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体外人皮肤暴露于稀三氯乙烯水溶液中的初始摄取动力学。

Initial uptake kinetics in human skin exposed to dilute aqueous trichloroethylene in vitro.

作者信息

Bogen K T, Keating G A, Meissner S, Vogel J S

机构信息

Health and Ecological Assessment Division, Lawrence Livermore National Laboratory, University of California, Livermore 94550-9900, USA.

出版信息

J Expo Anal Environ Epidemiol. 1998 Apr-Jun;8(2):253-71.

PMID:9577754
Abstract

In vitro uptake of 14C-labeled trichloroethylene (TCE) from dilute (approximately 5-ppb) aqueous solutions into human surgical skin was measured using accelerator mass spectrometry (AMS). We analyzed 105 breast-tissue samples obtained from three subjects, representing 27 separate exposure experiments conducted at approximately 20 degrees C for 0, 1, 5, 15, 30, or 60 min. The AMS data obtained positively correlate with (p approximately 0) and vary significantly nonlinearly with (p = 0.0094) exposure duration. These data are inconsistent (p approximately 0) with predictions made for TCE by a proposed U.S. Environmental Protection Agency (USEPA) dermal-exposure model, even when uncertainties in its recommended parameter values for TCE are considered, but are consistent (p = 0.17) with a 1-compartment model for exposed skin-surface tissue governed in vitro by a maximum effective permeability of Kp = 0.28 cm h-1 (+/- 7.0%) and a first-order rate constant of k1 = 1.2 h-1 (+/- 16%). The apparent compartment depth is estimated to be approximately 40-100 microns, i.e., to comprise much or all of the epidermis. In contrast, the USEPA model implies only negligible TCE penetration beyond SC during a 1-h exposure. The Kp estimate based on the 1-compartment model fit is consistent with estimates for TCE based on in vivo studies, which supports the hypothesis that the USEPA model underpredicts short-term dermal uptake of TCE from water. It is shown that for humans, this fit also implies that normalized total uptake of TCE from water by short-term dermal contact in vivo is predicted to be fK*p, where f is approximately 80% for longer normothermic exposures and approximately 95% during a brief hot shower or bath. This study illustrates the power of AMS to facilitate analyses of contaminant biodistribution and uptake kinetics at very low environmental concentrations.

摘要

使用加速器质谱法(AMS)测定了在约20℃下,从稀(约5 ppb)水溶液中14C标记的三氯乙烯(TCE)进入人体手术皮肤的体外摄取情况。我们分析了从三名受试者获得的105份乳腺组织样本,这些样本代表了在约20℃下进行的27次独立暴露实验,暴露时间分别为0、1、5、15、30或60分钟。获得的AMS数据与暴露持续时间呈正相关(p约为0),且与暴露持续时间呈显著非线性变化(p = 0.0094)。即使考虑到美国环境保护局(USEPA)提出的皮肤暴露模型中TCE推荐参数值的不确定性,这些数据与该模型对TCE的预测也是不一致的(p约为0),但与一个单室模型一致(p = 0.17),该模型用于体外暴露的皮肤表面组织,其最大有效渗透率Kp = 0.28 cm/h(±7.0%),一级速率常数k1 = 1.2 h-1(±16%)。表观室深度估计约为40 - 100微米,即包括大部分或全部表皮。相比之下,USEPA模型表明在1小时暴露期间,TCE穿透角质层(SC)的量可忽略不计。基于单室模型拟合得到的Kp估计值与基于体内研究的TCE估计值一致,这支持了USEPA模型低估了TCE从水中的短期皮肤摄取量这一假设。结果表明,对于人类而言,这种拟合还意味着体内短期皮肤接触从水中摄取TCE的归一化总摄取量预计为fK*p,其中对于较长时间的正常体温暴露,f约为80%,在短暂的热水淋浴或盆浴期间约为95%。本研究说明了AMS在促进分析极低环境浓度下污染物生物分布和摄取动力学方面的作用。

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