Barbero Ana M, Frasch H Frederick
Health Effects Laboratory Division, National Institute for Occupational Safety and Heath, 1095 Willowdale Road, Morgantown, West Virginia 26505, USA.
Toxicol In Vitro. 2009 Feb;23(1):1-13. doi: 10.1016/j.tiv.2008.10.008. Epub 2008 Oct 26.
Both human and animal skin in vitro models are used to predict percutaneous penetration in humans. The objective of this review is a quantitative comparison of permeability and lag time measurements between human and animal skin, including an evaluation of the intra and inter species variability. We limit our focus to domestic pig and rodent guinea pig skin as surrogates for human skin, and consider only studies in which both animal and human penetration of a given chemical were measured jointly in the same lab. When the in vitro permeability of pig and human skin were compared, the Pearson product moment correlation coefficient (r) was 0.88 (P<0.0001), with an intra species average coefficient of variation of skin permeability of 21% for pig and 35% for human, and an inter species average coefficient of variation of 37% for the set of studied compounds (n=41). The lag times of pig skin and human skin did not correlate (r=0.35, P=0.26). When the in vitro permeability of guinea pig and human skin were compared, r=0.96 (P<0.0001), with an average intra species coefficient of variation of 19% for guinea pig and 24% for human, and an inter species coefficient of variation of permeability of 41% for the set of studied compounds (n=15). Lag times of guinea pig and human skin correlated (r=0.90, P<0.0001, n=12). When permeability data was not reported a factor of difference (FOD) of animal to human skin was calculated for pig skin (n=50) and guinea pig skin (n=25). For pig skin, 80% of measurements fell within the range 0.3<FOD<3. For guinea pig skin, 65% fell within that range. Both pig and guinea pig are good models for human skin permeability and have less variability than the human skin model. The skin model of choice will depend on the final purpose of the study and the compound under investigation.
人体和动物皮肤体外模型均用于预测人体的经皮渗透性。本综述的目的是对人体和动物皮肤的渗透性和滞后时间测量进行定量比较，包括评估种内和种间变异性。我们将重点局限于家猪和啮齿动物豚鼠的皮肤作为人体皮肤的替代物，并且只考虑在同一实验室中同时测量给定化学物质在动物和人体中渗透率的研究。当比较猪和人体皮肤的体外渗透率时，皮尔逊积矩相关系数（r）为0.88（P<0.0001），猪皮肤渗透率的种内平均变异系数为21%，人体皮肤为35%，所研究化合物组（n=41）的种间平均变异系数为37%。猪皮肤和人体皮肤的滞后时间不相关（r=0.35，P=0.26）。当比较豚鼠和人体皮肤的体外渗透率时，r=0.96（P<0.0001），豚鼠的种内平均变异系数为19%，人体皮肤为24%，所研究化合物组（n=15）的渗透率种间变异系数为41%。豚鼠和人体皮肤的滞后时间相关（r=0.90，P<0.0001，n=12）。当未报告渗透率数据时，计算了猪皮肤（n=50）和豚鼠皮肤（n=25）的动物与人体皮肤的差异因子（FOD）。对于猪皮肤，80%的测量值落在0.3<FOD<3的范围内。对于豚鼠皮肤，65%落在该范围内。猪和豚鼠都是人体皮肤渗透性的良好模型，并且比人体皮肤模型具有更小的变异性。选择的皮肤模型将取决于研究的最终目的和所研究的化合物。
