Some aspects of prenatal toxicology

Abstract

This article discusses the frontiers of the emerging field of prenatal toxicology and makes several recommendations. The considerable confusion that has been created on nomenclature and definitions (confused especially since well-established aspects of general toxicology have been ignored) should be avoided. More basic research and information is required to elucidate the exact mechanism of action (which remains unknown for most agents, including thalidomide) and pharmacokinetic characteristics of teratogens, and to explain the permanent dysfunctions that may be induced prenatally in various organs, especially during the fetal period. In-vitro methods are of considerable value for ‘secondary’ testing in prenatal toxicology (elucidation of mechanisms of action, studies on dose-effect relationships, drug metabolism, etc.). So far, such methods can only be used exceptionally for ‘primary’ testing (that is for the purpose of obtaining first and conclusive evidence on the embryotoxic potential and potency of an agent). Standardization and validation of such methods are urgently needed. Basic principles for a risk assessment (with respect to man) have been less clearly established for prenatal toxicity than for other fields of toxicology. Questions of the existence of a ‘threshold’ (for practical purposes), the basis for an extrapolation of dose-response relationships and the evaluation of the embryonic effect of combinations of teratogens, need to be answered.