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使用胶带剥离法和生物监测评估二苯基甲烷-4,4'-二异氰酸酯的皮肤吸收情况。

Assessment of dermal uptake of diphenylmethane-4,4'-diisocyanate using tape stripping and biological monitoring.

作者信息

Hamada Haneen, Liljelind Ingrid, Bruze Magnus, Engfeldt Malin, Isaksson Marléne, Jönsson Bo, Tinnerberg Håkan, Lindh Christian, Axelsson Sara, Zimerson Erik

机构信息

Lund University, Department of Occupational and Environmental Dermatology, Skåne University Hospital, Malmö, Sweden.

Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, Umeå University, Umeå, Sweden.

出版信息

Eur J Dermatol. 2018 Apr 1;28(2):143-148. doi: 10.1684/ejd.2018.3247.

DOI:10.1684/ejd.2018.3247
PMID:29620002
Abstract

Very little is known about the dermal uptake of isocyanates, and dermal exposure to isocyanates has been discussed as a factor involved in the induction of respiratory diseases. To investigate the dermal uptake of diphenylmethane-4,4'-diisocyanate (4,4'-MDI). Four volunteers were dermally exposed to 10, 25, 49 and 50 mg 4,4'-MDI, respectively, for eight hours. The exposed areas were tape stripped. Urine and blood were biologically monitored for 48 hours. Tape strips, plasma, and urine were analysed by liquid chromatography-mass spectrometry. In total, 35-70% of the applied dose of 4,4'-MDI was absorbed by the skin. Very low fractions of applied dose were found in the tape strips. The 4,4'-MDA concentration in plasma and urine was low, but peaked in urine at 10-14 hours and plasma at 8-32 hours after exposure. 4,4'-MDI is readily absorbed by human skin. Only small fractions of 4,4'-MDI remain as such in the superficial skin layers. The amounts found in blood and urine were only small fractions of the total applied doses which indicates that very small amounts of 4,4'-MDI penetrate the skin and reach the blood stream. The dermal uptake and distribution of 4,4'-MDI is much slower compared to that associated with airway uptake. Our data strongly indicate that formation of 4,4'-MDA from 4,4'-MDI upon reacting with water in the skin can only occur to a very limited extent.

摘要

关于异氰酸酯的皮肤吸收情况,人们了解甚少,皮肤接触异氰酸酯已被视为引发呼吸系统疾病的一个因素。为了研究二苯基甲烷-4,4'-二异氰酸酯(4,4'-MDI)的皮肤吸收情况,四名志愿者分别接受了10毫克、25毫克、49毫克和50毫克4,4'-MDI的皮肤暴露,时长为八小时。对暴露部位进行胶带剥离。对尿液和血液进行了48小时的生物监测。通过液相色谱-质谱联用仪对胶带条、血浆和尿液进行分析。总体而言,所施用剂量的4,4'-MDI有35%-70%被皮肤吸收。在胶带条中发现的施用剂量比例非常低。血浆和尿液中的4,4'-MDA浓度较低,但在暴露后10-14小时尿液中浓度达到峰值,在8-32小时血浆中浓度达到峰值。4,4'-MDI很容易被人体皮肤吸收。只有一小部分4,4'-MDI以原样留在皮肤表层。在血液和尿液中发现的量仅占总施用剂量的一小部分,这表明只有极少量的4,4'-MDI穿透皮肤并进入血流。与气道吸收相比,4,4'-MDI的皮肤吸收和分布要慢得多。我们的数据有力地表明,4,4'-MDI在皮肤中与水反应生成4,4'-MDA的情况只能在非常有限的程度上发生。

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