DERMAL ABSORPTION OF CUTTING FLUID MIXTURES

切削液混合物的皮肤吸收

• 批准号: 6598154
• 负责人: Ronald E Baynes
• 金额: $ 27.37万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6598154
• 关键词: animal tissue; biomarker; chemical kinetics; environmental toxicology; industry; occupational disease /disorder; occupational hazard; occupational health /safety; skin absorption; skin irritation /irritant; skin pharmacology; solvents; swine; work site

The long-term goal is to understand chemical and biological interactions in a chemical mixture that modulate dermal disposition of irritants or chemicals and to be able to predict chemical and biological interactions in a chemically-defined mixture in the workplace. As it is very difficult to experimentally test all commercial cutting fluids or oils, the primary objective of this research project is to investigate the influence of chemical mixtures on the dermal disposition and cutaneous toxicity of several cutting fluid additives and contaminants using a novel experimental paradigm. Complete or partial factorial experiments can be designed to determine the various levels of interactions using appropriate skin models with various levels of biological complexity. The central hypothesis to be tested is that chemical-chemical and chemical- biological interactions can occur on or in the skin which eventually determine the fate of the irritant(s) and thus its potential to cause irritant dermatitis. The rationale for this proposed approach is that many of the chemical additives or components in a cutting fluid formulation behave as solvents, co-solvents, or surfactants, which can modulate percutaneous absorption by altering the normal anatomy and physiology of the skin by discrete mechanisms. The following three specific aims will be pursued to accomplish the stated objectives: 1) Determine statistically significant chemical-chemical and chemical-biological interactions for five component mixtures using three skin model systems possessing increasing levels of biological complexity. Silastic membranes, porcine skin sections, and isolated perfused porcine skin flaps (IPPSFs) will be used to probe for various levels of interactions. (2) Determine interactions with common cutting fluid contaminants, nickel and nitrosodiethanolamine, and a cleansing solvent, trichloroethylene. IPPSFs will be used in these reduced factorial experiments. (3) Using biomarkers of irritation, determine significant changes in epidermal barrier structure and function in skin flaps exposed to mixtures that significantly alter component(s) disposition within skin. These latter experiments will primarily focus on subclinical effects, such as prostaglandin and cytokine release. At the completion of this project, we expect to identify significant interactions between functional components of the mixture that will contribute to a better understanding of additive deposition and irritancy of related cutting fluid products. This experimental approach allows interaction models to be built which can be used to assess other workplace mixtures.

长期目标是了解化学和生物相互作用， 调节刺激物或化学品的皮肤处置的化学混合物 并能够预测化学和生物相互作用， 化学定义的混合物。因为很难 实验测试所有商业切削液或油，主要 本研究项目的目的是调查化学物质的影响 混合物对皮肤的处置和皮肤毒性的几个削减 流体添加剂和污染物使用一种新的实验范例。完成 或部分析因实验可以被设计来确定各种 使用适当的皮肤模型与各种水平的 生物复杂性 要检验的中心假设是化学-化学和化学- 生物相互作用可发生在皮肤上或皮肤中， 刺激物的命运及其引起刺激的可能性 皮炎提出这种方法的理由是， 切削液配方中的化学添加剂或组分表现为 溶剂、共溶剂或表面活性剂，其可以调节经皮 通过改变皮肤的正常解剖学和生理学， 离散机制 为实现上述目标，将努力实现以下三个具体目标 目的：1）确定统计学上显著的化学-化学和 使用三层皮肤的五组分混合物的化学生物相互作用 模型系统具有越来越高的生物复杂性。Silastic 膜、猪皮切片和离体灌注猪皮瓣 （IPPSFs）将用于探测各种水平的相互作用。（二） 确定与常见切削液污染物、镍和 亚硝基二乙醇胺和清洁溶剂三氯乙烯。IPPSF将 用于这些简化析因实验。(3)使用生物标志物 刺激，确定表皮屏障结构的显著变化， 暴露在混合物中的皮瓣功能会显著改变 皮肤内的成分分布。这些实验将主要 关注亚临床效应，如前列腺素和细胞因子释放。在 在这个项目完成后，我们预计将确定重要的互动 混合物的功能成分之间的关系，这将有助于更好地 了解相关切削液的添加剂沉积和刺激性 产品.这种实验方法允许建立相互作用模型 可用于评估其他工作场所的混合物。