In Vitro Assay to Determine Skin Corrosivity Packing Groups

确定皮肤腐蚀性包装组的体外测定

• 批准号: 7609215
• 负责人: Yulia Kaluzhny
• 金额: $ 24.44万
• 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: 2008-09-30 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609215
• 关键词: Acute; Advisory Committees; Animal Testing; Animal Testing Alternatives; Animal Welfare; Animals; Appendix; Archives; Biological Assay; Blinded; Chemicals; Classification; Code; Corrosion; Corrosives; Dermal; Development; Distress; Dose; Economics; End Point; Evaluation; Experimental Designs; Goals; Guidelines; Hazard Identification; Histology; Household; Human; In Vitro; Industrial Product; International; Label; Laboratories; Marketing; Materials Testing; Membrane; Methods; Modeling; Mono-S; Numbers; Oryctolagus cuniculus; Pain; Paris, France; Phase; Procedures; Process; Protocols documentation; Public Health; Publications; Purpose; Rattus; Reaction; Records; Regulation; Reporting; Reproducibility; Research; Running; Series; Severities; Site; Skin; Statistically Significant; Testing; Time; Tissue Viability; Title; Transportation; United States National Institutes of Health; Update; Validation; base; experience; in vitro Assay; in vitro Model; in vivo; irritation; research study; skin irritation; success; validation studies; young adult

DESCRIPTION (provided by applicant): US Department of Transportation and international regulations require testing of all chemicals for skin corrosivity, which is defined as destruction of human skin at the site of contact. For safe handling and transportation purposes, each corrosive is assigned a "packing group" designation, which depends on how quickly skin damage occurs. Previously accepted test methods have utilized rabbits to determine packing groups. However, corrosive chemicals are very harsh and can cause considerable discomfort and/or severe pain to the animals. A number of in vitro tests have been developed but none of them adequately meet all of the US regulatory and market needs. The goal of this project will be to utilize a human skin-like in vitro model, EpiDermTM, to develop and validate an in vitro assay to determine skin corrosivity packing groups. Phase I research will determine the assay parameters necessary to differentiate between the 4 corrosivity packing groups. A preliminary prediction model (PM) will be developed using 12 reference chemicals and PM will be tested with an additional 28 test materials. After fine tuning the PM, interlaboratory reproducibility and interlaboratory transferability of the assay will be assessed. Successful completion of the Phase I goals will constitute the pre-validation process for proceeding to formal assay validation studies in Phase II. PUBLIC HEALTH RELEVANCE: Skin corrosivity testing is necessary to insure the safe handling and transport of chemicals. Animal-based test methods suffer from animal welfare concerns and current in vitro methods do not meet all US regulatory requirements. This project will develop an in vitro assay to determine skin corrosivity packing groups and fulfill all testing and regulatory needs.

描述（由申请人提供）：美国运输部和国际法规要求对所有化学品进行皮肤腐蚀性测试，皮肤腐蚀性定义为接触部位对人体皮肤的破坏。出于安全处理和运输的目的，每种腐蚀剂都被分配了一个“包装类别”名称，这取决于皮肤损伤发生的速度。以前接受的测试方法是利用兔子来确定包装类别。然而，腐蚀性化学物质非常刺激，会给动物带来相当大的不适和/或剧烈疼痛。已经开发了许多体外测试，但没有一个能够充分满足美国所有监管和市场需求。该项目的目标是利用类人皮肤体外模型 EpiDermTM 来开发和验证体外测定，以确定皮肤腐蚀性包装基团。第一阶段研究将确定区分 4 种腐蚀性包装组所需的测定参数。将使用 12 种参考化学品开发初步预测模型 (PM)，并使用另外 28 种测试材料对 PM 进行测试。微调 PM 后，将评估检测的实验室间再现性和实验室间可转移性。第一阶段目标的成功完成将构成第二阶段正式测定验证研究的预验证过程。公共卫生相关性：皮肤腐蚀性测试对于确保化学品的安全处理和运输是必要的。基于动物的测试方法受到动物福利问题的困扰，并且当前的体外方法不符合美国的所有监管要求。该项目将开发一种体外测定法，以确定皮肤腐蚀性包装组并满足所有测试和监管需求。