Maurer J K, Parker R D
Procter & Gamble Co., Miami Valley Laboratories, Cincinnati, Ohio 45253-8707, USA.
Toxicol Pathol. 1996 Jul-Aug;24(4):403-11. doi: 10.1177/019262339602400403.
Limited information exists on the pathologic changes occurring with surfactant-induced ocular irritation in the context of accidental human exposures and animal tests used to assess for such irritation. The purpose of this study was to begin to characterize the pathologic changes that occur with surfactants in the context of standard animal tests and compare the response in rats to that in rabbits. Representative anionic, cationic, and nonionic surfactants causing slight to severe ocular irritation were directly applied to the corneas of rabbits and rats at a dose of 10 microliters. Eyes and eyelids of each animal were macroscopically examined for signs of irritation beginning 3 hr after dosing and periodically until recovery or day 35. Eyes and eyelids from animals in each group were collected for microscopic examination after 3 hr and at recovery or day 35. Microscopically, all of the surfactants caused erosion, denudation, and/or necrosis of the conjunctival and corneal epithelium in rabbits and rats. Necrosis of keratocytes was observed in rabbits and rats treated with the severely irritating cationic surfactant and in rats treated with anionic surfactants that were mildly irritating and moderately irritating. Corneal endothelial changes were observed in rabbits and rats with only the cationic surfactant. Changes in eyes of rabbits and rats that had not recovered by day 35 included decreased prominence of goblet cells, conjunctivalization of the corneal epithelium, neovascularization and fibrosis of the cornea, and presence of devitalized stroma. Overall, the changes in rabbits and rats were similar and suggest that the rat may be used as a surrogate for the rabbit in studies to understand better mechanisms of surfactant-induced eye irritation.
关于人类意外接触表面活性剂导致眼部刺激以及用于评估此类刺激的动物试验中所发生的病理变化,现有信息有限。本研究的目的是在标准动物试验的背景下,开始描述表面活性剂引起的病理变化,并比较大鼠与兔子的反应。将导致轻度至重度眼部刺激的代表性阴离子、阳离子和非离子表面活性剂以10微升的剂量直接滴入兔子和大鼠的角膜。给药后3小时开始对每只动物的眼睛和眼睑进行宏观检查,观察刺激迹象,并定期检查直至恢复或第35天。在给药3小时后以及恢复时或第35天,收集每组动物的眼睛和眼睑进行显微镜检查。在显微镜下,所有表面活性剂均导致兔子和大鼠结膜及角膜上皮的糜烂、剥脱和/或坏死。在用具有严重刺激性的阳离子表面活性剂处理的兔子和大鼠以及用轻度刺激性和中度刺激性阴离子表面活性剂处理的大鼠中,观察到角膜细胞坏死。仅在用阳离子表面活性剂处理的兔子和大鼠中观察到角膜内皮变化。到第35天仍未恢复的兔子和大鼠眼睛的变化包括杯状细胞突出度降低、角膜上皮结膜化、角膜新生血管形成和纤维化以及存在无活力的基质。总体而言,兔子和大鼠的变化相似,这表明在研究中为了更好地理解表面活性剂诱导的眼部刺激机制,大鼠可以作为兔子的替代动物。