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利用简单的体外测试评估在体外人体皮肤吸收研究中因挥发性导致的化学损失。

Use of a Simple in vitro Test to Assess Loss of Chemical due to Volatility during an in vitro Human Skin Absorption Study.

机构信息

L'Oreal Research and Innovation, Aulnay-sous-Bois, France.

Unilever, Sharnbrook, United Kingdom.

出版信息

Skin Pharmacol Physiol. 2019;32(3):117-124. doi: 10.1159/000497105. Epub 2019 Mar 19.

DOI:10.1159/000497105
PMID:30889606
Abstract

BACKGROUND

We tested the cutaneous distribution of 50 chemicals in frozen human skin. The mass balance (MB) values for 48% of the chemicals were < 90%, possibly due to evaporation.

METHODS

We confirmed the reduction in MB was due to evaporation for two chemicals tested in skin penetration experiments using a carbon filter above the skin to trap airborne chemical. An in vitro assay was used to predict the reduction in MB due to evaporation by comparing the recovery of chemicals after 4 h of incubation at room temperature in open and closed vials.

RESULTS

Evaporative losses in vitro correlated well with measured MBs (i.e., < 90%) in skin penetration experiments (R2 = 0.81). There was a correlation of the MB with the vapour pressure (VP) which could be used to group chemicals according to their likelihood to evaporate during the course of a skin penetration study. There was also a correlation of MB with Henry's law constants, melting and boiling points.

CONCLUSION

Our data support the use of a quick and simple test for volatility to account for the loss of MB in skin penetration experiment due to volatility. The best parameter to indicate the potential of a chemical to evaporate is the VP.

摘要

背景

我们测试了 50 种化学物质在冷冻人体皮肤中的分布情况。由于蒸发,48%的化学物质的质量平衡(MB)值<90%。

方法

我们通过在皮肤上方使用碳过滤器来捕获空气中的化学物质,证实了皮肤渗透实验中两种化学物质的 MB 减少是由于蒸发所致。体外测定法通过比较在室温下在开放和封闭小瓶中孵育 4 小时后化学物质的回收率,来预测由于蒸发而导致的 MB 减少。

结果

体外蒸发损失与皮肤渗透实验中测量的 MB(即<90%)相关性良好(R2 = 0.81)。MB 与蒸气压(VP)之间存在相关性,可根据化学物质在皮肤渗透研究过程中蒸发的可能性对其进行分组。MB 与亨利定律常数、熔点和沸点也存在相关性。

结论

我们的数据支持使用快速简便的挥发性测试来解释由于挥发性导致的皮肤渗透实验中 MB 的损失。表明化学物质蒸发潜力的最佳参数是 VP。

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