DERMATOPHARMACOKINETICS OF PAINT SOLVENTS

涂料溶剂的皮肤药代动力学

• 批准号: 6558672
• 负责人: KARLA D THRALL
• 金额: $ 27.9万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6558672
• 关键词: biological models; breath tests; chemical kinetics; chemical structure function; computer simulation; consumer product; environmental exposure; environmental toxicology; gas chromatography; ketones; laboratory rat; mass spectrometry; model design /development; nonwater solvent; occupational hazard; occupational health /safety; pharmacokinetics; physical model; skin absorption; skin pharmacology; solvents; toluene; transdermal drug delivery; water

DESCRIPTION: The research in this proposal is designed to provide a fundamental understanding of the influence of various types of paint product formulations on the dermatopharmacokinetics of two commonly encountered solvents, toluene and methyl ethyl ketone (MEK). This research will enhance the ability to accurately extrapolate animal studies to relevant human exposure scenarios and improve hazard and risk assessments. Experimental studies will be conducted with rats using a novel real-time breath analysis system coupled with physiologically based pharmacokinetic (PBPK) modeling to determine the penetration rate of toluene and MEK through the skin. The resultant data from these comprehensive evaluations are directly applicable to regulatory agencies in establishing dermal absorption guidelines that mimic actual occupational exposure situations. The specific research objectives are: (1) to describe dermal absorption of toluene and MEK using PBPK models in order to determine skin permeability constants; (2) to evaluate the kinetics and dermal bioavailability of exposure to aqueous and MEK; (3) to describe the dose-dependent kinetics of exposure to toluene and MEK in characterized paint products; and (4) to compare different paint product formulations on the percutaneous absorption of toluene and MEK.

描述： 该提案的研究旨在提供基本 理解各种涂料产品配方的影响 在两种常见的溶剂的皮肤上，甲苯 和甲基乙基酮（MEK）。这项研究将增强 准确推断动物研究到相关的人类暴露情况和 改善危害和风险评估。将进行实验研究 使用新颖的实时呼气分析系统的大鼠与 基于生理的药代动力学（PBPK）建模以确定 甲苯和MEK的穿透速率穿过皮肤。来自 这些全面的评估直接适用于监管机构 在建立模仿实际职业的皮肤吸收指南时 暴露情况。具体的研究目标是：（1）描述 使用PBPK模型来确定甲苯和MEK的真皮吸收 皮肤通透性常数； （2）评估动力学和皮肤 暴露于水和MEK的生物利用度； （3）描述 剂量依赖性的动力学在特征涂料中暴露于甲苯和mek的动力学 产品; （4）比较在 经皮吸收甲苯和梅克。