BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany.
Altern Lab Anim. 2010 Mar;38(1):39-52. doi: 10.1177/026119291003800109.
Data on eye irritation are generally needed for the hazard identification of chemicals. For the routine testing of a broad variety of chemicals and formulations, we have used the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) method. In the course of a tiered-testing strategy, and due to the lack of global regulatory acceptance of the HET-CAM method, we have also performed the Rabbit Eye Irritation test according to OECD Test Guideline 405. Of the 145 substances tested, 76% were classified as non-irritant/mild irritant and 13% were identified as irritant in vivo, according to the EU classification system (61% and 28%, respectively, with the GHS classification). The remaining 11% were severe irritants in vivo, based on the irreversibility of the effects and not due to sufficiently high irritation scores in the three days following application. The retrospective analysis revealed that the overall accuracy of the HET-CAM assay was 65% and the overall rates of false-negatives (FN) and false-positives (FP) were 50% and 33%, respectively. The HET-CAM assay was sufficiently specific (few FP) for water-soluble substances, but failed to identify nearly all the severe irritants within this group. In contrast, it was highly sensitive (no FN) for non-soluble and oil-soluble substances, but the specificity for this group was rather low. Therefore, we conclude that the HET-CAM assay is not useful in our tiered-testing strategy for eye irritation testing. However, for water-insoluble substances, it might be applicable in combination with another in vitro method, provided that regulatory acceptance is gained.
数据一般是在化学品危害识别时需要眼部刺激。对于各种化学品和制剂的常规测试，我们使用鸡胚绒毛尿囊膜（HET-CAM）方法。在分级测试策略中，由于全球监管部门不接受 HET-CAM 方法，我们还根据 OECD 测试指南 405 进行了兔眼刺激性测试。在测试的 145 种物质中，根据欧盟分类系统（分别为 61%和 28%），76%被归类为非刺激性/轻度刺激性，13%被鉴定为体内刺激性，而根据 GHS 分类，分别为 61%和 28%。其余 11%为体内严重刺激性，这是基于效果的不可逆性，而不是由于在应用后的三天内刺激评分足够高。回顾性分析显示，HET-CAM 测定的总准确性为 65%，总假阴性（FN）和假阳性（FP）率分别为 50%和 33%。HET-CAM 测定法对于水溶性物质具有足够的特异性（假阳性率低），但未能识别出该组中的几乎所有严重刺激性物质。相比之下，它对非水溶性和油溶性物质非常敏感（无假阴性），但对该组的特异性较低。因此，我们得出结论，HET-CAM 测定法在我们的眼刺激性测试分级测试策略中并不有用。然而，对于水不溶性物质，它可能适用于与另一种体外方法结合使用，前提是获得监管部门的认可。
