Kligman A M, Kligman L H
Department of Dermatology, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA.
Food Chem Toxicol. 1998 Sep-Oct;36(9-10):867-78. doi: 10.1016/s0278-6915(98)00045-3.
An enormous number of synthetic chemicals are incorporated in topical drugs, cosmetics and toiletries. These have the potential to cause irritant reactions when chronically applied to human skin. In predictive tests for assessing the irritancy potential of these chemicals, haired species, especially rabbits, guinea pigs and mice, have figured prominently. Customarily these tests, including the renowned Draize rabbit test, have entailed a single acute exposure or at most daily exposures over a few weeks. Estimation of inflammation and tissue injury in these models have relied on visual assessment. We submit that this approach is no longer acceptable. Visual assessments are unreliable. Reactions which are scored equivalently by the naked eye may differ strikingly when examined histologically. Moreover, tissue injury may be present in clinically normal skin. Short-term results. even when abetted by routine histological evaluations, cannot predict the degree of injury from long-term exposures. Cosmetics and toiletries, for example, are used daily for decades, often over most of the lifespan of persons who are well groomed. We present the hairless mouse as a convenient, reliable model for assessing the chronic toxicity of diverse chemicals. Histological examination enables a detailed description of the different tissue components which participate in the complex cascade of changes that comprise the inflammatory response.
大量合成化学品被用于外用药物、化妆品和洗漱用品中。当长期应用于人体皮肤时，这些化学品有可能引起刺激性反应。在评估这些化学品潜在刺激性的预测性试验中，有毛动物，尤其是兔子、豚鼠和小鼠，发挥了重要作用。通常，这些试验，包括著名的Draize兔子试验，都涉及单次急性暴露，或者最多在几周内每日暴露。在这些模型中，炎症和组织损伤的评估依赖于视觉评估。我们认为这种方法不再可接受。视觉评估是不可靠的。肉眼评分相同的反应，在组织学检查时可能有显著差异。此外，临床上正常的皮肤可能存在组织损伤。短期结果，即使辅以常规组织学评估，也无法预测长期暴露造成的损伤程度。例如，化妆品和洗漱用品会在几十年里每日使用，通常是在注重仪容整洁者的大部分寿命期间使用。我们提出无毛小鼠是评估多种化学品慢性毒性的方便、可靠模型。组织学检查能够详细描述参与构成炎症反应这一复杂变化级联的不同组织成分。
