Short-Term in Vitro Screening Studies Related to the Inhalation Toxicology of Potentially Toxic Aerosols
Final rept. Jun 1984-Apr 1986
ENVIRONMENTAL PROTECTION AGENCY RESEARCH TRIANGLE PARK NC INHALATION TOXICOLOGY DIV
Pagination or Media Count:
The toxicity of JCE001 particles was tested using the rabbit alveolvar macrophage RAM test, hamster tracheal cultures and in vivo pulmonary bactericidal activity in mice. In the RAM test, incubation of alveolar macrophages AM with the JCE001 particles decreased AM viability, cellular adenosine 5 -triphosphate ATP and total protein levels. The lowest effective dose as determined by Williams test was 50 ugmL of JCE001 particles for all parameters examined. The presence of soluble cytotoxic components was established. The nature and rate of release of soluble toxic components from the JCE001 particles were important contributing factors in the mechanism by which these particles produced their toxic effects. A single 1-hr in vitro exposure of hamster tracheal ring organ cultures to the JCE001 particles was conducted to determine the dose response on ciliated respiratory epithelium. JCE001 particles caused a significant decrease in cilia beating frequency and an increase in cytopathological alterations. Morphological alterations in the tracheal epithelium were observed with light microscopy and scanning electron microscopy. The effect of the JCE001 particles on the ability of AM to kill inhaled pneumoniae was also measured. Bactericidal activity of all groups treated with the JCE001 particles was markedly reduced compared to that of controls.