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烷基转移剂接触过敏潜力的定量构效/剂量反应关系。

A quantitative structure activity/dose response relationship for contact allergic potential of alkyl group transfer agents.

作者信息

Roberts D W, Basketter D A

机构信息

Unilever Research, Port Sunlight, The Wirral, Cheshire, England.

出版信息

Contact Dermatitis. 1990 Nov;23(5):331-5. doi: 10.1111/j.1600-0536.1990.tb05167.x.

DOI:10.1111/j.1600-0536.1990.tb05167.x
PMID:1965716
Abstract

As part of the investigation of structure activity relationships in contact allergy, it has been 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. The modified single injection adjuvant test has been used to investigate the sensitization potential of C12, C16 and unsaturated C18 alkyl transfer agents. Dose responses to challenge and the patterns of cross-reactivity between these materials and methyl transfer agents have been studied. All alkyl transfer agents examined were potent sensitizers in the guinea pig. There was evidence of mutual cross-reactivity between all alkyl transfer agents examined (including methyl transfer agents). Analysis of the data in terms of a modified relative alkylation index showed evidence of an overload effect. The sensitization data has been accurately modelled using a mathematical equation. These results emphasize the possibilities for relating physicochemical parameters and skin sensitization potential. Further studies with alkyl transfer agents are in progress of amplify the observations and conclusions presented in this report. No in vitro model is available for the prediction of skin sensitization potential. Therefore an approach based on a model using physicochemical criteria is the most likely route to a reduced requirement for animal testing.

摘要

作为接触性过敏结构活性关系研究的一部分,已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。改良的单次注射佐剂试验已用于研究C12、C16和不饱和C18烷基转移剂的致敏潜力。已研究了对激发的剂量反应以及这些物质与甲基转移剂之间的交叉反应模式。所有检测的烷基转移剂在豚鼠中都是强效致敏剂。有证据表明所有检测的烷基转移剂(包括甲基转移剂)之间存在相互交叉反应。根据改良的相对烷基化指数对数据进行分析显示存在过载效应。致敏数据已使用数学方程进行了精确建模。这些结果强调了将物理化学参数与皮肤致敏潜力相关联的可能性。正在对烷基转移剂进行进一步研究,以扩大本报告中的观察结果和结论。目前尚无用于预测皮肤致敏潜力的体外模型。因此,基于使用物理化学标准的模型的方法是最有可能减少动物试验需求的途径。

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