PREDICTING CHEMICAL IMPACTS ON VERTEBRATE ENDOCRINE SYSTEMS

Animals have evolved diverse protective mechanisms for responding to toxic chemicals of both natural and anthropogenic origin From a governmental regulatory perspective these protective responses complicate efforts to establish acceptable levels of chemical exposure To explore this issue we considered vertebrate endocrine systems as potential targets for environmental contaminants Using the hypothalamic pituitary thyroid (HPT) hypothalamic pituitary gonad (HPG) and hypothalamic-pituitary-adrenal (HPA) axes as case examples we identified features of these systems that allow them to accommodate and recover from chemical insults In doing so a distinction was made between effects on adults and those on developing organisms This distinction was required because endocrine system disruption in early life stages may alter development of organs and organ systems resulting in permanent changes in phenotypic expression later in life Risk assessments of chemicals that impact highly regulated systems must consider the dynamics of these systems in relation to complex environmental exposures A largely unanswered question is whether successful accommodation to a toxic insult exerts a fitness cost on individual animals resulting in adverse consequences for populations Mechanistically based mathematical models of endocrine systems provide a means for better understanding accommodation and recovery In the short term these models can be used to design experiments and interpret study findings Over the long term a set of validated models could be used to extrapolate limited in vitro and in vivo testing data to a broader range of untested chemicals, species and exposure scenarios With appropriate modification Tier 2 assays developed in support of the U S Environmental Protection Agency s Endocrine Disruptor Screening Program could be used to assess the potential for accommodation and recovery and inform the development of mechanistically based models Environ Toxicol Chem 2011,30 39-51 (C) 2010 SETAC