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对硫磷在猪皮中的体外经皮吸收:剂量、温度、湿度和灌注液成分对吸收通量的影响

Percutaneous absorption of parathion in vitro in porcine skin: effects of dose, temperature, humidity, and perfusate composition on absorptive flux.

作者信息

Chang S K, Riviere J E

机构信息

Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.

出版信息

Fundam Appl Toxicol. 1991 Oct;17(3):494-504. doi: 10.1016/0272-0590(91)90200-n.

Abstract

The effect of environmental factors on the percutaneous absorption of parathion in excised porcine skin was assessed in a flow-through diffusion cell system by varying the temperature (T), relative humidity (%RH), perfusate flow rate (F), and composition (porcine serum) at three parathion doses (4, 40, and 400 micrograms/cm2) compared to standard conditions (air temperature = 37 degrees C, perfusate temperature = 37 degrees C, %RH = 60, flow rate = 4 ml/hr, and standard bovine serum albumin medium). Parathion absorption was assessed by monitoring total radiolabeled activity appearing in the perfusate over time. High relative humidity significantly increased parathion penetration, as did two elevated temperature conditions. The effects of flow rate and perfusate composition were variable and dose dependent. In the present studies, lower applied doses appeared to be more sensitive to changes in the environmental conditions studied. These results suggest that these parameters have independent and different degrees of effect on parathion percutaneous absorption. Experimental conditions should be strictly controlled and dose-response studies need to be conducted when evaluating transdermal studies. Finally, if similar effects occur in vivo, the risk assessment calculations on percutaneous absorption should take these parameters into consideration.

摘要

在流通扩散池系统中,通过改变温度(T)、相对湿度(%RH)、灌注液流速(F)和成分(猪血清),在三种对硫磷剂量(4、40和400微克/平方厘米)下,评估环境因素对离体猪皮肤中对硫磷经皮吸收的影响,并与标准条件(气温 = 37摄氏度,灌注液温度 = 37摄氏度,%RH = 60,流速 = 4毫升/小时,以及标准牛血清白蛋白培养基)进行比较。通过监测随时间出现在灌注液中的总放射性标记活性来评估对硫磷的吸收。高相对湿度显著增加了对硫磷的渗透,两种升高的温度条件下也是如此。流速和灌注液成分的影响是可变的且依赖于剂量。在本研究中,较低的施用剂量似乎对所研究的环境条件变化更敏感。这些结果表明这些参数对对硫磷经皮吸收具有独立且不同程度的影响。在评估透皮研究时,应严格控制实验条件并进行剂量反应研究。最后,如果在体内出现类似效应,经皮吸收的风险评估计算应考虑这些参数。

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