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经猪皮的定量结构渗透关系分析研究 JP-8 喷气燃料碳氢化合物的剂量相关吸收。

Dose Related Absorption of JP-8 Jet Fuel Hydrocarbons Through Porcine Skin with Quantitative Structure Permeability Relationship Analysis.

机构信息

Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606.

出版信息

Toxicol Mech Methods. 2004;14(3):159-66. doi: 10.1080/15376520490429319.

DOI:10.1080/15376520490429319
PMID:20021142
Abstract

The effects of dosage on the percutaneous absorption of jet fuel hydrocarbons is not clear, yet is essential for human risk assessment. The present study is an ongoing approach to assess the dose-related percutaneous absorption of a number of aliphatic and aromatic hydrocarbons. The first treatment (1X) was comprised of mixtures containing undecane (4.1%), dodecane (4.7%), tridecane (4.4%), tetradecane (3%), pentadecane (1.6%), naphthalene (1.1%), and dimethyl naphthalene (1.3% of jet fuels) in hexadecane solvent using porcine skin flow through diffusion cell. Other treatments (n = 4 cells) were 2X and 5X concentrations. Perfusate samples were analyzed with gas chromatography-flame ionization detector (GC-FID) using head space solid phase micro-extraction fiber technique. We have standardized the assay to have a good linear correlation for all the tested components in media standards. Absorption parameters including diffusivity, permeability, steady state flux, and percent dose absorbed were estimated for all the tested hydrocarbons. This approach provides a baseline to access component interactions among themselves and with the diluent (solvents). A quantitative structure permeability relationship (QSPR) model was derived to predict the permeability of unknown jet fuel hydrocarbons in this solvent system by using their physicochemical parameters. Our findings suggested a dose related increase in absorption for naphthalene and dimethyl naphthalene (DMN).

摘要

燃料油中烃类经皮吸收的剂量效应尚不清楚,但对于人体风险评估至关重要。本研究旨在评估一系列脂肪族和芳香族烃类的剂量相关经皮吸收。第一次处理(1X)采用猪皮流通扩散池,使用十六烷溶剂,包含正十一烷(4.1%)、正十二烷(4.7%)、正十三烷(4.4%)、正十四烷(3%)、正十五烷(1.6%)、萘(1.1%)和二甲基萘(1.3%)的混合物。其他处理(n=4 个细胞)分别为 2X 和 5X 浓度。使用顶空固相微萃取纤维技术,通过气相色谱-火焰离子化检测器(GC-FID)对灌注液样品进行分析。我们已经将该测定方法标准化,以便在介质标准中对所有测试成分都具有良好的线性相关性。对所有测试烃类的扩散系数、渗透性、稳态通量和吸收剂量百分比等吸收参数进行了估计。该方法提供了一个基准,可用于评估各成分之间以及与稀释剂(溶剂)之间的相互作用。通过使用其物理化学参数,推导出了一个定量结构渗透关系(QSPR)模型,以预测该溶剂体系中未知喷气燃料烃类的渗透性。我们的研究结果表明,萘和二甲基萘(DMN)的吸收剂量呈相关性增加。

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