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）：研究者建议开发一种 一个复杂的，但容易理解的数学模型， 经皮渗透、组织浓度和人体皮肤清除率 vivo.这一发展将大大推进机械的理解 过敏性和刺激性皮炎以及皮肤接触机制 考核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，其结合了 目前用于估计皮肤接触的数学模型。成功 完成该建议的具体目标将导致：（1） 一个经过实验验证的人类阶层运输的微观模型 角质层和皮肤附属物（毛囊，汗腺）;（2）真皮 血管模型，可以准确预测渗透物浓度， 清除在可行的皮肤层;（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）皮肤水合作用模型，用于将 以上与目前使用的稳态渗透率模型;以及（5） 用于皮肤接触计算的易于使用的电子表格， 调查的重要特征。 研究方法包括： 复杂的数值技术，用于模拟非均匀介质中的输运 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镜技术。 选定渗透物的扩散系数和分配系数的测定 在角质层、表皮、真皮和皮下组织中的作用以及蛋白质的作用 对这些价值观的约束。