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

• 批准号: 7490591
• 负责人: GERALD B. KASTING
• 金额: $ 38.28万
• 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 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490591
• 关键词: Mechanistically; Based; Silico; Estimation; Dermal

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一种复杂且易于使用的数学模型并将其应用于职业风险评估，该模型密切模拟体内人体皮肤中化学物质的经皮渗透、组织浓度和清除率。在上一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品。将初步开发用于皮肤净化的瞬态膨胀和收缩模型以及用于相互作用的化学混合物的基于热力学的模型。皮肤净化模型将得到避蚊胺人体体内和体外研究的支持。单组分、多组分和膨胀模型将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打包，以便为职业健康和安全/工业卫生社区提供可访问性。皮肤吸收模型的关键技术特征包括：（1）依赖于水合作用的、基于显微镜的角质层渗透性模型； (2) 真皮血管模型，可以准确预测可行皮肤层中的渗透物浓度和清除率； (3) 定量估算挥发性渗透物的蒸发速率； (4)结合对流和表面活性剂及有机溶剂作用进行皮肤去污； (5) 表皮渗透性运输的详细微观模型； (6) 基于热力学活动的模型，用于研究接触皮肤的化学混合物中的相互作用。发生职业接触的主要途径是吸入和皮肤接触（皮肤接触）。对接触危险化学品（溶剂、杀虫剂、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计化学品的接触和吸收，以及对此事件可能的生物反应。评估清洗对于减轻皮肤风险的潜在有效性是该过程的重要组成部分。拟议项目的完成将为目前估计工作场所皮肤接触化学品吸收的方法提供重大改进。