Mixture Effects on the Dermal Absorption of Biocides

混合物对杀菌剂皮肤吸收的影响

• 批准号: 6980338
• 负责人: Ronald E Baynes
• 金额: $ 25.39万
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6980338
• 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

DESCRIPTION (provided by applicant): The long-term goal is to understand physicochemical and chemical-biological interactions in a mixture in order to predict quantitatively how cutting fluid additives influence dermal absorption of biocides often associated with irritant dermatitist in workers. Previous dermal risk assessments only evaluated absorption of single chemicals and given the multitude of diverse laboratory methodologies, robust extrapolation is limited, which ultimately impacts risk characterization. The primary objective of this project is to utilize the membrane-coated fiber (MCF) technique to characterize the partitioning behavior of biocides between a defined mixture such as cutting fluids and an inert membrane and to relate this phase distribution to solvatochromatic parameters within a linear salvation energy relationship (LSER) framework. The central hypothesis to be tested is that the presence of cutting fluid additives will alter the phase distribution of biocides between the mixture and the MCF. These changes in biocide distribution can be expressed in terms of interaction coefficients that can be extrapolated to a defined mixture. The rationale for this approach is that additives used in cutting fluid formulations can modulate bicocide absorption by discrete biological mechanism, but very little is known about the embedded physicochemical interactions. The MCF approach within the LSER framework allows for a mechanistic examination of these solvation effects using a non-biological membrane system. The following three specific aims will be pursued to accomplish the stated objectives: 1) Identify and quantify physicochemical parameters that influence solute transport from aqueous solution systems to the membrane-coated fibers (MCF). This first involves calibration of a diverse series of MCFs so as to capture as many physicochemical attributes of solute-membrane interaction. 2) Identify and quantify additive effects influencing biocide transport between mixtures and the MCF. This will provide interaction coefficients for a given mixture scenario. 3) Identify chemical biological interactions in a biological membrane system. Dermal in vitro experiments will calibrate permeability in the biological system and determine interaction coefficients in related mixtures. Comparative analysis of interaction coefficients between the MCF and biological systems will provide some insight into dominant physicochemical interactions influencing dermal absorption of biocides in chemical mixtures.

描述（由申请人提供）：长期目标是了解混合物中的物理化学和化学生物相互作用，以便定量预测切削液添加剂如何影响通常与工人的刺激性皮炎相关的杀菌剂的皮肤吸收。以前的皮肤风险评估仅评估单一化学物质的吸收，并且考虑到多种不同的实验室方法，稳健的外推是有限的，这最终影响风险特征。该项目的主要目标是利用膜涂层纤维（MCF）技术来表征杀菌剂在特定混合物（例如切削液）和惰性膜之间的分配行为，并将这种相分布与线性拯救能量关系（LSER）框架内的溶剂化显色参数联系起来。要测试的中心假设是切削液添加剂的存在将改变混合物和 MCF 之间杀菌剂的相分布。杀菌剂分布的这些变化可以用相互作用系数来表示，该系数可以外推到定义的混合物。这种方法的基本原理是，切削液配方中使用的添加剂可以通过离散的生物机制调节杀菌剂的吸收，但人们对其中嵌入的物理化学相互作用知之甚少。 LSER 框架内的 MCF 方法允许使用非生物膜系统对这些溶剂化效应进行机械检查。为了实现既定目标，将追求以下三个具体目标：1）识别和量化影响溶质从水溶液系统到膜涂层纤维（MCF）传输的物理化学参数。这首先涉及校准不同系列的 MCF，以便捕获尽可能多的溶质-膜相互作用的物理化学属性。 2) 识别并量化影响混合物和 MCF 之间杀菌剂传输的附加效应。这将为给定的混合场景提供相互作用系数。 3) 识别生物膜系统中的化学生物相互作用。皮肤体外实验将校准生物系统的渗透性并确定相关混合物中的相互作用系数。 MCF 和生物系统之间的相互作用系数的比较分析将提供对影响化学混合物中杀菌剂的皮肤吸收的主要物理化学相互作用的一些见解。