Renewal of the terminal bronchiolar epithelium in the rat following exposure to NO2 or O3

Rats were exposed to either NO2 or O3 to determine whether nonciliated cells (Clara cells) could divide and differentiate into ciliated cells in the terminal bronchioles. Dividing cells were labeled with tritiated thymidine, visualized in the light and electron microscopes using autoradiographic techniques, and studied for up to 15 days after labeling. Electron microscopic autoradiography 1 hour after injection of tritiated thymidine showed that all labeled cells in the terminal bronchioles were nonciliated. However, 4 days after injection of tritiated thymidine, 67.8 per cent of the labeled cells were nonciliated and 32.2 per cent were ciliated. Light microscopic autoradiography showed that the new labeled ciliated cell population was stable for up to 15 days. These results indicate that nonciliated cells divide and the sister cells may form new ciliated and nonciliated cells. Thus, nonciliated cells can act as progenitor cells for the terminal bronchiolar epithelium.     

Evaluation of the humoral immune response of CD rats following a 2-week exposure to the pesticide carbaryl by the oral, dermal, or inhalation routes

The objective of this study was to examine the immunotoxicological effects of the methyl-carbamate pesticide carbaryl via the oral, dermal, or inhalation routes. Male CD rats were exposed to carbaryl 5 d/wk for a 2-wk period. During nose-only inhalation exposures, rats received either 36, 137, or 335 mg/m3 carbaryl in acetone for 6 h. Air only and acetone/air controls were run concurrently. Orally exposed animals received either 1 ml corn oil or 10, 25, or 50 mg/kg carbaryl, while dermally exposed animals received either 2 ml acetone or 100, 500, or 1000 mg/kg carbaryl on their dorsal flank for 6 h. Four days prior to sacrifice, animals from all exposure groups were injected iv with 2 x 10(8) sheep red blood cells (SRBC). The primary immunoglobulin M (IgM) humoral immune response to SRBC was then assessed by measuring SRBC-specific antibody-forming cells (AFC) and levels of serum anti-SRBC IgM antibody, respectively, using the hemolytic plaque assay and an enzyme-linked immunosorbent assay. Individual body weights, spleen, thymus, and liver weights, spleen cell number, and red and white blood cell (RBC, WBC) counts were obtained for each animal. Following nose-only inhalation exposures, dose-dependent decreases in thymus weights, spleen cell number, AFC/spleen, AFC/10(6) splenocytes, and serum levels of SRBC-specific IgM antibody were observed. Significant decreases of 33, 57, and 22% in spleen cell number, AFC/spleen, and thymus weight, respectively, were found at the 335 mg/m3 exposure level. Animals exposed orally to 25 mg/kg carbaryl had a 34% decrease in WBC counts. A 34% decrease in WBC and a 13% increase in RBC counts were observed at the 50 mg/kg oral dose. Significant decreases in liver weights ranging from 11 to 13% were found at all oral exposure levels. Dermal exposure to carbaryl revealed no significant toxicological effects. Results indicate that humoral immune suppression was observed following inhalation, but not following oral or dermal exposures to carbaryl. Immunotoxicological studies evaluating pesticides need to consider relevant exposure routes and dosages for appropriate risk assessment procedures and exposure limits to be established.