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

摘要 目前，Draize活兔眼测试用于区分符合以下条件的消费品和材料 避免危险和可能造成可逆或不可逆的眼部损伤。然而，新的 法律目前正在或计划在加利福尼亚州、美国和欧洲实施 禁止在眼睛刺激测试中使用动物的联盟。尽管如此，目前还没有单一的 非动物试验或非动物试验的组合，可以准确地对眼睛刺激物进行分类。它是特别的 令人担忧的是，所有非动物测试通常都高估了损害最小的眼睛刺激物类别(EPA IV和 GHS非机密材料)，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)，它们的敏感率可低至50%。 更重要的是，目前经过验证的替代测试都不能检测到可逆刺激物(EPA II/III 和GHS 2A/B)或那些引起刺激性的材料，持续7至21天，但随后在 永久性的角膜损伤。这一目标分类代表了对正确通知的严重未满足需求 并就产品安全向消费者和制造商提供建议。我们最近开发并测试了一种 一种检测可逆性眼刺激物的新方法--体外眼部损伤深度刺激法 敏感度和特异度高。本应用的目的是为了进一步发展IVD EIT，使其具有更长的- 为可逆性眼刺激物的准确分类提供服务和/或产品套件的术语目标 满足这一未得到满足的需求，作为非动物眼刺激测试策略的一部分。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)：评估可重复性和再现性 对由EPA I-IV组成的四种化学测试集进行重复测量实验 用于确定角膜数量的化学物质和实现高重复性所需的阳性对照。目标 2(4个月)：进行预验证测试，以评估IVD EIT对30种测试物质进行分类的能力 根据GHS和EPA分类，进一步细化预测模型。《目标2》将明确 确定IVD EIT的准确性、敏感性和特异性，并确定任何应用领域 限制(刺激物类别的范围和检测到的化学/物理特性)。如果来自AIM 2的结果 验证并展示由检测能力定义的IVD EIT的商业和监管效用 对于可逆刺激性物质，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