Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
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


Papers
1. Kazunori Koga, Hyunwoong Seo, Akiyo Tanaka, Naho Itagaki, Masaharu Shiratani, Synthesis of nanoparticles using low temperature plasmas and its application to solar cells and tracers in living body, Symposium on Plasma Nano Science and Technology - 231st ECS Meeting 2017 Plasma Nano Science and Technology, 10.1149/07703.0017ecst, 77, 17-24, 2017.01, Three applications of nanoparticles synthesized using plasmas has been demonstrated such as third generation solar cells and biotechnology. We produced Si, Ge and In nanoparticles by reactive plasmas, rf sputtering and plasma in water, respectively. We have confirmed multiple exciton generation in cells using Si and Ge nanoparticles. Using In nanoparticles, we have realized high sensitive tracers for understanding nanoparticle kinetics in living body..
2. 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..
3. 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..
4. Takaaki Amano, Thapanut Sarinont, Kazunori Koga, Miyuki Hirata, Akiyo Tanaka, Masaharu Shiratani, Production of In, Au, and Pt nanoparticles by discharge plasmas in water for assessment of their bio-compatibility and toxicity, MRS Advances, 10.1557/adv.2016.41, 1, 18, 1301-1306, 2016.01, Nanoparticles have great potential for biomedical applications such as early detection, accurate diagnosis, and personalized treatment of cancer. Assessment of bio-compatibility and toxicity of nanoparticles body is an emerging topic for these applications. To study kinetics of nanoparticles in body, we synthesized indium, gold and platinum nanoparticles in aqueous suspension using pulsed electrical discharge plasmas in water. The average size of synthesized primary nanoparticles for indium, gold, and platinum are 6.2 nm, 6.7 nm, and 5.4 nm, whereas the average size of secondary nanoparticles for indium, gold, and platinum are 315 nm, 72.3 nm, and 151 nm, respectively. Synthesized indium nanoparticles are transported from subcutaneous to serum and brain. The indium content in serum for the synthesized nanoparticles is much higher than that for the In2O3 nanoparticles of 150 nm in primary size. For gold and platinum nanoparticles, preliminary examination of intratracheal administration revealed that administration of synthesized nanoparticles with 10 mg/kg BW (body weight) may cause bleedings and/or emphysema in lung..
5. 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..
6. 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..
7. 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..
8. 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..
9. Akiyo Tanaka, Miyuki Hirata, Nagisa Matsumura, Kazunori Koga, Masaharu Shiratani, Yutaka Kiyohara, Comparative study on the pulmonary toxicity of indium hydroxide, indium-tin oxide, and indium oxide following intratracheal instillations into the lungs of rats., MRS Symposium Proceedings/MRS Online Proceeding Library,CAMBRIDGE UNIVERSITY PRESS, DOI:http://dx.doi.org/10.1557/opl./2015.21, 1726, 8-13, 2015.07, We studied the pulmonary toxicity of indium hydroxide (In(OH)3), which is produced during a recycling process of indium-tin oxide (ITO), in comparison with that of ITO or indium oxide (In2O3), two raw materials of flat panel displays. One hundred and forty-four male Wistar rats were intratracheally given equivalent doses of 10 mg/kg indium as In(OH)3, ITO, or In2O3 particles, twice a week, for a total of 5 times for 2 weeks. Control rats were given distilled water as a vehicle. After 3 weeks, these rats were serially euthanized, and toxicological effects were determined. Body weight gain was significantly suppressed in the In(OH)3-treated rats compared to that in the control group, but not in the ITO- or In2O3-treated rats. Relative lung weights in all the indium-treated groups significantly increased compared to those in the control group throughout the observation period. Furthermore, lung weights in the In(OH)3 group were significantly higher than those in either the ITO or In2O3 group. Blood indium levels in the In(OH)3-treated rats were much higher, 70- to 200-fold, than those in the In2O3- or ITO-treated rats at each time point. Although the lung indium content decreased gradually during the observation periods, the content in the In(OH)3 group was significantly higher than that in either the ITO or In2O3 group. A histopathological analysis revealed foci indicating a slight to severe pulmonary inflammatory response, including exudation to alveolar spaces, were present in all the indium-treated groups. Interstitial fibrotic proliferation was seen only in the In(OH)3-treated rats. The severity of these lesions in the In(OH)3-treated rats was greater than that in either the ITO- or In2O3-treated rats.
The results of our study clearly demonstrated that In(OH)3 particles caused severe pulmonary toxicity when repeated intratracheal instillations were performed in rats. Furthermore, the toxic potency of In(OH)3 in the lung was much higher than that of ITO and In2O3. Accordingly, the toxicity of In(OH)3 particles should be considered in addition to that of ITO and In2O3 particles when indium exposure occurs..
10. Makiko Nakano, Kazuyuki Omae, Akiyo Tanaka, Hirata Miyuki, KL-6 is not ineffective biomarker of indium lung, Int Arch Occup Environ Health, 10.1007/s00420-013-0873-x, 86, 845-846, 2013.04.
11. 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..
12. Miyauchi H, Minozue Am TanakaS, Tanaka A, Hirata M, Nakaza M, Arito H, Eitaki Y, Nakano M, Omae K, Assessment of workplace air concentrations of indium dust in an indium-recycling plant, J Occup Health, 54, 103-111, 2012.02.
13. 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..
14. Makiko Nakano, kazuyuki Omae, Akiyo Tanaka, Miyuki Hirata, Takehiro Michikawa, Yuriko Kikuchi, Noriyuki Yoshioka, yuji Nishiwaki, Tatsuya Chonan, Causal relationship between indium compound inhalation and effects on the lungs, J. Occupational Health, 51, 6, 513-521, 2009.11.
15. T Hamaguchi, K Omae, T Takebayashi, Y Kikuchi, N Yoshioka, Y Nishiwaki, A Tanaka, M Hirata, O Taguchi, T Chonan, Exposure to hardly soluble indium compounds in ITO production and recycling plants is a new risk for interstitial lung damage, Occup Environ Med, 65, 51-56 , 2008.01.
16. Akiyo Tanaka, Toxicity of indium arsenide, gallium arsenide, and aluminiumu gallium arsenide, Toxicol. Appl. Pharmacol., 10.1016/j.taap.2003.10.019, 198, 3, 405-411, 198(3), 405-411, 2004.01.
17. Makita, Y., matsuura, T., Ogata, R., Omura, M., Tanaka, A., Hirata, M., Inoue, N., Systemic toxicity of p-p'-DDE in aged male Wistar rats following oral administration, Fukuoka Acta Medica, Vol. 94, pp. 59-65, 2003.04.
18. Omura, M., Tanaka, A., Hirata, M., Inoue, N., Testicular toxicity evaluation of two antimony compounds, antimony trioxide and antimony pottasium tartrate in rats and mice, Environ. Health Present. Med., Vol. 7, pp. 15-18, 2002.01.
19. Homma, T., Ueno, T., Sekizawa, K., Tanaka, A., Hirata, M., Interstitial pneumonia developed in a worker dealing with particles containing indium-tin oxide, J. Occup. Health, 10.1539/joh.45.137, 45, 3, 137-139, Vol. 45, pp. 137-139, 2003.01.
20. Tanaka, A., Hirata, M., Omura, M., Pulmonary squamous cyst induced by exposure to indium arsenide in hamsters, J. Occup. Health, 10.1539/joh.45.405, 45, 6, 405-407, Vol. 45, pp. 405-407, 2003.01.
21. Makita, y., Matsuura, T., Ogata, R., Romero, Y., Omura,M., Tanaka, A., Hirata, M., Inoue, N., Systemic effects of orally administered p,p'-DDE on immature male Wistar rats during pubertal period, J. Occup. Health, 10.1539/joh.45.223, 45, 4, 223-227, Vol., 45, 223-227, 2003.01.
22. Miyaki, K., Hosoda, K., Hirata, M., Tanaka, A., Nishiwaki, Y., Takebayashi, T., Inoue, N., Omae, K., Biological monitoring of indium using graphite furnace atomic absorption spectrophotometry in workers exposed to particles of indium compounds, J. Occup. Health, 10.1539/joh.45.228, 45, 4, 228-230, Vol. 45, pp. 228-230, 2003.01.
23. Omura, M., Yamazaki, K., Tanaka, A., Hirata, M., Makita, Y., Inoue, N., Changes in the testicular damage caused by indium arsenide and indium phosphide in hamsters during tow years after intratracheal instillations, J. Occup. Health, 10.1539/joh.42.196, 42, 4, 196-204, Vol. 42, pp. 196-204, 2000.01.
24. Yamazaki, K., Tanaka, A., Hirata, M., Omura, M., Makita, Y., Inoue, N., Long term pulmonary toxicity of indium arsenide and indium phosphide instilled intratracheally into hamsters, J. Occup. Health, 10.1539/joh.42.169, 42, 4, 169-178, Vol. 42, pp. 169-178, 2000.01.
25. Pulmonary toxicity of InAs, GaAs, AlGaAs following intratracheal instillations to the lung of Syrian golden hamsters.
26. Omura, M., Tanaka, A., Hirata, M., Inoue, N., Ueno, M., Homma, T.,Sekizawa, K, S., Testicular toxicity evaluation of indium-tin oxide, J. Occup. Health, 44, 2, 105-107, 2002.04.
27. Tanaka, A., Hirata, M., Omura, M., Inoue, N., Ueno, T., Homma, T., Sekizawa, K., Pulmonary toxicity of indium-tin oxide and indium phosphide after intratracheal instillations into the lung of hamsters, J. Occup. Health, 10.1539/joh.44.99, 44, 2, 99-102, Vol., 44, pp. 99-102, 2002.01.
28. Tissue distribution of antimony in rats and mice following multiple oral administrations of antimony trioxide or antimony potassium tartrate.
29. Comparative toxic effects of antimony trioxide and antimony potassium tartrate following multiple oral administrations to rats and mice.
30. Minoru Omura, Akiyo Tanaka, Mangen Zhao, Miyuki Hirata, Yuji Maxita, Naohide Inoue, Kaoru Gotoh, Short Communication Toxic Effects of Gallium Arsenide on Sperm in Rats by Repeated Intratracheal Instillations, Journal of Occupational Health, 10.1539/sangyoeisei.37.3_165, 37, 3, 1995.01, Gallium arsenide (GaAs) has superior properties for making high-frequency devices and photonemitters. In the future, this is going to be extensively used in the development of super computers, telecommunication systems, light-emitting diodes, and semiconductor lasers. This will inevitably lead to an increase in the exposure of workers manufacturing these products to GaAs..
31. Akiyo Tanaka, A. Hisanaga, Miyuki Hirata, M. Omura, Y. Makita, N. Inoue, N. Ishinishi, Chronic toxicity of tar from heavy-duty diesel exhaust following intratracheal instillations to the lungs of hamsters, Fukuoka Acta Medica, 86, 2, 65-73, 1995.01, Chronic toxicity of tar from heavy-duty diesel exhaust (HD tar) was studied in male Syrian golden hamsters which received 15 mg, 7.5 mg or 1.5 mg of HD tar as the total dosage by intratracheal instillations once a week for 15 weeks. As a control group, hamsters were treated with the 0.1 ml of Tween 60: ethanol: phosphate buffer (pH 6.88, 0.25 M) solution (5.8: 8.7: 100 by volume) once a week in the same manner. The survival rate during the instillation period in the group given 15 mg of HD tar, the high-dose group of HD tar, was the lowest, and the effect was dose-dependent. However, the survival rates during the subsequent observation period showed no marked differences among HD tar treated groups. During their total life span, one papilloma in the larynx was seen in the 44 hamsters in the group given 15 mg of HD tar, one papilloma in the larynx appeared in the 59 hamsters in the group given 1.5 mg of HD tar and one lung adenoma was developed in the 58 hamsters in the control group. There were no tumors in the respiratory tract in the group given 7.5 mg of HD tar. Concerning the histopathological findings of the lung, the incidence of alveolar cell or bronchiolar cell hyperplasia in the group given 1.5 mg of HD tar was significantly higher than that in the control group. From these results, although we could not observe any tumorigenicity or carcinogenic effect of HD tar, it would seem that HD tar caused weak but positive damage to the lungs of hamsters..
32. M. Omura, Miyuki Hirata, M. Zhao, Akiyo Tanaka, N. Inoue, Comparative testicular toxicities of two isomers of dichloropropanol, 2,3-dichloro-1-propanol, and 1,3-dichloro-2-propanol, and their metabolites alpha-chlorohydrin and epichlorohydrin, and the potent testicular toxicant 1,2-dibromo-3-chloropropane, Bulletin of Environmental Contamination and Toxicology, 10.1007/BF00212381, 55, 1, 1-7, 1995.07.
33. Minoru Omura, Akiyo Tanaka, Miyuki Hirata, Mangen Zhao, Yuji Makita, Naohide Inoue, Kaoru Gotoh, Noburu Ishinishi, Testicular toxicity of gallium arsenide, indium arsenide, and arsenic oxide in rats by repetitive intratracheal instillation, Toxicological Sciences, 10.1006/faat.1996.0108, 32, 1, 72-78, 1996.01, The testicular toxicities of two compound semiconductor materials, gallium arsenide (GaAs) and indium arsenide (InAs), and arsenic oxide (As2O3) were examined in rats by repetitive intratracheal instillation of these substances in suspension twice a week, a total of 16 times. A single instillation dose was 7.7 mg/kg in the GaAs and the InAs groups and 1.3 mg/kg in the As2O3 group. A significant decrease in sperm count and significant increase in the proportion of morphologically abnormal sperm were found in the epididymis in the GaAs group. Especially, abnormal sperm with a straight head increased markedly in this group. In the GaAs-treated rats, there was 40-fold increase in the degenerating late elongated spermatids at the postspermiation stages, stages IX, XI, and XI. From these results, it is indicated that GaAs disturbed the spermatid head transformation at the late spermiogenic phases and caused spermiation failure. InAs caused a sperm count decrease in the epididymis, though its testicular toxicity was relatively weak compared with that of GaAs. As2O3, a probable dissolution arsenic product of GaAs and InAs in vivo, did not show any testicular toxicities in this study. It seems likely that, along with arsenics, gallium and indium play a role in the testicular toxicities of GaAs and InAs..
34. Minoru Omura, Akiyo Tanaka, Miyuki Hirata, Mangen Zhao, Yuji Makita, Naohide Inoue, Kaoru Gotoh, Noburu Ishinishi, Testicular toxicity of gallium arsenide, indium arsenide, and arsenic oxide in rats by repetitive intratracheal instillation, Toxicological Sciences, 10.1093/toxsci/32.1.72, 32, 1, 72-78, 1996.01, The testicular toxicities of two compound semiconductor materials, gallium arsenide (GaAs) and indium arsenide (InAs), and arsenic oxide (As2O3) were examined in rats by repetitive intratracheal instillation of these substances in suspension twice a week, a total of 16 times. A single instillation dose was 7.7 mg/kg in the GaAs and the InAs groups and 1.3 mg/kg in the As2O3 group. A significant decrease in sperm count and significant increase in the proportion of morphologically abnormal sperm were found in the epididymis in the GaAs group. Especially, abnormal sperm with a straight head increased markedly in this group. In the GaAs-treated rats, there was 40-fold increase in the degenerating late elongated spermatids at the postspermiation stages, stages IX, XI, and XI. From these results, it is indicated that GaAs disturbed the spermatid head transformation at the late spermiogenic phases and caused spermiation failure. InAs caused a sperm count decrease in the epididymis, though its testicular toxicity was relatively weak compared with that of GaAs. As2O3, a probable dissolution arsenic product of GaAs and InAs in vivo, did not show any testicular toxicities in this study. It seems likely that, along with arsenics, gallium and indium play a role in the testicular toxicities of GaAs and InAs..
35. Akiyo Tanaka, A. Hisanaga, Miyuki Hirata, M. Omura, Y. Makita, N. Inoue, N. Ishinishi, Chronic toxicity of indium arsenide and indium phosphide to the lungs of hamsters., Fukuoka Acta Medica, 87, 5, 108-115, 1996.05, Chronic toxicity of indium arsenide (InAs) and indium phosphide (InP) was studied in male Syrian golden hamsters which received InAs or InP particles containing a total dose of 7.5 mg of arsenic or phosphorus by intratracheal instillations once a week for 15 weeks. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During their total life span, the cumulative body weight gain of hamsters in the InAs group was suppressed significantly compared with that in the control group, but not in the InP group when compared with that in the control group. Concerning the histopathological findings of the lung, the incidence rates of proteinosis-like lesions, alveolar or bronchiolar cell hyperplasia, pneumonia, emphysema and metaplastic ossification observed in the InAs or InP group were significantly higher than those observed in the control group. From these results, it would seem that InAs and InP produced severe damage to the lungs of hamsters..
36. Minoru Omura, Miyuki Hirata, Akiyo Tanaka, Mangen Zhao, Yuji Makita, Naohide Inoue, Kaoru Gotoh, Noburu Ishinishi, Testicular toxicity evaluation of arsenic-containing binary compound semiconductors, gallium arsenide and indium arsenide, in hamsters, Toxicology Letters, 10.1016/S0378-4274(96)03796-4, 89, 2, 123-129, 1996.12, The testicular toxicities of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were examined by repetitive intratracheal instillation using hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) were instilled twice a week a total of 16 times and InAs (7.7 mg/kg) was instilled a total of 14 times. GaAs caused testicular spermatid retention and epididymal sperm reduction, though the degrees were less severe than those in rats shown in our previous experiment. InAs and As2O3 did not show any testicular toxicities. Serum arsenic concentration in GaAs-treated hamsters was less than half of that in As2O3-treated hamsters in which no testicular toxicities were found. Serum molar concentration of gallium was 32-times higher than that of arsenic in GaAs-treated hamsters. Therefore gallium may play a main role in the testicular toxicity of GaAs in hamsters..
37. Tanaka, A., Hirata, M., Omura, M., Zhao, M., Makita, Y., Yamazaki, K., Inoue, N., Gotoh, K., Comparative study of the toxic effects of gallium arsenide, indium arsenide and arsenic trioxide following intratracheal instillations to the lung of Syrian golden hamsters, Fukuoka Acta Medica, Vol. 91, pp. 21-33, 2000.01.
38. Omura, M., Ogata, R., Kubo, K., Shimasaki, Y., Aou, S., Oshima, Y., Tanaka, A., Hirata, M., Makita, Y., Inoue, N., Two-generation reproductive toxicity study of tributyltin chloride in male rats, Toxicol. Sciences, 10.1093/toxsci/64.2.224, 64, 2, 224-232, Vol. 64, 224-232, 2000.01.
39. Omura, M., Masuda, Y., Hirata, M., Tanaka, A., Makita, Y., Ogata, R., Inoue, N., Onset of spermatogenesis is accelerated by gestational administration, Environ. Health Perspect.,, 10.2307/3454616, 108, 6, 539-544, Vol.108, pp. 539-544, 2000.01.
40. Comparative toxic effects of aluminium gallium arsenide, and gallium arsenide following intratracheal instillations to the lung of Syrian golden hamsters.
41. Miyuki Hirata, Akira Hisanaga, Akiyo Tanaka, Noburu Ishinishi, Glutathione and methylation of inorganic arsenic in hamsters, Applied Organometallic Chemistry, 10.1002/aoc.590020407, 2, 4, 315-321, 1988, The effect of giutathione (GSH) concentrations in livers and kidneys of hamsters on the toxicity and methylation of arsenite in these animals was studied. No significant changes in hepatic and renal GSH concentrations were observed after a single arsenite administration (5 mg As kg−1, p.o.). When buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, was given (4 mmol kg−1, i.p.) two hours before administration of arsenite, hepatic and renal GSH concentrations were more severely and persistently depressed than in the case of BSO administration not followed by arsenite. Hamsters treated with BSO plus arsenite suffered from severe nephrotoxicity (acute renal failure) characterized by increases in plasma creatinine and urea nitrogen and by proximal tubular necrosis. Concurrently, transient hepatotoxicity was observed in the BSO plus arsenite group. Neither arsenite alone nor BSO alone produced liver or kidney injury. The BSO plus arsenite‐treated animals excreted in the urine only 3.5% of the arsenic dose during the 72 h period after administration of arsenite, probably because of a decrease in urine volume caused by kidney injury, whereas the arsenite‐only group excreted 27%. In addition, BSO pretreatment influenced the relative proportion of arsenic metabolites excreted in the urine during the first 24 h after administration. Urinary metabolites in the BSO plus arsenite group were predominantly inorganic arsenic. These results suggest that GSH provides protection against arsenic toxicity..
42. Akiyo Tanaka, A. Hisanaga, T. Inamasu, Miyuki Hirata, N. Ishinishi, A comparison of the carcinogenicity of N-nitrosodiethylamine and N-nitrosodimethylamine after intratracheal instillation into Syrian golden hamsters, Food and Chemical Toxicology, 10.1016/0278-6915(88)90025-7, 26, 10, 847-850, 1988.01, N-Nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) were instilled intratracheally into male Syrian golden hamsters once a week for 15 wk. The total dosages were 1.5 mg and 7.5 mg of NDEA and 0.75 mg and 1.5 mg of NDMA. A control group simultaneously received phosphate buffer vehicle. Tumours related to instillation appeared principally in the respiratory tract and the liver. Over the entire lifespan of the animals tumour incidence rates in the respiratory tract were 100% in both the NDEA groups, 6% in both NDMA groups and 8% in the control group. The total incidences of liver tumours were 6% in the 0.75 mg NDMA group, 19% in the 1.5 mg NDMA group, zero in the NDEA groups, and 4% in the control group. These results indicate that, when administered by this route, NDEA is a much more potent carcinogen in the respiratory tract than is NDMA but NDMA alone seems to be carcinogenic to the liver, at a total dosage of 1.5 mg..
43. S. Ohyama, Akiyo Tanaka, A. Hisanaga, N. Ishinishi, Chronic toxicity tests of road dust which was produced by studded tires and intratracheally instilled into hamsters, Journal of Japan Society of Air Pollution, 24, 4, 270-275, 1989.01.
44. Noburu Ishinishi, Akiyo Tanaka, Akira Hisanaga, Takeo Inamasu, Miyuki Hirata, Comparative study on the carcinogenicity of N-nitrosodiethylamine, N-nitrosodhnethylamine, N-nitrosomorpholine, N-nitrosopyrrolidine and N-nitrosodi-N-propylamine to the lung of syrian golden hamsters following intermittent instillations to the trachea, Carcinogenesis, 10.1093/carcin/9.6.947, 9, 6, 947-950, 1988.06, N-Nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), N-mtrosomorpholine (NMOR), N-nitrosopyrroli dine (NPYR) and N-nitrosodi-N-propylainine (NDPA) were instilled into the lungs of male Syrian golden hamsters by intratracheal instillatlons once a week for 15 weeks. The total doses given were 1.5 mg of each drug. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During the total lifespan, tumor incidence rates in the respiratory organs were 100% in the NDEA group, 6% in the NDMA group, 43% in the NMOR group, 0% in the NPYR group, 72% in the NDPA group and 4% in the control group. The incidence rates in the liver were 19% in the NDMA group and 4% in the NPYR group. No liver tumors developed in the other groups. The carcinogenic potencies of these N-nitroso compounds to the respiratory organs was provisionally estimated to be in the following order: NDEA > NDPA> NMOR > NDMA ≒NPYR, at the 1.5 mg dosage level. However, the difference in the rates of tumor incidence between the NDMA or NPYR group and the control group was not significant..