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志愿者对纯2-丁氧基乙醇及其水溶液的经皮吸收情况。

Percutaneous absorption of neat and aqueous solutions of 2-butoxyethanol in volunteers.

作者信息

Jakasa I, Mohammadi N, Krüse J, Kezic S

机构信息

Coronel Institute, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE, Amsterdam, The Netherlands.

出版信息

Int Arch Occup Environ Health. 2004 Feb;77(2):79-84. doi: 10.1007/s00420-003-0456-3. Epub 2003 Aug 12.

Abstract

OBJECTIVES

To study the influence of the presence of water on the dermal absorption of 2-butoxyethanol (BE) in volunteers.

METHODS

Six male volunteers were dermally exposed to 50%, 90% or neat w/w BE for 4 h on the volar forearm over an area of 40 cm(2). An inhalation exposure with a known input rate and duration served as a reference dosage. The dermal absorption parameters were calculated from 24-h excretion of total (free + conjugated) butoxyacetic acid (BAA) in urine and BE in blood, measured after both inhalation and dermal exposure.

RESULTS

The dermal absorption of BE from aqueous solutions was markedly higher than that of neat BE. The time-weighted average dermal fluxes were calculated from the urine and blood data and expressed in milligrammes per square centimetre per hour. The dermal fluxes obtained from cumulative 24-h excretion of BAA amounted to 1.34+/-0.49, 0.92+/-0.60 and 0.26+/-0.17 mg cm(-2) h(-1 )for 50%, 90% and neat BE, respectively. The dermal fluxes calculated from the BE blood data amounted to 0.92+/-0.34 and 0.74+/-0.25 mg cm(-2) h(-1 )for 50% and 90% BE, respectively. The permeation rates into the blood reached a plateau between 60 and 120 min after the start of exposure, indicating achievement of steady-state permeation. The apparent permeability coefficient K(p), was 1.75+/-0.53x10(-3) and 0.88+/-0.42x10(-3) cm h(-1 )for 50% and 90% BE, respectively.

CONCLUSION

The percutaneous absorption of BE from aqueous solution increased markedly when compared with neat BE. Even water content as low as 10% led to an approximate fourfold increase in the permeation rates. These findings are important for the health risk assessment of occupational exposure to BE, since BE is commonly used in mixtures that contain water. Exposure to aqueous solutions of 50% and 90% of BE may result in substantial skin absorption: if a 60-min skin contact of 1,000 cm(2) is assumed, dermal uptake would be four-times higher than the pulmonary uptake of an 8-h occupational exposure at a TLV of 100 mg m(-3). This clearly justifies the skin notation for BE. For the purpose of biological monitoring, both BE in blood and BAA in urine were shown to be reliable indicators of exposure.

摘要

目的

研究水分的存在对志愿者皮肤吸收2-丁氧基乙醇(BE)的影响。

方法

6名男性志愿者在前臂掌侧40平方厘米的区域,分别接触50%、90%或纯的(重量/重量)BE,持续4小时。以已知输入速率和持续时间的吸入暴露作为参考剂量。根据吸入和皮肤暴露后尿液中总(游离+结合)丁氧基乙酸(BAA)和血液中BE的24小时排泄量,计算皮肤吸收参数。

结果

BE从水溶液中的皮肤吸收明显高于纯BE。根据尿液和血液数据计算时间加权平均皮肤通量,并以每平方厘米每小时毫克数表示。从BAA的24小时累积排泄量获得的皮肤通量,50%、90%和纯BE分别为1.34±0.49、0.92±0.60和0.26±0.17毫克/平方厘米·小时。根据BE血液数据计算的皮肤通量,50%和90% BE分别为0.92±0.34和0.74±0.25毫克/平方厘米·小时。暴露开始后60至120分钟内,进入血液的渗透速率达到平台期,表明达到稳态渗透。50%和90% BE的表观渗透系数K(p)分别为1.75±0.53×10(-3)和0.88±0.42×10(-3)厘米/小时。

结论

与纯BE相比,BE从水溶液中的经皮吸收显著增加。即使水含量低至10%,渗透速率也会增加约四倍。这些发现对于职业接触BE的健康风险评估很重要,因为BE常用于含水的混合物中。接触50%和90%的BE水溶液可能导致大量皮肤吸收:假设1000平方厘米皮肤接触60分钟,皮肤吸收量将比职业接触8小时、阈限值为100毫克/立方米时的肺部吸收量高四倍。这显然证明了BE的皮肤标注是合理的。为了进行生物监测,血液中的BE和尿液中的BAA均被证明是可靠的暴露指标。

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