THE EFFECTS OF BENOMYL AND ITS BREAKDOWN PRODUCTS CARBENDAZIM AND BUTYL ISOCYANATE ON THE STRUCTURE AND FUNCTION OF TRACHEAL CILIATED CELLS

The effects of the fungicide benomyl and its breakdown products, carbe ndazim and butyl isocyanate, were examined on canine tracheal epitheli al tissue in primary culture. Changes in ciliary frequencies were moni tored with an optical spectrum analysis system. Serial dilutions of th e test compounds were prepared in 100% corn oil and applied to the cel l cultures for intervals up to 6 hours and frequencies measured at int ervals of 15 minutes to 1 hour. Benomyl and butyl isocyanate caused co ncentration-dependent decreases in ciliary beat frequency. Benomyl at 300 mu g/ml (3 mM) caused ciliostasis within 75 minutes of exposure. B utyl isocyanate at a molar concentration three times lower than benomy l (1 mM) caused a similar response, although within 30 minutes. The IB C50 for benomyl was 0.75 mM, while for butyl isocyanate it was 0.52 mM . Carbendazim caused a moderate decrease in frequency over a 6 hour ex posure period. Benomyl caused moderate to severe swelling of the mitoc hondria of ciliated epithelial cells with other cell organelles appear ing normal. Butyl isocyanate did not cause any noticeable effect on ce ll ultrastructure and the apparently low rate of penetration of carben dazim into cells made it impossible to obtain an effect which justifie d ultrastructural analysis. It appears, at least for benomyl and butyl isocyanate, that while the physiological effect of these two compound s (inhibition of ciliary beat) is the same, the sites of action in the cell may be different.