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Akiyo Tanaka Last modified date:2019.08.20

Lecturer / Department of Environmental Health and Socio Medical Sciences
Department of Basic Medicine
Faculty of Medical Sciences


Graduate School
Undergraduate School


E-Mail
Phone
092-642-4729
Fax
092-642-4729
Academic Degree
Doctor of Medical Sciences
Country of degree conferring institution (Overseas)
No
Field of Specialization
Environmental Medicine
Total Priod of education and research career in the foreign country
00years00months
Outline Activities
Evaluation of health effects of environmental and industrial pollutants, especially arsenic antimony, rare earth, gallium arsenide, indium arsenide, indium phosphide, indium oxide, indium tin oxide, carbon nanotube, solar cells using experimental animals. Field study concerning health effects of workers treated with indium compounds

Education to medical students or after graduate students concerning the environtental and industrial hygiene.
Research
Research Interests
  • Health effects of indium metal
    keyword : Indium metal Health efects Lung toxicity Animal experiment
    2018.04~2022.03.
  • Effects of rare metals in workers
    keyword : rare metal indium ITO Health Effects Lung damage Environmental metal level
    2014.10~2020.03.
  • Toxic effects of plasma and nanomaterial nade fron plasma in vivo and in vitro.
    keyword : Plasma medicine, Evaluation of toxicity, Plasma nanomaterial
    2012.07~2020.03.
  • Experimental study concerning pulmonary toxicity caused by indium tin oxide (ITO)
    keyword : ITO indium lung
    2000.08~2020.08.
  • Risk assessment of solar cell materials
    keyword : solar cell rare metal risk assessment pulmonary toxicity
    2008.01~2020.05.
  • Next generation influence of antimony compounds in rat and mouse
    keyword : antimony compounds rat mouse next generation influence
    1996.04~2020.03.
  • Health effects of nano materials
    keyword : health effects carbon nanotubes fullerene nano material animal experiments
    2004.04~2022.03Health effects of nanomaterials, including carbonnanotube or fullerene, are evaluated in laboratory animals.
  • Epidemiological study of health effects among indium-handled workers
    keyword : indium ITO interstitial pneumonia lung damage
    2002.04~2020.03We have performed an epidemiological study of the health effects caused by inhaled indium compounds.Furthermore, risk communication is caried out among indium handleing plants.
  • Risk assessment of environmental pollutants
    keyword : Health effects assessments environmental pollutants heavy metals animal experiments
    1980.04~2020.03Health effects of environmental pollutants and industrial hazadous materials have been evaluated using experimental animals. Furthermore a research study among employees engaged in production of indium tin oxide (ITO), which is used in the making of thin-film trnsistor liquid crystal displays for televison screens,portable computor screens, cell phone displays and there is no available data of toxicityof ITO, is carried out as well as animal experiments..
Academic Activities
Reports
1. Owing to the increasing interest being paid to the issue of the global environment, the production of solar cells has increased rapidly in recent years. Copper indium gallium diselenide (CIGS) is a new efficient thin film used in some types of solar cell. Indium is a constitutive element of CIGS thin-film solar cells. It was thought that indium compounds were not harmful until the beginning of the 1990s because there was little information regarding the adverse health effects on humans or animals arising from exposure to indium compounds. After the mid-1990s, data became available indicating that indium compounds can be toxic to animals. In animal studies, it has been clearly demonstrated that indium compounds cause pulmonary toxicity and that the dissolution of indium compounds in the lungs is considerably slow, as shown by repeated intratracheal instillations in experimental animals. Thus, it is necessary to pay much greater attention to human exposure to indium compounds, and precautions against possible exposure to indium compounds are paramount with regard to health management..
2. Akiyo Tanaka, Hirata Miyuki, Kazunori Koga, Makiko Nakano, Mazuyuki Omae, Yutaka Kiyohara, Pulmonary Toxicity of Indium Tin Oxide and Copper Indium Gallium Diselenide, Cambridge Journals Online- MRS Online Proceedings Library, 2012.05, The aim of this review is to introduce the adverse health effects of indium compounds. This review consists of 2 parts: (1) a study of the toxic effects of indium compounds in humans, and (2) a study of the toxic effects of indium tin oxide (ITO) and copper indium gallium diselenide (CIGS) in animals.
To date, 4 epidemiological surveys have been conducted of indium-handling workers in Japan, and all who were studied showed that exposure to indium compounds caused pulmonary interstitial and emphysematous changes. There were clear dose-response and dose-effect relationships between the serum indium levels and the levels of Krebs von den Lungen-6 (KL-6), which is a serological indicator of interstitial pneumonia. Up until 2011, 8 cases of interstitial pneumonia in Japanese indium-exposed workers, 2 cases of pulmonary alveolar proteinosis (PAP) in US indium-exposed workers, and 1 case of PAP in a Chinese indium-exposed worker have been reported.
In animal studies, it has been clearly demonstrated that ITO and CIGS particles cause pulmonary toxicity and that the dissolution of ITO and CIGS particles in the lungs is considerably slow when repeated intratracheal instillations were given to experimental animals.
Thus, more studies are needed on the effects of human exposure to indium compounds..
Papers
1. Satoko Iwasawa, Makiko Nakano, Hiroyuki Miyauchi, Shigeru Tanaka, Yaeko Kawasumi, ichiro Higashikubo, Akiyo Tanaka, Hirata Miyuki, Kazuyuki Omae, Personal indium exposure concentration in respirable dusts and serum indium level, Ind. Health, DOI:org/10.2486/indhealth.2016-0015, 55, 1, 87-90, 2017.01, The aim of this study was to assess the relationship between indium exposure concentration in the respirable dust fraction (In-E) and indium in serum (In-S) in workers. Methods: A total of 39 workers were studied. The study subjects were categorized into 3 groups, namely, smelting workers (n=7), ITO workers (n=6) in an ITO grinding plant, and other workers (n=26). In-E and In-S ranged from 0.004–24.0 μg/m3 and 0.1–8.50 μg/L, respectively. The simple regression equation was log(In-S)=0.322×log(In-E)-0.443. The simple correlation coefficients for the smelting workers, ITO workers and other workers were 0.489, 0.812 and 0.163, respectively. The differences in the relationships among the three groups suggest that In-S may vary with the chemical form to which the workers were exposed. In-E and In-S seem to be positively correlated. The correlation coefficient was higher for both smelting and ITO workers than for other workers..
2. Makiko Nakano, Akiyo Tanaka, Hirata Miyuki, Hiroyuki Kumazoe, Kentaro Wakamatsu, Dan Kamada, Kazuyuki Omae, An advanced case of indium lung disease with progressive emphysem, J. Occup Health, Doi:org/10.1539/joh.16-0076-CS, 58, 5, 477-481, 2016.09,
Objectives: To report the occurrence of an advanced case of indium lung disease with severely progressive emphysema in an indium-exposed worker. Case report: A healthy 42-year-old male smoker was employed to primarily grind indium-tin oxide (ITO) target plates, exposing him to indium for 9 years (1998-2008). In 2004, an epidemiological study was conducted on indium-exposed workers at the factory in which he worked. The subject's serum indium concentration (In-S) was 99.7 μg/l, while his serum Krebs von den Lungen-6 level was 2,350 U/ml. Pulmonary function tests showed forced vital capacity (FVC) of 4.17 l (91.5% of the JRS predicted value), forced expiratory volume in 1 s (FEV1) of 3.19 l (80.8% of predicted), and an FEV1-to-FVC ratio of 76.5%. A high-resolution chest computed tomography (HRCT) scan showed mild interlobular septal thickening and mild emphysematous changes. In 2008, he was transferred from the ITO grinding workplace to an inspection work section, where indium concentrations in total dusts had a range of 0.001-0.002 mg/m3. In 2009, the subject's In-S had increased to 132.1 μg/l, and pulmonary function tests revealed obstructive changes. In addition, HRCT scan showed clear evidence of progressive lung destruction with accompanying severe centrilobular emphysema and interlobular septal thickening in both lung fields. The subject's condition gradually worsened, and in 2015, he was registered with the Japan Organ Transplant Network for lung transplantation (LTx). Conclusions: Heavy indium exposure is a risk factor for emphysema, which can lead to a severity level that requires LTx as the final therapeutic option..
3. Akiyo Tanaka, Hirata Miyuki, Nagisa Matsumura, Yutaka Kiyohara, Tissue distribution of indium after repeated intratrachal instillations of indium-tin oxide into the lungs of hamsters, J Occup Health, Doi:10.1539/joh.14-0123-BR, 57, 2, 189-192, 2015.07, Objectives: The aim of this study was to analyze the tissue distribution of indium after intratracheally instilling indium-tin oxide (ITO) into the lungs of hamsters. Methods: Male Syrian hamsters received an intratracheal dose of 3 mg/kg or 6 mg/kg of ITO particles containing 2.2 mg/kg or 4.5 mg/kg of indium, twice weekly for 8 weeks. In parallel, control hamsters received only an intratracheal dose of distilled water. A subset of hamsters was euthanized periodically throughout the study from 8 up to 78 weeks after the final instillation. The distribution of indium in the lungs, liver, kidneys and spleen, as well as pathological changes in the liver, kidneys, and spleen, was determined. Results: The contents of indium in the lungs in the two ITO groups gradually decreased over the 78-week observation period, with elimination half-lives of approximately 142 weeks for the 3 mg/kg ITO group and 124 weeks for the 6 mg/kg ITO. The indium concentrations in the liver, kidneys, and spleen gradually increased throughout the observation period. Although foci of the lesions were observed histopathologically in the extrapulmonary organs among the two ITO groups, the control group showed similar lesions. Conclusions: The results clearly demonstrate that the clearance of indium from the body is extremely slow after intratracheal instillation in hamsters..
4. Makiko Nakano, Akiyo Tanaka, Hirata Miyuki, Satoko Iwasawa, Kazuyuki Omae, Pulmonary effects in workers exposed to indium metal: A cross-sectional study, Journal of Occupational Health, Doi:org/10.1539/joh.14-0262-OA, 57, 4, 346-352, 2015.07, Objectives: Indium was added to the list of substances regulated by the Ordinance on Prevention of Hazards due to Specified Chemical Substances (OPHSCS) in 2013. Indium metal (IM), however, is not regulated by the OPHSCS due to insufficient information on pulmonary effects following exposure. Methods: From 2011 to 2013, a cross-sectional study was conducted on 141 IM-exposed workers at 11 factories. Subjective symptoms were assessed, including levels of serum biomarkers, spirometry readings and total and diffuse lung capacity. Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) were selected as biomarkers of interstitial pneumonia. Indium serum concentration (In-S) and personal air sampling data were used to estimate exposure. Subjects were categorized into 5 groups based on occupation and type of exposure: smelting, soldering, dental technician, bonding and other. Results: The highest level of In-S was 25.4 µg/l, and the mean In-S level was significantly higher in the smelting group than in other groups. In the smelting group, the prevalence of increased In-S levels was 9.1%, while that of abnormal KL-6 was 15.2%. A significant dose-effect relationship was observed between the In-S and KL-6 levels. No marked differences were observed between any of the groups in SP-D values, pulmonary symptoms, or pulmonary function test results. A total of 31% of the subjects worked in an environment with IM levels exceeding 0.3 µg/m3, which requires a protective mask to be worn. Conclusions: For workers exposed to IM, work environments should be monitored, appropriate protective masks should be worn, and medical monitoring should be conducted according to the OPHSCS..
5. Takaaki Amano, Thapanut Sarinont, Kazunori Koga, Hirata Miyuki, Akiyo Tanaka, Masaharu Shiratani, Synthesis of indium-containing nanoparticles in aqueous suspension using plasmas in water for evaluating their kinetics in living body, Journal of nanoscience and nanotechnology, Doi:10.1166/jnn.2015.11427, 15, 11, 9298-9302, 2015.11, Nanoparticles have great potential for medical applications such as cancer therapy, whereas their toxic effects on human body are pointed out. To study kinetics and toxicity of nanoparticles in living body, we synthesized indium-containing nanoparticles in aqueous suspension using pulsed electrical discharge plasmas in water, because no indium compounds exist in the living body in the normal situation and hence indium-containing nanoparticles are useful tracer materials for analyzing kinetics of nanoparticles in living body. The mean size of synthesized primary nanoparticles is 7 nm, whereas the mean size of secondary nanoparticles is 315 nm. EDX and XRD analysis reveal that nanoparticles are indium crystalline and indium hydroxide crystalline with the mass ratio of 8:2. Preliminary subcutaneous administration of nanoparticles to mice shows that indium is transported from subcutaneous to blood. These results show that synthesized indium-containing nanoparticles are useful for analyzing kinetics of nanoparticles in living body..
6. Makiko Nakano, Omae Kazuyuki, Kazuhiko Uchida, Takehiro Michikawa, Noriyuki Yoshioka, Hirata Miyuki, Akiyo Tanaka, Five-year cohort study : emphysematous progression of indium-exposed workers., Chest, DOI: 10.1378/chest.13-2484, 146, 1166-1175, 2014.07, Background: Dose-dependent adverse lung effects due to indium exposure have been reported in a
cross-sectional study. This is a 5-year longitudinal cohort study of indium-exposed and unexposed
workers, assessing indium exposure levels and its clinical lung effects.
Methods: From 2008 to 2011, a 5-year follow-up study was conducted on 40 unexposed and 240
formerly or currently indium-exposed workers at 11 factories. Indium exposure was assessed by serum
indium (In-S, μg/L). Lung effects were assessed by subjective symptoms, serum biomarkers, spirometry,
and chest high-resolution computer tomography (HRCT). Effect biomarkers used were Krebs von den
Lungen (KL-6) and surfactant protein D (SP-D).
Results: Mean values of In-S, KL-6 and SP-D among the workers exposed to indium at baseline
declined during the five-year follow-up by 29.8%, 27.2% and 27.5%, respectively. 26.3% of the
exposed subjects with In-S higher than 20 μg/L experienced emphysematous progression on HRCT.
90.0% (18 out of 20) workers with emphysematous progression during follow-up were current smokers at
baseline, and a trend of increasing incidence of emphysematous progression at higher In-S levels was
observed among the smokers (p=0.005). Emphysematous changes among subjects with In-S levels
higher than 20 μg/L were likely to progress, after adjusting for age, mean duration since initial indium
exposure, and smoking history (OR = 10.49, 95% CI = 1.54 – 71.36).
Conclusions: Long-term adverse effects on emphysematous changes were observed. The results
suggest indium-exposed workers with In-S levels higher than 20 μg/L should be immediately removed
from exposure..
7. Akiyo Tanaka, Hirata Miyuki, Masaharu Shiratani, Kazunori Koga, Yutaka Kiyohara, Subacute pulmonary toxicity of copper indium gallium diselenide following intratracheal instillations into the lungs of rats, J Occup Health, 54, 3, 187-195, 2012.06, OBJECTIVES:

The aim of this study was to clarify the pulmonary toxicity of copper indium gallium diselenide (CIGS) solar cells on 62 8-wk-old rats.

METHODS:

Male Wistar rats were given 0.5, 5 or 50 mg/kg of CIGS particles, intratracheally, 3 times for a week. Control rats were given vehicle, distilled water, only. These rats were euthanized 0, 1 or 3 wk after the final instillation serially, and toxicological effects were determined.

RESULTS:

None of the CIGS-treated groups exhibited suppression of body weight gain compared with the control group. The relative lung weight in the CIGS 5 mg/kg-treated and 50 mg/kg-treated groups were significantly increased compared with that in the control group throughout the observation period. Although serum copper (Cu) and selenium (Se) concentrations were not affected by instillations of CIGS particles, the indium (In) levels increased with the passage of time in the CIGS 5 mg/kg-treated and 50 mg/kg-treated groups. However, the serum gallium (Ga) levels decreased in the CIGS 50 mg/kg-treated group from 0 to 3 wk. The content of each metal in the lung increased depending on the dose instilled and was constant during observation periods. Histopathologically, foci of slight to severe pulmonary inflammatory response and exudation were present among all the CIGS-treated groups, and the severity of these lesions worsened with the passage of time.

CONCLUSION:

The present results clearly demonstrate that CIGS particles caused subacute pulmonary toxicity and that dissolution of CIGS particles in the lung was considerably slow when repeated intratracheal instillations were given to rats..
8. Akiyo Tanaka, Hirata Miyuki, Toshiaki Homma, Yutaka Kiyohara, Chronic pulmonary toxicity study of indium-tin oxide and indium oxide following intratracheal instillations into the lungs of hamsters, J. Occupational Health, http://doi.org/10.1539/joh.L9097, 52, 1, 14-22, 2010.01, Objectives: The aim of this study was to clarify the chronic toxicological effects of indium-tin oxide (ITO) and indium oxide (In2O3) on laboratory animals. Methods: Male Syrian golden hamsters were intratracheally administered 3 mg/kg or 6 mg/kg of ITO particles, or 2.7 mg/kg or 5.4 mg/kg of In2O3 particles, containing 2.2 mg/kg or 4.5 mg/kg of indium, twice a week, for 8 wk. Control hamsters were given vehicle of distilled water only. The hamsters were euthanized serially up to 78 wk after the final instillation and the toxicological effects were determined. Results: Body weight gain was significantly suppressed in the ITO 6 mg/kg-treated hamsters compared with the control group, but not in the ITO 3 mg/kg-treated or In2O3-treated hamsters. Relative lung weights among all the indium-treated groups were significantly increased compared to that in the control group throughout the observation period. The serum indium concentration among all the indium-treated groups gradually increased up to the end of the observation period. Histopathologically, foci of slight to severe pulmonary inflammatory response with diffuse alveolar or bronchiolar cell hyperplasia, expansion of the alveolar spaces and interstitial fibrotic proliferation were present in all the indium-treated hamsters and the severity of these lesions worsened with the passage of time. Lung benign adenomas were only manifest in 3 out of 15 of the ITO 6 mg/kg-treated hamsters. Conclusions: The present results clearly demonstrate that ITO and In2O3 particles caused chronic pulmonary toxicity when repeated intratracheal instillations were given to hamsters..
Presentations
1. AkiyoTanaka, Miyuki Hirata, Nagisa Matsumura, Kazunori Koga, Masaharu Shiratani, Yutaka Kiyohara, Health Effects of indium nanoparticles, The 10th Asian-European International Conference on Plasma Surface Engineering, 2015.09, Owing to the recent increase in the use of nanoparticles for medicinal applications, the potential health hazards arising from their exposure have attracted much attention. There are limited data regarding the adverse health effects or metabolism of nanoparticles in humans or animals. Accordingly, precautions against possible exposure to nanoparticles are critical with regard to health management. To clarify the health effects of nanoparticles, we evaluated the toxicity and tissue distribution of indium nanoparticles in animals. Available data have indicated that indium compounds, such as indium-tin oxide (ITO), indium oxide, indium hydroxide, indium-copper-gallium-selenide (CIGS) can be toxic to animals when instilled into the lung via trachea. Pulmonary inflammatory response and interstitial fibrotic proliferation or exudation to alveolar spaces including necrotic cell debris were evident in all indium-treated animals. Furthermore, levels of serum surfactant protein D (SP-D), which is a biomarker of interstitial pneumonia, increased compared to the baseline value. The clearance of indium from the body is extremely slow after intratracheal instillation in animals. The lung indium content decreased gradually, and indium was absorbed and retained in the lungs for a long time. Blood indium concentrations gradually increased, and this increase was particle size-dependent. Indium was significantly absorbed in peripheral organs after respiratory exposure, and the absorption continued to increase long after the instillation of indium compounds .
It is necessary to consider the effects of exposure to indium nanoparticles in humans, and precautions against such exposure are paramount with regard to health management..
Membership in Academic Society
  • THE JAPANESE SOCIETY FOR HYGIENE
  • Japan Society for Occupational Health
  • Japan Society for Biomedical Research on Trace Elements
  • Japan Society for Atomospheric Environment
  • Society of Indoor Environment, Japan
Awards
  • chronic health effects of metals using intratracheal instillation on experimental animals
Educational
Educational Activities
Education to medical students or after graduate students concerning the environtental and industrial hygiene.