Imidazole fungicides provoke histamine release from mast cells and induce airway contraction.

The effects of imidazole fungicides on rat mast cells and on guinea-pig airway smooth muscle contraction were studied. The dose-effect studies on mast cells were performed to prove our hypothesis that imidazole fungicides are potential histamine releasing agents and thus may induce bronchoconstriction in vivo. Indeed, all imidazole fungicides tested (i. e. ketoconazole, miconazole, prochloraz) and an agricultural formulation of prochloraz (i. e. Sportak) were able to elicit histamine release from mast cells in the concentration range of 30-300 microM, although there were marked differences in potency and efficacy. The in vivo experiments clearly showed that inhaled Sportak aerosols induce a significant bronchoconstriction in guinea-pigs. Moreover, after a single 5 min exposure to Sportak aerosols the animals developed airway hyperreactivity against histamine. From the results of our study it may be concluded that certain imidazole fungicides provoke histamine release by a non-immunological mechanism, induce airway constriction in guinea-pigs and hence may be harmful to spray operators who might inhale fungicide aerosols used for plant protection.