin-receptor antagonist (TKRA)-treated rats, but the number of neutrophils was approximately twofold greater in the TKRA- treated rats. In contrast, TKRA treatment had no effect on baseline pulmonary mechanics or airway responsiveness. After O₃ exposure, the number of neutrophils in BAL fluid was also greater in Cap- than in Veh-treated rats. O₃ reduced V̇E in both Veh- and Cap-treated rats, but the response was greater (reduction of 44.7 ± 3.7 vs. 27.8 ± 6.8%) and occurred earlier (10 vs. 70 min) in Cap- than in Veh-treated rats (P < 0.02). These results suggest that tachykinins mediate protective effects of C fibers against O₃- induced lung inflammation. The results also indicate that the more pronounced effect of O₃ on BAL neutrophils in Cap-treated rats is not the result of a greater inhaled dose of O₃ resulting from greater V̇E.

Acute liver dysfunction among workers exposed to 2,2-dichloro-1,1,1- trifluoroethane (HCFC-123)

Takebayashi Toru, Kabe Isamu, Endo Yu'ichi, Tanaka Shigeru, Miyauchi Hiroyuki, Nozi Kazuko, Takahashi Ken, Omae Kazuyuki

Journal of Occupational Health 40 （ 3 ） 169 - 170 1998年07月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Cross-sectional observation of the effects of carbon disulfide on arteriosclerosis in rayon manufacturing workers

Omae Kazuyuki, Takebayashi Toru, Nomiyama Tetsuo, Ishizuka Chizuru, Nakashima Hiroshi, Uemura Takamoto, Tanaka Shigeru, Yamauchi Tsuneyuki, O'uchi T, Horichi T, Sakurai Haruhiko

Occupational and Environmental Medicine 55 （ 7 ） 468-472 1998年07月

研究論文（学術雑誌）, 共著

Cross-sectional observation of the effects of carbon disulfide on the nervous system, endocrine system, and subjective symptoms in rayon manufacturing workers

Takebayashi Toru, Omae Kazuyuki, Ishizuka Chizuru, Nomiyama Tetsuo, Sakurai Haruhiko

Occupational and Environmental Medicine 55 （ 7 ） 473-479 1998年07月

研究論文（学術雑誌）, 共著

Cross sectional observation of the effects of carbon disulphide on the nervous system, endocrine system, and subjective symptoms in rayon manufacturing workers

Takebayashi Toru, Omae Kazuyuki, Ishizuka Chizuru, Nomiyama Tetsuo, Sakurai Haruhiko

Occupational and Environmental Medicine 55 （ 7 ） 473 - 479 1998年

研究論文（学術雑誌）, 共著, ISSN 1351-0711

Objectives - A prospective cohort study was initiated to clarify whether the current level of exposure to carbon disulphide (CS₂) is low enough to prevent occurrence of subclinical health impairments or to ameliorate health effects due to past high exposure. This paper describes the effects of exposure to CS₂ on the nervous and endocrine systems, and the subjective symptoms in a baseline observation. Methods - The effects were evaluated of CS₂ on the median nerve conduction velocity, neurobehavioural and psychological tests, and subjective symptoms related to solvents in 432 male workers exposed to CS₂ and 402 reference workers from 11 rayon factories in Japan. Adjustment was made for potential confounding factors such as age or alcohol drinking. Exposure to CS₂ was either dichotomised or categorised into three groups by job type. Results - Reductions were observed in motor (- 1.9 m/s) and sensory (-0.91 m/s for orthodromic and -1.1 m/s for antidromic) nerve conduction velocities in the workers exposed to CS₂ at the spinning and refining processes. Small but significant increases were found in self rated depression scale score and decrease in digit span (backward) in the workers exposed to CS₂. Of 54 subjective symptoms many were increased- namely, heavy feeling in the head, light headedness, fainting after suddenly standing up, tremor, dullnes, and increased sensitivity of skin in the extremities, reduced grasping power, reduced sexual desire, and increased rough skin. The endocrinological indicator-the concentration of glycosylated haemoglobin-was also increased in the workers exposed to CS₂. Conclusions - Subclinical effects on the nervous system and on glucose metabolism were found in the workers exposed to CS₂. One interpretation is that relatively higher exposure to CS₂ in the past may induce these, but the effects are still not entirely ameliorated under the current exposure to CS₂. Another possibility is that the current exposure to CS₂ may cause these positive findings. A follow up observation is necessary to clarify these questions.

Cross sectional observation of the effects of carbon disulphide on arteriosclerosis in rayon manufacturing workers

Omae Kazuyuki, Takebayashi Toru, Nomiyama Tetsuo, Ishizuka Chizuru, Nakashima Hiroshi, Uemura Takamoto, Tanaka Shigeru, Yamauchi Tsuneyuki, O'Uchi Toshihiro, Horichi Yasushi, Sakurai Haruhiko

Occupational and Environmental Medicine 55 （ 7 ） 468 - 472 1998年

研究論文（学術雑誌）, 共著, ISSN 1351-0711

Objective - A prospective cohort study was designed no clarify the relations between occupational exposure to carbon disulphide (CS₂) and its effects on arteriosclerosis in workers in 11 Japanese rayon manufacturing factories. This report is a cross sectional baseline observation in the first study year. Methods - Study subjects were 432 male rayon workers (mean (range) age 35.5 (19.1-47.8); duration of exposure 13.4 (0.3-29.0)) and 402 male referent workers (age 35.8 (18.9-49.8)). Exposure to CS₂ was assessed by determining the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine. Mean (SD) TTCA was 3.42 (2.73) mg/g creatinine (Cr) (n=422). About a quarter of the urine samples were >5 mg/g Cr, a biological exposure index recommended by the American Conference of Governmental Industrial Hygienists. Health effects on arteriosclerosis were evaluated by measuring blood pressure, serum lipids, pulse wave velocity of the aortas stiffness and blood flow of the carotid artery, and blood coagulation and fibrinolysis indices, and by use of brain magnetic resonance imaging, electrocardiogram (at rest and after exercise), ophthalmograph, and Rose's questionnaire. Information on potential confounding factors was collected by self administered questionnaire. Results - Prevalence of microaneurysm of the retinal artery was significantly higher in workers exposed to CS₂ (8.1%) than in referent workers (3.4%), and increased with age. Other examinations did not show any differences between the two groups even after allowance for confounding factors. Conclusions - Significant effects of CS₂ on arteriosclerosis were not found in current rayon manufacturing workers, with the exception of induction of microaneurysm of the retinal artery.

Effects of intratracheally administered indium phosphide on male fischer 344 rats

Uemura Takamoto, Oda Kenichi, Omae Kazuyuki, Takebayashi Toru, Nomiyama Tetsuo, Ishizuka Chizuru, Hosoda Kanae, Sakurai Haruhiko, Yamazaki Kazuto, Kabe Isamu

Journal of Occupational Health 39 （ 3 ） 205 - 210 1997年07月

研究論文（学術雑誌）, 共著, ISSN 1341-9145

Objective - To examine the effects of intratracheally administered indium phosphide (InP) and distribution of indium on male Fischer 344 rats. Materials and methods - Rats were intratracheally given 0, 1, 10 or 100 mg/kg of InP with a mean diameter of 0.8 μm and observed for 1 and 7 days. The bronchoalveolar lavage fluid (BALF) was examined biochemically and cytologically. Serum biochemical, hematological and histopathological examinations were done, and the indium concentration in organs and serum was determined. Findings - The number of neutrophils in BALF remarkably increased in a dose-effect manner 1 and 7 days after administration and InP particles were phagocytized in the macrophages. Total protein (TP), lactate dehydrogenase (LDH), total phospholipid (TPL) and total cholesterol (T-Cho) in BALF showed a clear dose-effect relationship 7 days after administration. Indium was detected in the liver and spleen and increased in a dose-related manner on the next day and 7 days after administration. Serum indium was detected in the group given more than 10 mg/kg but did not reveal a dose relationship. Histopathological examination of the lungs showed phagocytized InP particles in the macrophages and the migration of neutrophiles in the alveoli. InP particles remained in the bronchioles and alveoli until 7 days after. No histopathological changes were detected in the liver or spleen . A hematological study did not reveal significant findings. Interpretation - Intratracheally administered InP particles cause pulmonary inflammation and those particles remain in the lower airways for at least 7 days. Phagocytosis of macrophages may contribute to their disposal and distribution to the liver and spleen. Further study is required with particles with a lower toxic activity than InP and with the same particle size as the InP used in this study, to clarify their specific toxicity. Simultaneously longer observation is needed to assess toxicity in the other organs after distribution.

A simple method for carbon disulfide monitoring using a diffusive sampler, thermal desorption and a stain tube

Tanaka Shigeru, Yamauchi Tuneyuki, Takebayashi Toru, Omae Kazuyuki, Seki Yukio

Industrial Health 35 （ 4 ） 474 - 479 1997年

研究論文（学術雑誌）, 共著, ISSN 0019-8366

A simple sampling and analytical method for monitoring carbon disulfide (CS₂) vapor was investigated to assess exposure to low levels of CS₂ in a viscose rayon factory. CS₂ vapor was adsorbed on polymer beads (poly (2,6- diphenyl-p-phenylene oxide)) packed in a diffusive sampling tube. The sampling tube was heated at 180°C for 7 min using a Daily Exposure Limit Test Apparatus, and thermally desorbed CS₂ was measured by a stain tube for CS₂. In laboratory experiments, the indicated CS₂ levels measured by this method were highly correlated with calibrated CS₂ concentrations (1-40 ppm), exposure duration (1-8 hr) and cumulative exposure levels. The CS₂ values were stable up to 7 days after sampling when the diffusive tubes were stored at 4°C and 20°C. The effects of relative humidity, wind velocity and hydrogen sulfide on the measured values were negligible. In a field survey, 65 workers in a viscose rayon factory wore both the diffusive sampling tube and a commercially available 3M 3500 organic vapor monitor on their collar during their 8-hr work period. CS₂ concentrations obtained by the two methods were comparable and the correlation coefficient was 0.931. This method proved to be useful in determining the concentrations of CS₂ to which workers were exposed.

Respiratory diseases and working in a copper or an aluminum product plant. A case control study using medical records

Kabe Isamu, Endo Yuichi, Takahashi Ken, Takebayashi Toru, Omae Kazuyuki, Sakurai Haruhiko

J Occup Health 39 343-344 1997年

研究論文（学術雑誌）, 共著

産業保健の倫理学的側面

武林亨

産業医学ジャーナル 19 （ 6 ） 69-73 1996年11月

研究論文（学術雑誌）, 単著

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