Should oral gavage be abandoned in toxicity testing of endocrine disruptors?

For decades, hazard assessments for environmental chemicals have used intra-gastric gavage to assess the effects of ‘oral’ exposures. It is now widely used – and in some cases required – by US federal agencies to assess potential toxicity of endocrine disrupting chemicals (EDCs). In this review we enumerate several reasons why gavage is not appropriate for the assessment of EDCs using bisphenol A (BPA) as a main example. First, whereas human dietary exposures interact with the oral mucosa, gavage exposures avoid these interactions, leading to dramatic differences in absorption, bioavailability and metabolism with implications for toxicokinetic assumptions and models. Additionally, there are well acknowledged complications associated with gavage, such as perforation of the esophagus that diminish its value in toxicological experiments. Finally, the gavage protocol itself can induce stress responses by the endocrine system and confound the assessment of EDCs. These serious flaws have not been taken into account in interpreting results of EDC research. We propose the exploration of alternatives to mimic human exposures when there are multiple exposure routes/sources and when exposures are chronic. We conclude that gavage may be preferred over other routes for some environmental chemicals in some circumstances, but it does not appropriately model human dietary exposures for many chemicals. Because it avoids exposure pathways, is stressful, and thus interferes with endocrine responses, gavage should be abandoned as the default route of administration for hazard assessments of EDCs.