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Nan Liu,1 Yi Guan,1 Chunling Zhou,2 Yongheng Wang,1 Zhanfei Ma,3 Sanqiao Yao1,4 1School of Public Health, North China University of Science and Technology, Tangshan, 063210, Hebei, People’s Republic of China; 2Baoding Center for Disease Control and Prevention, Baoding, 071030, Hebei, People’s Republic of China; 3Institute of Industrial Hygiene of Ordnance Industry, Xian, 710065, Shanxi, People’s Republic of China; 4XinXiang Medical University, Xinxiang, 453003, Henan, People’s Republic of ChinaCorrespondence: Sanqiao Yao, North China University of Science and Technology, Bohai Avenue 21, Tangshan, 063210, Hebei, People’s Republic of China, Fax +86-315-8805583, Email sanqiaoyao@xxmu.edu.cnPurpose: The main objective of this study was to clarify the biodistribution and in vivo toxicological effects of indium-tin oxide nanoparticles (Nano-ITO) in male rats.Methods: Dose-response (three divided doses) and time-course studies (six exposure durations) were performed to examine Nano‑ITO-induced pulmonary and systemic toxicity. At the end of the experiment, hematology and serum biochemical parameters were determined, and cytokines levels and oxidative stress were analyzed in the bronchoalveolar lavage fluid. In addition, indium biodistribution following Nano‑ITO exposure was determined using inductively coupled plasma mass spectrometer to measure indium concentration in the lung, spleen, brain, liver, kidney, and testis. Rat lung tissues were also harvested for staining with hematoxylin and eosin, periodic acid Schiff stain, Masson’s trichrome, and Sirius red.Results: Relative lung weights were significantly increased in all Nano-ITO-exposed groups. All organs exhibited a statistically significant difference in indium levels. Rat exposure to Nano‑ITO resulted in a dose-response increase in acute systemic inflammation and injury. BALF analysis revealed significantly elevated levels of lung oxidative stress, pulmonary injury, and inflammatory markers across most groups. Serum biochemistry results showed that Nano-ITO could affect the liver and renal functions of rats when exposed for 3 days. Compared with the control group, significant inflammatory responses or pathological changes were observed in the liver, kidney, and testis of rats at different sampling times and three doses examined. Histopathologically, foci of slight-to-severe pulmonary inflammatory response along with acute inflammatory, pulmonary fibrosis and alveolar proteinosis were detected, and the severity of these lesions worsened in a dose- and time-dependent manner.Discussion: These findings provide novel evidence that enhanced progressive massive pulmonary fibrosis, diffuse interstitial fibrosis, and collagen accumulation play a role in the development of pulmonary alveolar proteinosis following Nano-ITO exposure.Keywords: indium-tin oxide nanoparticles, pulmonary fibrosis, pulmonary alveolar proteinosis

Acute lung injury (ALI) caused by gas explosion is common, and warrants research on the underlying mechanisms. Specifically, the role of abnormalities of coagulation and fibrinolysis in this process has not been defined. It was hypothesized that the abnormal coagulation and fibrinolysis promoted ALI caused by gas explosion. Based on the presence of ALI, 74 cases of gas explosion injury were divided into the ALI and non‐ALI groups. The results of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and platelet count (PLT) were collected within 24 hours and compared between the groups. ALI models caused by gas explosion were established in Sprague Dawley rats, and injuries were evaluated using hematoxylin and eosin (HE) staining and histopathological scoring. Moreover, the bronchoalveolar lavage fluid (BALF) was collected to examine thrombin‐antithrombin complex (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor‐1 (PAI‐1) levels by enzyme‐linked immunosorbent assay (ELISA). The patients in ALI group had shorter PT and longer APTT, raised concentration of FIB and decreased number of PLT, as compared to the non‐ALI group. In ALI rats, the HE staining revealed red blood cells in alveoli and interstitial thickening within 2 hours which peaked at 72 hours. The levels of TAT/TF in the BALF increased continually until the seventh day, while the PAI‐1 was raised after 24 hours and 7 days. The TFPI was elevated after 2 hours and 24 hours, and then decreased after 72 hours. Abnormalities in coagulation and fibrinolysis in lung tissues play a role in ALI caused by gas explosion.

Many studies have documented the abnormal concentrations of metals/metalloids in serum or urine of occupational workers, but no works systematically analysed the concentrations of elements in serum or urine of indium-exposed workers. This study was aimed to assess 28elementsin serum and urinefrom 57individuals with occupational exposureto indium and its compounds. Control subjects were 63 workers without metal exposure. We collected information on occupation and lifestyle habits by questionnaire.Biological sampleswere collected to quantify elements by inductive coupled plasma-mass spectrometer.Air in the breathing zones was drawn at flow rates of 1.5-3 L/min for a sampling period of 6 to 8 h, using a Model BFC-35 pump. The average ambient indiumlevel was 0.078mg/m3.Serum/urineIndium levelswere significantly higher in indium-exposed workers than in controls (P< 0.01).Moreover, serum/urine indium concentrations in the group with 6-14 years and ≥15 years of employment were significantly higher than those with ≤5employment years(P< 0.05). Tenof the other 27 elements/metals measured were higher in serum/urine in indium-exposed workers compared to the controls (aluminum, beryllium, cadmium, cesium, chromium, lithium, manganese, magnesium, molybdenumand vanadium). Zinclevels in serum/urinewere significantly decreased in the indium-exposed workers.Additionally, other elements/metals were higher in one specimen (serum or urine) but lower in the other (Selenium was lower in serum but higher in urine in the indium-exposed workers compared with the controls; Likewise Thallium and Rubidium were higher in serum but lower in urine).Linear regression analyses, revealed significant correlations between serum and urine for indium, aluminum, arsenic, barium, cadmium, cesium, cobalt, selenium, silver, and zinc(P < 0.05). These datassuggest that occupational exposure to indium and its compounds may disturb the homeostasis of trace elements in systemic circulation, indium concentrations in serum or urine appear reflective of workers’ exposure to ambientindium and their years of working, respectively. The serum/urine levels of essential metals are modified by exposure to indium in occupationally exposed workers.