DERMAL ABSORPTION OF CHEMICALS FROM LIQUID MIXTURES

描述：工作场所是有害化学物质接触皮肤的最常见场所之一。认识到皮肤暴露的危害是控制其危害的关键。不幸的是，目前对化学物质皮肤吸收危害的识别是不一致的，缺乏文献记载，而且是定性的。因此，那些负责在工作场所保护人类健康和安全的人，被迫在几乎没有信息的情况下，对安全或危险水平以及所需的个人保护类型做出判断。这项研究的最终目标是为职业安全和健康从业者提供关于潜在危险水平的职业皮肤暴露的更好指导。虽然大多数职业性皮肤暴露涉及多种化学物质的混合物，但多种成分与皮肤之间的相互作用仍不清楚。拟议的研究旨在确定和理解 暴露于化学混合物，尤其是非水溶液的影响。了解到实验评估将限于职业上遇到的所有混合物的一小部分，我们建议通过将数据与数学模型相结合来发展对潜在机制的基本理解。具体地说，我们将(I)通过实验研究几种测试溶质在水和四种非水溶液(甲苯、正辛醇、正辛烷和选定的氯代烃)中相互作用或相互作用以改变速率的程度。 (Ii)开发用于估计含有两种或两种以上有机化合物的水溶液和非水溶液的皮肤吸收的计算程序，以及(Iii)展示并使用一种新的测量电化学阻抗的方法来表征皮肤屏障功能以及非水溶液对皮肤的影响。初步研究将涉及甲苯和正辛醇中的四种溶质(萘、菲、1-萘酚和1，3-萘二酚)。选择这种溶质和溶剂的组合来检查相似和不同化学物质之间的相互作用，并评估吸收化学物质和皮肤之间氢键相互作用的重要性。这项研究的最终目标是建立一个框架，以实用指南的形式将液体混合物的皮肤吸收测量和预测与工业健康科学家联系起来。有了这些信息，就有可能规划有效的暴露控制和/或干预措施。

DESCRIPTION: The workplace is one of the most common venues for hazardous chemical contact with skin. Recognition of the dermal exposure hazard is essential for its control. Unfortunately, the present identification of chemicals as skin absorption hazards is inconsistent, poorly documented, and qualitative. As a result, those charged with protecting human health and safety in the workplace are forced to make judgments about safe or dangerous levels, and the type of personal protection required, with little or no information. The ultimate goal of this research effort is to provide occupational safety and health practitioners with improved guidance regarding potentially dangerous levels of occupational dermal exposure. While most occupational exposures of skin involve mixtures of chemicals, the interactions between multiple components and skin remain unknown. The proposed research is directed toward identifying and understanding the effect of exposures to chemical mixtures and especially non-aqueous solutions. Understanding that experimental evaluations will be limited to a small fraction of all mixtures encountered occupationally, we propose to develop a fundamental understanding of the underlying mechanisms by combining data with mathematical models. Specifically, we will (i) examine experimentally the extent to which several test solutes in water and in four non-aqueous solutions (toluene, n-octanol, n-octane and a selected chlorinated hydrocarbon) interact with each other or skin to alter the rate and/or amount of chemical absorption, (ii) develop computational procedures for estimating dermal absorption from aqueous and non-aqueous solutions containing two or more organic compounds, and (iii) demonstrate and use a new method for measuring electrochemical impedance to characterize skin barrier function and the effect of non-aqueous solutions thereon. Initial studies will involve four solutes (naphthalene, phenanthrene, 1-naphthol, and 1,3-naphthalenediol) in toluene and n-octanol. This combination of solutes and solvents were selected to examine interactions between similar and dissimilar chemicals, and to assess the importance of hydrogen bonding interactions between absorbing chemicals and skin. The ultimate goal of this research effort is a framework for relating dermal absorption measurements and predictions for liquid mixtures to industrial health scientists in the form of useful guidelines. With such information in-hand, it will be possible to plan effective exposure controls and/or interventions.