Mechanistically-Based In Silico Estimation of Dermal Absorption in the Workplace

基于机械的工作场所皮肤吸收的计算机估计

基本信息

批准号：
8094265
负责人：
GERALD B. KASTING
金额：
$ 36.72万
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 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8094265
关键词：
Mechanistically Based Silico Estimation Dermal

项目摘要

DESCRIPTION (provided by applicant): The investigators propose to further develop and apply to occupational risk assessment a sophisticated, yet accessible mathematical model that closely mimics percutaneous penetration, tissue concentrations and clearance of chemicals in human skin in vivo. The working model, developed during the previous period of support, will be calibrated by means of new experiments and extended to include a wider range of chemicals. Initial development of a transient swelling and shrinkage model for skin decontamination and a thermodynamically-based model for interacting chemical mixtures will be undertaken. The skin decontamination model will be supported by human in vivo and in vitro studies with DEET. Single component, multicomponent and swelling models wll be used to interpret complex skin absorption phenomena found in occupational health practice. Model software will be packaged in a spreadsheet format to provide accessibility to the occupational health and safety/industrial hygiene communities. Key technical features in the skin absorption model include: (1) a hydration-dependent, microscopically-based model for stratum corneum permeability; (2) a dermal vascular model that allows accurate prediction of permeant concentrations and clearance in the viable skin layers; (3) quantitative estimation of the evaporation rates of volatile permeants; (4) incorporation of convective flow and surfactant and organic solvent effects for skin decontamination; (5) a detailed microscopic model for permeant transport in the epidermis; and (6) a thermodynamic activity-based model for interactions in chemical mixtures contacting the skin. The primary routes by which occupatational exposures occur are inhalation and dermal exposure (skin contact). Effective dermal risk assessment for workers involved with hazardous chemicals (solvents, pesticides, cleaning fluids, etc.) requires accurate methods for estimating exposure to and absorption of the chemical, and the probable biological response to this event. Evaluation of the potential effectiveness of washing for purposes of mitigating dermal risk is an essential part of this process. Completion of the proposed project will provide a significant improvement to current methods for estimating absorption of chemicals subsequent to dermal exposures in the workplace.

描述（由申请人提供）：研究人员建议进一步开发并应用于职业风险评估，这是一个复杂但可访问的数学模型，它密切模仿经皮渗透，组织浓度和体内化学物质的清除率。在上一个支持期间开发的工作模型将通过新的实验进行校准，并扩展到包括更广泛的化学物质。将开发用于皮肤去污染的瞬时肿胀和收缩模型，以及用于相互作用化学混合物的基于热力学的模型。皮肤去污染模型将得到人体体内和DEET的体外研究的支持。单个成分，多组分和肿胀模型可用于解释职业健康实践中发现的复杂皮肤吸收现象。模型软件将以电子表格格式包装，以便为职业健康和安全/工业卫生社区提供可访问性。皮肤吸收模型中的关键技术特征包括：（1）一种基于水合的，基于显微镜的角膜渗透性的模型；（2）一种皮肤血管模型，可准确预测可行的皮肤层中的渗透浓度和清除率；（3）挥发性渗透率蒸发率的定量估计；（4）对流动流以及表面活性剂和有机溶剂效应的融合；（5）表皮中渗透性转运的详细微观模型；（6）基于热力学活性的模型，用于接触皮肤的化学混合物中的相互作用。发生占领的主要路线是吸入和皮肤暴露（皮肤接触）。对危险化学物质（溶剂，农药，清洁液等）的工人进行有效的皮肤风险评估，需要准确的方法来估算化学物质的接触和吸收，以及对此事件的可能生物学反应。评估洗涤的潜在有效性是为了减轻皮肤风险，这是该过程的重要组成部分。拟议项目的完成将为当前方法提供显着改善，以估计工作场所真皮暴露后的化学物质吸收。