Abstract
Male Sprague-Dawley rats were exposed to a water-soluble metal working fluid (MWF) (5% v/v) contaminated with endotoxins (10,000 eu/ml or 100,000 eu/ml) at 10 mg/m3 for six hours per day for three days (acute exposure) or two weeks (subacute exposure). The geometric mean diameter of the MWF aerosols was 1.56 μm, and the airborne endotoxin concentrations ranged from 1,231 to 2,173 eu/m3 (10,000 eu/ml in the bulk MWF) for the low dose and 19,263–27,386 eu/m3 (100,000 eu/ml in the bulk MWF) for the high dose. Minimal effects were observed after exposure to 10 mg/m3 of the MWF without endotoxins for three days or two weeks. However, an increase in the number of polymorphonuclear cells (PMNs) and the level of protein was noted in the bronchoalveolar lavage (BAL) fluid from the rats acutely exposed to the MWF with endotoxins. The acute exposure produced a greater increase in the number of PMNs and total cell number in the BAL fluid than the subacute exposure. The number of white blood cells in the peripheral blood and the weight of the lungs both increased after the subacute exposure to the MWF aerosol with endotoxins, indicating increased vascular permeability in response to the endotoxin exposure. The levels of cyotokines such as IL-4, INF-γ, and IL-1β in the BAL fluid from the rats exposed to the MWF with or without endotoxins remained unchanged. Although the level of nitric oxide (NO x ) in the BAL supernatant did not show any change, the induction of NO x from the alveolar macrophages increased in the rats acutely or subacutely exposed to the MWF contaminated with endotoxins. The ConA-induced proliferation response showed no change, yet the LPS-induced proliferation response was significantly increased in the splenocytes from the rats subacutely exposed to the MWF with and without endotoxins. The level of TNF-α in the spleen cell culture obtained from the rats exposed to the MWF with or without endotoxins increased without changing the levels of IL-1β, IL-4, and INF-γ. The level of endotoxin-specific IgE in the serum obtained from the rats exposed to the MWF with endotoxins increased dose-dependently, while the levels of total immunoglobulins (IgG1, IgG2a and IgE) and endotoxin-specific IgG1 and IgG2a remained unchanged. Accordingly, the current results indicate that lung inflammation can be immediately induced by acute or subacute exposure to an MWF contaminated with endotoxins, and macrophages would appear to play a role in the induction of inflammation along with B-cell functions rather than T-cell functions, after subacute exposure to an MWF with endotoxins. In addition, endotoxin-specific IgE is an early marker for endotoxin exposure in the workplace.
Similar content being viewed by others
References
Abrams L, Seixas N, Robins T, Burge H, Muilenberg M, Franzblau A (2000) Characterization of metalworking fluid exposure indices for a study of respiratory effects. Appl Occup Environ Hyg 15:492–502
Bernstein DI, Lummus ZL, Santilli G, Siskosky J, Bernstein IL (1995) A hypersensitivity pneumonitis disorder associated with exposure to metalworking fluid aerosols. Chest 108:636–641
Brown ME, White EM, Feng A (2000) Effects of various treatments on the quantitative recovery of endotoxins from water-soluble metalworking fluids. AIHA J 61:517–520
Castranova V (2004) Role of nitric oxide in the progression of pneumoconiosis. Biochemistry (Moscow) 69:32–37
Choi BS, Chu KD, Jung JD, Seo KB, Lee JS, Choi SB, Lee YH, Lee YJ, Shin JH, Lee SJ, Seo HK, Kwak HS, Yuk HS (2003) Epidemic report on the chronic sinusitis of workers exposed to rotten MWF. Technical report of Occupational Safety and Health Research Institute, Inchon, South Korea
Delorme MP, Gao X, Doyon-Reale N, Barraclough-Mitchell H, Bassett DJ (2003) Inflammatory effect of inhaled endotoxin-contaminated metal working fluid aerosols in rats. J Toxicol Environ Health 66:7–24
Gaston B, Drazen JM, Loscalzo J, Stamler JS (1994) The biology of nitrogen oxides in the airways. Am J Respir Crit Care Med 149:538–551
Gordon T (1992) Acute respiratory effects of endotoxin-contaminated machining fluid aerosols in guinea pigs. Fundam Appl Toxicol 19:117–123
Gordon T, Galdanes G (1999) Factors contributing to the acute and subchronic adverse respiratory effects of machining fluid aerosols in guinea pigs. Toxicol Sci 49:86–92
Hendy MS, Beattie BE, Psurge PS (1985) Occupational asthma due to emulsified oil mist. Br J Ind Med 42:51–54
Huffman LJ, Prugh DJ, Millecchia L, Schuller KC, Cantrell S, Porter DW (2003) Nitric oxide production by rat bronchoalveolar macrophages or polymorphonuclear leukocytes following in tracheal intratracheal instillation of lipopolysaccharide or silica. J Biosci 28:29–37
Ialenti A, Ianar S, Van Overfield FJ, Di Rosa M (1992) Modulation of acute inflammation by endogenous nitric oxide. Eur J Pharmacol 211:177–182
Inger MB, Sandin M, Ahlstr MB, Allenmark S, Edebo M, Falsen E, Pedersen K, Robin N, Thompson RA, Edebo L (1989) Microbial growth and accumulation in industrial metal-working fluids. Appl Environ Microbiol 55:2681–2689
Laitinen S, Linnainmaa M, Laitinen J, Kiviranta H, Reiman M, Liesivuori J (1999) Endotoxins and IgG antibodies as indicators of occupational exposure to the microbial contaminants of metal-working fluids. Int Arch Occup Environ Health 72:443–450
Lim CH, Kim HY, Chung YH, Lee SB, Han JH (2002) Effect of water-soluble metal working fluid (MWF) aerosols on respiratory system after 13 weeks of repeated inhalation exposure in F344 rats. Study report of Occupational Safety and Health Research Institute, Korean Occupatonal Safety and Health Agency, Daejeon, South Korea
Milton DK (1995) Endotoxin. In: Burge HA (ed) Bioaerosols. CRC, Boca Raton, FL, pp 77–86
Moilanen E, Vapaatalo H (1995) Nitric oxide in inflammation and immune response. Ann Med 27:359–367
Paik NW, Park DW, Toon CS, Kim SW, Kim SB, Kim KS (1998) Control and investigation for hazardous characteristics of metalworking fluids used in Korea. Korean Ind Hyg Assoc J 8:67–75
Park D, Teschke K, Bartlett K (2001) A model for predicting endotoxin concentrations in metalworking fluid sumps in small machine shops. Ann Occup Hyg 45:569–576
Rosenman KD, Reilly MJ, Kalinowski DK (1997) Work-related asthma and respiratory symptoms among workers exposed to metal-working fluids. Am J Ind Med 32:325–331
Rossmoore HW (1981) Antimicrobial agents for water-based metalworking fluids. J Occup Med 23:247–254
Savill JS, Wyllie AH, Henson JE, Walport MJ, Henson PM, Haslett C (1989) Macrophage phagocytosis of aging neutrophils in inflammation Programmed well death in the neutrophil leads to its recognition by macrophages. J Clin Invest 83:865–875
Simpson AT, Stear M, Groves JA, Piney M, Bradley SD, Stagg S, Crook B (2003) Occupational exposure to metalworking fluid mist and sump fluid contaminants. Ann Occup Hyg 47:17–30
Thorne PS, DeKoster JA (1996) Pulmonary effects of machining fluids in guinea pigs and mice. Am Ind Hyg Assoc J 57:1168–1172
Whyte MK, Meagher LC, MacDermot I, Haslett C (1993) Impairment of function in aging neutrophils is associated with apoptosis. J Immunol 150:5124–5134
Woskie SR, Virji MA, Kruebel D, Sama SR, Eberiel D, Milton DK, Hammond SK, Eraso RM (1996) Exposure assessments for a field investigation of the acute respiratory effects of metalworking fluids. I. Summary of findings. Am Ind Hyg Assoc J 57:1154–1162
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Lim, CH., Yu, I.J., Kim, HY. et al. Respiratory effect of acute and subacute exposure to endotoxin-contaminated metal working fluid (MWF) aerosols on Sprague-Dawley rats. Arch Toxicol 79, 321–329 (2005). https://doi.org/10.1007/s00204-004-0640-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-004-0640-6