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: 7249351
• 负责人: Ronald E Baynes
• 金额: $ 21.51万
• 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/7249351
• 关键词: Mixture; Effects; Dermal; Absorption; Biocides

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 solvation 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.

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， 为了定量预测切削液添加剂如何影响杀菌剂的皮肤吸收， 与工人的刺激性皮炎有关。以前的皮肤风险评估仅评价了吸收 考虑到单一化学品的多样性和多种不同的实验室方法， 有限，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）技术来表征生物杀灭剂之间的分配行为， 定义的混合物，如切削液和惰性膜，并将该相分布与 在线性溶剂化能量关系（LSER）框架内的溶剂化色参数。中央 要检验的假设是，切削液添加剂的存在将改变 混合物和MCF之间的生物杀灭剂。杀生物剂分布的这些变化可以表示为： 可以外推到定义的混合物的相互作用系数项。这样做的理由 一种方法是，切削液配方中使用的添加剂可以通过离散调节杀生物剂的吸收， 生物学机制，但很少有人知道嵌入的物理化学相互作用。的MCF LSER框架内的方法允许使用以下方法对这些溶剂化效应进行机械检查： 非生物膜系统。为实现这一目标，将努力实现以下三个具体目标： 所述目标：1）识别和量化影响溶质从 水溶液系统的膜涂布纤维（MCF）。这首先涉及校准各种 一系列的MCF，以捕捉尽可能多的溶质-膜相互作用的物理化学属性。（二） 确定和量化影响混合物和MCF之间的杀菌剂运输的加性效应。这将 为给定的混合方案提供相互作用系数。3)确定化学-生物相互作用， 生物膜系统皮肤体外实验将校准生物学中的渗透性。 系统，并确定相关混合物的相互作用系数。相互作用比较分析 MCF和生物系统之间的系数将提供一些洞察主导 影响化学混合物中杀生物剂皮肤吸收的物理化学相互作用。