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Absorption and evaporation of volatile organic solvents from human skin in vitro.

机译：人体皮肤中挥发性有机溶剂的吸收和蒸发。

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摘要

Accurate estimation of evaporation and permeation rates of volatile organic solvents through human skin in vivo is important for occupational and environmental risk assessments, which include factors such as the solvent's capacity to be a local sensitizer or a systemic toxin. Current risk assessment models for volatile organic solvents often include the assumption that 100% of the dermal dose of toxicant is absorbed, which results in an overly conservative risk assessment. The overall goal of this research was to further develop and improve an existing skin diffusion model by experimentally confirming the predicted evaporation and absorption rates of volatile, topically applied organic compounds based on their physicochemical properties, the known biological properties of skin and principles of diffusion theory.;Twenty-one compounds with varying physicochemical properties were studied to determine evaporation rates from human skin in vitro mounted on Franz diffusion cells under two exposure conditions, bench top and fume hood. Correlations of the data according to five evaporative mass transfer models from the occupational and environmental safety literature were examined. We found the US EPA evaporation model (Peress J. Chem Eng Prog April, 2003, 32-34) to be the most suitable model for the analysis of laboratory skin diffusion studies with volatile compounds. The effective values for wind velocity in bench top and fume hood experiments were found to be 0.23 and 0.92 m s-1, respectively.;In vitro human skin permeation of two hydrophilic solvents (acetone and ethanol) and two lipophilic solvents (benzene and 1,2-dichloroethane) were studied in the same diffusion cells under the fume hood conditions. Four doses of each compound were tested -- 5, 10, 20, 40 muL cm-2 , corresponding to specific doses ranging in mass from 5.0 to 63 mg cm-2. 14C-radiolabed compounds were employed. A decrease in percent of absorption of each solvent with increasing dose was observed. This decreased could be explained in terms of a stratum corneum deposition region in the diffusion model. Overall permeation of acetone, benzene and 1,2-dichloroethane was under predicted; however the diffusion model satisfactorily described ethanol. As large doses of the first three compounds are known to extract skin lipids, lipid disruption by even small doses of these compounds was postulated to contribute to the under prediction.;In order to more closely describe the permeation data, two key parameters in diffusion model required modification: the stratum corneum/water partition coefficient, KSC and diffusion coefficient of the permeant in the stratum corneum, DSC. In most cases the magnitude of change of the fitted values of KSC and the corresponding skin concentrations were not physically realistic when a fixed stratum corneum thickness was employed. This finding provided strong evidence for both skin swelling and barrier disruption. Recommendations for future work included conducting accurate stratum corneum-water partitioning studies for solvents under varying levels of skin hydration and the development of a more flexible skin-swelling model to count for co-solvent interaction with the stratum corneum.
机译：体内人体皮肤中挥发性有机溶剂的蒸发和渗透率的准确估算对于职业和环境风险评估至关重要，评估包括诸如溶剂成为局部敏化剂或全身性毒素的能力等因素。当前挥发性有机溶剂的风险评估模型通常包括以下假设：真皮吸收了100％的有毒物质，这导致风险评估过于保守。这项研究的总体目标是，通过根据其理化特性，已知的皮肤生物学特性和扩散原理，通过实验确定挥发性，局部应用的有机化合物的预计蒸发和吸收速率，从而进一步开发和改善现有的皮肤扩散模型。研究了二十一种具有不同理化性质的化合物，以确定在两种暴露条件（台式和通风橱）下，体外安装在Franz扩散池上的人皮肤的蒸发速率。根据来自职业和环境安全文献的五个蒸发传质模型，对数据的相关性进行了检验。我们发现美国EPA蒸发模型（Peress J. Chem Eng Prog，2003年4月，第32-34页）是最适合分析挥发性化合物的实验室皮肤扩散研究的模型。在台式和通风橱实验中，风速的有效值分别为0.23和0.92 m s-1 .;体外人体皮肤中两种亲水性溶剂（丙酮和乙醇）和两种亲脂性溶剂（苯和1 ，在通风橱条件下，在相同的扩散池中研究了（2-二氯乙烷）。测试了每种化合物的四剂量-5、10、20、40μLcm-2，对应于质量范围为5.0至63 mg cm-2的特定剂量。使用了14 C-放射性化合物。观察到随着剂量增加，每种溶剂的吸收百分比降低。这种减少可以用扩散模型中的角质层沉积区域来解释。丙酮，苯和1,2-二氯乙烷的总渗透率低于预期；然而，扩散模型令人满意地描述了乙醇。由于已知大剂量的前三种化合物会提取皮肤脂质，因此假设即使小剂量的这些化合物也会破坏脂质，这有助于预测不足。;为了更准确地描述渗透数据，扩散模型中的两个关键参数所需的修改：角质层/水分配系数KSC和渗透物在角质层中的扩散系数DSC。在大多数情况下，当采用固定的角质层厚度时，KSC拟合值和相应皮肤浓度的变化幅度在物理上并不现实。这一发现为皮肤肿胀和屏障破坏提供了有力的证据。对未来工作的建议包括对在不同皮肤水合作用水平下的溶剂进行准确的角质层-水分配研究，以及开发一种更灵活的皮肤膨胀模型以计算与角质层的共溶剂相互作用。

著录项

  • 作者

    Gajjar, Rachna.;

  • 作者单位

    University of Cincinnati.;

  • 授予单位 University of Cincinnati.;
  • 学科 Chemistry Organic.;Health Sciences Pharmacy.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 159 p.
  • 总页数 159
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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