Improved Methods for Dermal Exposure Estimation

皮肤暴露估计的改进方法

基本信息

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
项目类别：
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

项目摘要

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）：调查人员建议开发密切模仿的精致而易于访问的数学模型经皮渗透，组织浓度和人类皮肤中的间隙体内。这种发展将大大提高机械理解过敏和刺激性皮炎以及皮肤暴露的力学评估。这个目标将通过施工来完成，基于生理和物理特性模型的实验验证对于经皮吸收，结合了未发现的特征目前用于估计皮肤暴露的数学模型。成功的提案的具体目的的完成将导致以下内容：（1）经过实验验证的人类层中传输的微观模型角质和皮肤附属物（毛囊，汗腺）；（2）真皮血管模型，可以准确预测统一浓度和在可行的皮肤层中清除；（3）瞬态扩散模型计算低到中度暴露后的皮肤吸收潜在挥发性化合物；（4）用于连接的皮肤水合模型上面有目前正在使用的稳态渗透率模型；（5）易于使用的电子表格用于皮肤暴露计算，包括最多调查的重要特征。研究方法包括：用于在异质中建模传输的复杂数值技术这些结果的结构和高级图形表示。详细检查角质层超结构和微转移的详细检查使用激光扫描共聚焦显微镜，荧光的性能光漂白和其他光学微观技术。确定选定胶原的扩散和分区系数在角质层，表皮，真皮和皮下注射以及蛋白质的作用对这些值结合。