Department of Statistics, North Carolina State University, Raleigh, NC 27695-8203, USA.
Wells Fargo and Company, Charlotte, NC 28202-0901, USA.
Molecules. 2018 Nov 24;23(12):3076. doi: 10.3390/molecules23123076.
Permeation of chemical solutes through skin can create major health issues. Using the membrane-coated fiber (MCF) as a solid phase membrane extraction (SPME) approach to simulate skin permeation, we obtained partition coefficients for 37 solutes under 90 treatment combinations that could broadly represent formulations that could be associated with occupational skin exposure. These formulations were designed to mimic fluids in the metalworking process, and they are defined in this manuscript using: one of mineral oil, polyethylene glycol-200, soluble oil, synthetic oil, or semi-synthetic oil; at a concentration of 0.05 or 0.5 or 5 percent; with solute concentration of 0.01, 0.05, 0.1, 0.5, 1, or 5 ppm. A single linear free-energy relationship (LFER) model was shown to be inadequate, but extensions that account for experimental conditions provide important improvements in estimating solute partitioning from selected formulations into the MCF. The benefit of the Expanded Nested-Solute-Concentration LFER model over the Expanded Crossed-Factors LFER model is only revealed through a careful leave-one-solute-out cross-validation that properly addresses the existence of replicates to avoid an overly optimistic view of predictive power. Finally, the partition theory that accompanies the MCF approach is thoroughly tested and found to not be supported under complex experimental settings that mimic occupational exposure in the metalworking industry.
化学溶质透过皮肤渗透会引发重大健康问题。我们采用涂覆有膜的纤维（MCF）作为固相膜萃取（SPME）方法来模拟皮肤渗透，在 90 种处理组合下获得了 37 种溶质的分配系数，这些组合可以广泛代表与职业性皮肤接触相关的配方。这些配方旨在模拟金属加工过程中的液体，本文中使用以下定义进行描述：矿物油、聚乙二醇-200、可溶性油、合成油或半合成油中的一种；浓度为 0.05 或 0.5 或 5%；溶质浓度为 0.01、0.05、0.1、0.5、1 或 5ppm。结果表明，单一线性自由能关系（LFER）模型不充分，但考虑实验条件的扩展模型可显著提高从选定配方估算溶质分配到 MCF 的能力。与交叉因子扩展 LFER 模型相比，扩展嵌套溶质浓度 LFER 模型的优势仅通过仔细的单溶质排除交叉验证来揭示，该验证可正确处理重复项的存在，避免对预测能力的过度乐观。最后，MCF 方法所伴随的分配理论在模拟金属加工业职业性接触的复杂实验条件下未得到验证。
