The Gastrointestinal Tract and Short-term Toxici~ Tests

The primary role of the gastrointestinal tract is the digestion and absorption of nutrients. This is critical for normal body homeostasis. The gastrointestinal tract also forms a barrier against unwanted materials, and is a major site of biotransformation and excretion. Its immunological function is defence against infection and the prevention of hypersensitivity reactions are dependent upon effective microenvironmental immunoregulation at the mucosal level. The implications of the symbiotic relationships of the gastrointestinal microflora are still being elucidated, while the complexities of the overall control of gut motility, secretion and growth are now recognized to depend on interactions between the autonomic nervous system and the neuroendocrine connections of the peptidergic nerves. The importance of the gut with respect to toxicology arises from its central role in the absorption of ingested materials. It is the major portal of entry for a wide variety of compounds including those which have no nutritional or other functional value (xenobiotics). Most of our knowledge about absorption, transport and metabolism of xenobiotics relates to the normal adult gut, however, the expected effects following ingestion of a particular compound depend on the integrity of the intestinal mucosa. In infancy, many aspects of gut function are immature and, at any age, there are many situations in which mucosal function is compromised; infections, hypersensitivity reactions and malnutrition can all alter permeability of the gut due to epithelial cell damage, with varying effects on absorption of the compound in question.