Sartorelli P, Aprea C, Cenni A, Novelli M T, Orsi D, Palmi S, Matteucci G
Institute of Occupational Medicine, Siena University, Italy.
Ann Occup Hyg. 1998 May;42(4):267-76. doi: 10.1016/s0003-4878(98)00021-0.
Correlations between in vitro percutaneous absorption data and physicochemical properties of industrial chemicals are evaluated in order to develop predictive mathematical models based on said properties. Percutaneous diffusion of 16 pounds of occupational interest, eight of which were polycyclic aromatic hydrocarbons (acenaphthene, anthracene, benzo(a)anthracene, chrysene, phenanthrene, fluorene, naphthalene, pyrene), six organophosphorus insecticides (acephate, chlorpyrifos, dimethoate, fenitrothion, methamidophos, omethoate) and two phenoxycarboxylic herbicides (2,4-D, MCPA), were tested in vitro using monkey (Cercopithecus aetiops) skin. The test apparatus consisted of nine static diffusion cells with normal saline, gentamycin sulphate and 4% bovine serum albumin as receiving solution. Test compounds were applied at various concentrations in 30 microliters of acetone solution and determined, in the receiving phase, by chemical analysis. Values for ln Kow (octanol/water partition coefficient) were correlated with experimentally determined values of the permeability constant Kp (r = 0.90, P < 0.001) and lag time (r = 0.81, P < 0.01). Analysis of variance in a model of multiple linear regression between Kp, ln Kow and water solubility [water] of the compounds, showed that the data had a highly significant fit (P < 0.0001). A more general model which also included molecular weight (MW) and vapour pressure was evaluated as well, but the two variables made no substantial difference. Multiple regression analysis between lag time, ln Kow and [water] was significant (P < 0.0001), whereas introduction of vapour pressure and MW as independent variables did not significantly improve the predictive effect on lag time. Our experimental system, therefore, enables the values of Kp and lag time to be predicted with reasonable precision on the basis of ln Kow and [water] values, using the algorithm derived from the multiple linear regression equation.
为了基于工业化学品的物理化学性质开发预测性数学模型，对体外经皮吸收数据与这些性质之间的相关性进行了评估。使用猴（食蟹猴）皮肤在体外测试了16种具有职业相关性的化合物的经皮扩散情况，其中8种是多环芳烃（苊、蒽、苯并(a)蒽、 Chrysene、菲、芴、萘、芘），6种有机磷杀虫剂（乙酰甲胺磷、毒死蜱、乐果、杀螟硫磷、甲胺磷、氧乐果）和2种苯氧羧酸类除草剂（2,4-滴、灭草灵）。测试装置由9个静态扩散池组成，接收液为生理盐水、硫酸庆大霉素和4%牛血清白蛋白。将测试化合物以不同浓度溶于30微升丙酮溶液中涂抹，在接收相中通过化学分析进行测定。辛醇/水分配系数（ln Kow）值与实验测定的渗透常数Kp值（r = 0.90，P < 0.001）和滞后时间（r = 0.81，P < 0.01）相关。对化合物的Kp、ln Kow和水溶性[水]进行多元线性回归模型的方差分析，结果表明数据拟合度非常显著（P < 0.0001）。还评估了一个更通用的模型，该模型也包括分子量（MW）和蒸气压，但这两个变量没有显著差异。滞后时间、ln Kow和[水]之间的多元回归分析具有显著性（P < 0.0001），而引入蒸气压和MW作为自变量并没有显著提高对滞后时间的预测效果。因此，我们的实验系统能够根据ln Kow和[水]值，使用从多元线性回归方程导出的算法，以合理的精度预测Kp和滞后时间的值。
