Autoradiographic analyses of guinea pig airway tissues following inhalation exposure to 14c-labeled methyl isocyanate.
Kennedy-AL; Singh-G; Alarie-Y; Brown-WE
Fundam Appl Toxicol 1993 Jan; 20(1):57-67
The localization and penetration of methyl-isocyanate (624839) (MIC) into airway tissues were studied in English-short-hair-guinea-pigs. The animals were exposed to 0 to 15.2 parts per million (ppm) carbon- 14 (C14) labeled MIC for 1 to 6 hours. Tracheotomized guinea-pigs were exposed to 0, 0.55, or 3.05ppm C14 labeled MIC for 1 hour. Selected animals were killed after each exposure and the amounts of MIC derived radioactivity in the nasal tissues, trachea, lungs, and other tissues were determined by autoradiography. Histopathological changes were also noted. Guinea-pigs exposed to 2.82ppm MIC for 1 to 6 hours were killed at various times up to 168 hours postexposure and the trachea and lungs were removed and assayed for C14 activity to determine the persistence of MIC. The highest levels of MIC derived radioactivity in intact animals were found in the nasal, trachea, and lung tissues. When expressed as ppm hours, accumulations of radioactivity in the airway tissues was dose dependent. Detectable amounts of radioactivity were also found in the spleen, kidneys, and liver. Significant amounts of C14 activity were found in the lungs and trachea 24 hours after exposure to 2.82ppm MIC. Minimal histological changes were found in the airway tissues only after exposure to 15.2ppm MIC. Within the nasal cavity, most of the radioactivity was localized in the respiratory epithelium. No radiolabeling was observed in the nasal tissues of tracheotomized animals. The primary site of radiolabeling in the trachea was the subepithelial region. In the lungs, most radiolabeling also occurred in the subepithelial region. At higher MIC concentrations a dose related increase in epithelial cell labeling was observed. The intensity of radiolabeling decreased with migration into the distal airways. The authors conclude that despite its high reactivity MIC is selectively deposited in airway tissues. The extent of deposition depends on the airway region and the specific cell types involved.
NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; Isocyanates; In-vivo-studies; Laboratory-animals; Dose-response; Inhalation-studies; Nasal-cavity; Pulmonary-system; Histopathology; Tissue-distribution
Biological Sciences Carnegie-Mellon University 4400 Fifth Ave Pittsburgh, PA 15213
Fundamental and Applied Toxicology
Carnegie-Mellon University, Pittsburgh, Pennsylvania