J Occup Health 2009; 51: 513–521
Journal of Occupational Health
Causal Relationship between Indium Compound Inhalation and Effects on the Lungs Makiko NAKANO1, Kazuyuki OMAE1, Akiyo TANAKA2, Miyuki HIRATA2, Takehiro MICHIKAWA1, Yuriko KIKUCHI1, Noriyuki YOSHIOKA1, Yuji NISHIWAKI1 and Tatsuya CHONAN3 1
Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 2Department of Hygiene, Graduate School of Medical Sciences, Kyushu University and 3Department of Medicine, Nikko Memorial Hospital, Japan
Abstract: Causal Relationship between Indium Compound Inhalation and Effects on the Lungs: Makiko N AKANO, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—Background: Recent case reports and epidemiological studies suggest that inhalation of indium dust induces lung damage. Objectives: To elucidate the dose-dependent effects of indium on the lungs and to prove a causal relationship more clearly. Methods: A baseline observation was conducted on 465 workers currently exposed to indium, 127 workers formerly exposed to indium and 169 workers without indium exposure in 12 factories and 1 research laboratory from 2003 to 2006. Indium in serum (In-S) was determined as an exposure parameter, and its effects on the lungs were examined. Results: The means of In-S in the current, former and no exposure workers were 8.35, 9.63 and 0.56 ng/ml, respectively. The current and former exposure workers had significantly higher levels of KL-6, and showed significant dose-dependent increases in KL-6, SP-D, and SP-A. Current exposure workers with In-S of 3 ng/ml or above demonstrated a significant increase of KL-6 in both GM and prevalence exceeding the reference value. Approximately a quarter of the former exposure workers had interstitial changes as seen on chest HRCT. In-S of exposed workers who had been working before improvements of the working environment (Group Bef) and those who started working after improvements (Group Aft) were 12.29 and 0.81 ng/ml, respectively. Adjusted odds ratios indicated 87%, 71% and 44% reductions among Group Aft workers who exceeded the reference values of KL-6, Received May 25, 2009; Accepted Aug 26, 2009 Published online in J-STAGE Oct 16, 2009 Correspondence to: M. Nakano, Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku, Tokyo 160-8582, Japan (e-mail:
[email protected])
SP-D and SP-A, respectively. Conclusion: Dosedependent lung effects due to indium exposure were shown, and a decrease of indium exposure reduced the lung effects. An In-S value of 3 ng/ml may be a cut-off value which could be used to prevent early effects on the lungs. (J Occup Health 2009; 51: 513–521) Key words: Cross-sectional study, Indium, Interstitial pneumonitis, KL-6, HRCT, SP-D
Due to the rapid expansion of flat panel displays and solar cells, indium demand has increased every year, and in 2007, Japan consumed over 90% of the indium in the world1). Until the early 1990’s, there was little information on the toxic effects of indium on humans or animals. In the mid 1990’s, intra-tracheal instillation studies of particles of compound semiconductors such as indium phosphide, indium arsenide and indium trichloride revealed that metal compounds containing indium had a strong potential to induce severe lung damage2–6). In 2003, Homma et al.7) disclosed a case of interstitial pneumonia in a 27-yr-old male worker engaged in the wet surface polishing process of indium-tin oxide (ITO) target plates, high-density plates made of very hard ceramics composed of indium oxide and tin oxide, which are used to laminate transparent electroconductive thin-film on flat displays and solar cells. The worker started this job in 1994, and at the beginning of 1998 was admitted to a hospital with the complaint of increasing dry cough and breathlessness. After a detailed medical examination, he was diagnosed with interstitial pneumonia, possibly caused by the inhalation of ITO particles. Up to the end of 2008, seven indium-induced cases of lung injury were disclosed7–11). After the first case was found, two epidemiological studies were performed in two different populations of indium-exposed workers12, 13). Both studies suggested strong relationships between indium in serum
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Table 1. Characteristics of study population and concentrations of indium in serum
n Male (%) Age (yr): Mean ± SD Smokers (%) In-S (ng/ml): Mean (range ) Exposure duration (mo): Mean (range) Duration after the end of indium exposure (mo): Mean (range)
No exposure
Former exposure
Current exposure
169 81.9 40.9 ± 10.89 116 (67.8) 0.56 (n.d.–3.0) –
127 91.1** 39.1 ± 9.61 76 (60.8) 9.63 (n.d–126.8)** 60.4 (1–252)
465 91.6** 35.9 ± 11.30** 278 (72.8) 8.35 (n.d.–116.9)** 55.1 (0.25–455)
–
58.3 (2–201)
**: p43.2) %FVC (
