Globally Harmonized In Vitro Skin Irritation Assay

全球统一的体外皮肤刺激测定

• 批准号: 7539643
• 负责人: PATRICK J HAYDEN
• 金额: $ 25.6万
• 依托单位: MATTEK CORPORATION
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-08 至 2009-08-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7539643
• 关键词: Advisory Committees; Affect; Amendment; Animal Model; Animal Testing; Animals; Appendix; Applications Grants; Australia; Authorization documentation; Biological Assay; Biological Markers; Blinded; Categories; Chemicals; China; Classification; Complex; Corrosion; Cosmetics; Country; Development; Dinoprostone; Discrimination; End Point; Environmental Health; Europe; European; European Union; Evaluation; Experimental Designs; Goals; Government Agencies; Guidelines; Hazard Assessment; Hazard Identification; Household; Household Products; Human; IL8 gene; In Vitro; Institutes; International; Irritants; Japan; Journals; Label; Laboratories; Laws; Letters; Marketing; Methods; Modeling; Mono-S; Mucous Membrane; National Toxicology Program; New York; Numbers; Operative Surgical Procedures; Oryctolagus cuniculus; Performance; Pharmacology; Phase; Phase II Clinical Trials; Predictive Value; Procedures; Process; Production; Public Health; Publications; Purpose; Reporting; Reproducibility; Research; Running; Science; Sensitivity and Specificity; Series; Skin; Statistically Significant; Statutes and Laws; System; Testing; Therapeutic; Time; Tissue Viability; Topical application; Toxic effect; Treaty; United Nations; United States Environmental Protection Agency; United States National Institutes of Health; Update; Validation; Work; consumer product; cost; health science research; in vitro Model; in vivo; irritation; member; model development; programs; research study; response; skin irritation; success; tapir; validation studies

DESCRIPTION (provided by applicant):PUBLIC HEALTH RELEVANCE Determination of skin irritation potential is an international regulatory requirement for hazard identification/assessment of chemicals, and is important in establishing procedures for the safe handling, packaging, labeling and transport of chemicals and chemical mixtures, as well as evaluation of irritation potential of cosmetic products, ingredients and household productions. Recently enacted legislation including the European Union Registration, Labeling and Authorization of Chemicals (REACH) program, the US EPA High Production Volume (HPV) Chemical Challenge and EU "cosmetics directive" ban on the testing of cosmetics on animals will dramatically increase the need for in vitro skin irritation assessment methods. To fulfill the urgent need for a regulatory accepted in vitro skin irritation test method, the goal of the present grant proposal is to validate the EpiDerm in vitro human skin model for skin irritation according to the "Globally Harmonized System" (GHS). Validation guidelines developed by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and European Center for the Validation of Alternative Methods (ECVAM) will be utilized. Initially, test chemicals with known in vivo skin irritation potential will be applied to the EpiDerm model to identify in vitro skin irritation biomarkers. A prediction model will be established for converting in vitro biomarker responses into in vivo GHS skin irritation classifications (i.e. irritant, mild irritant and non-irritants). The model and test methods will be further evaluated with a larger test set of chemicals to determine its validity and overall predictive ability. Finally, additional tests will determine intra-laboratory reproducibility and inter-laboratory transferability of the assay method. Successful completion of these Phase I Aims will constitute the pre-validation process for establishing the feasibility of proceeding to full formal validation in Phase II studies. Determination of skin irritation potential is an international regulatory requirement for hazard identification/assessment of chemicals, and is important in establishing procedures for the safe handling, packaging, labeling and transport of chemicals and chemical mixtures, as well as evaluation of irritation potential of cosmetic products, ingredients and household productions. Recently enacted legislation including the European Union Registration, Labeling and Authorization of Chemicals (REACH) program, the US EPA High Production Volume (HPV) Chemical Challenge and EU "cosmetics directive" ban on the testing of cosmetics on animals will dramatically increase the need for in vitro skin irritation assessment methods. To fulfill the urgent need for a regulatory accepted in vitro skin irritation test method, the goal of the present grant proposal is to validate the EpiDerm in vitro human skin model for skin irritation according to the "Globally Harmonized System" (GHS). Validation guidelines developed by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and European Center for the Validation of Alternative Methods (ECVAM) will be utilized. Initially, test chemicals with known in vivo skin irritation potential will be applied to the EpiDerm model to identify in vitro skin irritation biomarkers. A prediction model will be established for converting in vitro biomarker responses into in vivo GHS skin irritation classifications (i.e. irritant, mild irritant and non-irritants). The model and test methods will be further evaluated with a larger test set of chemicals to determine its validity and overall predictive ability. Finally, additional tests will determine intra-laboratory reproducibility and inter- laboratory transferability of the assay method. Successful completion of these Phase I Aims will constitute the pre-validation process for establishing the feasibility of proceeding to full formal validation in Phase II studies.

描述（由申请人提供）：皮肤刺激潜力的公共卫生相关性确定是对化学物质的危害识别/评估的国际调节要求，对于建立安全处理，包装，标记和化学化学混合物的安全，包装，标签和运输的程序很重要，以及评估刺激性的刺激性产品，食品和家庭生产的刺激性。最近制定的立法包括欧盟注册，化学品的标签和授权（覆盖范围），美国EPA高生产量（HPV）化学挑战和欧盟“化妆品指令”禁止对动物的化妆品测试的禁令，将大大增加对体外皮肤刺激评估方法的需求。为了满足对体外皮肤刺激测试方法的迫切需求，目前的赠款提案的目的是根据“全球统一的系统”（GHS）验证体外人体皮肤模型的表皮模型。机构间协调委员会在验证替代方法（ICCVAM）和欧洲验证中心（ECVAM）制定的验证指南将被使用。最初，具有已知体内皮肤刺激潜力的测试化学物质将应用于表皮模型，以鉴定体外皮肤刺激生物标志物。将建立一个预测模型，用于将体外生物标志物反应转化为体内ghs皮肤刺激分类（即刺激性，轻度刺激性和非辐射剂）。该模型和测试方法将通过较大的测试集进一步评估，以确定其有效性和整体预测能力。最后，其他测试将确定测定方法的实验室内的可重现性和实验室间可转移性。这些阶段I目标的成功完成将构成验证过程，以确立在II阶段研究中进行完全正式验证的可行性。确定皮肤刺激潜力是对化学物质危害识别/评估的国际调节要求，对于建立安全处理，包装，标记和运输化学品和化学混合物的程序以及评估化妆品，成分和家用生产的刺激潜力的程序很重要。最近制定的立法包括欧盟注册，化学品的标签和授权（覆盖范围），美国EPA高生产量（HPV）化学挑战和欧盟“化妆品指令”禁止对动物的化妆品测试的禁令，将大大增加对体外皮肤刺激评估方法的需求。为了满足对体外皮肤刺激测试方法的迫切需求，目前的赠款提案的目的是根据“全球统一的系统”（GHS）验证体外人体皮肤模型的表皮模型。机构间协调委员会在验证替代方法（ICCVAM）和欧洲验证中心（ECVAM）制定的验证指南将被使用。最初，具有已知体内皮肤刺激潜力的测试化学物质将应用于表皮模型，以鉴定体外皮肤刺激生物标志物。将建立一个预测模型，用于将体外生物标志物反应转化为体内ghs皮肤刺激分类（即刺激性，轻度刺激性和非辐射剂）。该模型和测试方法将通过较大的测试集进一步评估，以确定其有效性和整体预测能力。最后，其他测试将确定测定方法的实验室内的可重现性和实验室间可传递性。这些阶段I目标的成功完成将构成验证过程，以确立在II阶段研究中进行完全正式验证的可行性。