Quantitative structure-activity relationship model for the fetal-maternal blood concentration ratio of chemicals in humans.

Abstract

A quantitative structure-activity relationship (QSAR) model of the fetal-maternal blood concentration ratio (F/M ratio) of chemicals was developed to predict the placental transfer in humans. Data on F/M ratio of 55 compounds found in the literature were separated into training (75%, 41 compounds) and testing sets (25%, 14 compounds). The training sets were then subjected to multiple linear regression analysis using the descriptors of molecular weight (MW), topological polar surface area (TopoPSA), and maximum E-state of hydrogen atom (Hmax). Multiple linear regression analysis and a cross-validation showed a relatively high adjusted coefficient of determination (Ra(2)) (0.73) and cross-validated coefficient of determination (Q(2)) (0.71), after removing three outliers. In the external validation, R(2) for external validation (R(2)pred) was calculated to be 0.51. These results suggested that the QSAR model developed in this study can be considered reliable in terms of its robustness and predictive performance. Since it is difficult to examine the F/M ratio in humans experimentally, this QSAR model for prediction of the placental transfer of chemicals in humans could be useful in risk assessment of chemicals in humans.