* Center for Occupational Toxicology, Occupational Safety & Health Research Institute, Daejeon, 305380, Korea; Department of Environmental Engineering, Yonsei University, Wonju, Korea;
College of Veterinary Medicine, Seoul National University, Seoul, Korea; and
Department of Preventive Medicine, Kosin University, Pusan, Korea
Received July 7, 2004; accepted September 22, 2004
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key Words: welding fume; pulmonary function test; tidal volume; welder's pneumoconiosis; lung fibrosis.
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Previously, the current authors developed a three-phase welding-fume-exposure-induced fibrosis animal model that was used to investigate the induction and recovery processes of lung fibrosis induced by welding-fume exposure based on rats exposed to welding fumes up to 90 days followed by a 90-day recovery period (Yu et al., 2001, 2003
). The results revealed that the critical point for the induction and recovery of welding-fume-exposure-induced lung fibrosis was 30 days of welding-fume exposure at a high concentration, at which point early and delicate fibrosis was observed in the perivascular and peribronchiolar regions (Yu et al., 2003
), accompanied by elevated inflammatory cells and markers (Yu et al., in press). However, the current study investigated the change of pulmonary function during 60 days of welding-fume exposure using manual metal arc stainless steel (MMA-SS) and a 60-day recovery period.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Sampling and analysis of welding fumes. The welding fumes were collected using NIOSH method 0500 (NIOSH, 1999) and sampled with a personal sampler (MSA 484107, Pittsburgh) that contained a mixed cellulose ester filter (0.8 mm pore size, 37 mm diameter, Millipore AAWP 03700, Bedford) every 30 min for 2 h at a flow rate of 2 l/min. The welding fumes were analyzed for their metal composition using an atomic absorption spectrophotometer (SpectAA-800, Varian, Palo Alto) based on the NIOSH method (1999)
. The gaseous fumes, O3, NO2, and nitrous fumes were measured using Dräger tubes (Cat. No. 6733181, CH 31001, and CH30001, respectively), and the gaseous fumes were sampled using a gas detector pump (6400000, Dräger, Lübeck), according to the manufacturer's direction, 1 h after initiating the welding-fume exposure. The metal concentrations and gaseous fractions of the welding fumes are shown in Table 1. The chemical composition of the welding fumes was not evenly separated between the low and high dose, which may have been attributable to other components, such as silicon oxide, titanium oxide, and calcium oxide, that were not analyzed and moisture in the fume particles captured during sampling.
|
Pulmonary function test. Any change of pulmonary function in the rats exposed to welding fumes was evaluated every week during 60 days using a ventilated bias flow whole-body plethysmograph (WBP) (SFT3816, Buxco Electronics, Sharon, CT) consisting of a reference chamber and animal chamber interconnected by a pressure transducer (MAX1320, Buxco Electronics, Sharon, CT), thereby decreasing the errors due to anesthesia or trachea intubation. The parameters for the pulmonary function test included the tidal volume (TV, ml), minute volume (MV, ml/min), frequency (BPM, breath/min), inspiratory time (Ti, s), expiratory time (Te, s), peak inspiratory flow (PIF, ml/s), and peak expiratory flow (PEF, ml/s). After being exposed to the welding fumes for 2 h, the rats were put in the animal chamber, left for 40 min to stabilize, and the plethysmography was initiated by measuring the selected parameter values for 5 min.
Bronchoalveolar lavage (BAL). A BAL was performed on animals from each exposure group one day after the designated 2 h, 15, 30, and 60 days of welding-fume exposure and from each 60-day recovery group. The rats were deeply anesthetized with an overdose of sodium pentobarbital, then exsanguinated by severing the abdominal aorta. The lungs were lavaged 14 times with 3-ml aliquots of a warm calcium- and magnesium-free phosphate buffer solution (PBS), pH 7.4. The samples were also centrifuged for 7 min at 500 x g, and the cell-free BAL fluid was discarded. The cell pellets from all washes for each rat were then combined, washed, and resuspended in 1 ml of a PBS buffer and evaluated, as described below (Antonini et al., 1996, 1997
; Lemaire and Ouellet, 1996
).
BAL cell evaluation. The total cell numbers were determined using a hemocytometer. The cells were cultured for 40 min to attach a coverslip in a 24-well culture dish, then stained with Wright Giemsa Sure Stain (Adamson et al., 1995). Nonspecific esterase (NSE) staining to differentiate alveolar macrophages from granulocytes was also performed using an alpha-Naphthyl acetate esterase staining kit (Sigma, St. Louis, MO). The attached cells were fixed in a citrate-acetone-methanol fixative for 30 s at room temperature, washed with distilled water, and air-dried. The samples were then stained with a Trizmal buffer containing Fast blue RR salt (pH 7.6, maleate 1 M), alpha Naphthyl acetate, and ethylene glycol monomethyl ether for 30 min at 37°C. Thereafter, the samples were washed again with distilled water for 3 min, counterstained with Leukostat, and air-dried. The NSE-positive cells, mostly macrophages, were identifiable due to their black granulation, whereas granulocytes are NSE-negative.
Statistical analysis. All results are expressed as means ± standard error (SE). An analysis of variance (ANOVA) test and Duncan's multiple range tests were used to compare the body weight, brochoalveolar lavaged cell distribution, and parameters from the pulmonary function test obtained from the two dose groups with those obtained from the unexposed control rats. The level of significance was set at p < 0.05 and p < 0.01.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Except for the tidal volume, none of the other pulmonary function parameters exhibited any noticeable change during the 60-day welding-fume exposure and recovery period (Sung et al., 2004). It should be noted that the time of the pulmonary function measurements may have resulted in no noticeable changes, except for the tidal volume, as the measurements were performed without exposure to any substances, such as metacholine or other inducers, seen in many obstructive pulmonary parameter changes in other studies (Arts et al., 2003
; Michielsen et al., 2001
).
Extensive studies have already investigated chronic effects on lung function. For example, welders exposed to welding fumes showed a significantly impaired lung function and, with advancing years, greater deterioration of lung function compared to controls (Akbar-Khanzadeh, 1980). Some of the main effects of welding-fume exposure on the pulmonary function are: (1) usual day-to-day welding exposure in the absence of acute inhalation injury does not necessarily not lead to a severe or apparent degree of lung function impairment (Sferlazza and Beckett, 1991
); (2) a transient effect on the pulmonary function can occur at the time of exposure, yet this can be spontaneously reversed during the unexposed period before the next exposure (Beckett et al., 1996
; Sferlazza and Beckett, 1991
); and (3) stainless steel welders tend to have more significant across-shift reductions in lung function when compared with mild steel welders with similar exposure histories, while manual metal arc welders show a decreased across-shift in lung function compared with gas metal arc welders. However, it is still possible that heavily exposed or more susceptible workers could experience a different outcome from the above welders and control populations. Welders in confined and poorly ventilated spaces, like shipbuilding, have been found to exhibit more negative lung function effects than welders in well-ventilated areas (Akbar-Khanzadeh, 1980
, 1993
; Chinn et al., 1990
; Mur et al., 1985
; Oxhoj et al., 1979
). Although interstitial lung fibrosis is usually conceived to have purely restrictive defects, a mixed pattern of obstructive and restrictive defects has also been seen. The lung function parameters for restrictive defects show a reduced lung volume, reflected in the vital capacity, residual volume, functional residual capacity, and total lung preserving FEV1/FVC ratio, and decreased DLCO (diffusing capacity for carbon monoxide) (Redlich, 1996
). In the present study, only the tidal volume among the lung function parameters was significantly decreased in a dose-dependant manner from day 35 to day 60 during the exposure period and even after the 60-day recovery period, indicating fibrosis induction and progression after 30 days of exposure and that the diffusely progressed fibrosis after 60 days of exposure could not be eradicated even after a sufficient recovery period.
![]() |
NOTES |
---|
1 To whom correspondence should be addressed at Center for Occupational Toxicology, 1048 Munji-dong, Yuseong-gu, Daejeon 305380, Korea. Fax: +82-42-863-8361. E-mail: u1670916{at}chollian.net.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Akbar-Khanzadeh, F. (1980). Long-term effects of welding fumes upon respiratory symptoms and pulmonary function. J. Occup. Med. 22, 337341.[ISI][Medline]
Akbar-Khanzadeh, F. (1993). Short-term respiratory function changes in relation to work shift welding fume exposures. Int. Arch. Occup. Environ. Health 64, 393397.[ISI][Medline]
Antonini, J. M., Krishna-Murthy, G. G., and Brain, J. D. (1997). Responses to welding fume: Lung injury inflammation and release of tumor necrosis factor-alpha and interleukin-1 beta. Exp. Lung. Res. 23, 205227.[ISI][Medline]
Antonini, J. M., Krishna-Murthy, G. G., Rogers, R. A., Albert, R., Ulrich, G. D., and Brain, J. D. (1996). Pneumotoxicity and pulmonary clearance of different welding fumes after intratracheal instillation in the rat. Toxicol. Appl. Pharmacol. 114, 188199.
Artfield, M. D., and Ross, D. S. (1978). Radiologic abnormalities in electric-arc welders. Br. J. Ind. Med. 35, 117122.[ISI][Medline]
Arts, J. H. E., Bloksma, N., Leusink-Muis, T., and Kuper, C. F. (2003). Respiratory allergy and pulmonary irritation to trimellitic anhydride in Brown Norway rats. Toxicol. Appl. Pharm. 187, 3849.[CrossRef][ISI][Medline]
Beckett, W. S. (1996). Industries associated with respiratory diseases. In Welding: Occupational and Environmental Respiratory Diseases (P. Harber, M. B. Schenker, and J. R. Balmes, Eds.), pp. 704717. Mosby, St. Louis, MO.
Beckett, W. S., Pace, P. E., Sferlazza, S. J., Perman, G. D., Chen, A. H., and Xu, X. P. (1996). Airway reactivity in welders: A controlled prospective cohort study. J. Occup. Environ. Med. 38, 12291238.[CrossRef][ISI][Medline]
Buerke, U., Schneider, J., Muller, K. M., and Woitowitz, H. J. (2003). Interstitial pulmonary siderofibrosis: Requirements for acceptance as new occupational disease. Pneumologie 57, 914.[CrossRef][Medline]
Buerke, U., Schneider, J., Rösler, J., and Woitowitz, H. J. (2002). Interstitial pulmonary fibrosis after severe exposure to welding fumes. Am. J. Ind. Med. 41, 259268.[CrossRef][ISI][Medline]
Chinn, D., Stevenson, I., and Cotes, J. (1990). Longitudinal respiratory survey of shipyard workers: Effects of trade and atopic status. Br. J. Ind. Med. 47, 8390.[ISI][Medline]
Choi, H., Kim, K., Ahn, S. H., Park, W. M., Kim, S. J., Lee, Y. J., and Chung, K. C. (1999). Airborne concentrations of welding fume and metals of workers exposed to welding fume. Korean Ind. Hyg. Assoc. J. 9, 5672.
Kwag, Y. S., and Paik, N. S. (1997). A study on airborne concentration on welding fumes and metals in confined spaces of a shipyard. Korean Ind. Hyg. Assoc. J. 7, 107126.
Lemaire, I., and Ouellet, S. (1996). Distinctive profile of alveolar macrophage-derived cytokine release induced by fibrogenic and nonfibrogenic mineral dusts. J. Toxicol. Environ. Health 47, 465478.[CrossRef][ISI][Medline]
Michielsen, C. P., Leusink-Muis, A., Vos, J. G., and Bloksma, N. (2001). Hexachlorobenzene-induced eosinophilic and granulomatous lung inflammation is associated with in vivo airways hyperresponsiveness in the Brown Norway rat. Tox. Appl. Pharm. 172, 1120.[CrossRef][ISI][Medline]
Morgenroth, K., and Verhagen-Schröter, G. (1984). Light and electron microscopic examination and energy dispersive radiologic microanalysis of biopsy probes for the pathogenesis of arc-welders lung. Atemw-Lungenkrkh 10, 451456.
Müller, K. M., and Verhoff, M. A. (2000). Graduation of sidero-pheumoconiosis. Atemw-Lungenkrkh 18, 428436.
Mur, J. M., Teculescu, D., Pham, Q. T., Gaertner, M., Massin, N., Meyer-Bisch, C., Moulin, J. J., Diebold, F., and Pierre, F. (1985). Lung function and clinical findings in a cross sectional study of arc welders: An epidemiological study. Int. Arch. Occup. Environ. Health 57, 118.[CrossRef][ISI][Medline]
NIOSH, (1999). NIOSH manual of analytical methods, method No. 0500, 7300. National Institute for Occupational Health, Cincinnati.
Oxhoj, H., Bake, B., Wedel, H., and Wihelmsen, L. (1979). Effects of electric arc welding on ventilatory function. Arch. Environ. Health 34, 211217.[ISI][Medline]
Redlich, C. A. (1996). Pulmonary fibrosis and interstitial lung diseases. In Occupational and Environmental Respiratory Diseases (P. Harber, M. B. Schenker, and J. R. Balmes, Eds.) pp. 216227. Mosby, St. Louis, MO.
Sferlazza, S. J., and Beckett, W. S. (1991). The respiratory health of welders. Am. Rev. Respir. Dis. 143, 11341148.[ISI][Medline]
Stanulla, H., and Liebtrau, G. (1984). Electrowelder's lung. Prax. Klin. Pneumol. 38, 1418.[Medline]
Stern, R. M., Pigott, G. H., and Abraham, J. L. (1983). Fibrogenic potential of welding fumes. J. Appl. Toxicol. 3, 1830.[Medline]
Sung, J. H., Choi, B. G., Maeng, S. H., Kim, S. J., Chung, Y. H., Han, J. H., Hyun, J. S., Song, K. S., Cho, Y. B., and Yu, I. J. (2004). Changes of pulmonary function during 60 days of welding fume exposure period. J. Toxicol. Pub. Health 20(1), 5561.
Yu, I. J., Kim, K. J., Chang, H. K., Song, K. S., Han, K. T., Han, J. H., Maeng, S. H., Chung, Y. H., Park, S. H., Chung, K. H., et al. (2000). Pattern of deposition of stainless welding fume particle inhaled into the respiratory systems of Sprague-Dawley rats exposed to a novel welding fume generating system. Toxicol. Lett. 116, 103111.[CrossRef][ISI][Medline]
Yu, I. J., Song, K. S., Chang, H. K., Han, J. H., Chung, Y. H., Han, K. T., Chung, K. H., and Chung, H. K. (2003). Recovery from manual arc-stainless steel welding-fume exposure induced lung fibrosis in Sprague-Dawley rats. Toxicol. Lett. 143, 247259.[CrossRef][ISI][Medline]
Yu, I. J., Song, K. S., Chang, H. K., Han, J. H., Kim, K. J., Chung, Y. H., Maeng, S. H., Park, S. H., Han, K. T., Chung, K. H., et al. (2001). Lung fibrosis in Sprague-Dawley rats. Induced by exposure to manual metal arc-stainless steel welding fumes. Toxicol. Sci. 63, 99106.
Yu, I. J., Song, K. S, Maeng, S. H., Kim, S. J., Sung, J. H., Han, J. H., Chung, Y. H., Cho, M. H., Chung, K. H., Han, K. T., et al. (2004). Inflammatory and genotoxic responses during 30-day welding-fume exposure period. Toxicol. Lett. 154, 105115.[CrossRef][Medline]
Zober, A. (1981). Symptoms and finding at the bronchopulmonay system of electric arc welder. Zbl. Bakt. Mikrobiol. Hyg. 173, 92119.
|