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豚鼠和人体皮肤对工业催化剂二甲基乙胺的体外皮肤吸收,以及人体志愿者对气态二甲基乙胺的吸收。

Skin absorption of the industrial catalyst dimethylethylamine in vitro in guinea pig and human skin, and of gaseous dimethylethylamine in human volunteers.

作者信息

Lundh T, Boman A, Akesson B

机构信息

Department of Occupational and Environmental Medicine, Lund University, Sweden.

出版信息

Int Arch Occup Environ Health. 1997;70(5):309-13. doi: 10.1007/s004200050223.

Abstract

OBJECTIVES

The aims of the study were three-fold: to assess the skin uptake of the industrial catalyst dimethylethylamine (DMEA) (a) in vitro from water solutions by fresh guinea-pig and human skin specimens, (b) in gaseous form in vivo in human volunteers, and (c) to estimate the relevance of the uptake as an occupational hazard.

METHODS

Specimens from the in vitro and in vivo experiments were analysed by gas chromatography using a nitrogen-sensitive detector.

DESIGN

DMEA, diluted with water or isotonic saline solution was applied to fresh human or guinea-pig skin, mounted in Teflon flow-through cells with a perfusion fluid flow rate of 1.5 ml/h, samples being collected at 2-h intervals for 48 h. Three healthy male volunteers each had their right forearm exposed (in a Plexiglass chamber) for 4 h to DMEA at each of three different levels (250, 500 and 1000 mg/m3 air). Urine was collected up to 24 h after the start of each experiment.

RESULTS

DMEA penetrated both guinea-pig and human skin. The median steady-state flux and permeability coefficient (Kp) values, were 0.009 mg/cm2 x h and 0.001 cm/h, respectively, for guinea-pig skin, and 0.017 mg/cm2 x h and 0.003 cm/h, respectively, for human skin. The median uptake in the three volunteers at the different DMEA exposure levels (250, 500 or 1000 mg/m3) was 44, 64 and 88 micrograms, respectively. The median Kp for all experiments was 0.037 cm/h.

CONCLUSION

Uptake of DMEA through the skin is of far less importance than simultaneous uptake via the airways. Thus, the amount of DMEA excreted in urine is a variable of limited use for the purposes of biological monitoring. Although a wide range of Kp values was obtained in the in vitro experiments, both for guinea-pig and human skin, there was no marked difference in median Kp values between the two types of skin. The Kp values were lower than those obtained for human forearm skin in vivo. However, future studies of other tertiary aliphatic amines may show the in vitro method to yield values predictive of those obtained in in vivo studies.

摘要

目的

本研究有三个目的:(a) 在体外通过新鲜豚鼠和人体皮肤标本评估工业催化剂二甲基乙胺(DMEA)从水溶液中的皮肤吸收情况;(b) 在体内以气态形式评估人体志愿者对其的吸收情况;(c) 评估这种吸收作为职业危害的相关性。

方法

使用氮敏感检测器通过气相色谱法分析体外和体内实验的标本。

设计

将用水或等渗盐溶液稀释的DMEA应用于新鲜的人体或豚鼠皮肤,皮肤安装在特氟龙流通池中,灌注液流速为1.5 ml/h,每隔2小时收集样本,持续48小时。三名健康男性志愿者每人将其右前臂(置于有机玻璃舱中)在三种不同浓度水平(250、500和1000 mg/m³空气)下暴露于DMEA 4小时。在每个实验开始后直至24小时收集尿液。

结果

DMEA可穿透豚鼠和人体皮肤。豚鼠皮肤的稳态通量中位数和渗透系数(Kp)值分别为0.009 mg/cm²·h和0.001 cm/h,人体皮肤的相应值分别为0.017 mg/cm²·h和0.003 cm/h。在不同DMEA暴露水平(250、500或1000 mg/m³)下,三名志愿者的吸收中位数分别为44、64和88微克。所有实验的Kp中位数为0.037 cm/h。

结论

通过皮肤吸收DMEA的重要性远低于同时通过呼吸道吸收。因此,尿液中排出的DMEA量作为生物监测指标的用途有限。尽管在体外实验中,豚鼠和人体皮肤都获得了广泛的Kp值范围,但两种皮肤的Kp中位数没有明显差异。这些Kp值低于人体前臂皮肤在体内获得的值。然而,未来对其他叔脂肪胺的研究可能表明,体外方法得出的值可预测体内研究获得的值。

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