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 活兔眼测试用于区分消费产品和材料 远离那些危险且可能导致可逆或不可逆眼部损伤的物质。 这些法律目前正在或计划在加利福尼亚州、美国和欧洲实施 联盟禁止使用动物进行眼部刺激测试，尽管如此，目前还没有单一的措施。 可以准确分类眼部刺激物的非动物测试或非动物测试组合。 担心所有非动物测试通常都会高估损害最小的一类眼部刺激物（EPA IV 和 GHS 非分类材料）并且无法确定（或以低灵敏度确定）最极端的类别 （EPA I 和 GHS 1 不可逆/腐蚀性材料），它们的敏感度可低至 50%。 更重要的是，目前经过验证的替代测试都无法检测到任何一种可逆刺激物（EPA II/III 和 GHS 2A/B) 或那些引起刺激持续 7 至 21 天但随后消失的物质 该目标分类代表了正确告知的关键未满足需求。 我们最近开发并测试了一项针对消费者和制造商的产品安全建议。 新方法——体外损伤深度眼刺激试验（IVD EIT）检测可逆性眼刺激物 该应用的目的是进一步开发具有长期优势的 IVD EIT。 术语目标是提供服务和/或产品套件，以准确分类可逆性眼部刺激物 作为非动物眼刺激测试策略的一部分来满足这一未满足的需求这一目标将通过以下方式实现。 实现以下具体目标： 目标 1（2 个月）：评估实验的重复性和再现性 IVD EIT，通过对由 EPA I–IV 组成的四种化学测试装置进行重复测量实验 化学物质来确定实现高重复性目标所需的角膜和阳性对照的数量。 2（4 个月）：执行预验证测试以评估 IVD EIT 对 30 种测试物质进行分类的能力 目标2将具体根据GHS和EPA分类，进一步细化预测模型。 确定 IVD EIT 的准确性、灵敏度和特异性并确定任何应用领域 限制（检测到的刺激物类别和化学/物理特性的范围）。 验证并展示 IVD EIT 的商业和监管效用（由检测能力定义） 对于可逆的刺激物，我们将提出第二阶段 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