Bast G E, Taeschner D, Kampffmeyer H G
Walther-Straub-Institute for Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.
Arch Toxicol. 1997;71(3):179-86. doi: 10.1007/s002040050373.
Isolated rabbit ears were single-pass perfused with a protein-free medium. Permethrin (0.05-23.5%, w/w) was applied in four distinct ointments. Permethrin, 3-phenoxybenzyl alcohol, 3-phenoxybenzaldehyde, and 3-phenoxybenzoic acid were analysed by HPLC. Permethrin was not detected in the effluent. The permeation coefficient, calculated from the detection limit was < 7.3 x 10(-12) (cm/sec). The appearance rate of the 3-phenoxybenzyl moieties in the effluent agreed with the absorption of the corresponding impurities in the various ointments. In supernatant of homogenised skin, the hydrolysis rate of permethrin was linear; about 4 pmol/min per cm2 at 10 microM substrate concentration. The proportion of 3-phenoxybenzoic acid, a further metabolite of 3-phenoxybenzyl alcohol increased when an oxidizing co-factor system was added. The appearance rate in the effusate of 3-phenoxybenzyl alcohol following the lipophobic ointment was five times faster than from isopropyl myristate. The formation rate of 3-phenoxybenzoic acid followed saturation kinetics. Occupational systemic poisoning by dermal absorption of permethrin seems very unlikely since humans bear more epithelial cell layers than rabbits. These experiments do not contradict, however, possible paraesthesia during systemic poisoning after inhalation or ingestion of the pyrethroid-containing aerosols used in agriculture.
将离体兔耳用无蛋白培养基进行单次灌注。将氯菊酯(0.05 - 23.5%,w/w)制成四种不同的软膏剂使用。采用高效液相色谱法分析氯菊酯、3 - 苯氧基苄醇、3 - 苯氧基苯甲醛和3 - 苯氧基苯甲酸。流出液中未检测到氯菊酯。根据检测限计算的渗透系数<7.3×10⁻¹²(cm/秒)。流出液中3 - 苯氧基苄基部分的出现率与各种软膏剂中相应杂质的吸收情况一致。在匀浆皮肤的上清液中,氯菊酯的水解速率呈线性;在底物浓度为10微摩尔时,约为每平方厘米每分钟4皮摩尔。当添加氧化辅因子系统时,3 - 苯氧基苄醇的另一种代谢产物3 - 苯氧基苯甲酸的比例增加。疏油性软膏剂处理后流出液中3 - 苯氧基苄醇的出现速率比肉豆蔻酸异丙酯处理后的快五倍。3 - 苯氧基苯甲酸的形成速率遵循饱和动力学。由于人类的上皮细胞层数比兔子多,经皮肤吸收氯菊酯导致职业性全身中毒似乎不太可能。然而,这些实验并不排除在吸入或摄入农业用含拟除虫菊酯气雾剂后全身中毒期间可能出现的感觉异常。