正丙醇（壬酸载体）在累积皮肤刺激中的刺激潜力：两种不同人体体内试验模型的验证研究。

The irritant potential of n-propanol (nonanoic acid vehicle) in cumulative skin irritation: a validation study of two different human in vivo test models.

作者信息

Clemmensen A, Andersen F, Petersen T K, Kalden H, Melgaard A, Andersen K E

机构信息

Department of Dermatology, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.

出版信息

Skin Res Technol. 2008 Aug;14(3):277-86. doi: 10.1111/j.1600-0846.2008.00291.x.

DOI:10.1111/j.1600-0846.2008.00291.x

PMID:19159372

Abstract

BACKGROUND/PURPOSE: Human in vivo cumulative irritation tests with low-grade irritants simulate real-life exposure to skin irritants. The test outcome depends not only on the substance tested but also on the design of the assay. More than one experimental irritant is usually used because chemicals have diverse mechanisms of action on the skin. We used sodium lauryl sulfate (SLS) and nonanoic acid (NON) in three different concentrations plus their vehicles, water and n-propanol, respectively, to validate our test models and to optimize test concentrations.

METHODS

Healthy volunteer forearm skin was exposed in two different cumulative test models: a repeated open model (ROAT) and an exaggerated wash test model. ROAT: 10-min daily exposures for 5+4 days (no irritation on weekend) to SLS 0% (water), 0.5%, 1.0% and 2.0% on the right arm and NON 0% (n-propanol neat), 10%, 20% and 30% on the left arm. Wash test: induction of irritation by three daily washings for 6 days and maintenance of the dermatitis by two daily washings for 12 days with SLS 0%, 5%, 10% and 15% or NON 0%, 30%, 40% and 50%. Reactions were evaluated clinically and instrumentally (transepidermal water loss, colorimetry and hydration) at sequential time points. Additionally, for the wash test, subjective pain scores were obtained from the volunteers.

RESULTS

In the ROAT, n-propanol exhibited irritation potential at the level of SLS 1.0% and, by visual scoring, was only found to be significantly different from the two highest concentrations of NON (20% and 30%). In the wash test, n-propanol was much less irritating than SLS, and it could only be distinguished statistically from NON (any concentration) by visual reading. For both test models, n-propanol, by instrumental measurements, was not significantly different from any NON concentration.

CONCLUSION

In cumulative irritation test assays, n-propanol appears to be quite irritant itself and may thus be a significant contributor to NON irritation. Moreover, n-propanol was more irritant in the ROAT compared with the wash test.

摘要

背景/目的：使用低刺激性物质进行人体体内累积刺激试验可模拟现实生活中皮肤接触刺激物的情况。试验结果不仅取决于所测试的物质，还取决于试验设计。通常会使用不止一种实验性刺激物，因为化学物质对皮肤有多种作用机制。我们分别使用三种不同浓度的十二烷基硫酸钠（SLS）和壬酸（NON）及其赋形剂水和正丙醇，以验证我们的测试模型并优化测试浓度。

方法

在两种不同的累积测试模型中对健康志愿者的前臂皮肤进行暴露：重复开放模型（ROAT）和强化洗涤试验模型。ROAT：右臂每天暴露10分钟，持续5 + 4天（周末无刺激），分别使用0%（水）、0.5%、1.0%和2.0%的SLS；左臂使用0%（纯正丙醇）、10%、20%和30%的NON。洗涤试验：连续6天每天洗涤3次诱导刺激，然后连续12天每天洗涤2次维持皮炎状态，分别使用0%、5%、10%和15%的SLS或0%、30%、40%和50%的NON。在连续的时间点对反应进行临床和仪器评估（经表皮水分流失、比色法和皮肤水合作用）。此外，对于洗涤试验，从志愿者处获取主观疼痛评分。

结果

在ROAT中，正丙醇在SLS 1.0%的水平表现出刺激潜力，通过视觉评分，仅发现其与两种最高浓度的NON（20%和30%）有显著差异。在洗涤试验中，正丙醇的刺激性远低于SLS，仅通过视觉读数在统计学上可与NON（任何浓度）区分开来。对于两种测试模型，通过仪器测量，正丙醇与任何NON浓度均无显著差异。