Compilation of historical local lymph node data for evaluation of skin sensitization alternative methods

被引:399
作者
Gerberick, GF
Ryan, CA
Kern, PS
Schlatter, H
Dearman, RJ
Kimber, I
Patlewicz, GY
Basketter, DA
机构
[1] Procter & Gamble Co, Miami Valley Innovat Ctr, Cincinnati, OH 45253 USA
[2] Procter & Gamble Co, Brussels Valley Innovat Ctr, Brussels, Belgium
[3] Procter & Gamble Co, Schwalbach Tech Ctr, Schwalbach, Germany
[4] Syngenta Cent Toxicol Lab, Macclesfield, Cheshire, England
[5] Unilever Res Labs Colworth, Colworth Lab, Safety & Environm Assurance Ctr, Sharnbrook MK44 1LQ, Beds, England
关键词
D O I
10.2310/6620.2005.05040
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background. Within the toxicology community, considerable effort is directed toward the development of alternative methods for skin sensitization testing. The availability of high-quality, relevant, and reliable in vivo data regarding skin sensitization is essential for the effective evaluation of alternative methodologies. Ideally, data derived from humans would be the most appropriate source because the test methods are attempting to predict a toxicologic effect in humans. Unfortunately, insufficient human data of the necessary quality are available, so it is necessary to rely on the best available animal data. In recent years, the local lymph node assay (LLNA) has emerged as a practical option for assessing the skin sensitization potential of chemicals. In addition to accurately identifying skin sensitizers, the LLNA can also provide a reliable measure of relative sensitization potency, information that is pivotal to the successful management of human health risks. Objective To provide a database of robust in vivo data to calibrate, evaluate, and eventually validate new approaches for skin sensitization testing. Methods: LLNA data derived from previously conducted studies were compiled from the published literature and unpublished sources. Results: We provide a database that comprises LLNA data on 211 individual chemicals. This extensive chemical data set encompasses both the chemical and biologic diversity of known chemical allergens. To cover the range of relative allergenic potencies, the data set includes data on 13 extreme, 21 strong, 69 moderate, and 66 weak contact allergens, classified according to each allergen's mathematically estimated concentration of chemical required to induce a threefold stimulation index. In addition, there are also 42 chemicals that are considered to be nonsensitizers. In terms of chemical diversity, the database contains data pertaining to the chemical classes represented by aldehydes, ketones, aromatic amines, quinones, and acrylates, as well as compounds that have different reactivity mechanisms. In addition to two-dimensional chemical structures, the physicochemical parameters included are log Kp, log K-O/W, and molecular weight. Conclusions: The list of chemicals contained in the data set represents both the chemical and biologic diversity that is known to exist for chemical allergens and non-allergens. It is anticipated that this database will help accelerate the development, evaluation, and eventual validation of new approaches to skin sensitization assessment.
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页码:157 / 202
页数:46
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