大鼠透皮电阻实验替代皮肤腐蚀性实验的验证

The in vitro rat skin transcutaneous electrical resistance test used as a alternative for traditional skin corrosion test

目的通过建立大鼠皮肤透皮电阻(TER)实验,研究运用体外方法替代动物试验检测化学品皮肤腐蚀性的可行性。方法参照经济合作与发展组织(OECD)体外实验方法指南430(透皮电阻分析法)建立测定系统,使用11种参考物质对该实验体系进行评估。根据本实验系统对参考物质的实测数据,可判定TER值>15 kΩ为阴性(非腐蚀性),TER<5 kΩ为阳性(腐蚀性),TER介于两者之间或3个平行样的TER测定值在界值上下波动时为可疑阳性,进一步进行染料渗透量测定,以8 mol/L盐酸测得的染料渗透量作为判断标准。结果整个实验的灵敏度为100%(5/5),特异度100%(6/6)。结论大鼠TER测定和染料渗透量分析相结合能成功判断本研究所选的11种标准化学物质的皮肤腐蚀性。此方法在实际运用中的有效性还需更多化学物质的检测来验证。

Objective The rat skin transcutaneous electrical resistance（TER） test was established to investigate the practicality of the in vitro method as a alternative for animal experiment to determine skin corrosion of chemicals. Methods The equipment for TER detection was assembled referring to OECD guideline for the testing of chemicals ： Guideline 430, in vitro skin corrosion ： transcutaneous electrical resistance test （TER）. A group of 11 reference chemicals was adopted to evaluate the performance of this test system. Based on the data obtained from this test system, skin corrosion determination procedure was adjust as below：the test substance was considered to be noncorrosive if the TER values obtained were greater than 15 kΩ; the test substance was considered to be corrosive if the TER values obtained were less than 5 kΩ; when the TER values were between 5 kΩ and 15 kΩ or on either side of the dividing values, the salforhdamine B dye infiltration capacity was analyzed, if the mean disc dye content was greater than or equal to that of 8 M HC1 positive control obtained concurrently, the test substance was considered to be corrosive, otherwise it was considered to be noncorrosive. Results The sensitivity and the specificity of this test system to the reference chemicals adopted were all 100% . Conclusion Although the rat skin transcutaneous electrical resistance test combined with sulforhdamine B dye infiltration capacity analysis had determined the skin corrosion of these limited reference chemicals successfully, more chemicals should be employed to further check the validity of this test system in practice.