The interaction of chemicals during pregnancy: an update

The role of chemical interactions in the genesis of induced embryotoxicity in humans and in experimental animals is a point of current concern and interest. This review summarizes the current knowledge in this field and demonstrates that, under appropriate conditions, the observed results of chemical interactions can be explained, in part, through an understanding of the underlying pharmacokinetic and pharmacodynamic parameters. These define the concentration of the "primary" teratogen at its receptor site in cells and tissues that are particularly sensitive to its embryotoxic action. The interacting "secondary" or "coteratogen" is viewed as an agent that is capable of altering these parameters in a way that is correlated with an observed alteration in the embryotoxic response. A series of recent experiments (diazouracil: 5-fluouracil; hydroxyurea: 5-bromodeoxyuridine; caffeine: 5-bromodeoxyuridine; caffeine: phenytoin) are reported which demonstrate both the validity and the limitations of such an approach and attempt to interpret observations, which are primarily empirical in nature, in pharmacologic terms.