In Vitro Assay for Chemical Allergens

化学过敏原的体外测定

• 批准号: 7393603
• 负责人: Seyoum Ayehunie
• 金额: $ 47.5万
• 依托单位: MATTEK CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7393603
• 关键词: Allergens; Allergic; Allergic Contact Dermatitis; Animal Experiments; Animal Model; Animal Welfare; Animals; Antigen-Presenting Cells; Biological Assay; Biological Markers; Biological Models; Blinded; Case Study; Cavia; Cell surface; Cells; Characteristics; Chemicals; Communities; Contact Dermatitis; Cosmetics; Databases; Dendritic Cells; Developed Countries; Drug Formulations; Economics; End Point; Evaluation; Exposure to; Food Preservatives; Goals; Haptens; Hazard Assessment; Health; Household Products; Human; Hygiene; Hypersensitivity; In Vitro; Industry; Interleukin-6; International; Laboratories; Laboratory Animals; Langerhans cell; Local Lymph Node Assay; Marketing; Materials Testing; Measurable; Metals; Methods; Modeling; Mus; N(delta)-acetylornithine, -isomer; N-dodecanoylglutamic acid, -isomer, sodium salt; Numbers; Ointments; Patch Tests; Pattern; Perfume; Pharmacologic Substance; Phase; Process; Public Health; Regulation; Reproducibility; Research; Risk; Screening procedure; Sensitivity and Specificity; Skin; System; Testing; Textiles; Topical application; Training; Uncertainty; Up-Regulation; Validation; Variant; alpha-difluoromethyl-DOPA, -isomer; alpha-methylornithine dihydrochloride, -isomer; assay development; base; chemical allergen; cost; cytokine; day; hazard; improved; in vitro Assay; in vivo; occupational hazard; research study; response; tool; validation studies

DESCRIPTION (provided by applicant): Allergic contact dermatitis (ACD) is one of the most common and costly health problems in industrialized countries. Currently, more than 100,000 chemicals are in commercial use and another 2,000 new chemicals and numerous new-product formulations are tested or marketed every year. All of these materials must be screened for allergenicity. During Phase I, a human dendritic cell based assay was developed which gives sensitive and specific responses to allergens. The non-optimized assay is approximately a factor of 10 less expensive than current animal based tests. In addition, the assay avoids animal welfare issues and uncertainty related to species extrapolation. During Phase II, the database of materials tested will be expanded and the in vitro assay method and prediction model will be finalized. The reproducibility of the assay will be assessed and, after demonstration of interlaboratory transferability, a multi-lab GLP validation study will be performed. Finally, an optimized assay kit which further enhances the economic advantages of the in vitro method will be developed. Allergic contact dermatitis, in vitro testing, plasmacytoid DC. PUBLIC HEALTH RELEVANCE: A predictive test system for assessing the allergic contact dermatitis potential of chemicals will have far reaching application in industries involved in cosmetic, personal hygiene and topical pharmaceutical products. Evaluation of allergenicity is important to minimize the hazards of occupational and public exposure to chemicals and products. The proposed human cell based assay will provide a sensitive and specific method of allergen screening without the use of laboratory animals and at a reduced cost.

描述（由申请人提供）：过敏性接触性皮炎（ACD）是工业化国家最常见和最昂贵的健康问题之一。目前，有100 000多种化学品投入商业使用，每年还有2 000种新化学品和许多新产品配方得到测试或销售。所有这些材料都必须进行过敏性筛查。 在第一阶段，开发了一种基于人树突状细胞的测定法，该测定法对过敏原产生敏感和特异性反应。非优化的测定比目前基于动物的测试便宜约10倍。此外，该测定避免了动物福利问题和与种属外推相关的不确定性。在第二阶段，将扩大测试材料的数据库，并最终确定体外测定方法和预测模型。将评估试验的重现性，在证明实验室间可转移性后，将进行多实验室GLP验证研究。最后，将开发一种优化的检测试剂盒，进一步提高体外方法的经济优势。 变应性接触性皮炎，体外试验，浆细胞样树突状细胞。公共卫生关系：用于评估化学品的变应性接触性皮炎潜力的预测测试系统将在涉及化妆品、个人卫生和局部药物产品的行业中具有深远的应用。过敏原性的评估对于减少职业和公众接触化学品和产品的危害非常重要。所提出的基于人类细胞的测定将提供一种灵敏且特异的过敏原筛选方法，而无需使用实验室动物，且成本较低。