Abstract
Changes in bronchoalveolar lavage fluid (BALF) and blood were examined to assess the toxic effects of diborane (B2H6, CAS: 19287-45-7) on the lung. Male Wistar rats were exposed to diborane at 20 ppm (intended concentration) for 4 h (phase I study) to evaluate time-course changes up to 14 days, and at 10 or 1 ppm (intended concentrations) to assess the dose-effect relationship after 3 days (phase II study). BALF parameters [leukocyte counts, α1-antitrypsin (α1-AT), superoxide dismutase (SOD), total protein, phospholipids etc.] were examined and biochemical and histopathological studies were also carried out. In the phase I study, neutrophils (%) in BALF increased on the day of exposure and then decreased gradually for 3 days. Rapid and marked increases in α1-AT and SOD activity in BALF were detected on the day of exposure, and phospholipids had sharply increased on day 3. After 14 days, these parameters in the exposed rats had returned to their background level and α1-AT decreased significantly. In the phase II study, total protein, α1-AT activity and phospholipids in BALF showed dose-dependent increases, and serum α1-AT activity increased significantly. Alveolar capillary and alveolar cell damage were confirmed in rats exposed to 20 ppm, 10 ppm or 1 ppm diborane for 4 h by evaluating the parameters examined. The protection system appeared to start operating immediately after exposure, and the recovery mechanism seemed to start operating 1 day after exposure and cease by day 14. The no-observed-effect level could not be observed.
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Chen SS-H, Kou AY (1982) High-performance liquid chromatography of methylated phospholipids. J Chromatogr 232: 237–249
Cordasco EM, Cooper RW, Murphy JV, Anderson C (1962) Pulmonary aspects of some toxic experimental space fuels. Dis Chest 41: 68–74
Dietz AA, Rubinstein HM, Teague PO, Rennert OM, Freier EF, Lieberman J, Franey RJ (1974) Measurement of alpha1-antitrypsin in serum, by immunodiffusion and by enzymatic assay. Clin Chem 20: 396–399
German Society for Clinical Chemistry (1972) Standard method for determination of alkaline phosphatase activity. J Clin Chem Clin Biochem 10: s281-s291
Hallman M, Spragg R, Harrell JH, Moser KM, Gluck L (1982) Evidence of lung surfactant abnormality in respiratory failure: study of bronchoalveolar lavage phospholipids, surface activity, phospholipase activity and plasma myoinositol. J Clin Invest 70: 673–683
Hayem A (1982) Study of proteins in bronchoalveolar washings. Ann Biol Clin 40: 231–233
Henderson RF, Rebar AH, Pickrell LA, Newton GJ (1979) Early damage indicators in the lung. III. Biochemical and cytological response of the lung to inhaled metal salts. Toxicol Appl Pharmacol 50: 123–136
Homma H, Yamanaka A, Tanimoto S, Tamura M, Chijimatsu Y, Kira S, Izumi T (1983) Diffuse panbronchiolitis. A disease of the transitional zone of the lung. Chest 83: 63–69
Janoff A (1985a) Elastase and emphysema. Current assessment of protease-antiprotease hypothesis. Am Rev Respir Dis 132: 417–433
Janoff A (1985b) Elastase in tissue injury. Annu Rev Med 36: 207–216
Katagiri K, Ito K, Miyaji M, Takeuchi T, Yoshikane K, Sasaki M (1979) Succinyl trialanine p-nitroanilide-hydrolytic enzymes in human serum. An improved method for clinical diagnosis. Clin Chim Acta 95: 401–404
Kawanami O, Ferrons VS, Crystal RG (1982) Structure of alveolar epithelial cells in patients with fibrotic lung disorders. Lab Invest 46: 39–53
Krackow EH (1953) Toxicity and health hazards of boron hydrides. Arch Ind Health 8: 335–339
Kunkel AM, Murtha EF, Oikemus AH, Stabile DE, Saunders JP, Wills JH (1956) Some pharmacologic effects of diborane. Arch Ind Health 13: 346–351
Liau DF, Barrett CR, Bell ALL, Ryan SF (1985) Normal surface properties of phosphatidylglycerol deficient surfactant from dogs after acute lung injury. I Lipid Res 26: 1338–1344
Linder J, Sisson JH (1994) Lung defenses. In: Dail DH, Hammar SP (eds) Pulmonary pathology. Springer, New York, pp 45–56
McCord JM, Fridovich I (1968) The reduction of cytochrome c by milk xanthine oxidase. J Biol Chem 243: 5753–5760
MDA Scientific (1993) Instrument accuracy and precision. Technical note No. 971131
Miller BE, Hook GER (1990) Hypertrophy and hyperplasia of alveolar type II cells in response to silica and other pulmonary toxicants. Environ Health Perspect 85: 15–23
Mornex JF, Chytil-Weir A, Martinet Y, Courtney M, LeCocq JP, Crystal RG (1986) Expression of the alpha-1-antitrypsin gene in mononuclear phagocytes of normal and alpha-1-antitrypsin-deficient individuals. J Clin Invest 77: 1952–1961
Nippon Sanso (1986) The resolution analysis of diborane. Technical report
Nomiyama T, Omae K, Uemura T, Nakashima H, Takebayashi T, Ishizuka C, Yamazaki K, Sakurai H (1995) No effect level of diborane on respiratory organs of male mice in acute and subacute inhalation experiment. J Occup Health 37: 157–160
Perlmutter DH, Travis J, Punsal PI (1988) Elastase regulates the synthesis of its inhibitor, α1-proteinase inhibitor, and exaggerates the defect in homozygous PiZZ α1-PI deficiency. J Clin Invest 81: 1774–1780
Richards RJ, Curtis CG (1984) Biochemical and cellular mechanisms of dust-induced lung fibrosis. Environ Health Perspect 55: 393–416
Rooney SA (1985) The surfactant system and lung phospholipid biochemistry. Am Rev Respir Dis 131: 439–460
Ryan SF, Liau DF, Bell ALL, Hashim SA, Barrett CR (1981) Correlation of lung compliance and quantities of surfactant phospholipids after acute alveolar injury from N-nitroso-N-methylurethane in dog. Am Rev Respir Dis 123: 200–204
Sendelbach LE, Witschi HP (1987) Bronchoalveolar lavage in rats and mice following beryllium sulfate inhalation. Toxicol Appl Pharmacol 90: 322–329
Thrall RS, Swendsen CL, Shannon TH, Kennedy CA, Frederick DS, Grunze MF, Sulavik SB (1987) Correlation of changes in pulmonary surfactant phospholipids with compliance in bleomycin induced pulmonary fibrosis in the rats. Am Rev Respir Dis 136: 113–118
Uemura T, Omae K, Nakashima H, Sakurai H, Yamazaki K, Shibata T, Mori K, Kudo M, Kanoh H, Tati M (1995) Acute and subacute inhalation toxicity of diborane in male ICR mice. Arch Toxicol 69: 397–404
Wang NS (1994) Anatomy. In: Dail DH, Hammar SP (eds) Pulmonary pathology. Springer, New York, pp 21–44
Wroblewski F, LaDue JS (1955) Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med 90: 210–213
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Nomiyama, T. Inhalation toxicity of diborane in rats assessed by bronchoalveolar lavage examination. Arch Toxicol 70, 43–50 (1995). https://doi.org/10.1007/s002040050247
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DOI: https://doi.org/10.1007/s002040050247