Chromate inhibition of metabolism by rat tracheal explants II. In vivo exposures

We have previously shown that incubation of rat tracheal slices in tissue culture medium containing 0.4-2.6 mm (mmol/liter) Na₂CrO₄ causes inhibition of secretion of mucus glycoproteins by such explants. At concentrations of Na₂CrO₄ of 0.27 mm and above, the inhibition of secretion rate could be correlated with damage to the tracheal epithelium evaluated by histopathologic observations. In the present study we extend these findings by determination of the effects of Na₂CrO₄, administered to rats in vivo (for 24 hr) as an aerosol with a mass median aerodynamic diameter of 1-2 μm at concentrations of 0.051 and 0.173 mmol/m³, upon the previously evaluated parameters. With the aid of several simplifying assumptions, the in vivo dosages of Na₂CrO₄ can be compared with the equivalent concentrations to which trachaea were exposed in vitro in the earlier study. When such calculations are made, there is an excellent correlation between the toxicity observed at equivalent dosages of Na₂CrO₄ in vivo and in vitro. Such data may be used to calculate the tracheal deposition factor, F, the percentage of the total Na₂CrO₄ mass from the inhaled aerosol deposited upon the trachea. The value of F so obtained, 0.4-0.7%, compares favorably with results calculated previously on the basis of deposition of radiolabeled fused aluminosilicate particles. Thus, the tracheal explant technique may prove useful as a dosimeter for studying the quantitative in vivo deposition of freely diffusable, water-soluble agents on various airway surfaces of experimental animals.