Development of pulmonary tolerance in mice exposed to zinc oxide fumes

Details

• Personal Author:
  Chen LC ; Gordon T ; Wesselkamper SC
• Description:
  As a result of repeated exposures to inhaled toxicants such as zinc oxide (ZnO), numerous individuals acquire tolerance to the exposures and display reduced symptoms. To ascertain whether tolerance is developed in an animal model, NIH-Swiss mice were exposed to 1.0 mg/m(3) ZnO for 1, 3, or 5 days (1X, 3X, or 5X), and polymorphonuclear leukocyte (PMN) and protein levels in bronchoalveolar lavage (BAL) were measured. Mice acquired tolerance to neutrophil infiltration into the lungs, as total PMNs returned near baseline in 5X-exposed animals as compared to that of the 1X exposure group (1X = 2.7 +/- 0.4 x 10(4), 5X = 0.2 +/- 0.1 x 10(4), mean +/- SE, p < 0.05). Development of tolerance to changes in lavageable protein, however, was not observed (1X = 313 +/- 29 microg/ml, 5X = 684 +/- 71 microg/ml, p < 0.05). Tolerance to PMN influx did not persist following re-exposure to ZnO after 5 days of rest. In contrast to ZnO exposure, following single and repeated exposure to aerosolized endotoxin there was development of tolerance to protein in BAL (1X = 174 +/- 71 microg/ml, 5X = 166 +/- 14 microg/ml, p > 0.05), but not to PMN influx (1X = 5.5 +/- 1.7 x 10(4), 13.9 +/- 1.7 x 10(4), p < 0.05). Induction of lung metallothionein (MT) was also observed in mice exposed once or repeatedly exposed to ZnO, suggesting that MT may play a role in its molecular mechanism. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Endotoxins Environmental Monitoring Hazardous Substances Inhalation Exposure Laboratories Lung Metals Occupational Health Respiratory System Safety Zinc Compounds

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• Keywords:
  Adaptation Alveolar-cells Author Keywords: Zinc-oxide Clinical-symptoms Endotoxin Exposure-assessment Exposure-levels Fumes Inhalants Laboratory-animals Laboratory-testing Leukocytes Lung-irritants Metal-fume-fever Metal-fumes Metal Fume Fever Metalloproteins Metallothionein Neutrophils Proteins Pulmonary-function Pulmonary-system Tolerance Tolerance-threshold Toxic-vapors Toxins Zinc-compounds

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  144-151
• Volume:
  60
• Issue:
  1
• NIOSHTIC Number:
  nn:20040772
• Citation:
  Toxicol Sci 2001 Mar; 60(1):144-151
• Contact Point Address:
  Terry Gordon, Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, New York 10987, USA
• Email:
  gordont@env.med.nyu.edu
• CAS Registry Number:
  Zinc (CAS RN 7440-66-6) ; Zinc oxide (ZnO) (CAS RN 1314-13-2)
• Federal Fiscal Year:
  2001
• NORA Priority Area:
  Pulmonary System Disorders
• Performing Organization:
  Yale University, New Haven, Connecticut
• Peer Reviewed:
  True
• Start Date:
  19920930
• Source Full Name:
  Toxicological Sciences
• End Date:
  19950929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:99781bb3ebb318107d0846d79aaef0dcc807f188ff82d45f05459ac1e0c22f22563fc8bb1f1815c7f69ec07784ed6429ae9e4adbd5838db50d78bac90c7e2619
• Download URL:
  https://stacks.cdc.gov/view/cdc/193523/cdc_193523_DS1.pdf
• File Type:
  [PDF - 298.66 KB ]