In Vitro Assay to Determine Skin Corrosivity Packing Groups

描述（申请人提供）：美国交通部和国际法规要求对所有化学品进行皮肤腐蚀性测试，皮肤腐蚀性定义为接触部位人类皮肤的破坏。为了安全装卸和运输的目的，每种腐蚀剂都要根据皮肤损坏的速度而定一个“包装类别”名称。以前接受的试验方法使用家兔来确定包装类别。然而，腐蚀性化学品是非常苛刻的，并可能导致相当大的不适和/或严重的疼痛的动物。已经开发了许多体外试验，但没有一种能够充分满足美国监管和市场的所有需求。本项目的目标是利用人体皮肤样体外模型EpiDermTM，开发和验证一种体外测定方法，以确定皮肤腐蚀性包装组。第一阶段研究将确定区分4种腐蚀性包装组所需的分析参数。将使用12种参考化学品开发初步预测模型（PM），并使用另外28种测试材料对PM进行测试。微调PM后，将评估试验的实验室间重现性和实验室间可转移性。第一阶段目标的成功完成将构成预验证过程，以继续进行第二阶段的正式测定验证研究。公共卫生相关性：皮肤腐蚀性测试是必要的，以确保安全处理和运输化学品。基于动物的测试方法受到动物福利问题的困扰，并且目前的体外方法不符合所有美国法规要求。该项目将开发一种体外试验，以确定皮肤腐蚀性包装组，并满足所有测试和监管需求。

DESCRIPTION (provided by applicant): US Department of Transportation and international regulations require testing of all chemicals for skin corrosivity, which is defined as destruction of human skin at the site of contact. For safe handling and transportation purposes, each corrosive is assigned a "packing group" designation, which depends on how quickly skin damage occurs. Previously accepted test methods have utilized rabbits to determine packing groups. However, corrosive chemicals are very harsh and can cause considerable discomfort and/or severe pain to the animals. A number of in vitro tests have been developed but none of them adequately meet all of the US regulatory and market needs. The goal of this project will be to utilize a human skin-like in vitro model, EpiDermTM, to develop and validate an in vitro assay to determine skin corrosivity packing groups. Phase I research will determine the assay parameters necessary to differentiate between the 4 corrosivity packing groups. A preliminary prediction model (PM) will be developed using 12 reference chemicals and PM will be tested with an additional 28 test materials. After fine tuning the PM, interlaboratory reproducibility and interlaboratory transferability of the assay will be assessed. Successful completion of the Phase I goals will constitute the pre-validation process for proceeding to formal assay validation studies in Phase II. PUBLIC HEALTH RELEVANCE: Skin corrosivity testing is necessary to insure the safe handling and transport of chemicals. Animal-based test methods suffer from animal welfare concerns and current in vitro methods do not meet all US regulatory requirements. This project will develop an in vitro assay to determine skin corrosivity packing groups and fulfill all testing and regulatory needs.