Maurer J K, Parker R D, Carr G J
Procter & Gamble Co., Miami Valley Laboratories, Cincinnati, Ohio 45253-8707, USA.
Toxicol Pathol. 1998 Mar-Apr;26(2):217-25. doi: 10.1177/019262339802600205.
The pathology of surfactant-induced ocular irritation, especially in the context of accidental human exposures and animal tests used to assess a surfactant's potential ocular irritation, is not well understood. The purpose of this study was to characterize the microscopic changes in rats at 3 hr and on days 1, 2, 3, 4, 7, 14, and 35 following treatment with anionic, cationic, and nonionic surfactants of differing irritancy. The right eye of each rat was treated by placing 10 microliters of a surfactant directly on the cornea. Untreated left eyes served as the controls. At each time point, eyes and eyelids were macroscopically examined and collected for microscopic examination. Macroscopically, the differing levels of irritation were characterized by differences in incidence and magnitude of scores, reflecting involvement of the cornea, conjunctiva, and iris, as well as by the incidence of neovascularization and time to recovery. Microscopically, differences in the area and depth of injury paralleled the differences seen grossly and the relative irritancy of the various surfactants. All surfactants affected the corneal and conjunctival epithelium. All surfactants, except the slightly irritating anionic surfactant, caused corneal stromal changes, with this involvement being proportional to their overall level of irritation. Corneal endothelial cell effects principally occurred with only the severely irritating cationic surfactant. Over time, responses to surfactants of differing irritancy were qualitatively and quantitatively different, and these differences correlated with the extent of initial injury. Qualitative differences in response included presence of keratocyte regeneration, corneal neovascularization, and conjunctivalization of the corneal epithelium with all of the surfactants except the slight irritant. Quantitative differences in response occurred in the extent of epithelial regeneration, edema, and inflammation for surfactants of slight to severe irritancy, and with neovascularization, keratocyte regeneration, and conjunctivalization for surfactants of mild to severe irritancy. These results suggest that by defining initial area and depth of injury associated with an ocular irritant, it may be possible to predict the subsequent response and final outcome. Such an approach would be applicable to the development of mechanistically based in vitro assays.
表面活性剂引起的眼部刺激的病理学，尤其是在人类意外接触以及用于评估表面活性剂潜在眼部刺激性的动物试验背景下，目前尚未得到充分了解。本研究的目的是描述大鼠在用不同刺激性的阴离子、阳离子和非离子表面活性剂处理后3小时以及第1、2、3、4、7、14和35天的微观变化。每只大鼠的右眼通过将10微升表面活性剂直接滴在角膜上进行处理。未处理的左眼作为对照。在每个时间点，对眼睛和眼睑进行宏观检查并收集用于微观检查。宏观上，不同程度的刺激表现为评分的发生率和幅度差异，反映角膜、结膜和虹膜的受累情况，以及新生血管形成的发生率和恢复时间。微观上，损伤的面积和深度差异与肉眼所见差异以及各种表面活性剂的相对刺激性平行。所有表面活性剂均影响角膜和结膜上皮。除轻度刺激性阴离子表面活性剂外，所有表面活性剂均引起角膜基质变化，这种受累程度与它们的总体刺激水平成正比。角膜内皮细胞效应主要仅发生在具有严重刺激性的阳离子表面活性剂中。随着时间的推移，对不同刺激性表面活性剂的反应在质量和数量上存在差异，这些差异与初始损伤的程度相关。反应的质量差异包括角膜细胞再生、角膜新生血管形成以及除轻度刺激物外所有表面活性剂引起的角膜上皮结膜化。对于轻度至重度刺激性表面活性剂，反应的数量差异表现为上皮再生、水肿和炎症的程度差异，对于轻度至重度刺激性表面活性剂，还表现为新生血管形成、角膜细胞再生和结膜化的差异。这些结果表明，通过确定与眼部刺激物相关的初始损伤面积和深度，有可能预测后续反应和最终结果。这种方法将适用于基于机制的体外试验的开发。
