Shared models and mechanisms? The examples of DES and phthalate syndrome

Abstract

Background: Historically, major environmental toxicants could be linked to human health outcomes because these early exposures were large and visible and risks to individuals were dramatic. The challenge we are now facing is that of detecting human health risks from invisible, low-level exposures that impact health predominantly at the population level. Endocrine disruption is, I suggest, the primary means by which such exposures impact health. To identify the impacts of these chronic low-levels exposures on human populations, animal toxicology studies can be invaluable as they can provide data that can then be assessed in epidemiology studies. Epidemiology studies can also inform animal toxicology as to possible links between exposures and effects. Aims: 1) To use the example of the drug diethylstilbestrol (DES) to examine how human studies can inform animal toxicology; and 2) to use the example of the phthalate syndrome to discuss how animal toxicology can inform epidemiology. Methods: I will review the historical interplay of animal and human studies in these two examples. Many outcomes of prenatal DES exposure in humans are seen in rodent studies, but not all. Similarly, not all aspects of the phthalate syndrome described first in rodents have been observed in humans. Examining the similarities and differences between outcomes of these exposures in humans and animals demonstrates the value (and challenges) of these cross-species comparisons. Conclusions: When animal and human data are available on an exposure-outcome relationship, and scientists in both areas are willing to learn from each other both the epidemiology and the toxicology benefit. Ultimately the conclusions of both are strengthened, with the result that public health is better protected.