A Nonanimal Test Method to Determine the Ocular Safety of Consumer Products and Chemicals: Commercialization

确定消费品和化学品眼部安全性的非动物测试方法：商业化

• 批准号: 10696247
• 负责人: Stewart Lebrun
• 金额: $ 16.8万
• 依托单位: LEBRUN LABS, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10696247
• 关键词: Address; Animal Cruelty; Animal Testing; Animal Welfare; Animals; Applications Grants; Area; Businesses; Cell Culture Techniques; Chemicals; Classification; Code; Complex; Consumer Product Safety; Corrosion; Corrosives; Cosmetics; Custom; Detection; Development; Diagnostic Reagent Kits; Dissection; Ensure; Environment; Ethics; European Union; Evaluation; Eye; Funding; Funding Opportunities; Government; Government Agencies; Grant; Hour; Image; India; Industry; Injections; Interagency Coordinating Committee on the Validation of Alternative Methods; International; Irritants; Israel; Label; Laboratories; Laws; Legal patent; Lesion; Life; Manufacturer; Marketing; Methods; Molds; Movement; NIH Program Announcements; National Institute of Environmental Health Sciences; National Toxicology Program; Oryctolagus cuniculus; Outsourcing; Performance; Phase; Plumbing; Population; Privatization; Process; Production; Recording of previous events; Reliability of Results; Safety; Sales; Self Care; Shipping; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Specific qualifier value; Standardization; Statutes and Laws; System; Techniques; Testing; Time; Tissues; Toxicology; Training; Work; Writing; blind; chemical standard; commercialization; commercialization readiness; consumer product; cost effective; design; experience; hazard; improved; irritation; manufacture; manufacturing process; manufacturing test; packaging material; personal care products; pressure; prevent; programs; prototype; quality assurance; response; retinal toxicity; safety testing; skills; working group

ABSTRACT The phase I and II Small Business Innovation Research (SBIR) applications, from which this application is a continuation, was in response to the National Institute of Environmental Health Sciences’ solicitation for “Improved Test Systems for Prioritization and Safety Evaluation.” Specifically, the application was written to address the need for a nonanimal ocular safety test to differentiate ocular nonirritant substances from irritant and corrosive substances. Ocular safety tests have routinely been conducted on live animals with a time to results of up to 21 days and are considered by many to be inhumane. Recent government legislation and consumer pressure are directed at reducing or eliminating the use of live animals for the routine testing of consumer products and cosmetics. However, limited options exist for nonanimal testing. Currently, accepted nonanimal test methods require the advanced purchase (up to three weeks) of live tissues and a technician skilled in aseptic technique; additionally, such tests do not have a long shelf life or misclassify ocular corrosives as nonirritants, are time intensive, and require other advanced laboratory techniques including cell culture or dissection and subjective interpretation of ocular lesions. The subject of this proposal is the production of a rapid, irritancy-predictive, quantitative, standardized test kit with a one-year shelf life to provide standardized results more accurately and with higher sensitivity than any other available nonanimal ocular irritation test. Using chemicals selected and coded by a government agency [National Toxicology Program (NTP)’s Interagency Center for the Evaluation of Alternative Toxicological Methods] and evaluated by representatives from other U.S. governmental agencies (NTP’s Interagency Coordinating Committee on the Validation of Alternative Methods Ocular Toxicology Working Group] during the prior SBIR grants, it was demonstrated that the test kit has a transferability of 92%, according to results from a blind transferability study. Overall, for the detection of nonirritants, out of the 90 chemicals evaluated, no false-negative results were obtained (100% sensitivity) using the Globally Harmonized System of Classification and Labelling of Chemicals. The overall sensitivity and accuracy outperformed all other available nonanimal ocular irritation test methods. In addition to the test being rapid and shelf stable, test kit performance for the detection of nonirritant compounds was excellent. A major new development for the OptiSafe test is that it is now moving towards international regulatory acceptance. International regulatory acceptance is anticipated to greatly expand OptiSafe sales, if the product can be effectively manufactured to meet the need, the subject of this grant application. The scope of the SBIR/STTR Commercialization Readiness Pilot (CRP) Program, as provided on the funding opportunity announcement, includes “technical assistance associated with manufacturing.” The aims of this application are to seek technical assistance to improve manufacturing of the test kit, including a complex part manufacturing process and packaging so that the kit can be shipped without damage domestically and internationally to meet the worldwide need for an accurate, shelf-stable nonanimal eye irritation test. An accurate, rapid, stable, nonanimal eye safety test kit represents a significant business opportunity in the current market of consumer products and cosmetics and will make a needed solution available to both private industry and regulatory agencies.

抽象的 第一阶段和第二阶段小型企业创新研究 (SBIR) 申请，本申请是其中的一个 继续，是为了响应国家环境健康科学研究所的征集 “改进的优先级排序和安全评估测试系统。” 满足非动物眼部安全测试的需求，以区分眼部非刺激性物质和刺激性物质 定期对活体动物进行眼部安全测试。 长达 21 天的结果被许多人认为是不人道的。 消费者的压力旨在减少或消除使用活体动物进行常规检测 然而，目前接受的非动物测试选择有限。 非动物测试方法需要提前购买（最多三周）活体组织和技术人员 熟练掌握无菌技术；此外，此类测试的保质期不长，也不会错误分类眼部腐蚀物。 由于无刺激性，需要大量时间，并且需要其他先进的实验室技术，包括细胞培养或 本提案的主题是制作一份眼部病变的解剖和主观解释。 快速、刺激性预测、定量、标准化测试套件，保质期为一年，可提供标准化测试 与任何其他可用的非动物眼刺激测试相比，结果更准确，灵敏度更高。 使用由政府机构选择和编码的化学品[国家毒理学计划 (NTP) 替代毒理学方法评估机构间中心]并由代表评估 来自其他美国政府机构（NTP 验证机构间协调委员会） 替代方法眼毒理学工作组]在之前的 SBIR 资助期间，事实证明 总体而言，根据盲法可转移性研究的结果，该测试套件的可转移性为 92%。 检测非刺激性物质，在评估的 90 种化学物质中，未获得假阴性结果（100% 敏感性）使用全球化学品统一分类和标签制度。 灵敏度和准确性优于除动物眼刺激测试之外的所有其他可用方法。 该测试快速且货架稳定，测试套件检测非刺激性化合物的性能为 出色的。 OptiSafe 测试的一个重大新发展是它现在正在走向国际监管 如果该产品得到国际监管机构的认可，预计将大大扩大 OptiSafe 的销量。 可以有效地制造以满足需要，这是本拨款申请的主题。 SBIR/STTR 商业化准备试点 (CRP) 计划的范围（如资金规定） 机会公告，包括“与制造相关的技术援助”。 申请是寻求技术援助以改进测试套件的制造，包括复杂的零件 制造工艺和包装，使套件可以在国内运输时不受损坏 满足全球对准确、耐储存的非动物眼刺激测试的需求。 准确、快速、稳定的非动物眼部安全测试套件代表了该领域的重大商机 当前的消费品和化妆品市场，将为私人和私营部门提供所需的解决方案 行业和监管机构。

项目成果

Expansion of the application domain of a macromolecular ocular irritation test (OptiSafe™).

• DOI: 10.1016/j.tiv.2022.105515
• 发表时间: 2023-02
• 期刊: Toxicology in vitro : an international journal published in association with BIBRA
• 作者: Lebrun S;Chavez S;Nguyen L;Chan R
• 通讯作者: Chan R