Gietzen K, Penka L, Eisenburger R
Department of Pharmacology and Toxicology, University of Ulm, Germany.
Exp Toxicol Pathol. 1996 Nov;48(6):529-31. doi: 10.1016/S0940-2993(96)80075-3.
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.
研究了咪唑类杀菌剂对大鼠肥大细胞和豚鼠气道平滑肌收缩的影响。对肥大细胞进行剂量效应研究，以验证我们的假设，即咪唑类杀菌剂是潜在的组胺释放剂，因此可能在体内诱发支气管收缩。事实上，所有测试的咪唑类杀菌剂（即酮康唑、咪康唑、咪鲜胺）以及咪鲜胺的一种农用制剂（即施保克）在30 - 300微摩尔浓度范围内均能引起肥大细胞释放组胺，尽管在效力和效果上存在显著差异。体内实验清楚地表明，吸入施保克气雾剂可在豚鼠中诱发显著的支气管收缩。此外，在单次暴露于施保克气雾剂5分钟后，动物对组胺产生了气道高反应性。从我们的研究结果可以得出结论，某些咪唑类杀菌剂通过非免疫机制引发组胺释放，在豚鼠中诱发气道收缩，因此可能对吸入用于植物保护的杀菌剂气雾剂的喷雾操作人员有害。
