Dermatopharmacokinetics: In Vivo Analysis of Solvents

皮肤药代动力学：溶剂的体内分析

基本信息

批准号：
6904614
负责人：
KARLA D THRALL
金额：
$ 28.27万
依托单位：
BATTELLE PACIFIC NORTHWEST LABORATORIES
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2006-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6904614
关键词：
benzene biological models breath tests chemical kinetics chemical structure function environmental exposure environmental toxicology hydropathy laboratory rat occupational health /safety pharmacokinetics skin absorption skin pharmacology solvents toluene transdermal drug delivery vapor water

项目摘要

DESCRIPTION (provided by applicant): This project is a continuation of NIOSH 5-RO1-OH03658-02, "Dermatopharmacokinetics of paint solvents." The overall research objective for this continuation project is to expand prior studies to evaluate the percutaneous absorption of compounds commonly encountered within similar industries (styrene and ethylbenzene) along with focused studies to evaluate the dermal bioavailability of compounds with both lipophilic and hydrophilic properties. The first part of this study demonstrated that the dermal absorption of toluene in an aqueous matrix was substantially less than previous estimates, and that aqueous methyl ethyl ketone was absorbed to a much greater degree than previously determined. Additionally, studies conducted to evaluate the dermal absorption of methyl ethyl ketone have revealed a biphasic absorption pattern, with an initial rapid appearance of compound in the exhaled breath, indicative of high permeability, followed by a more sustained moderate permeability. Furthermore, our studies with complex paint matrices indicate that the matrix impacts toluene dermal absorption to a lesser degree than concentration within the matrix. The next phase of study, as proposed here, will explore the biphasic absorption in more detail by evaluating additional compounds with both lipophilic and hydrophilic properties, will evaluate the dermal bioavailability of additional compounds commonly encountered in the occupational setting, and will evaluate the dermal bioavailability of solvents as vapors. This continuation proposal has the following Specific Aims: 1. To compare the dermal absorption of compounds with both lipophilic and hydrophilic properties with prior studies using methyl ethyl ketone in F344 rats; 2.To evaluate the kinetics and dermal bioavailability of ethylbenzene and styrene in an aqueous matrix using F344 rats; 3.To evaluate the kinetics and dermal bioavailability of ethylbenzene, styrene, and toluene vapor using F344 rats.

描述（由申请人提供）：该项目是NIOSH 5-RO1-OH03658-02的延续，“油漆溶剂的Dermatopharmacokinetics”。该延续项目的总体研究目标是扩大先前的研究，以评估类似行业（苯乙烯和乙烯苯）在类似行业（苯乙烯和乙烯苯）中常见的化合物的经皮吸收以及重点研究，以评估具有亲脂性和水生特性的化合物的真皮生物利用度。这项研究的第一部分表明，水基质中甲苯的皮肤吸收大大低于以前的估计，并且甲基乙基酮水的吸收程度比以前确定的程度要大得多。另外，进行的研究是为了评估甲基酮的皮肤吸收的研究表明，双相吸收模式，在呼出的呼吸中最初快速出现化合物，表明渗透率很高，随后是更持续的中度通透性。此外，我们对复杂油漆矩阵的研究表明基质将甲苯皮肤吸收的程度比基质内的浓度较低。如这里提出的那样，下一阶段的研究将通过评估具有亲脂性和亲水性特性的其他化合物来探索双相吸收，将评估职业环境中常见的其他化合物的真皮生物可利用度，并将评估vapors of Vapors的溶剂溶液的皮肤生物可利用性。该延续建议具有以下特定目的：1。将化合物与亲脂性和亲水性特性的真皮吸收以及先前的研究使用F344大鼠中的甲基乙基酮的先前研究； 2.使用F344大鼠在水性基质中评估乙烯和苯乙烯的动力学和皮肤生物利用度； 3.使用F344大鼠评估乙烯，苯乙烯和甲苯蒸气的动力学和真皮生物利用度。