Integrated In Vitro and Alternative Ocular (IIVAO) Irritation Testing Strategy

综合体外和替代眼部 (IIVAO) 刺激测试策略

• 批准号: 8906199
• 负责人: George L. DeGeorge
• 金额: $ 22.49万
• 依托单位: MB RESEARCH LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8906199
• 关键词: Accidents; Acute; Address; Animal Welfare; Animals; Biological Assay; Blood Vessels; Categories; Cattle; Chemicals; Classification; Cornea; Corneal Opacity; Corrosion; Corrosives; Cosmetics; Data; Data Set; Drug Formulations; Effectiveness; Ensure; Evaluation; Exhibits; Eye; Eye Injuries; Family suidae; Goals; Grant; Guidelines; Household Products; In Vitro; Irritants; Label; Life; Materials Testing; Measures; Membrane; Methods; Oryctolagus cuniculus; Performance; Permeability; Phase; Protocols documentation; Public Health; Regulation; Safety; Self Care; Solutions; System; Test Result; Testing; Tetanus Helper Peptide; Toxic effect; Toxicology; United States Environmental Protection Agency; Validation; Visual impairment; analog; base; chorioallantoic membrane; comparative; consumer product; corneal epithelium; human tissue; in vitro testing; irritation; light transmission; public health relevance; safety testing; screening

 DESCRIPTION (provided by applicant): Ocular irritation testing is extremely relevant to assuring adequate safety levels of public health as new formulations of chemicals and products are introduced. In most cases, these safety assessments are performed using the Draize Rabbit Eye test, resulting in thousands of rabbits used in testing every year. Alternatives have been discussed since the 80s without any appreciable acceptance from regulators. As more governmental agencies mandate the replacement of using live animals in regulatory safety assessment of consumer products, chemicals and cosmetics, the need for a complete alternative solution to ocular irritation testing grows. Currently, there is no single or set of tets that have been validated and accepted by regulatory agencies as a full replacement for rabbit ocular irritation testing. The aim of this project is to evaluate the applicability of the Integratd In vitro/Alternative Ocular (IIVAO) pronounced -/eye vay o/ Toxicology Testing Strategy to categorize potential ocular irritants into regulatory toxicity classes using four integrated in vito and alternative ocular irritation assays. IIVAO will demonstrate it is possible to effectively replace mandated acute ocular irritation testing using the Draize Rabbit Eye Test with non-animal test methods. For the purpose of this project, we have focused on assessing the performance of IIVAO using Environmental Protection Agency (EPA) testing classifications. IIVAO, an integrated testing strategy (ITS), comprises in vitro and alternative tests that have been chosen for their ability to effectively detect specific ranges of ocular irritation, which correspond to regulatory classifications of ocular irritation/corrosivity - the Chorioallantoic Membrane Vascular Assay (CAMVA), the Bovine Cornea Opacity/Permeability test (BCOP), the Porcine Cornea Opacity/Reversibility Assay (PorCORA), the MatTek EpiOcular(EO)-3D human tissue construct and the Porcine Confocal Assay (PorFocal). This grant project will confirm and validate a comprehensive testing protocol that allows for a thorough evaluation and categorization of test materials for ocular irritancy potential ranging from non-irritating to oculr corrosion without using live animals. We intend to perform validations of each assay and collectively as an integrated system using a test set of chemicals that are well characterized for specific categories of ocular irritancy. Additionally, we propose to utilize the finalized integratd testing protocol to evaluate a number of `Off-The-Shelf' commercial products for those categories of ocular irritancy to demonstrate the effectiveness of the IIVAO testing strategy with mixtures and final product formulations. The long-term project goal is to submit the IIVAO testing strategy to the EPA for consideration as a standalone alternative to the Draize Rabbit Eye test. Validation and acceptance of IIVAO will significantly reduce the number of rabbits used in the toxicological assessment of consumer products, chemicals and raw materials by replacing rabbits with an ITS of in vitro and alternative assays.

 描述（由申请方提供）：随着化学品和产品的新配方的引入，眼部刺激试验与确保公共卫生的适当安全水平极其相关。在大多数情况下，这些安全性评估是使用Draize兔眼测试进行的，每年有数千只兔子用于测试。自80年代以来，人们一直在讨论替代方案，但监管机构没有明显接受。随着越来越多的政府机构要求在消费品、化学品和化妆品的监管安全评估中取代使用活体动物，对眼刺激测试的完整替代解决方案的需求不断增长。目前，没有一种或一组经监管机构验证和接受的tet可完全替代兔眼刺激试验。本项目的目的是评价整合体外/替代眼部（IIVAO）明显/眼部毒性试验策略的适用性，以使用四种整合体外和替代眼部刺激试验将潜在眼部刺激物分类为监管毒性类别。IIVAO将证明可以用非动物试验方法有效地替代使用Draize兔眼试验的强制性急性眼刺激试验。为了这个项目的目的，我们重点评估的性能IIVAO使用环境保护署（EPA）的测试分类。IIVAO是一种综合测试策略（ITS），包括体外和替代测试，这些测试已被选择用于有效检测特定范围的眼刺激，这对应于眼刺激/腐蚀性的监管分类-绒毛膜尿囊膜血管试验（CAMVA），牛角膜混浊/渗透性试验（BCOP），猪角膜混浊/可逆性试验（PorCORA），MatTek EpiOcular（EO）-3D人体组织构建体和猪共聚焦试验（PorFocal）。该资助项目将确认和验证一个全面的测试方案，该方案允许在不使用活体动物的情况下对测试材料的眼部刺激潜力进行彻底的评估和分类，范围从无刺激性到眼部腐蚀。我们打算使用一组化学品对每种检测试剂盒进行验证，并将其作为一个集成系统，这些化学品已充分表征特定类别的眼刺激性。此外，我们建议使用最终的集成测试方案来评估一些“现成”的商业产品的眼睛刺激性类别，以证明IIVAO测试策略与混合物和最终产品配方的有效性。长期项目目标是将IIVAO测试策略提交给EPA，作为Draize兔眼测试的独立替代方案进行考虑。IIVAO的验证和验收将通过用体外试验和替代试验的ITS替代家兔，显著减少消费品、化学品和原材料毒理学评估中使用的家兔数量。