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

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