Improved Methods for Dermal Exposure Estimation

皮肤暴露估计的改进方法

• 批准号: 6900233
• 负责人: GERALD B. KASTING
• 金额: $ 32.78万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6900233
• 关键词: confocal scanning microscopy; dermatitis; diffusion; environmental exposure; evaporation; hair follicle; human tissue; light microscopy; mathematical model; model design /development; occupational hazard; occupational health /safety; protein binding; skin; skin absorption; skin circulation; skin irritation /irritant; sweat glands; tissue /cell culture

DESCRIPTION (provided by applicant): The investigators propose to develop a sophisticated, yet accessible mathematical model that closely mimics percutaneous penetration, tissue concentrations and clearance in human skin in vivo. This development will significantly advance the mechanistic understanding of allergic and irritant dermatitis and the mechanics of dermal exposure assessment. This objective will be accomplished through the construction and experimental verification of physiological and physical properties-based models for percutaneous absorption incorporating features not found in the mathematical models presently used to estimate dermal exposure. Successful completion of the specific aims of the proposal will lead to the following: (1) an experimentally verified, microscopic model of transport in human stratum corneum and skin appendages (hair follicles, sweat glands); (2) a dermal vascular model that allows accurate predictions of permeant concentrations and clearance in the viable skin layers; (3) a transient diffusion model for calculating dermal absorption subsequent to low-to-moderate exposures to potentially volatile compounds; (4) a skin hydration model for linking the above with steady-state permeability models presently in use; and (5) an easy-to-use spreadsheet for dermal exposure calculations incorporating the most important features from the investigation. The research methods include: Sophisticated numerical techniques for modeling transport in heterogeneous structures and advanced graphical representation of these results. Detailed examination of stratum corneum ultra structure and microtransport properties using laser scanning confocal microscopy, fluorescence photobleaching,and other light microscopic techniques. Determination of diffusivities and partition coefficients of selected permeants in stratum corneum, epidermis, dermis, and hypodermis and the role of protein binding on these values.

描述（由申请人提供）：研究人员建议开发一种 复杂但易于理解的数学模型，非常模仿 经皮渗透、组织浓度和人体皮肤清除率 体内。这一发展将显着促进对机制的理解 过敏性和刺激性皮炎的发病机制以及皮肤暴露的机制 评估。这一目标将通过建设和 基于生理和物理特性的模型的实验验证 用于经皮吸收，结合了现有技术中未发现的功能 目前用于估计皮肤暴露的数学模型。成功的 完成提案的具体目标将导致以下结果：(1) 经过实验验证的人体地层运输微观模型 角质和皮肤附属器（毛囊、汗腺）； (2) 真皮层 血管模型可以准确预测渗透物浓度和 活性皮肤层的间隙； (3) 瞬态扩散模型 计算低至中度暴露后的皮肤吸收 潜在挥发性化合物； (4) 皮肤水合模型 以上是目前使用的稳态渗透率模型； (5) 一个 易于使用的电子表格，用于计算皮肤暴露量，包含最 调查的重要特征。 研究方法包括： 用于建模异构传输的复杂数值技术 这些结果的结构和高级图形表示。 角质层超微结构和微运输的详细检查 使用激光扫描共聚焦显微镜、荧光 光漂白和其他光学显微技术。 选定渗透物的扩散率和分配系数的测定 角质层、表皮、真皮、皮下组织及蛋白质的作用 绑定这些值。