Proteins are broken into increasingly smaller fragments in the mammalian digestive system. Intact proteins are, for the most part, not absorbed across the gut wall per se (Gardner, 1988). One exception would be a special class of milk-borne immunoglobulins (IgA) that are specifically designed to be absorbed to provide passive immunity for newborn mammals (Gardner, 1988). A second exception is that very low levels of intact proteins or large fragments of proteins are taken up by mononuclear leukocytes, possibly through macropinocytosis, as part of the immune system surveillance of gut contents (Tsume et al., 1996). From a nutritional perspective, proteins are typically classified as either non-digestible (excreted in the feces) or digestible (absorbed as small peptides and amino acids). Digestible proteins are largely soluble in water or acid whereas the indigestible proteins are typically insoluble, being bound primarily to sugars or fiber. Within the stomach, hydrochloric acid and pepsin denature and fragment the soluble proteins (Webb, 1990). Later in the small intestine, protein-digesting enzymes secreted by the pancreas and intestinal wall further fragment the protein chains into peptides of decreasing size, typically ranging in length from a few hundred amino acids down to the component individual amino acids and extremely short peptides (two to six amino acids). The stability of proteins introduced in transgenic plants is routinely determined in an in vitro digestive fate study as part of the regulatory assessment of allergenic potential (Genetically Modified Pest-Protected Plants: Science and Regulation, 2000). This approach to assess the safety relative to food allergy is consistent with the guidance provided by the International Life Science Institute (ILSI) and which has served as primary source of guidance for regulatory agencies around the world (Metcalf et al., 1996).

Roberts et al. (1999) evaluated the oral bioavailability of three bioactive peptides of varying size: thyrotropin-releasing hormone, lutenizing hormone-releasing hormone and insulin that are 3, 10 and 51 amino acid in size, respectively. This study showed that the oral bioavailability of these peptides was inversely related to their length such that peptides longer than 10 amino acids were very poorly absorbed intact. In addition, in most cases if small peptides are absorbed by intestinal epithelial cells they are degraded intracellularly to amino acids before being absorbed into the circulation. In another study, it was shown that 0.007-0.008% of ovalbumin orally administered to humans was detectable in their circulation (Tsume et al., 1996). The authors concluded that the digestive tract provides a strong barrier to the absorption of macromolecular proteins into the body. Amino acids that enter the blood stream are used to synthesize new proteins. Any non-essential amino acids in excess of nutritional requirements are further degraded to carbon and nitrogen that are oxidized as a source of energy (carbon), or to ammonia (nitrogen), that is converted to urea by the liver and excreted. Although the indigestible proteins pass through the digestive tract, they may be partially fermented by enteric bacteria in the large intestine as a source of energy and nitrogen.

To date, the proteins introduced into biotech products approved for food and feed usage have been shown to be readily degraded in simulated gastric digestion studies (Betz et al., 2000; Metcalf et al., 1996). Hence, the introduced proteins are unlikely to be detectable in animal products consumed by humans.