IVD EIT: A Nonanimal Kit and Service for the Detection of Reversible Ocular Irritants

IVD EIT：用于检测可逆眼部刺激物的非动物试剂盒和服务

• 批准号: 10007220
• 负责人: Stewart Lebrun
• 金额: $ 21.83万
• 依托单位: LEBRUN LABS, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10007220
• 关键词: Analysis of Variance; Animal Sources; Animals; Biological Assay; Biological Markers; California; Categories; Cell Death; Cell Survival; Chemicals; Classification; Code; Cornea; Corrosives; Dangerousness; Detection; European Union; Evaluation; Eye; Eye Injuries; Food; Goals; Government; Hour; In Vitro; Individual; Injury; Irritants; Label; Laboratories; Laws; Legal patent; Manufacturer Name; Measurement; Measures; Methods; Oryctolagus cuniculus; Outcome Study; Phase; Procedures; Publications; Publishing; Reproducibility; Running; Safety; Sampling; Sensitivity and Specificity; Services; Small Business Innovation Research Grant; Standardization; Statutes and Laws; Surface; System; Test Result; Testing; Training; United States; Validation; Work; base; consumer product; experience; experimental study; functional group; improved; in vitro testing; irritation; phase 2 study; physical property; predictive modeling; success

Abstract Currently, the Draize live rabbit eye test is used to distinguish consumer products and materials that are safe from those that are hazardous and can cause reversible or irreversible ocular damage. However, new laws are currently being, or are planned to be, implemented in California, the United States, and the European Union to ban the use of animals in ocular irritation testing. Despite this fact, there is currently no single nonanimal test or combination of nonanimal tests that can accurately classify ocular irritants. It is of particular concern that all nonanimal tests generally overpredict the least damaging class of ocular irritants (EPA IV and GHS nonclassified materials) and cannot determine (or determine with low sensitivity) the most extreme class (EPA I and GHS 1 irreversible/corrosive materials) for which they can have sensitivity rates as low as 50%. More importantly, none of the currently validated alternative tests can detect either reversible irritants (EPA II/III and GHS 2A/B) or those materials that cause irritation that lasts from 7 to 21 days but then clears without permanent corneal damage. This target classification represents a critical UNMET NEED for correctly informing and advising consumers and manufacturers about product safety. We have recently developed and tested a new method—the in vitro depth of injury eye irritation test (IVD EIT) to detect reversible ocular irritants with high sensitivity and specificity. The purpose of this application is to further develop the IVD EIT with the long- term goal of providing a service and/or product kit for the accurate classification of reversible ocular irritants to meet this UNMET NEED as part of a nonanimal ocular irritation testing strategy. This goal will be achieved by accomplishing the following specific aims: Aim 1 (2 months): Assess the repeatability and reproducibility of the IVD EIT by performing a repeat-measures experiment of a four-chemical test set composed of EPA I–IV chemicals to determine the number of corneas and positive controls needed to achieve high repeatability. Aim 2 (4 months): Perform a prevalidation test to assess the ability of the IVD EIT to categorize 30 test substances according to GHS and EPA classifications and further refine the prediction model. Aim 2 will specifically determine the accuracy, sensitivity, and specificity of the IVD EIT and identify any application domain limitations (the range of irritant categories and chemical/physical properties detected). If the results from Aim 2 validate and demonstrate the commercial and regulatory utility of the IVD EIT as defined by the ability to detect reversible irritants, we would then propose a phase II SBIR project. 1

抽象的 目前，Draize Live Rabbit Eye Test用于区分消费产品和材料 避免那些危险的人，并可能造成可逆或不可逆的眼部损害。但是，新的 法律目前正在加利福尼亚州，美国和欧洲实施或计划实施 联合禁止在眼部刺激测试中使用动物。尽管这一事实，目前没有一个 可以准确对眼部刺激物分类的非动物测试的非动物测试或组合。这是特别的 担心所有非动物测试通常通常预测到最小破坏性的眼刺激物（EPA IV和 GHS非分类材料），无法确定（或低灵敏度）最极端的类别 （EPA I和GHS 1不可逆/腐蚀性材料），它们的灵敏度速率低至50％。 更重要的是，当前经过验证的替代测试都无法检测到可逆刺激物（EPA II/III 和GHS 2a/b）或那些引起7到21天的刺激的材料，然后没有 永久性角膜损伤。该目标分类代表了正确告知的至关重要的未满足需求 以及有关产品安全的咨询消费者和制造商。我们最近开发并测试了 新方法 - 损伤眼睛刺激测试（IVD EIT）的体外深度，以检测可逆的眼部刺激物 高灵敏度和特异性。本应用的目的是进一步开发IVD EIT 提供服务和/或产品套件的任期目标，以准确地分类可逆的眼刺激物 作为非动物眼刺激测试策略的一部分，满足这种未满足的需求。这个目标将通过 完成以下特定目的：目标1（2个月）：评估重复性和繁殖 通过执行由EPA I – IV组成的四化学测试集的重复测量实验。 化学物质以确定实现高可重复性所需的角膜数和阳性对照的数量。目的 2（4个月）：执行一个流行测试，以评估IVD EIT分类30种测试物质的能力 根据GHS和EPA分类，并进一步完善了预测模型。 AIM 2将专门 确定IVD EIT的准确性，灵敏度和特异性并确定任何应用域 局限性（检测到刺激性类别和化学/物理特性的范围）。如果AIM 2的结果 验证和证明IVD EIT的商业和调节效用，以检测能力定义 然后，我们将提出一个可逆的刺激性，然后提出一个II期SBIR项目。 1

项目成果

Same-chemical comparison of nonanimal eye irritation test methods: Bovine corneal opacity and permeability, EpiOcular™, isolated chicken eye, ocular Irritection®, OptiSafe™, and short time exposure.

• DOI: 10.1016/j.tiv.2020.105070
• 发表时间: 2021-04
• 期刊: Toxicology in vitro : an international journal published in association with BIBRA
• 作者: Lebrun S;Nguyen L;Chavez S;Chan R;Le D;Nguyen M;Jester JV
• 通讯作者: Jester JV