Roberts D W, Basketter D A
Unilever Research, Port Sunlight, The Wirral, Cheshire MK44 1LQ, UK.
Toxicol In Vitro. 1990;4(4-5):686-7. doi: 10.1016/0887-2333(90)90142-g.
Since no in vitro model is available, or indeed likely, to predict or investigate skin sensitization potential of substances, an approach based on a model using physicochemical criteria is the most likely route to a reduced requirement for animal testing. As part of the investigation of structure-activity relationships in contact allergy, it was shown that methyl transfer agents are capable of acting as skin sensitizers. This work has now been extended to a more general examination of alkyl transfer reactions. In vivo dose responses to challenge and the patterns of cross reactivity between C(12), C(16), unsaturated C(16) and methyl transfer agents were examined to form the basis of the mathematical model. All alkyl transfer agents examined were potent sensitizers, with evidence of mutual cross reactivity between them. The sensitization data have been accurately modelled using a mathematical equation. Analysis in terms of a modified relative alkylation index model showed evidence of an overload effect.
由于目前没有可用的体外模型，实际上也不太可能有，来预测或研究物质的皮肤致敏潜力，因此基于物理化学标准模型的方法是最有可能减少动物试验需求的途径。作为接触性过敏结构 - 活性关系研究的一部分，研究表明甲基转移剂能够作为皮肤致敏剂。这项工作现已扩展到对烷基转移反应更全面的研究。研究了对激发的体内剂量反应以及C(12)、C(16)、不饱和C(16)和甲基转移剂之间的交叉反应模式，以形成数学模型的基础。所有检测的烷基转移剂都是强效致敏剂，它们之间存在相互交叉反应的证据。致敏数据已使用数学方程进行了精确建模。根据修正的相对烷基化指数模型进行分析显示存在过载效应的证据。
