Critical periods of neuroendocrine development: effects of prenatal xenobiotics.

Phenobarbital, when administered prenatally in a small dose to animals, produced profound, and permanent effects on reproductive function in the offspring. Preliminary analysis of a unique cohort of adolescents who were exposed to phenobarbital in utero, suggests that long-term effects are also evident in the human. The precise nature of these effects is currently being determined and will be reported separately. These effects may be qualitatively and quantitatively different from effects seen in animals because of species difference in the timing or neuroendocrine differentiation. Of greater importance, however, is the fact that biologic and pharmacologic effects can be seen in the human following exposure to xenobiotics perinatally. Implications for other pharmacologic agents await further investigation. The rat model appears to have validity for extrapolation to man.